Acta Universitatis Medicinalis Anhui

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Anhui Provincial Education Department

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Anhui Medical University

Editor-in-chief

Weng Jianping

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Editorial Board of Acta Universitatis Medi-cinalis Anhui Meishan Road , Hefei 230032

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China Code No . MO5933

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ISSN 1000 - 1492

CN 34 - 1065/R

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Influences of inter-implant distances on the accuracy of intraoral scanning techniques

Fang Shiyan; Xia Rong

DOI: DOI：10.19405/j.cnki.issn1000-1492.2024.10.026

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The characteristic analysis of lipid metabolism and intestinal flora in platinum-resistant ovarian cancer at stage Ⅲ-Ⅳ based on the theory of “tumour toxicity” in traditional Chinese medicine

Jiang Haili; Ye Yingquan; Hu Die; Sheng Rui; Gao Chaozheng; Zhan Shuqi; Zhang Mei; Wang Ting

DOI: DOI：10.19405/j.cnki.issn1000-1492.2024.10.024

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abstract:
Objective To compare the differences in lipid metabolism between platinum-resistant and platinum-sensitive ovarian cancer patients at stage Ⅲ-Ⅳ, to analyze the differential intestinal flora using 16S rRNA sequencing, and to explore the associations among intestinal flora, lipid metabolism characteristics and platinum resistance in ovarian cancer. Methods Patients diagnosed with ovarian cancer at stage Ⅲ-Ⅳ through surgical pathology were selected, including a platinum-resistant group(11 cases) and a platinum-sensitive group(11 cases). The differences in lipid metabolism between the two groups were compared. The differences in gut microbiota between the two groups were investigated using fecal 16S rRNA sequencing. The association among gut microbiota, lipid metabolism characteristics, and platinum resistance in ovarian cancer was analyzed. Results Significant differences were observed in lipid metabolism-related indicators[total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), non-high-density lipoprotein cholesterol(n-HDL), low-density lipoprotein cholesterol(LDL-C), apolipoprotein(B)] between the two groups, with higher levels in the platinum-resistant group. The Shannon index(P=0.008 3) and Simpson index(P=0.008 2) both showed higher diversity of gut microbiota in platinum-resistant ovarian cancer patients compared to the platinum-sensitive group. However, based on OTUs species clustering and relative abundance statistics, certain bacterial abundances differed significantly between the groups. Species such asParabacteroides,Akkermansia,Blautia,Lachnoclostridium,Fusicatenibacter, andMegamonashad significantly higher abundances in the platinum-sensitive ovarian cancer group, andAkkermansia(a lipid metabolism-related bacterial group) was the most prevalent. Conclusion The platinum-resistant group of ovarian cancer exhibits significantly higher levels of lipid metabolism and gut microbiota diversity compared to the platinum-sensitive group. This suggests that the increase in lipid metabolism levels and fecal microbiota diversity may be associated with the development of platinum resistance. However, certain microbial taxa are reduced in abundance in the platinum-resistant group, such as the distinctAkkermansiagenus(a lipid metabolism-related microbial community), which may serve as one of the factors inducing platinum-resistance in ovarian cancer.

New insights into the relationship between Sjogren′s syndrome and primary biliary cholangitis and abnormal liver function: a Mendelian randomization study

Zhou Lihan; Xu Jun; Guo Sheng; Li Yixue; Xu Zihao; Cheng Liangbin

DOI: DOI：10.19405/j.cnki.issn1000-1492.2024.10.023

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Investigation of the interaction and adverse reactions between voriconazole and tacrolimus based on CYP2C19 gene polymorphism and therapeutic drug monitoring

