1.Establishment and evaluation of a mouse model of schistosomiasis liver disease induced by portal vein injection of worm eggs
LE Bin ; TANG Rui ; JIANG Pengyue ; HE Xing ; FAN Xiaobin
China Tropical Medicine 2023;23(10):1023-
Abstract: Objective To construct a mouse model of Schistosoma japonicum liver disease induced by direct injection of Schistosoma japonicum eggs through the portal vein and evaluate its effectiveness, in order to provide a new animal model for schistosomiasis liver disease research. Methods Fifteen 8-week-old C57BL/6 male mice were randomly divided into control group and egg injection group, with 5 in the control group and 10 in the egg injection group. On day -14, 5 000 live eggs were injected into the abdominal cavity of mice, and on day 0, the mice were anesthetized and the abdominal cavity was opened. 5 000 live eggs were injected through the portal vein, and the control group was injected with equal volume of phosphate buffer (PBS). 5 mice in the egg group were killed on day 10 and 30, respectively. The control group mice were killed on day 10, and their serum and liver tissue were collected. Hematoxylin eosin staining (HE) and Masson staining were performed, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver hydroxyproline (HYP) content were detected using a microplate spectrophotometer. Liver fibrosis-related genes, Th1 and Th2 type immune response-related genes were analyzed by real-time fluorescence quantitative PCR (qPCR). Liver injury, egg granuloma and fibrosis, and adaptive immune response were detected to evaluate the effect of portal vein injection of eggs while inducing mouse model of schistosomiasis liver disease. Results The results showed that significant egg granulomas appeared in the liver of mice after injection of eggs into the portal vein for 10 and 30 days. There was no statistically significant difference in the area of egg granulomas between the 10-day group and the 30-day group (t=0.975, P=0.332). Masson staining and liver hydroxyproline content detection showed significant fibrosis in the liver. The qPCR results showed that, compared with the control group, the expression levels of fibrosis marker genes, such as α⁃Sma (alpha smooth muscle actin), Col1a1 (collagen type Ⅰ alpha 1), and Tgfb1 (transforming growth factor beta 1), were significantly increased (t=6.380, 7.533, 5.314; P=0.002, 0.001, 0.007), and then decreased on the 30th day, with no statistical difference compared to the control group (t=0.940, 1.529, 1.746; P=0.778, 0.543, 0.457). At the same time, the expression levels of Th1 type immune response-related genes, such as tumor necrosis factor alpha (Tnf), interferon gamma (Ifng), and Th2 type immune response-related genes, such as interleukin-5 (Il5), interleukin-13 (Il13), significantly increased 10 days after eggs injection (t=6.163, 4.589, 5.651, 5.367; P=0.003, 0.018, 0.020, 0.009). In addition, there was no significant change in the levels of AST and ALT in the serum of each group of mice (t=0.982, 3.450; P=0.771, 0.074. t=1.164, 0.564; P=0.697, 0.917). Conclusions A mouse model of schistosomiasis liver disease induced by portal vein injection of worm eggs was constructed. The study provides a new modeling method for studying the mechanism of liver fibrosis in schistosomiasis..
