abstract:
Objective To explore the protective effect and mechanism of Rhodiola rosea(Rho) bionic nanomedicine in rats with acute pancreatitis. Methods Erythrocyte membrane vesicles(EMV) were used as biomimetic nanomedicine coating materials to construct Rho biomimetic nanomedicine. Meanwhile, rat models of acute pancreatitis were constructed and divided into acute pancreatitis model(AP) group, Rho group, EMV group and Rhodiola rosea erythrocyte membrane vesicles(R-EMV) group. R-EMV group rats were further treated with NLRP3 activator BMS-986299(R-EMV+BMS-986299 group) and inhibitor MCC950(R-EMV+MCC950 group). The changes of abdominal water volume were observed, and serum levels of interleukin(IL-6), IL-1β, endothelin(ET), diamine oxidase(DAO), malondialdehyde(MDA), superoxide dismutase(SOD) and glutathione(GSH) were detected by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe the pathological changes of pancreatic tissue. Immunohistochemistry, reverse transcription-polymerase chain reaction(RT-PCR) and Western blot were used to analyze the expression of NOD-like receptor protein 3(NLRP3) and nuclear transcription factor-Kappa B(NF-κB) in pancreatic tissue. Results The prepared R-EMVs were nearly circular, the average particle size was(244.61±1.08) nm, and the Zeta potential was-(11.13±1.25) mV. At the same time, the EMV could load(58.67±0.79) μg of Rho. Compared with Sham group, the abdominal water volume of rats in AP group was significantly higher(t=33.79,P<0.01), and the levels of peripheral blood immune indexes IL-1β, IL-6, ET and DAO increased(t=38.25, 42.54, 29.20, 34.92, allP<0.01). In AP group, there were obvious tissue hyperemia and edema, widening of lobular space, infiltration of a large number of inflammatory cells, and increased pancreatic pathological score(t=30.06,P<0.01). Compared with AP group, abdominal water volume, dry-wet weight ratio of pancreas, pathological score, amylase and lipase levels in Rho group decreased(F=1 523.7, 543.3, 839.9, 446.1, 172.2,P<0.05). Compared with other groups, the levels of serum IL-1β, IL-6, ET and DAO in AP group decreased to some extent. Compared with AP group, NF-κB p65 and NLRP3 protein levels and NF-κB and NLRP3 immunohistochemical staining scores decreased in R-EMV group(t=24.54 and 26.91, bothP<0.001). At the same time, the levels of serum IL-1β, IL-6, ET, DAO, MDA, SOD and GSH in R-EMV+MCC950 group were significantly lower than those in AP group, R-EMV group and R-EMV+BMS-986299 group.Conclusion R-EMV has a good pancreatic protection effect in acute pancreatitis, which is related to reducing the activity of NF-κB/NLRP3 pathway and down-regulating the expression of inflammatory factors such as IL-6 and oxidative stress indicators such as MDA.

abstract:
Objective To investigate the brain microvascular tissue block culture method for extracting primary rat brain microvascular endothelial cells and identify its effect. Methods Brain tissue from 4-week-old Sprague Dawley rats was screened, pre-digested and solidified to obtain brain microvascular segments. These segments were subsequently placed in a CO2incubator for primary culture. The target cells were identified by cell morphology and immunocytochemical staining for factor Ⅷ-related antigen. Results After a 48-hour culture periodin vitro, the short spindle cells crawled out from around the brain microvascular segments. After 72 hours, island-like cell culsters formed. After 96 hours the clusters fused and the cells formed a typical monolayer, cobble stone-like, and mosaic arrangement. Factor Ⅷ-related antigen immunocytochemical staining showed that the cytoplasm of the cells appeared brown-red, indicating positive expression; DAB stained the nucleus, showing blue-dark. Conclusion The brain microvascular tissue block culture method can isolate and culture primary rat brain microvascular endothelial cells.

abstract:
Objective To explore the role of lysophosphatidylcholine acyltransferase 3(LPCAT3) in Erastin-induced ferroptosis of acute myeloid leukemia(AML) cells and its related molecular regulatory mechanisms. Methods Tetrazolium salt(MTS) method was used to detect the sensitivity of different AML cells to the classic ferroptosis inducer Erastin, real time quantitative polymerase chain reaction(qPCR) was used to detect the basal expression level ofLPCAT3mRNA, and the correlation between them was analyzed. Lentivirus-mediatedLPCAT3overexpression AML cell lines(OE group) and negative control lines(NC group) were constructed. After Erastin intervention, MTS, flow cytometry, and micromethods were used to detect cell viability, lipid reactive oxygen species(ROS), and Malondialdehyde(MDA), respectively. qPCR and Western blot were used to detect unfolded protein response(UPR) classic pathway signaling molecules(PERK, ATF4, GRP78, etc.) expression levels. The above ferroptosis-related indicators were detected after combined intervention with the UPR inhibitor 4-phenylbutyric acid(4-PBA), and the regulatory relationship was analyzed. Results Four different types of AML cells had different sensitivities to ferroptosis, among which K562 cells were relatively insensitive. The IC50of the four types of AML cells to Erastin was negatively correlated with the expression level ofLPCAT3(r=-0.919,P<0.001). After Erastin intervention, the cell viability of K562 cells in the OE group was significantly inhibited by Erastin compared with the NC group(P<0.001), and the levels of lipid ROS and MDA increased(P<0.001). The results of qPCR and Western blot showed that, compared with the NC group, the mRNA and protein expression of UPR classic pathway moleculesPERK,ATF4, andGRP78mRNA and protein increased in the OE group(P<0.01). After inhibiting the UPR pathway by 4-PBA, the viability of K562 cells decreased(P<0.01), and lipid ROS and MDA levels increased(P<0.01) compared with the uninhibited state. Conclusion Overexpression ofLPCAT3can promote ferroptosis in K562 cells, and this process is negatively regulated by the classical UPR pathway PERK/ATF.