Chen Xueli Sun Xiaoshan Song Shuai Su Yong Xia Quan Liu Jiatao

DOI: DOI：10.19405/j.cnki.issn1000-1492.2024.10.022

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abstract:
Objective To analyze the interaction between voriconazole(VRC) and immunosuppressants such as tacrolimus and cyclosporine and the effect of CYP2C19 gene polymorphism on the interaction and adverse reactions(ADR) based on the results of CYP2C19 gene polymorphism and therapeutic drug monitoring, so as to provide a basis for the development of individualized VRC combined with immunosuppressants. Methods Two-dimensional liquid chromatography and pyrosequencing was used to detect the concentration of VRC and the CYP2C19 gene polymorphism, respectively. And the concentration of immunosuppressants was detected at the same time. The relationship among CYP2C19 gene polymorphism, the concentration of VRC and immunosuppressant and ADR was analyzed. Results A total of 61 patients were enrolled in this study, and the mutation rates of CYP2C19*2 and CYP2C19*3 were 54.1%(33/61) and 9.84%(6/61), respectively. The concentrations of VRC in patients with extensive metabolism(EMs), intermediate metabolism(IMs) and poor metabolism(PMs) were(4.44±3.46),(3.62±3.02) and(10.05±1.46) μg/ml(P<0.05), respectively. The concentration of tacrolimus after combined with VRC significantly increased compared to tacrolimus alone [(13.4±9.2) ng/mlvs(6.5±3.6) ng/ml;P=0.002], and the concentration of tacrolimus increased along with an increasing of VRC concentration. The concentration of VRC in patients combined with tacrolimus was lower than that in patients without immunosuppressants [(3.81±3.48) μg/mlvs(5.84±3.71) μg/ml;P=0.032]. The concentration of VRC in patients with cyclosporine significantly decreased(P<0.01), while tacrolimus and mycophenolate mofetil had no significant effect on the concentration of VRC. 45.90%(28/61) of the patients had adverse reactions, the concentration of VRC in patients with ADR was significantly higher than that in patients without ADR [(7.07±3.43) μg/mlvs(3.06±2.90) μg/ml;P<0.001]. And the concentration of VRC in patients with ADR was higher than patients without ADR with based on CYP2C19 genotype. Conclusion CYP2C19 gene polymorphism can significantly affect the concentration and adverse reactions of VRC, and VRC has significant interaction with immunosuppressants such as tacrolimus. CYP2C19 gene polymorphism combined with therapeutic drug monitoring can improve the individualized treatment of tacrolimus and voriconazole, and is expected to minimize toxicity and improve treatment effects.

Survival time and influencing factors analysis of clinically diagnosed sporadic Creutzfeldt-Jakob disease patients in China from 2020 to 2022

Zhang Weiwei; Liang Donglin; Zhou Donghua; Wang Yuan; Xiao Kang; Zhou Wei; Dong Xiaoping; Shi Qi

DOI: DOI：10.19405/j.cnki.issn1000-1492.2024.10.021

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abstract:
Objective To investigate the survival time of patients diagnosed with sporadic Creutzfeldt-Jakob disease in China between 2020 and 2022 and explore the associated factors influencing survival. Methods A retrospective analysis was conducted on clinically diagnosed cases with complete information on sporadic Creutzfeldt-Jakob disease diagnosed by the China Creutzfeldt-Jakob disease surveillance network from 2020 to 2022, baseline information of patients was obtained from the case files, telephone follow-up was used to obtain the treatment and survival status of the patients after the diagnosis, life-table method was used for estimating the survival rate, Kaplan-Meier method was used for calculating the median survival time and the 95%CI, Cox regression model was used for univariate and multivariate analyses were used to screen for factors influencing survival time. Results The median survival time of the 300 patients was 5 months(95%CI: 4.165-5.835). Univariate analysis revealed that factors such as age at onset, regional distribution, presence of corticobasal or extrapyramidal symptoms as initial manifestations, number of initial symptoms, presence of corticobasal or extrapyramidal functional abnormalities, number of major clinical manifestations, presence of typical electroencephalogram findings, and use of nasal feeding during the course of the disease were potential factors influencing survival time(P<0.1). Multivariate analysis showed that the risk of death in patients with onset age>65 years was 1.350 times higher than in patients with onset age ≤65 years(P=0.021, 95.0%CI: 1.046-1.742). Patients without pyramidal or extrapyramidal dysfunction had a 0.674-fold lower risk of death compared to those with these symptoms(P=0.020, 95.0%CI: 0.483-0.939). Patients who did not receive nasal feeding had a 1.817-fold higher risk of death compared to those who did(P<0.001, 95.0%CI: 1.406-2.349). Conclusion Age at onset, the presence of pyramidal or extrapyramidal functional abnormalities, and the use of nasal feeding during the disease course are factors influencing the survival time of patients clinically diagnosed with sCJD.

Screening of mitochondria-targeting markers in alveolar macrophages of silicosis patients based on bioinformatics analysis