2.miR-195 regulates FOXK1 gene and inhibits PI3K/Akt pathway’s biological behavior in stomach adenocarcinoma
Xiaobin FAN ; Fengfeng SONG ; Xiaoqing LI ; Wenxing LI ; Xianying FAN ; Yanwei HU ; Zhigang SONG ; Qiang WANG ; Yanjun LIAN
Chinese Journal of Endocrine Surgery 2022;16(6):655-661
Objective:To investigate the effect and mechanism of miR-195 regulating FOXK1 gene and PI3K/Akt pathway on stomach adenocarcinoma proliferation, invasion and migration ability.Methods:Public database samples were employed to analyze the expression differences and prognostic significance of miR-195 in stomach adenocarcinoma. After overexpression of mir-195-5p in two cell lines, MGC803 and AGS, altered cell proliferation, invasion, and migration abilities were detected by Alamar Blue, Wound healing, and Transwell assays. The potential target genes and binding sites of miR-195 were predicted by the starBase. Western blot was used to detect the expression levels of foxk1 and phosphorylation sites in the PI3K/Akt pathway of target genes after overexpression of mir-195-5p. A Dual-luciferase reporter assay was used to verify the relationship between mir-195-5p and foxk1. Statistical analyses were performed with IBM SPSS 22 software and R 4.0.3.Results:Our results showed a significant over-expression of miR-195 in the tumor tissues, compared with the paired normal tissues ( P<0.001) , which could inhibit the proliferation and invasion of stomach carcinoma cells and significantly correlated with survival ( P=0.011) . Moreover, our study indicated that miR-195 depressed the expression of FOXK1 and significantly reduced the activation of the PI3K/Akt pathway, which had a negative effect on the proliferation and invasion of stomach carcinoma cells. The phosphorylated Akt (s473 site) expression in the PI3K/Akt pathway was significantly decreased after overexpression of miR-195. Conclusion:Overall, our studies clarify the important function of the miR-195 in the diagnosis and therapy of patients with stomach carcinoma and reveal the FOXK1 and PI3K/Akt pathway regulation by the miR-195, which are of important clinical significance in the differential diagnosis.
3.VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses.
Yilan SHEN ; Wei CHEN ; Lei HAN ; Qi BIAN ; Jiajun FAN ; Zhonglian CAO ; Xin JIN ; Tao DING ; Zongshu XIAN ; Zhiyong GUO ; Wei ZHANG ; Dianwen JU ; Xiaobin MEI
Acta Pharmaceutica Sinica B 2021;11(1):127-142
Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses
4.Correlation between systemic immune-inflammation index and prognosis in patients with hepatic alveolar echinococcosis
Xiaobin CHEN ; Jiaqi YUAN ; Zhixin WANG ; Haining FAN ; Zhaojun XU ; Xuepeng MEI ; Haijiu WANG ; Jiamin MA ; Ying ZHOU ; Lizhao HOU
Journal of Clinical Hepatology 2021;37(2):375-379
ObjectiveTo investigate the correlation between systemic immune-inflammation index (SII) and prognosis in patients with hepatic alveolar echinococcosis. MethodsA retrospective analysis was performed for the clinical data of 242 patients who were admitted to Department of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, from January 2015 to December 2018 and underwent surgery for hepatic alveolar echinococcosis, and SII was calculated. The chi-square test was used for comparison of categorical data between two groups, and a Spearman correlation analysis was performed. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of SII; the Kaplan-Meier method was used to plot survival curves and analyze overall survival time in the two groups, and the log-rank test was used for comparison of survival rates between the two groups; univariate and multivariate Cox regression analyses were used to identify the influencing factors for the prognosis of patients with hepatic alveolar echinococcosis. ResultsThe Spearman correlation analysis showed that SII was positively correlated with the postoperative fatality rate of patients with hepatic alveolar echinococcosis (r=0.267, P<0.001). The ROC curve showed that the optimal cut-off value of SII before surgery was 758.92, and based on this, 242 patients with hepatic alveolar echinococcosis were divided into low SII (SII ≤758.92) group with 126 patients and high SII (SII >758.92) group with 116 patients. The low SII group had 1-, 3-, and 5-year survival rates of 98.20%, 88.47%, and 6610%, respectively, and the high SII group had 1-, 3-, and 5-year survival rates of 90.80%, 53.05%, and 27.40%, respectively. The low SII group had a cumulative survival rate of >50% and a mean survival time of 55.584 months (95% confidence interval[CI]: 53550-57.617), while the high SII group had a cumulative survival rate of <50%, a mean survival time of 39.384 months (95% CI: 35.070-43.698), and a median survival time of 43 months (95% CI: 34.694-51.306). The low SII group had a significantly better survival rate than the high SII group, and there was a significant difference in overall survival rate between the two groups (χ2=46.979, P<005). The univariate analysis showed that SII >758.92 (hazard ratio [HR]=5.907, 95% CI: 3.386-10.306, P=0.001) was an influencing factor for the overall survival time of patients with hepatic alveolar echinococcosis, and the multivariate Cox regression analysis showed that preoperative peripheral blood SII (HR=3.507, 95% CI: 1.911-6.435, P=0.001) was an independent risk factor for the overall survival rate of patients with hepatic alveolar echinococcosis. ConclusionPreoperative SII level is clearly correlated with the prognosis of patients with hepatic alveolar echinococcosis and can thus be used as a clinical indicator to evaluate the prognosis of patients. The higher the peripheral blood SII before surgery, the worse the prognosis of patients.