abstract:
Objective To investigate the mechanism of puerarin in the treatment of rheumatoid arthritis(RA) by network pharmacology and animal experiments. Methods Traditional Chinese Medicine Systems Pharmcolog Database(TCMSP) and SwissTargetPrediction database were used to collect puerarin targets, and the targets of RA were obtained from GeneCards database and OMIM database. The PPI network was established by Cytoscape 3.7.2 software. Gene ontology(GO) function and Kyotoencyclopedia of genes(KEGG) enrichment analysis were performed through the Metascape database. RA rat-collagen-induced arthritis(CIA) model was reproduced using type Ⅱ collagen emulsion, 49 Wistar rats were randomly assigned to seven groups: control group, CIA model group, low-dose, medium-dose and high-dose puerarin group, methotrexate group, Tripterysium Glycosides Tablets group. Except for the control group, the other groups were given continuous gavage for 28 days after the CIA in rats model were prepared. The redness and swelling of the joints and ankle joint pathological changes were observed in each group. Western blot was used to detect the expression of Glycogen synthase kinase3β(GSK-3β), beta-catenin(β-catenin) proteins in the synovium. Real-time quantitative polymerase chain reaction(qPCR) was used to detect the expression of GSK-3β, β-catenin and c-Myc mRNA in the synovium. Results Puerarin had 134 targets genes, RA had 5 821 target genes, and there were 102 overlapping target genes of puerarin and RA. It involved 184 signaling pathways, including JAK-STAT signaling pathway, NF-κB signaling pathway, Wnt signaling pathway, et al. The results of animal experiments showed that after the intervention of M-puerarin and MTX, the symptoms of redness and swelling of the hind foot were alleviated, the inflammatory cell infiltration in the synovium of the joint was significantly reduced, and the damage of cartilage and bone tissue was reduced. Compared with CIA group, the expressions of GSK-3β, β-catenin protein and GSK-3β, β-catenin and c-Myc mRNA in synovial tissue of rats after M-puerarin intervention decreased(P<0.05). Conclusion Puerarin has the characteristic of multi-components, multi-targets and multi-pathway intervention in RA. Puerarin may alleviate synovial hyperplasia, reduce articular cartilage erosion and bone destruction in CIA in rats by inhibiting Wnt/β-catenin signaling pathway.

abstract:
Objective To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis. Methods An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression. Results Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01). Conclusion Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.

abstract:
Objective To explore the molecular mechanism by which long non-coding RNA Surfactant Associated 1 Pseudogene(SFTA1P) promotes the proliferation and migration of clear cell renal cell carcinoma(ccRCC) cells by regulating the microRNA-182-5p(miR-182-5p)/fibronectin 1(FN1) pathway. Methods GEPIA2 software was utilized to analyze the expression ofSFTA1Pin ccRCC tissues from the TCGA database. Quantitative real-time PCR(qPCR) was employed to detect the expression ofSFTA1Pin ccRCC tissues, normal kidney tissues and ccRCC cell lines. A subcellular localization experiment was performed to explore the localization ofSFTA1Pwithin the human renal cell adenocarcinoma cell line(ACHN) derived from ccRCC. ACHN cells were then divided into the following groups: si-Con group, si-SFTA1P #2 group, mimic NC group, miR-182-5p mimic group, anti-miR-Con group, anti-miR-182-5p group, anti-miR-182-5p+si-FN1 group, si-Con+anti-miR-Con group, si-SFTA1P #2+anti-miR-Con group, and si-SFTA1P #2+anti-miR-182-5p group. CCK-8 and Transwell chamber experiments were conducted to assess cell proliferation and migration abilities. qPCR, Western blot, and dual-luciferase reporter assays were employed to elucidate the regulatory interactions amongSFTA1P,miR-182-5p, andFN1. Results Analysis of The Cancer Genome Atlas(TCGA) database indicated thatSFTA1Pwas overexpressed in ccRCC tissues(P<0.05). When compared to normal kidney tissues,SFTA1Pexpression was markedly elevated in ccRCC tissues(P<0.01). Furthermore, the expression levels ofSFTA1Pin ccRCC cell lines 786-O, SN12-PM6, ACHN, and A498 were significantly higher than those in human renal proximal tubule cells(HK-2)(allP<0.01). Subcellular localization experiments revealed thatSFTA1Ppredominantly localized in the cytoplasm of ACHN cells. Compared to the si-Con group, the si-SFTA1P #2 group exhibited a significant reduction in proliferation and migration abilities of ACHN cells, accompanied by a decrease inFN1mRNA and protein expression(P<0.05). Compared to the mimic NC group, the expression ofFN1mRNA and protein in ACHN cells in the miR-182-5p mimic group reduced(P<0.01). In comparison to the anti-miR-Con group, the expression levels ofFN1mRNA and protein in ACHN cells were significantly elevated in the anti-miR-182-5p group. Additionally, there was a significant enhancement in both cell proliferation and migration capabilities(P<0.05). Conversely, the proliferation and migration abilities of ACHN cells in the anti-miR-182-5p+si-FN1 group were significantly reduced compared to the anti-miR-182-5p group(P<0.05). Furthermore, relative to the si-SFTA1P #2+anti-miR-Con group, the ACHN cells in the si-SFTA1P #2+anti-miR-182-5p group demonstrated increased proliferation and migration abilities, along with elevatedFN1mRNA and protein expression levels(P<0.05). Conclusion SFTA1Pexhibits elevated expression levels in ccRCC and facilitates the proliferation and migration of ccRCC cells through the modulation of themiR-182-5p/FN1signaling pathway.