Cheng Hongming; He Hailan; Wang Yuan; Hao Xiaohui; Wang Hongli; Liu Heliang

DOI: DOI：10.19405/j.cnki.issn1000-1492.2024.10.019

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abstract:
Objective To screen mitochondria-targeting differential genes in alveolar macrophages of silicosis patients and explore the role of mitochondrial homeostasis in alveolar macrophages of silicosis patients. Methods High-throughput sequencing dataset GSE174725 was downloaded, and differentially expressed genes were screened with R software andP<0.05, |LogFC|>1, and then intermixed with mitochondrial gene bank MitoCarta3.0 to obtain mitochondria-targeted differentially expressed genes. Then enrichment analysis was carried out to obtain the biological processes and pathways involved in differential genes, and the protein-protein interaction network was constructed. In addition, alveolar macrophages from silicosis patients and healthy controls were collected, the expression levels of differential genes were detected by RT-qPCR, and the expressions of mitochondria-related factors mitochondrial fusion protein 1(MFN1), optic atrophy 1(OPA1) and dynamin-related protein 1(DRP1) in alveolar macrophages of silicosis patients were investigated by Western blot. Results A total of 204 differentially expressedgenes were screened in silicosis patients, among which 62 differentially expressed genes were up-regulated, 142 differentially expressed genes were down-regulated, and 22 differentially expressed genes were mitochondria-targeted. The concentration analysis of differentially expressed genes targeted by mitochondria showed that the cell components mainly enriched included mitochondrial membrane, endoplasmic membrane side components, etc. The biological processes mainly enriched included mitochondrial electron transfer from NADH to ubiquinone, inflammatory response, immune response, etc. The main molecular functions enriched included the rotation mechanism of proton transport ATP synthase activity, NADH dehydrogenase activity, chemokine activity, etc. KEGG enrichment analysis mainly focused on the involvement in chemical carcinogenesis-ROS, IL-17 signaling pathway, toll-like receptor signaling pathway, chemokine signaling pathway, TNF signaling pathway, etc. In addition, RT-qPCR results showed that the expressions of mitochondrial cytochrome coxidase 1, mitochondrial cytochrome coxidase 2, mitochondrial cytochrome coxidase 3, mitochondrially encoded NADH dehydrogenase 1, mitochondrially encoded NADH dehydrogenase 3, mitochondrially encoded NADH dehydrogenase 5, superoxide dismutase and mitochondrially encoded ATP synthase 6 gene were down-regulated in silicosis patients(P<0.05). Western blot and RT-qPCR results showed that, in silicosis patients, the expression of MFN1 and OPA1 decreased(P<0.05), while the expression of DRP1 increased(P<0.05). Conclusion Bioinformatics analysis and validation, eight mitochondrial targeted differential genes(MT-CO1, MT-CO2, MT-CO3, MT-ND1, MT-ND3, MT-ND5, SOD and MT-ATP6) were finally obtained, which were enriched in mitochondrial respiratory chain and oxidative stress pathways and might play an important role in the process of silicosis.

Effect of leflunomide regulating HIF-1α signal pathway on autophagy of synoviocytes in rheumatoid arthritis

Lan Weiya; Ma Wukai; Yao Xueming; Jiang Zong; Xiong Lang; Yang Shufen; Tang Fang

DOI: DOI：10.19405/j.cnki.issn1000-1492.2024.10.018

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The effect of mandibular retrusion on cerebral blood flow and stroke recovery in rats

Fu Chunfeng; Liu Xiaoyu; Han Quancheng; Zheng Xiuyun; Mei Qin; Cheng Yuhe; Wu Tingting

DOI: DOI：10.19405/j.cnki.issn1000-1492.2024.10.017

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abstract:
Objective To explore the changes in cerebral blood flow caused by mandibular retrusion, as well as the impact and potential mechanisms on stroke recovery. Methods 6-week-old SD male rats were selected as experimental subjects. The metal cannula was bonded to the rat maxillary incisor for one week, forcing mandibular retrusion(MR). Cerebral blood flow was detected by laser speckle imaging. Cognitive function was detected by the Morris water. Then, the stroke model was constructed in MR rats by using the middle cerebral artery occlusion(MCAO) method for one week. Meanwhile, metal cannulae were then removed in rats to restore the lower jaw′s position(MCAO RO), serving as a positive control group. Consequently, rats were randomly divided into the following groups: Sham groups, MCAO groups, MCAO MR groups, and MCAO RO groups. Neurological recovery was assessed through the modified neurological severity score(mNSS). The area of cerebral infarction was evaluated by using triphenyltetrazolium(TTC) staining. The changes in nerve cells were observed by using hematoxylin eosin(HE) staining. The protein expression level of vascular endothelial growth factor(VEGF) was detected by immunohistochemistry. The protein expression levels of platelet-endothelial cell adhesion molecule(CD31), sirtuin 6(SIRT6), and thioredoxin interaction protein(TXNIP) were detected by Western blot. The mRNA expression levels of SIRT6, TXNIP, and VEGF were determined by qRT-PCR. Microglia activation marker molecule 1(IBA-1) was detected by immunofluorescence. Resluts Because of mandibular retrusion, laser speckle showed decreased cerebral blood flow, and the water maze showed decreased cognitive function. Compared to other groups, MCAO MR showed a larger ischemic area in TTC staining, while HE staining and neurological scoring showed poorer neurological function recovery. Western blot and qRT-PCR showed that the MCAO MR group inhibited the mRNA and protein expression levels of SIRT6, upregulated the mRNA and protein expression levels of TXNIP, and increased the activation of microglia. Conclusion Mandibular retrusion reduces cerebral blood flow and alters cognitive function in rats. Mandibular retrusion inhibits recovery in stroke through the SIRT6/TXNIP axis.

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