5.Puncture assisted by a "TINAVI" orthopaedic robot versus freehand puncture in vertebroplaty for osteoporotic vertebral compression fracture of the upper thoracic vertebra
Bolong ZHENG ; Dingjun HAO ; Bin LIN ; Zhen CHANG ; Lin GAO ; Liang YAN ; Xiaobin YANG ; Hua HUI ; Shunwu FAN ; Zhongliang DENG ; Yue ZHU ; Baorong HE
Chinese Journal of Orthopaedic Trauma 2021;23(1):20-26
Objective:To compare the clinical efficacy between puncture assisted by a "TINAVI" orthopaedic robot versus freehand puncture in vertebroplaty for osteoporotic vertebral compression fracture(OVCF) of the upper thoracic vertebra.Methods:A retrospective study was conducted of the 19 patients (20 vertebral bodies) with OVCF of the upper thoracic vertebra who had been treated at Department of Spine Surgery, Honghui Hospital from January 2018 to March 2019 by robotic vertebroplasty (robot group) and of another 21 counterpart patients (21 vertebral bodies) who had been treated by conventional vertebroplasty from January 2016 to December 2017 (freehand group). Puncture was conducted by a "TINAVI" orthopaedic robot in the robotic vertebroplasty but freehand in the conventional vertebroplasty. The robot group had 5 males and 14 females, aged from 62 to 88 years; the freehand group had 6 males and 15 females, aged from 64 to 83 years. The 2 groups were compared in terms of operation time, bone cement volume, postoperative complications (cement leakage, infection and embolism), visual analogue scale (VAS), Oswestry disability index (ODI), anterior height (AH) and kyphosis angulation (KA) of the injured vertebra at day 1 and last follow-up after surgery.Results:The 2 groups were comparable because there were no significant differences between them in the preoperative general data ( P>0.05). Vertebroplasty via unilateral puncture approach was completed uneventfully in the 19 patients (20 vertebral bodies) in the robot group and in the 21 patients (21 vertebral bodies) in the freehand group. The 40 patients were followed up for 6 to 12 months (mean, 8.3 month). The operation time [(37.9±8.2) min], bone cement volume [(2.3±0.9) mL] and rate of cement leakage (10.0%, 2/20) in the robot group were all significantly less or lower than those in the freehand group [(46.2±9.4) min, (4.2±1.3) mL and 42.9% (9/21)] ( P<0.05). No infection or embolism was observed in either group. There were no significant differences between the 2 groups in VAS, ODI, AH or KA of the injured vertebra at day 1 or last follow-up after surgery ( P>0.05). Conclusion:In vertebroplaty for OVCF of the upper thoracic vertebra, compared with conventional freehand puncture, puncture assisted by a "TINAVI" orthopaedic robot can lead to satisfactory clinical efficacy because it reduces operation time, volume of bone cement injection, and thus incidence of bone cement leakage.