abstract:
Objective To explore the effect of YTH domain family protein 1(YTHDF1) on the activation, proliferation and migration of hepatic stellate cells(HSCs) by regulating mitochondrial fission mediated by mitochondrial fission protein 1(Fis1). Methods The mouse hepatic stellate cell line JS-1 was treated with 5 ng/ml TGF-β1 for 24 h to induce its activation and proliferation, andYTHDF1-siRNA was used to construct aYTHDF1silencing model.The experiment was divided into Control group, TGF-β1 group, TGF-β1+si-NC group and TGF-β1+si-YTHDF1 group.Expression changes ofYTHDF1,Fis1and key indicators of fibrosis, type Ⅰ collagen(CollagenⅠ) and α-smooth muscle actin(α-SMA) were detected through reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot; CCK-8 was used to detect cell proliferation ability; Transwell migration assay and cell scratch assay were used to detect cell migration ability; immunofluorescence staining experiment was used to detect the effect ofYTHDF1onFis1-mediated mitochondrial fission; finally, JC-1 staining was used to experimentally detect the effect ofYTHDF1on mitochondrial membrane potential. Results Compared with the Control group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1increased in the TGF-β1 group(P<0.05,P<0.01;P<0.000 1), as well as the fibrosis markersCollagenⅠand the expression level of α-SMA increased(P<0.01;P<0.001,P<0.000 1); while adding CCK-8, the experimental results showed that the proliferation ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); Transwell experimental results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.01); the cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); the immunofluorescence experiment results showed that the TGF-β1 group Mito-Tracker Red staining andFis1co-localization signal increased(P<0.05); JC-1 staining experiment results showed that the mitochondrial membrane potential increased in the TGF-β1 group(P<0.01). Compared with the TGF-β1+si-NC group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1in the TGF-β1+si-YTHDF1 group was reduced(P<0.01;P<0.001), and fibrosis markers the levels ofCollagenⅠandα-SMAwere reduced(P<0.01;P<0.001,P<0.01).CCK-8 experimental results showed that the proliferation ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); Transwell experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.001); cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); immunofluorescence experiment results showed that the Mito-Tracker Red staining andFis1co-localization signal decreased in the TGF-β1+si-YTHDF1 group(P<0.01); JC-1 staining experiment results showed that mitochondrial membrane potential decreased in the TGF-β1+si-YTHDF1 group(P<0.05). Conclusion YTHDF1promotes the activation, proliferation and migration capabilities of HSCs by positively regulatingFis1-mediated mitochondrial fission. This suggests thatYTHDF1may be a key gene involved in regulating the activation, proliferation and migration of HSCs.

abstract:
Objective To study the protective effect of asiaticoside(AS) on Isoproterenol Hydrochloride(ISO)-induced myocardial injury in mice. Methods Sixty male C57BL/6 mice were randomly divided into blank control(CON) group, model group [ISO,ISO 10/(kg·d)], Low dose group [ISO+AS-L,ISO 10 mg/(kg·d)+AS 5 mg/(kg·d)], Medium dose group [ISO+AS-M, ISO 10 mg/(kg·d)+AS 10 mg/(kg·d)], High dose group [ISO+AS-H, ISO 10 mg/(kg·d)+AS 20 mg/(kg·d)]. Heart mass ratio was counted; changes were observed in electrocardiogram; Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-1β and cardiac troponin T(cTn-T) in serum; Masson staining was used to observe the fibrosis of mouse myocardial tissue; Western blot was used to detect the ratio of Bax and Bcl-2 protein expression levels(Bax/Bcl-2) and the expression levels of Caspase-3 and NLRP3 proteins in myocardial tissue; real-time quantitative polymerase chain reaction(qPCR) was used to detect the mRNA expression levels ofANP,BNP,β-MHC,TNF-α, IL-6, Type Ⅰ collagen(COLⅠ), and Type Ⅲ collagen(COLⅢ). Results Compared with the CON group, the ISO group had an elevated heart-to-mass ratio(P<0.01), a lower heart rate(P<0.05), a prolonged QT interval(P<0.05), elevated expression of myocardial injury markers cTn-T,ANP,BNP, andβ-MHC(P<0.01); increased expression of IL-1β in the serum(P<0.01), increased expression ofTNF-αin the cardiac tissue and increasedIL-6expression(P<0.001), and NLRP3 protein expression was elevated(P<0.05); myocardium showed a large number of collagen fibers bluish staining(P<0.001),COLⅠ,COLⅢmRNA expression levels increased(P<0.001), and Bax/Bcl-2 ratio(P<0.001) and Caspase-3 expression were significantly elevated(P<0.05). Compared with ISO group, heart-to-mass ratio of mice in ISO+AS-L and ISO+AS-M groups decreased(P<0.05), heart rate increased, QT interval was shortened, cTn-T, ANP, BNP and β-MHC decreased(P<0.001), myocardial collagen fiber blue-staining decreased(P<0.01). The mRNA expression levels ofCOLⅠandCOLⅢdecreased(P<0.05). The expression levels of IL-1β and TNF-α decreased(P<0.01). NLRP3, Caspase-3 protein expression and Bax/Bcl-2 ratio decreased(P<0.05). The expression level ofIL-6in ISO+AS-M group decreased(P<0.01). The expression levels ofANP,BNP, andTNF-αmRNA expression were reduced in the ISO+AS-H group(P<0.001); the degree of myocardial fibrosis was improved(P<0.05), and the expression levels ofCOLⅠandCOLⅢmRNA were reduced(P<0.05). Conclusion AS has a protective effect against ISO-induced myocardial injury in mice by ameliorating cardiac fibrosis, inhibiting cardiomyocyte apoptosis and attenuating myocardial tissue inflammatory response.

abstract:
Objective To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.

