1.Association of growth hormone secretagogue receptor rs2922126 gene polymorphism with susceptibility to non-alcoholic fatty liver disease
Xue HAN ; Hongcheng WANG ; Shousheng LIU ; Yongning XIN ; Zhenzhen ZHAO
Journal of Clinical Hepatology 2025;41(9):1802-1807
ObjectiveTo investigate growth hormone secretagogue receptor (GHSR) rs2922126 gene polymorphisms and their association with genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) in the Chinese Han population in Qingdao, China, and to provide a basis for diagnosis and treatment. MethodsA total of 220 patients who were admitted to Qingdao Municipal Hospital from June 2022 to June 2023 and were diagnosed with NAFLD based on radiological examination were enrolled as NAFLD group, and 167 healthy individuals during the same period of time were enrolled as control group. Fasting blood samples were collected from all subjects, and related biochemical parameters were measured. Whole blood DNA was extracted, and polymerase chain reaction and MALDI-TOF mass spectrometer were used for genotyping. The chi-square test was used for comparison of categorical data between groups, and the independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups. The binary logistic regression analysis was used to investigate the risk of NAFLD. ResultsCompared with the control group, the NAFLD group had significantly higher age, body mass index (BMI), fasting plasma glucose, triglyceride, gamma-glutamyl transpeptidase, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase, as well as a significantly lower level of high-density lipoprotein (all P0.05). The distribution of GHSR rs2922126 genotypes was consistent with the Hardy-Weinberg equilibrium, suggesting population representativeness in the subjects enrolled (NAFLD group: P=0.106; control group: P=0.849). There was no significant difference in the distribution of AA, TA, and TT genotypes at GHSR rs2922126 locus between the control group and the NAFLD group (P=0.099), and there was also no significant difference in allele frequency between the two groups (P=0.063). In the recessive model of A allele, there was a significant difference in the distribution of AA homozygote and TA+TT genotype between the NAFLD group and the control group (P=0.032). The binary logistic regression analysis showed that in the recessive model of A allele, AA homozygote carriers had an increased risk of NAFLD compared with TA+TT genotype carriers (odds ratio [OR]=1.712, 95% confidence interval [CI]: 1.045 — 2.807, P=0.033). There was still a significant difference after adjustment for sex, age, and BMI (OR=2.156, 95%CI: 1.221 — 3.808, P=0.008). In the NAFLD group, AA genotype carriers had a significantly higher serum level of total cholesterol (TC) than TT+TA carriers (Z=-1.99,P=0.046). ConclusionGHSR rs2922126 AA genotype may be associated with the increased risk of NAFLD in the Chinese Han population in Qingdao, and GHSR rs2922126 AA genotype is associated with the increase in TC in NAFLD patients.
2.A tailored database combining reference compound-derived metabolite, metabolism platform and chemical characteristic of Chinese herb followed by activity screening: Application to Magnoliae Officinalis Cortex.
Zhenzhen XUE ; Yudong SHANG ; Lan YANG ; Tao LI ; Bin YANG
Journal of Pharmaceutical Analysis 2025;15(4):101066-101066
A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex (MOC) was developed and implemented to rapidly profile and discover bioactive metabolites in vivo derived from traditional Chinese medicine (TCM). The strategy possessed four characteristics: 1) The tailored database consisted of metabolites derived from big data-originated reference compound, metabolites predicted in silico, and MOC chemical profile-based pseudomolecular ions. 2) When profiling MOC-derived metabolites in vivo, attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds, as reported by most papers, but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites. 3) Metabolite traceability was performed, especially to distinguish isomeric prototypes-derived metabolites, prototypes of MOC compounds as well as phase I metabolites derived from other MOC compounds. 4) Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification. Using this strategy, 134 metabolites were swiftly characterized after the oral administration of MOC to rats, and several metabolites were reported for the first time. Furthermore, 17 potential active metabolites were discovered by targeting the motilin, dopamine D2, and the serotonin type 4 (5-HT4) receptors, and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model. This study extends the application of mass spectrometry (MS) to rapidly profile TCM-derived metabolites in vivo, which will help pharmacologists rapidly discover potent metabolites from a complex matrix.