6.Analysis of reasons of insufficient blood collected in Guangzhou during 2018~2020
MingYue LIANG ; Hong LUO ; Boquan HUANG ; Ailingling TAN ; Bin FAN ; Bo HE ; Xiaobin HUANG
Chinese Journal of Blood Transfusion 2021;34(5):514-516
【Objective】 To retrospectively analyze the reasons of insufficient blood collected, to provide evidences for further taking targeted measures, to reduce the discard of insufficient whole blood and prevent the loss of blood donors. 【Methods】 Calculate the total number of whole blood donors and the number of whole blood donors donating insufficient blood during 2018~2020 annually in Guangzhou Blood Center Information System, and the data was analyzed in SPSS (22.0) software for χ2test and linear trend test. 【Results】 During 2018~2020, the incidence of insufficient blood collected was 0.066 4%(531/799 439), and the incidence of insufficient blood collected because of poor blood flow, needle-sickness and other reasons were 0.048 7%(389/799 439), 0.010 6%(85/799 439) and 0.007 1%(57/799 439). Furthermore, the incidence of insufficient blood collected of the three above reasons had statistically significant difference between the years respectively (P<0.05), meanwhile the incidence of insufficient blood collected because of poor blood flow was in a general rising trend significantly (0.036 3%<0.038 2%<0.072 7%, P<0.05). 【Conclusion】 The incidence of insufficient blood collected because of poor blood flow was in the rising trend and further precautions should be considered. Under the normalization of the novel corona-virus pneumonia (COVID-19), the professional knowledge of epidemic prevention and control should be learned and trained, in addition the puncture technique, the ability of offering psychological care and dealing with adverse events during blood collection should be also improved among nurses continually, so as to provide high quality services for blood donors.
7.Retrospective cohort study on the coagulation characteristics of adult patients with extensively severe burn in shock stage and its alarming value
Qimin MA ; Xiaobin LIU ; Guosheng WU ; Wenjia HOU ; Xiaoming FAN ; Tuo SHEN ; Kang′an WANG ; Feng ZHU
Chinese Journal of Burns 2021;37(2):150-156
Objective:To study the coagulation characteristics of adult patients with extensively severe burn in shock stage and its alarming value.Methods:Retrospective cohort study was performed on medical records of 37 adult patients with extensively severe burn who were admitted to the First Affiliated Hospital of Naval Medical University from January 2014 to December 2019 and met the inclusion criteria. The patients were divided into survival group ( n=23, 17 males and 6 females, aged 41 (31, 51) years) and death group ( n=14, 11 males and 3 females, aged 50 (43, 58) years) according to the prognosis of within 60 d after burn. Basic data of patients in the two groups and their routine coagulation indexes during shock period including prothrombin time (PT), thrombin time, activated partial thromboplastin time (APTT), D-Dimer, fibrinogen degradation product (FDP), fibrinogen, platelet, and international normalized ratio (INR) were recorded. Data were statistically analyzed with Wilcoxon rank sum test and Fisher′s exact probability test, prognosis-related factors was analyzed with single factor and multivariate logistic regression analysis (α selected=0.05, α excluded=0.1), and receiver operating characteristic (ROC) curve analysis were established to screen out the risk factors. All the patients were grouped into high score group and low score group according to the optimal threshold value, Kaplan-Meier method was used for survival analysis and Log-rank test was performed between the two groups. Results:Total burn surface area (TBSA) of patients in death group was