abstract:
Objective To investigate the effects of resveratrol(Res) on fibroblast-like synoviocytes(FLS) in patients with rheumatoid arthritis(RA), and to explore the possible mechanism of Res inhibiting the release of inflammatory factors from FLS. Methods FLS from RA patients were culturedin vitroand treated with different concentrations of Res(0, 20, 40, 80, 160, 320 μmol/L). The viability of FLS cells was detected by CCK-8 assay after 12 and 24 h. The contents of inflammatory factor interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in cell supernatant were detected by ELISA. The expression levels of cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS) and stimulator of interferon gene(STING) were measured by Western blot; After lentivirus infection with FLS caused the cells to overexpress cGAS, the cells were divided into Control group(blank control), cGAS group(cGAS overexpression), Res+cGAS group(Res 160 μmol/L+cGAS overexpression) and Res group(Res 160 μmol/L). The expression level of STING protein in cells of each group was determined by Western blot, the viability of FLS cells in each group was detected by CCK-8, and the contents of inflammatory factor IL-6 and TNF-α in the supernatant of cells of each group were detected by ELISA method. Results The results of CCK-8 experiment showed that under 40, 80, 160 μmol/L Res treatment, FLS viability decreased significantly after 24 h compared with blank control group(P<0.01). ELISA results showed that the contents of IL-6 and TNF-α in cell supernatant were also significantly decreased after treatment with Res of 40, 80 and 160 μmol/L(P<0.01). Meanwhile, Western blot results showed that Res could significantly decrease the protein expression levels of STING and cGAS in FLS cells after treatment of 40, 80 and 160 μmol/L(P<0.05,P<0.01). Compared with the Control group, the expression level of STING protein in FLS increased after overexpression of cGAS(P<0.05); compared with the Res group, the content of inflammatory factors in the supernatant of FLS and the expression level of STING protein in FLS significantly increased after overexpression of cGAS(P<0.01,P<0.05). Conclusion The appropriate concentration of Res can inhibit the release of inflammatory cytokines in FLS cells, which may be related to the blocking of cGAS-STING signaling pathway.

abstract:
Objective To investigate the antidepressant effects and the underlying mechanisms of tetrahydrocurcumin(THC) and its nanoparticle formulation(THCN). Methods Forty-six male ICR mice were randomly divided into Con group, LPS group, THC group, THCN group and SER group. A mouse depression model was established by intraperitoneal administration of LPS. The anxiety and depression-like behaviors of mice were evaluated by open field test(OFT) and forced swimming test(FST). Myelin staining was applied to assess the extent of demyelination in the prefrontal cortex of the mice. The prefrontal cortex and hippocampus were further examined for the expression levels of glial fibrillary acidic protein(GFAP) and Toll-like receptor 4(TLR4) through quantitative immunofluorescence assays. Results Compared with the Con group, the LPS group showed increased anxiety-like and depressive-like behaviors in both the long-term and short-term experiments(P<0.05); the degree of demyelination increased in the LPS group of the long-term experiment(P<0.01); the expression of GFAP was reduced in the LPS group of the short-term experiment(P<0.01), while the expression of TLR4 increased(P<0.05); the expression of TLR4 decreased in the THC group(P<0.01); the expression of GFAP in the prefrontal cortex of the THCN group was reduced(P<0.01), while the expression of TLR4 increased(P<0.05). Compared with the LPS group, the THC group showed reduced depressive-like behaviors in the long-term experiment(P<0.05), while the anxiety-like and depressive-like behaviors of the THCN group and the SER group were reduced(P<0.05), and the anxiety-like and depressive-like behaviors of the THC group and the THCN group were reduced in the short-term experiment(P<0.05); the degree of demyelination was reduced in the THC group, THCN group and SER group in the long-term experiment(P<0.05); the expression of GFAP increased in the THC group of the short-term experiment(P<0.05), while the expression of TLR4 was reduced(P<0.05), and the expression of GFAP increased in the THCN group(P<0.05). Compared with the THC group, the THCN group and the SER group showed reduced anxiety-like behaviors in the long-term experiment(P<0.05); the expression of GFAP in the prefrontal cortex of the THCN group was reduced in the short-term experiment(P<0.05), while the expression of TLR4 in the hippocampal DG area increased in the short-term experiment(P<0.01). Conclusion Tetrahydrocurcumin and its nanoparticle formulation both exert significant ameliorative effects on depression-like behaviors and demyelination in mice induced by lipopolysaccharide. The antidepressant mechanism of THC appears to be mediated through the down-regulation of TLR4 and the up-regulation of GFAP. The mechanism underlying the antidepressant action of THCN seems predominantly focused on the enhancement of GFAP expression.

abstract:
Objective To explore the effects of acute sleep deprivation on manic-like behavior in mice and its possible molecular mechanisms. Methods Seventy-three 8-week male C57BL/6 mice were randomly divided into two groups: control group(ctrl group,n=36) and acute sleep deprivation group(SD group,n=37). After acute sleep deprivation, the motor and exploration ability of mice were evaluated by open field test and elevated plus maze. Depression-like behavior of mice was evaluated by tail suspension test. Neuronal activation in brain tissue was observed by c-fos staining, neurotransmitter levels in hippocampus(HIP) and medial prefrontal cortex(mPFC) were detected by ELISA Kit, and glycogen synthase kinase-3β(GSK-3β) and phosphorylated GSK-3β(p-GSK-3β) levels in HIP and mPFC were detected by Western blot. Results Compared with the ctrl group, the total movement distance(P<0.05) and the time in the central area(P<0.05) of the mice in SD group significantly increased in the open field test, and the open arm time(P<0.000 1) and open arm distance(P<0.01) significantly increased in the elevated plus maze. In the tail suspension test, the immobility time(P<0.01) was significantly reduced. In SD group, the expression of c-fos in HIP and mPFC increased(P<0.01), and the level of neurotransmitter DA in HIP(P<0.05) and mPFC(P<0.01) significantly increased. Western blot results showed that compared with ctrl group, the ratio of p-GSK-3β and GSK-3β in mPFC and HIP significantly decreased in SD group(P<0.000 1,P<0.05), while the level of p-GSK-3β protein significantly decreased in mPFC(P<0.05), but there was no significant change in HIP. Conclusion Acute sleep deprivation may regulate the level of GSK-3 through DA in mPFC of mice, inhibiting the serine phosphorylation of GSK-3 and eventually leading to manic-like behavior in mice.