3.Evaluation of a nude mouse model of endometriosis fibrosis via the human xenograft subcutaneous transplantation method
Xue ZHOU ; Guiping WAN ; Zhenzhen ZHANG
Chinese Journal of Comparative Medicine 2024;34(8):19-26
Objective To assess the feasibility of establishing a nude mouse model of endometriosis fibrosis of human origin and to determine whether endometrial mesenchymal stem cells are involved in inducing endometriosis fibrosis.Methods Four endometrial tissue specimens were collected and transplanted 1∶3 into 12 BABL/c nude mice by subcutaneous injection.The morphology and volume of the lesions were recorded.The nude mice were sacrificed on the 15th day after transplantation to observe the morphology of the lesions and their adhesion to the periphery of the abdominal wall.HE staining was used to judge the result of modelling,Masson staining was used to assess the extent of fibrosis,and immunofluorescence was used to track the role of endometrial mesenchymal stem cells in the fibrotic process of endometriosis.Results The volume of ectopic lesions in nude mice increased over time and showed restricted,vesicular-like changes.The tight adhesion of the lesions to the abdominal wall,endometrioid glands,and collagen fiber deposition were seen microscopically.The success rate of the modelling was 83.4%,and the collagen fiber volume fraction of the lesions was significantly higher after modelling(P<0.01).Confocal imaging suggested that endometrial mesenchymal stem cells(SUSD2+)differentiated into myofibroblasts(α-SMA+)in vivo.Conclusions The nude mouse model established by human allogeneic transplantation via subcutaneous injection was consistent with the lesion characteristics of endometriosis fibrosis.The modelling method is simple and feasible and provides a better reference model for further investigating the pathogenesis of endometriosis fibrosis.In addition,in vivo observations using the model indicated that endometrial mesenchymal stem cells are involved in inducing the formation of endometriosis fibrosis.
4.Clinical application of digital subtraction angiography in treatment of iatrogenic vascular injury caused by central venous catheterization
Zhenzhen CHEN ; Xue CHEN ; Xuegang WEN ; Anming CUI ; Xianzhong WANG ; Hongbin ZHANG
Chinese Journal of Digestive Surgery 2024;23(9):1227-1230
Central venous catheterization plays an important role in the rescue of critically patients. Commonly used central veins in clinical practice include subclavian vein, internal jugular vein, and femoral vein. Serious complications after catheterization can endanger patients′ lives in severe cases. It is necessary to improve the understanding and treatment of serious complications of central vein catheterization in clinical work. A case of iliac vein dissection caused by right femoral vein catheterization was summarized in this article, and the catheter was successfully removed under digital subtraction angiography direct vision after the distal end of the catheter penetrated the vascular wall and reached the peritonea, which provided reference for the treatment of iatrogenic injury caused by central vein catheterization.
5.Outcomes of allograft from donor kidney microthrombi and secondary recipient thrombotic microangiopathy: should we consider loosening the belt?
Yamei CHENG ; Luying GUO ; Xue REN ; Zhenzhen YANG ; Junhao LV ; Huiping WANG ; Wenhan PENG ; Hongfeng HUANG ; Jianyong WU ; Jianghua CHEN ; Rending WANG
Journal of Zhejiang University. Science. B 2023;24(6):524-529
There is currently a huge worldwide demand for donor kidneys for organ transplantation. Consequently, numerous marginal donor kidneys, such as kidneys with microthrombi, are used to save patients' lives. While some studies have shown an association between the presence of microthrombi in donor kidneys and an increased risk for delayed graft function (DGF) (McCall et al., 2003; Gao et al., 2019), other studies have demonstrated that microthrombi negatively impact the rate of DGF (Batra et al., 2016; Hansen et al., 2018), but not graft survival rate (McCall et al., 2003; Batra et al., 2016; Gao et al., 2019). In contrast, Hansen et al. (2018) concluded that fibrin thrombi were not only associated with reduced graft function six months post-transplantation but also with increased graft loss within the first year of transplantation. On the other hand, Batra et al. (2016) found no significant differences in the DGF rate or one-year graft function between recipients in diffuse and focal microthrombi groups. To date, however, the overall influence of donor kidney microthrombi and the degree of influence on prognosis remain controversial, necessitating further research.
Humans
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Thrombotic Microangiopathies
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Transplantation, Homologous
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Tissue Donors
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Kidney
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Allografts
6.Distribution characteristics of Mycobacterium tuberculosis and streptomycin and ethambutol resistance patterns by high⁃resolution melt analysis
Tengfei Guo ; Zhenzhen Wang ; Yi Hou ; Zhanqin Zhao ; Xiangyang Zu ; Tao Jiang ; Yun Xue
Acta Universitatis Medicinalis Anhui 2023;58(7):1227-1232
Objective :
To study the resistance pattern of streptomycin and ethambutol in Mycobacterium tuberculosis in Luoyang area , guide clinical medication and supplement epidemiological data on local drug⁃resistant tuberculosis .
Methods :
The positive results of high⁃resolution melting curve (HRM) in 2 941 cases in Luoyang area were analyzed to assess the risk factors associated with streptomycin and ethambutol resistance .