obviously larger than that in survival group ( Z=2.980, P<0.01), while there were no statistically significant difference in the other indexes between the two groups ( P>0.05). Compared with those in survival group (16.10 (14.30, 16.90) s, 40.80 (36.20, 42.80) s, 1.30 (1.10, 1.40)), PT (18.70 (16.30, 22.70) s), APTT (46.45 (41.00, 57.10) s) and INR (1.55 (1.30, 1.96)) of patients in death group were significantly increased ( Z=2.540, 2.330, 2.300, P<0.05), there were no statistically significant difference in the other indexes between the two groups ( P>0.05). Single factor logistic regression analysis showed TBSA, PT, and APTT were factors related to death of adult patients with extensively severe burn within 60 d after burn (odds ratio (OR)=1.190, 1.214, 1.109, 95% confidence interval (CI)=1.053-1.346, 1.008-1.461, 1.012-1.215, P<0.05 or P<0.01). FDP and INR were potential factors related to death of adult patients with extensively severe burn within 60 d after burn (OR=1.040 and 4.559, 95% CI =0.998-1.083 and 0.918-22.641, P<0.1). Multivariate logistic stepwise regression was used to build models of APTT+ FDP+ TBSA and APTT+ FDP. Area under the curve (AUC) of APTT+ FDP+ TBSA model score was 0.944 (95% CI= 0.873-1.000), which was higher than AUC of APTT+ FDP model score (0.843, 95% CI=0.713-0.973) by ROC curve analysis. Optimal threshold value of APTT+ FDP+ TBSA model score was -0.879 4 with sensitivity of 100% (95% CI=100%-100%) and specificity of 87% (95% CI=74%-100%). Survival ratio of patients in high score group with optimal threshold value higher than -0.879 4 was significantly lower than that in low score group with optimal threshold value lower than -0.879 4, χ2=27.090, P<0.01. Conclusions:The coagulation state of adult patients with extensively severe burn in shock stage is characterized with procoagulant and hemostatic dysfunctions accompanied by enhanced fibrinolytic activity. The risk of death is significantly increased in adult patients with extensively severe burn with APTT+ FDP+ TBSA model score higher than -0.879 4.
8.Impaired Parahippocampal Gyrus-Orbitofrontal Cortex Circuit Associated with Visuospatial Memory Deficit as a Potential Biomarker and Interventional Approach for Alzheimer Disease.
Lin ZHU ; Zan WANG ; Zhanhong DU ; Xinyang QI ; Hao SHU ; Duan LIU ; Fan SU ; Qing YE ; Xuemei LIU ; Zheng ZHOU ; Yongqiang TANG ; Ru SONG ; Xiaobin WANG ; Li LIN ; Shijiang LI ; Ying HAN ; Liping WANG ; Zhijun ZHANG
Neuroscience Bulletin 2020;36(8):831-844
The parahippocampal gyrus-orbitofrontal cortex (PHG-OFC) circuit in humans is homologous to the postrhinal cortex (POR)-ventral lateral orbitofrontal cortex (vlOFC) circuit in rodents. Both are associated with visuospatial malfunctions in Alzheimer's disease (AD). However, the underlying mechanisms remain to be elucidated. In this study, we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice, and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging (MRI) in patients on the AD spectrum. We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice. Moreover, MRI measurements of the PHG-OFC circuit had an accuracy of 77.33% for the classification of amnestic mild cognitive impairment converters versus non-converters. Thus, the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD, thereby providing a potential predictor for AD progression and a promising interventional approach for AD.
9. Clinical efficacy and safety analysis of retrograde intrarenal stone surgery for treatment of upper urinary calculi
Chengcun ZHU ; Fan CHENG ; Ting RAO ; Weimin YU ; Xiaobin ZHANG ; Yuan RUAN ; Run YUAN ; Yuqi XIA ; Cheng WU
Chinese Journal of Urology 2020;41(1):41-45
Objective:
To evaluate efficacy and safety of retrograde intrarenal stone surgery for treatment of upper urinary calculi.