abstract:
Objective To investigate the effect of chromosome instability(CIN) associated gene polypeptide N-acetylgalactosaminyltransferase 7(GALNT7) on proliferation and apoptosis of HCT116 colon cancer cells. Methods The HCT116 cell line withGALNT7knockdown was constructed by lentiviral infection. The correlation betweenGALNT7and CIN was verified by chromosome spread assay. The effect ofGALNT7on cell proliferation was detected by live cell counting, and the effect ofGALNT7on cell cycle distribution was detected by flow cytometry and Western blot. Caspase-3 activity and Western blot assays were used to detect the effect ofGALNT7on apoptosis. Results HCT116 cells showed a slower proliferation rate upon knocking down ofGALNT7, and exhibited a more scattered karyotype distribution and a phenotype of increased degree of CIN. Inhibition ofGALNT7in HCT116 cells resulted in cell cycle arrest, upregulation of P21 and downregulation of CDK6 protein levels, as well as increased levels of Caspase-3 activity, cleaved PARP1 and PUMA protein expression, and decreased levels of BCL-2 protein expression. Conclusion TheGALNT7gene may promote proliferation and inhibit apoptosis of HCT116 colon cancer cells through the suppression of CIN generation.

abstract:
Objective To explore the correlation between the expression levels of endoplasmic reticulum stress(ERS) and trophoblast apoptosis-related markers and severe preeclampsia(SPE) in placental tissues of pregnant women with early-and late-onset SPE and normal pregnancy. Methods Placental tissues from 20 early and late haired severe preeclamptic singleton pregnant women who attended the Hospital were collected(early-onset group, late-onset group), and 20 cases pregnant women of normal blood pressure and no other pregnancy complications who delivered in our hospital during the same period were selected as the normal group. Transmission electron microscopy was used to observe the ultrastructure of the endoplasmic reticulum of trophoblast cells in placental tissues. Protein blotting assay was used to detect the expression levels of endoplasmic reticulum stress-related proteins, including Glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), Phosphorylated eukaryotic translation initiation factor 2α(p-eIF2α) and Phosphatidylinositol-requiring enzyme 1(p-IRE1)α. Immunohistochemistry assay was used to detect the expression of proliferating cell nuclear antigen(Ki67), a proliferation marker, in placental tissues, and TUNEL staining was used to detect placental tissue trophoblast apoptosis. Results The endoplasmic reticulum of trophoblast cells in the placental tissues of the normal pregnant women group was normal in volume, with no dilatation or swelling. In contrast, the endoplasmic reticulum of placental tissues in the severe preeclampsia group showed obvious edema and significant dilatation, and the dilatation was more obvious in the early-onset group than in the late-onset group. The expression level of endoplasmic reticulum stress-related proteins GRP78(P<0.001,P<0.05) and CHOP(P<0.01,P<0.001), the phosphorylation levels of eIF2α(P<0.000 1,P<0.01) and IRE1α(P<0.000 1,P<0.001) increased in placental tissues of both early-onset and late-onset groups compared to those of the normal group. The p-eIF2α/eIF2α(P<0.001) to p-IRE1α/IRE1α ratio(P<0.05) and GRP78(P<0.01) protein expression levels were significantly higher in the early-onset group than in the late-onset group. Compared with the normal group, the number of Ki67-positive cells per field of view was significantly reduced in the early-onset and late-onset groups(P<0.000 1,P<0.05), and the number of Ki67-positive cells was significantly lower in the early-onset group than in the late-onset group(P<0.01). There were more positive apoptotic cells per field of view in the placental tissues of the early-onset group, and the apoptosis rate of trophoblast cells was significantly higher than that in the other two groups(P<0.001,P<0.01). Conclusion Increased trophoblast apoptosis and suppressed proliferation in placental tissues of patients with severe preeclampsia may be associated with endoplasmic reticulum stress overactivation, and the activation level is higher in placental tissues of early-onset severe preeclampsia than that of late-onset group.

abstract:
Objective To construct a phenolamine cross-linked coating composed of epigallocatechin gallate(EGCG) and poly-L-lysine(PLL) on the surface of the porous pure Ti integrated with the antibacterial substance chlorhexidine(CHX), and to study the antibacterial property and biosafety. Methods A porous structure(pTi group) was formed on the surface of titanium samples by alkaline heat treatment. Then the pTi group was immersed in the mixed solution of EGCG and PLL in an alkaline aerobic environment for 24 h to obtain the phenolamine group samples(EP group). Finally, the titanium tablets were further immersed in the aqueous solution of chlorhexidine(CHX) for 24 h to obtain the antibacterial groups(EPC group). Microstructure and properties of the surface were characterized by scanning electron microscopy(SEM), X-ray photoelectron spectrometer(XPS) and water contact angle measuring instrument. The antibacterial properties of coating were observed and evaluated by nephelometry, inhibition zone method and live/dead bacterial staining. The cytocompatibility of the coating was evaluated by MTT method and cell fluorescence staining, and the cell adhesion and proliferation ability in bacterial environment were evaluated by the co-culture of bacteria and cells. Results SEM results showed that the pore size of samples after alkali heat treatment decreased with the deposition of the phenolamine coating. The measurement of water contact angle showed that the contact angle increased significantly with the grafting of coating. The intensity of N1s and C1s peaks increased and Ti2p and O1s peaks decreased detected by XPS tests. The Cl2p peak appeared in EPC group referred to the control group. The antibacterial experimentsin vitroshowed that the antibacterial samples could perform effective antibacterial effects on Staphylococcus aureus and Aggregatibacter actinomycetem-comitans for at least 7 days. In the biocompatibility experiments, MTT and cell fluorescence staining results showed that the adherent cells had good morphology and proliferative activity. The bacteria-cell co-culture results showed that the EPC groups could provide a good environment for cell proliferation and growth with excellent antibacterial properties. Conclusion Chlorhexidine-grafted phenolamine deposited on porous titanium surface displays an effective antibacterial effect with good biosafety performance, which can play an antibacterial role in the bacterial environment while ensuring cell adhesion and proliferation.