Results :
Of the 2 941 HRM⁃positive patients , 18 . 4% were resistant to streptomycin and 8. 0% were ethambutol . Both streptomycin and ethambutol and resistance rates were higher in men than those in women ( 19. 0% vs 16. 9% , P = 0. 129 ; 8. 0% vs 7. 9% , P = 0. 987) . The resistance rates to streptomycin and ethambutol were higher in urban than those in rural areas (21 . 3% vs 16. 6% , P = 0. 002 ; 9. 8% vs 6. 9% , P = 0. 004) . The resistance rate was much higher in previously treated patients than those newly diagnosed for MTB infection (25 . 8% vs 17. 3% , P < 0. 001 ; 12. 1% vs 7. 4% , P = 0. 002) . The resistance rates to streptomycin were higher in the < 51 years than those in the > 50 years group (21 . 1% vs 16. 1% , P < 0. 001) . According to age , the highest resistance rates to streptomycin and ethambutol occurred in the age range of 31 - 35 years and 56 - 60 years in men , respectively , while in the age range of 21 - 25 years and 56 - 60 years in women , respectively . In multivariate models , prior treatment history , age less than 51 years , and urban area were positively associated with streptomycin and ethambutol resistance after adjusting for smear results and year testing .
Conclusion
Men , prior treatment history , age less than 51 years , and urban residents are key monitoring targets for streptomycin and ethambutol resistant tuberculosis .
7.Development of molecular markers of Mycobacterium tuberculosis rifampicin resistance gene rpoB by PARMS technology.
Xiaohui LIU ; Xiangyang ZU ; Zhenzhen WANG ; Pengchao ZHAO ; Lei GAO ; Zhanqin ZHAO ; Yun XUE
Chinese Journal of Biotechnology 2021;37(7):2503-2512
The purpose of this study is to provide a simple and reliable genetic typing approach for molecular drug susceptibility test of Mycobacterium tuberculosis, through the developing of fluorescence molecular marker of rifampicin resistance gene rpoB. Eleven fluorescent molecular markers of the rpoB gene were established by using the sequence difference between the amino acid positions 531, 526, 516, 511 and 513 of rpoB gene of rifampicin-resistant strains and the alleles of rifampicin-sensitive strains, combined with the PARMS technique (Penta-primer amplification refractory mutation system). We used 104 clinical isolates of Mycobacterium tuberculosis to validate this marker and it was verified by sequencing as 100% correct. These samples were also tested with proportional drug sensitivity test. The coincidence rate was 94.23%. The molecular markers had high reliability for genotyping of rpoB gene. It can also detect low-concentration drug-resistant samples (511/533 unit point mutations) whose phenotypic susceptibility cannot be detected. The eleven sets of fluorescent molecular markers could cover 92%-96% of rpoB gene mutation types of rifampicin-resistant strains, and provide new idea for rapid detection of rifampin-resistant Mycobacterium tuberculosis.
Bacterial Proteins/genetics*
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DNA-Directed RNA Polymerases/genetics*
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Drug Resistance, Bacterial/genetics*
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Microbial Sensitivity Tests
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Mutation
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Mycobacterium tuberculosis/genetics*
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Reproducibility of Results
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Rifampin/pharmacology*
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Technology
8.Comparison of roles of inflammatory response in acute lung injury induced by blunt chest trauma versus by blunt chest trauma-hemorrhagic shock and resuscitation in rats
Meng JIANG ; Xiaojing WU ; Zhongyuan XIA ; Rui XUE ; Zhenzhen LIU ; Qingtao MENG
Chinese Journal of Anesthesiology 2014;34(4):497-499
Objective To compare the roles of inflammatory response in acute lung injury (ALI) induced by blunt chest trauma verus by blunt chest trauma-hemorrhagic shock and resuscitation (double hits) in rats.Methods Thirty male Sprague-Dawley rats,aged 8 weeks,weighing 240-280 g,were randomly assigned into 3 equal groups (n =10 each) using a random number table:sham operation group (S group),blunt chest trauma group (T group),and blunt chest trauma and hemorrhagic shock and resuscitation group (THSR group).Lung contusion was induced in anesthetized rats by dropping a 300 g weight onto a precordial protective shield to direct the impact force away from the heart and toward the lungs.Blood was withdrawn via the left femoral artery 5 min later until MAP was decreased to 35-45 mmHg within 15 min and maintained at this level for 60 min,followed by resuscitation.At 6 h after the model was established,the arterial blood samples were collected for blood gas analysis and detection of serum concentrations of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),IL-1β and IL-10 (by ELISA).The rats were then sacrificed and pulmonary specimens were obtained for determination of contents of TNF-α,IL-6,IL-1β and IL-10 in lung tissues and for microscopic examination.Results Compared with group S,PaO2 was significantly decreased,and the levels of TNF-α,IL-6,IL-1β and IL-10 in serum and lung tissues were increased in T and THSR groups.Compared with group T,PaO2 was significantly decreased,and the levels of TNF-α,IL-6,IL-1β and IL-10 in serum and lung tissues were increased in group THSR.The histopathological damage to lung tissues was aggravated in THSR group as compared with T group.Conclusion The role of inflammatory response in ALI induced by blunt chest trauma-hemorrhagic shock and resuscitation (double hits) is significantly stronger than that in ALI induced by blunt chest trauma alone in rats.


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