Methods:
The clinical data of 640 patients with upper urinary tract calculi treated by retrograde intrarenal stone surgery (RIRS) in Renmin Hospital of Wuhan University from April 2016 to January 2019 were retrospectively analyzed. There were 424 males and 216 females. The awerage age was (46.2±12.8) years old, ranging 18 to 76 years old. The maximum diameter of the stone is (1.4±0.7) cm, ranging 0.6-3.2 cm. There were 126 cases with inferior calculi and 514 cases with non-lurgical calculi. There were 196 cases with unilateral ureteral calculi, 118 unilateral ureteral calculi cases with renal calculi, 236 cases with unilateral renal stones, and 90 cases with double kidney stones. 104 cases were placed with double J tube before operation and 496 cases were not placed before operation. There were 8 cases of horseshoe kidney, 30 cases of isolated kidney with renal insufficiency, 4 cases of pelvic ectopic kidney with dysplasia, 6 cases of congenital ureteral malformation and 2 cases of sponge kidney. Preoperative average hemoglobin was (133.2±5.6)g/L, ranging 126-188 g/L.And average serum creatinine was (84.4±12.2)μmol/L, ranging 74-242μmol/L before operation. All patients were treated with general anesthesia under the lithotomy position. The ureteroscopy combined with holmium laser lithotripsy was performed.The 200μm fiber was used, which the parameters were set as 12-45 W(0.5-1.5 J/10-30 Hz). The stone baskets were used to take stones according to actual conditions. The operation was performed by doctors of the same qualifications.
Results:
All patients underwent successful operation. The mean operation time was (45.6±14.6)min. The average postoperative hospitalization was (4.8±1.5)d. The postoperative serious complication rate was 0.9%, including(2 cases of sepsis and 1 case of subcapsular hematoma. Of the 640 patients, 596 were admitted to the hospital for a double J tube and 44 were lost of follow-up. 552 patients met the stone removal criteria, 44 patients did not meet the stone removal criteria for other treatments, such as extracorporeal shock wave lithotripsy, ureteroscopy or observed regularly. The stone-free rate (SFR) was 92.6% (552/596) after 1-3 months. On the first postoperative day, serum creatinine was (76.0±10.6)(58-156) μmol/L, and postoperative hemoglobin was (126.4±9. 6)(120-176) g/L. There was no significant difference in preoperative and postoperative hemoglobin (t=2.02,
10.Effect of improved urethral irrigation on urethral stricture in patients with closed bulbar urethral injury
Xuhui ZHANG ; Fan LIU ; Qiqi QIN ; Xiaobin YUAN ; Tao ZHANG
Chinese Journal of Postgraduates of Medicine 2020;43(5):385-388
Objective:To explore the effect of improved urethral irrigation on urethral stricture in patients with closed bulbar urethral injury.Methods:The clinical data of 65 male patients with closed bulbar urethral injury complicated with difficult catheterization from January 2014 to January 2018 in the First Hospital of Shanxi Medical University were retrospectively analyzed. Among them, 30 cases were treated with flexible cystoscope-guided catheterization and external urethral orifice nursing (routine group), and 35 cases were treated with flexible cystoscope-guided catheterization and urethral drug flushing (improved group). The incidence of urethral stricture 1 and 6 months after catheter removal, number of urethral dilatation and maximum urinary flow rate 6 months after catheter removal, visual analogue score (VAS) during indwelling catheter were compared between 2 groups.Results:Both groups indwelled the catheters successfully. During indwelling catheter, the inflammatory secretion in improved group was less and thinner than that in routine group. There was no significant difference in the incidence of urethral stricture 1 month after catheter removal and VAS during indwelling catheter between 2 groups ( P>0.05); the incidence of urethral stricture and number of urethral dilatation 6 months after catheter removal in improved group were significantly lower than those in routine group: 5.7% (2/35) vs. 26.7% (8/30) and (7.1±1.0) times vs. (11.4±1.8) times, the maximum urinary flow rate 6 months after catheter removal was significantly higher than that in routine group: (19.8 ± 2.9) ml/s vs. (16.3±2.3) ml/s, and there were statistical differences ( P<0.05 or <0.01). Conclusions:The system of improved urethral irrigation can be easily fabricated and can achieve convenient application. This improved treatment can facilitate the discharge of urethral secretions, alleviate the urethral inflammation, reduce the urethral scar formation, and can prevent the incidence of bulbar urethral stricture effectively.

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