abstract:
Objective To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

abstract:
Objective To explore the effect of the addition of N-acetylcysteine(NAC) on the abnormal increase of reactive oxygen species(ROS) during platelet cold storage, and to clarify its function of preventing the platelets from being recognized and cleared by macrophages and hepatocytes. Methods Platelets Concentrates were divided into room temperature group(22C), cold storage group(4C) and NAC addition group. In NAC addition group, the platelets were supplemented with 5 mmol/L(N5) and 25 mmol/L(N25) NAC. After 5-day storage, the levels of ROS, activation markers and other index of platelets in each group were detected by flow cytometry. Platelet phagocytosis was detected by PMA-activated THP-1 cells or by primary cultured HepG2 cells. Results After 5 days of storage, ROS increased significantly in 4C group than those in 22C group(P<0.05), and after NAC addition, ROS level reduced significantly(P<0.05). The expression of CD62P and PS and the exposure of β-GlcNAc on platelets in N5 group significantly decreased compared with those in 4C group(P<0.05). The platelet phagocytosis by THP-1 and HepG2 cells were also significantly lower in N5 group than those in 4C group(P<0.05). However, the addition of 5 mmol/L NAC did not significantly affect the count, pH, CD42b expression, β-Gal exposure and coagulation function of cold-stored platelet after 5-day storage. Conclusion The addition of NAC to refrigerated platelets can significantly decrease the level of platelet ROS and effectively reduce their phagocytosis by cells, suggesting that NAC addition may protect refrigerated platelets from being cleared by phagocytosis after transfusion.

abstract:
Objective To explore the relationship between single nucleotide polymorphisms(SNPs) in D-loop region of mitochondrial DNA(mtDNA) and mtDNA copy number and the risk of dermatomyositis(DM), and its influencing factors. Methods 74 patients with DM and 92 healthy controls were included in the study. Genomic DNA was extracted from peripheral blood and the target fragment of mtDNA D-loop region was amplified by PCR technique, and the products were subsequently sequenced. Serum levels of ROS were assessed using a high-sensitivity reactive oxygen species detection kit. The expression levels of cytokines, interleukin(IL)-5, IL-13, interferon-γ(IFN-γ), IL-2, IL-6, IL-10, tumor necrosis factor-α(TNF-α) and IL-4 were measured using Flow Fluorescence Immunmicrobeads Assay. Wilcoxon rank-sum test was used to assess the potential correlation between cytokines and SNPs associated with DM risk.The relative copy number of mtDNA was measured using quantitative real-time polymerase chain reaction(qPCR) analysis. Results Two SNPs(16304T/C, 16519T/C) were found to be associated with the risk of developing DM, and alleles 16304C(χ2=4.937,P=0.026) and 16519C(χ2=4.405,P=0.036) in the mitochondrial D-loop region were confirmed to be associated with DM development risk. The DM risk-associated allele 16304C was significantly associated with lower IL-4 expression(P=0.016). The mtDNA copy number was significantly higher in DM patients than in controls(P<0.001). Conclusion Mitochondrial D-loop SNPs can be potential biomarkers for DM risk, and SNPs may be involved in DM by influencing cytokines. DM shows high expression of mtDNA copy number, and the increase in mtDNA copy number may lead to mitochondrial dysfunction, which triggers the pathogenesis of DM.

abstract:
Objective To explore the association between serum γ-aminobutyric acid(GABA) levels and the risk of developing type 2 diabetes(T2DM). Methods 187 cases of T2DM patients attending the hospital were selected as the T2DM group, and 187 cases of non-T2DM population attending the same period of time were selected as the control group according to age(±3 years) and gender 1 ∶1. On-site questionnaires and physical examination were conducted for the study subjects, and serum levels of GABA, Malondialdehyde(MDA) and activities of superoxide dismutase(SOD) and Glutathione peroxidase(GSH-Px) were detected by using ELISA kits. The differences in the levels of GABA and oxidative stress indicators(SOD, GSH-Px, MDA) between the two groups were compared, and the correlation between GABA and oxidative stress indicators was analyzed by Spearman′s method; GABA and oxidative stress indicators were divided into three groups according to their control quartiles, respectively [low level group(Q1:<P25), medium level group(Q2:P25-P75), high level group(Q3:>P75)], and conditional logistic regression was applied to analyze the relationship between GABA, oxidative stress indicators and the risk of developing T2DM; the dose-response relationship between GABA, oxidative stress indicators and the risk of developing T2DM was analyzed by using restricted cubic spline(RCS). Results Compared with the control group, GABA level and GSH-Px activity decreased and MDA level increased in the T2DM group(P<0.05). Spearman′s correlation analysis showed that GABA level was positively correlated with SOD and GSH-Px activities and negatively correlated with MDA level(P<0.001). Conditional logistic regression analysis showed that medium levels of SOD and GSH-Px as well as medium and high levels of GABA were protective factors for T2DM compared with low levels in each group(P<0.05). RCS results showed that a negative dose-response relationship between GABA, GSH-Px and the risk of developing T2DM, and SOD showed a trend of decreasing and then increasing the risk of developing T2DM(P<0.05). Conclusion Serum GABA levels have been associated with the risk of developing T2DM. As serum GABA levels increase, the risk of developing T2DM may decrease.

abstract:
Objective To explore identification and resistance characteristics of CAMP-negativeStreptococcus agalactiae. Methods Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS) and the CAMP assay, 33 presumptive strains ofStreptococcus agalactiaewere identified. The CAMP-negative strains were further validated through 16S rDNA, while the CAMP factor encoding gene(cfb) was detected using real-time fluorescence quantitative polymerase chain reaction(qPCR). Antimicrobial susceptibility testing was conducted using the microbroth dilution method, and the resistance rates of CAMP-negative and CAMP-positive strains were compared. Results Based on MALDI-TOF MS identification, all 33 strains were classified asStreptococcus agalactiae. Among them, 7 strains tested negative for CAMP were subsequently confirmed asStreptococcus agalactiaethrough 16S rDNA. The qPCR results indicated that, only 1 strain showedcfbpresence. The CAMP-negative and CAMP-positive strains were sensitive to penicillin G, cefepime, cefotaxime, vancomycin, and linezolid. The resistance rates of the former to chloramphenicol and tetracycline(28.57%, 85.71%) were slightly higher than the latter(15.38%, 57.69%), while the resistance rates to moxifloxacin, levofloxacin, and erythromycin(14.29%, 14.29%, 42.86%) were slightly lower than the latter(34.62%, 34.62%, 57.69%), but was not significant. Conclusion Drug risistance of CAMP-negativeStreptococcus agalactiaeis the same as CAMP-positive strains, but traditional CAMP assay andcfb-targeted qPCR can result in missed detections. MALDI-TOF MS offers a quick, simple, and accurate identification method that merits wider adoption.

abstract:
Objective To investigate the diagnostic value of linear array endoscopic ultrasonography(EUS) for common bile duct microlithiasis. Methods Data of patients who attended in the hospital and diagnosed as common bile duct microlithiasis and biliary sludge by EUS were selected. A total of 85 patients with magnetic resonance cholangiopancreatography(MRCP) examination and ERCP treatment during hospitalization were enrolled. The results of endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy(ERCP/EST) were the gold standard for diagnosis. The results of EUS, MRCP, and diagnostic ERCP were compared with the gold standard, and the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the three methods were calculated, respectively. The chi-square test was used for comparison of the above indices. Results Of all 85 patients, 63 had positive EUS results, among whom 5 had false positive results; 22 had negative EUS results, among whom 1 had false negative results. Of all 85 patients, 49 had positive MRCP results, among whom 4 had false positive results; 36 had negative MRCP results, among whom 14 had false negative results. Of all 85 patients, 59 had positive diagnostic ERCP results, among whom 10 had false positive results; 26 had negative diagnostic ERCP results, among whom 10 had false negative results. The sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV), and accuracy of EUS in diagnosing common bile duct microlithiasis were 98.3%, 80.8%, 92.1%, 95.4% and 92.9%, respectively. For MRCP, these values were 76.3%, 84.6%, 91.8%, 61.1% and 78.8%, respectively. For diagnostic ERCP, these values were 83.1%, 61.5%, 83.1%, 61.5% and 76.5%, respectively. The EUS group had a significantly higher accuracy than the MRCP group(χ2=6.986,P<0.05) and diagnostic ERCP group(χ2=8.900,P<0.05). The areas under the ROC curves(AUC) and 95%CIof EUS group, MRCP group and diagnostic ERCP were 0.895(95%CI: 0.802-0.988,P<0.001), 0.804(95%CI: 0.702-0.907,P<0.001) and 0.723(95%CI: 0.598-0.848,P=0.001), respectively. Conclusion EUS has a high diagnostic value in the diagnosis of common bile duct microlithiasis and thus can be used as the preferred examination before therapeutic ERCP.

abstract:
Objective To explore the risk factors of biliary stricture after liver transplantation and to construct a nomogram prediction model. Methods The clinical data of 208 liver transplant recipients in hospital were retrospectively analyzed, including 54 cases in the biliary stricture group and 154 cases in the non-biliary stricture group. Multivariate Logistic regression analysis was used to screen out independent predictors, fit the prediction model and construct a visual nomogram to evaluate the prediction model. Survival curves were drawn and multivariate Cox regression analysis was performed. Results Autoimmune liver diseases(OR=6.610,95%CI: 1.410-30.99), alanine aminotransferase(ALT)(OR=1.007,95%CI: 1.003-1.011), warm ischemia time(OR=1.972,95%CI: 1.399-2.780), cold ischemia time(OR=1.016,95%CI: 1.010-1.022), cytomegalovirus infection(OR=6.037,95%CI: 1.480-24.63) and hepatic vascular stenosis(OR=7.784,95%CI: 2.312-26.20) were independent predictors of biliary stricture after liver transplantation. The area under the curve(AUC) of the nomogram prediction model was 0.921, the cut-off value was 0.238, the sensitivity was 0.889, and the specificity was 0.838. The model showed good discrimination. The Brier score was 0.092, Hosmer-Lemeshow goodness-of-fit testP=0.253, Calibration curve(B=1 000) was in good agreement, and the model showed good calibration. Decision curve analysis(DCA) showed that the application of the model could benefit liver transplant recipients. The postoperative follow-up time was 27-60 months. The cumulative survival rate of the non-biliary stricture group was better than that of the biliary stricture group(P=0.019), but multivariate Cox regression analysis showed that biliary stricture(HR=1.194, 95%CI: 0.624-2.285) was not an independent risk factor for survival after liver transplantation. Conclusion The nomogram model based on autoimmune liver diseases, ALT, warm ischemia time, cold ischemia time, cytomegalovirus infection and hepatic vascular stenosis performs well and can be used to predict the occurrence of biliary stricture after liver transplantation.

abstract:
Objective To investigate the independent prognostic factors affecting disease-free survival(DFS) after radical surgery in Ⅱ and Ⅲ adenocarcinoma of gastroesophageal junction(AEG) patients, and to construct a nomogram prediction model. Methods A retrospective analysis was conducted on a cohort comprising 326 patients who were diagnosed with AEG. Chi-square test was used for categorical variable analysis. The survival analysis was drawn by Kaplan-Meier method and tested by log-rank method. Univariate and multivariate Cox regression analyses identified independent prognostic factors, and based on these factors, a nomogram was constructed to predict 3-year and 5-year DFS in AEG patients. The calibration curves evaluated the performance of nomogram. Results Among 326 AEG patients, 281 were in the young group(<70 years old) and 45 were in the old group(≥70 years old). Kaplan-Meier curve showed that patients with advanced age, TNM stage Ⅰ-Ⅱ and no history of hepatitis B had longer DFS. Univariate and multivariate analysis showed that age, TNM stage and history of hepatitis B were independent prognostic factors for DFS. The 3-year and 5-year correction curves showed that the prediction efficiency of nomogram was good. The decision curve analysis showed that the model had a good clinical net benefit. Conclusion Age, TNM stage and history of hepatitis B are independent prognostic factors for DFS in AEG patients. The nomogram constructed and validated can be used to predict DFS in AEG patients.

abstract:
Objective To explore the adverse effects of mild traumatic brain injury(MTBI) on the memory monitoring function of patients. Methods This study adopted a paired control research method, combined neuropsychological background tests and memory monitoring task(feeling of knowing, FOK) to conduct cognitive assessments on two groups of subjects: the patient group(n=42) and the matched control group(n=42). Results In neuropsychological background test, the patients′ performance in digit span test, Stroop color task, digit link task and auditory verbal learning test were significantly lower than those in the control group(P<0.05). In addition, there was significant difference in accuracy of FOK task between the two groups(P<0.05). The ratio of right judgement/right recognition was relatively high in the control group, while the ratio of correct judgement/wrong recognition was relatively high in the patient group. Conclusion This study confirms that memory impairment in MTBI patients is centered on damage to memory monitoring function. Moreover, the damage to attention, execution, and item content memory abilities in MTBI patients are important driving factors for their memory monitoring dysfunction.

abstract:
Objective To investigate the factors affecting the outcome of high-risk human papillomavirus( HRHPV) infection in patients with normal cervix examined by colposcopy in Hefei area and the relationship between persistent HR-HPV infection and cervical cytology. Methods Data of colposcopy patients were collected from 478HR-HPV infected patients with normal cervix through colposcopy. Their age,number of sexual partners,contraceptive methods and other relevant basic information were recorded. Vaginal interferon use,HR-HPV infection at year1 and year 2,and cervical liquid-based cytology test( LCT) results were tracked,univariate and multivariate analyses were performed based on basic information,and ROC curves were plotted. Results The HR-HPV clearance rate at 1 year was 59. 41%,and the clearance rate at 2 years was 66. 75%. The other 12 types of infection( 31,33,35,39,45,51,52,56,58,59,66,68) were more common than the 16 and 18 types. Univariate and multivariate analyses showed that age>50 years,number of sexual partners ≥2,and history of cervical conectomy increased the risk of persistent HR-HPV infection( χage2= 21. 676,P<0. 001; χnumber2of sexual partners= 8. 262,P =0. 004; χ(history of cervical conectomy)2= 11. 267,P = 0. 001). The risk of HR-HPV infection was significantly lower when condom or vaginal interferon was used( χ(condom use)2= 10. 885,P = 0. 001; χ(interferon use)2= 4. 099,P = 0. 043). The area under the ROC curve( AUC) of combined diagnosis of HR-HPV persistent infection was higher than that of single diagnosis,and the AUC of combined diagnosis was 0. 737. Persistent HR-HPV infection was an independent risk factor for abnormal LCT,and the AUC predicted by the model was 0. 755. No cancer was found in patients with persistent HR-HPV infection for 2 years,and the proportion of abnormal LCT was higher than that in patients with negative HR-HPV. The difference was statistically significant( χ2= 39. 64,P<0. 001). Conclusion The combined ROC model constructed for patients>50 years old,with multiple sexual partners,history of cervical surgery,no vaginal interferon use,and no condom use has certain value in predicting persistent HR-HPV infection,and persistent HR-HPV infection has predictive value in predicting LCT abnormalities.

abstract:
Bisphenol S is commonly utilized in the industry as a substitute for bisphenol A. However, numerous studies have indicated that bisphenol S also exhibits a wide range of toxicity. Bisphenol S has been found to cause adverse effects on the nervous system, endocrine system, reproductive system, etc., with more extensive studies on the reproductive system. Specifically, bisphenol S exposure causes a decrease in sperm count, decreases motility and increases malformations, and decreases testosterone levels in males; on the other hand, bisphenol S exposure causes a significant reduction in ovarian volume and relative weight, affectes oocyte quality, decreases gonadotropins follicle-stimulating hormone, and luteinizing hormone in females. The mechanisms by which bisphenol S affects the body are complex and varied, involving oxidative stress, cell death, and epigenetic modifications. Notably, the reproductive toxicity of bisphenol S varies in different studies. As a result, this paper reviews the reproductive toxicity of bisphenol S and its underlying mechanisms.