1.Structural insights into the distinct ligand recognition and signaling of the chemerin receptors CMKLR1 and GPR1.
Xiaowen LIN ; Lechen ZHAO ; Heng CAI ; Xiaohua CHANG ; Yuxuan TANG ; Tianyu LUO ; Mengdan WU ; Cuiying YI ; Limin MA ; Xiaojing CHU ; Shuo HAN ; Qiang ZHAO ; Beili WU ; Maozhou HE ; Ya ZHU
Protein & Cell 2025;16(5):381-385
2.Prognostic factors analysis for chronic HBV-infected patients who achieved clinical cure with pegylated interferon-α-2b therapy
CHANG Lijun ; LI Yijun ; LUO Limin ; ZHANG Ye
China Tropical Medicine 2025;25(3):297-
Objective To analyze the clinical characteristics and prognostic factors for clinical cure in chronic hepatitis B virus (HBV) infected patients with pegylated interferon-α-2b (PEG-IFN-α-2b) based therapy. Methods This is a retrospective study. Chronic HBV infected patients receiving PEG-IFN-α-2b therapy were enrolled in Yuncheng Central Hospital affiliated to Shanxi Medical University between August 2020 and November 2023. Treatment-naïve patients received PEG-IFN-α-2b monotherapy, while nucleoside (acid) analogs (NAs)-experienced patients received PEG-IFN-α-2b add-on therapy. The study endpoint was hepatitis B surface antigen (HBsAg) negative in accompany with HBV DNA below the detection limit (course of treatment < 48 weeks) or treatment for 48 weeks. The general characteristics, virological variables, blood routine test, and liver function of patients were collected at baseline and study endpoint. Student’s t test or Mann-Whitney U test was used for comparison. The prognostic factors of clinical cure were examined using univariate and multivariate stepwise logistic regression models. Results A total of 61 chronic HBV infected patients were enrolled, including 39 males and 22 females. The age were (39.13±7.53) years. Twenty-one cases were treatment-naïve, while 40 patients were NAs-experienced. Nineteen cases were positive for HBV DNA at baseline. The baseline HBsAg levels were 211.30(50.93, 2 110.00) IU/mL. Thirty-four patients achieved clinical cure at the study endpoint with 25.50 weeks of median course of PEG-IFN-α-2b treatment. Twenty-seven patients did not achieve clinical cure at the study endpoint, and the course of treatment was 48 weeks. Clinical cure group had significant lower baseline HBsAg level when compared with non-clinical cure group [78.66(19.54, 204.60) IU/mL vs 2 078.00(442.20, 4 237.00) IU/mL, P<0.001]. At the study endpoint, the white blood cell, platelet, red blood cell, hemoglobin levels were lower than those in baseline (P<0.05), while alanine aminotransferase and asparatate aminotransferase levels were higher than those in baseline (P<0.05). There were no remarkable differences in blood routine tests or liver function between clinical cure and non-clinical cure group at either baseline or study endpoint (P>0.05). Baseline low HBsAg level was a predictor for clinical cure in patients receiving PEG-IFN-α-2b therapy (OR=0.998, 95%CI: 0.998-0.999). No severe adverse events were happened during therapy. Conclusion PEG-IFN-α-2b-based therapy was well-tolerant, and could achieve high rate of clinical cure in chronic HBV-infected patients who had low baseline HBsAg level.
3.Improvement effect of Xuebijing injection on blood-brain barrier damage in mice with anti-NMDAR encephalitis and its regulatory effect on Th17/Treg imbalance
Chaosheng ZENG ; Lin CHEN ; Limin YAN ; Huaijie XING ; Li LI ; Shaozhu HUANG ; Min CHEN ; Yong CHANG ; Bing KUANG ; Xiaoyan LI
Journal of Jilin University(Medicine Edition) 2025;51(5):1211-1220
Objective:To investigate the effect of Xuebijing injection against blood-brain barrier(BBB)damage in the mice with anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis,and to elucidate its regulatory effect on the imbalance of helper T cells 17(Th17)/regulatory T cells(Treg).Methods:The active immunization models of anti-NMDAR encephalitis in the mice were established using glutamate receptor N1 subunit(GluN1)356-385 antigen peptide,and the serum anti-NMDAR immunoglobulin G(IgG)antibody levels were detected by enzyme-linked immunosorbent assay(ELISA).The healthy mice without modeling were served as control group,and the mice with successful modeling were randomly divided into model group,low dose of Xuebijing injection(XBJ-L)group,and high dose of Xuebijing injection(XBJ-H)group,with 10 mice in each group.After modeling,the mice in XBJ-L and XBJ-H groups were intraperitoneally injected with 5 and 10 mL·kg-1 Xuebijing injection,respectively.The Longa score was used to assess the neurological impairment of the mice in various groups;evans blue(EB)staining was used to determine the BBB permeability;immunofluorescence staining was used to detect the expressions of zonula occludens 1(ZO-1)and Occludin in cerebral cortex of the mice in various groups;Western blotting method was used to determine the expression levels of ZO-1,Occludin,Claudin-5,and neuron-specific nuclear protein(NeuN)in cerebral cortex of the mice in various groups;ELISA method was used to determine the levels of Th17-and Treg-related cytokines including interleukin(IL)-17,IL-22,and IL-10 in serum of the mice;flow cytometry was used to determine the percentages of Th17 and Treg cells in peripheral blood of the mice in various groups,and the Th17/Treg ratio was calculated.Results:The serum of the mice induced with the GluN1 356-385 antigen peptide was positive for NMDAR IgG antibodies,indicating that the models were successfully established.Compared with control group,the neurological impairment score of the mice in model group was significantly increased(P<0.05),and the EB level in brain tissue was significantly increased(P<0.05);the fluorescence staining intensities of ZO-1 and Occludin in the cerebral cortex were decreased,and the expression levels of ZO-1,Occludin,Claudin-5,and NeuN proteins in the cerebral cortex were significantly decreased(P<0.05);the serum levels of IL-17 and IL-22 were significantly increased(P<0.05),while the IL-10 level was significantly decreased(P<0.05);the percentage of Th17 cells in peripheral blood was significantly increased(P<0.05),while the percentage of Treg cells was significantly decreased(P<0.05),and the Th17/Treg ratio was significantly increased(P<0.05).Compared with model group,the neurological impairment scores of the mice in XBJ-L and XBJ-H groups were significantly decreased(P<0.05),the EB levels in brain tissue were significantly decreased(P<0.05),the fluorescence staining intensities of ZO-1 and Occludin in cerebral cortex were increased,and the expression levels of ZO-1,Occludin,Claudin-5,and NeuN proteins were significantly increased(P<0.05);the levels of IL-17 and IL-22 in serum were significantly decreased(P<0.05),and the level of IL-10 was significantly increased(P<0.05);the percentages of Th17 cells in peripheral blood were significantly decreased(P<0.05),the percentages of Treg cells were significantly increased(P<0.05),and the Th17/Treg ratios were significantly decreased(P<0.05).Compared with XBJ-L group,the neurological function injury score of the mice in XBJ-H group was significantly decreased(P<0.05),the EB level in brain tissue was significantly decreased(P<0.05);the fluorescence staining intensities of ZO-1 and Occludin in the cerebral cortex were increased,and the expression levels of ZO-1,Occludin,Claudin-5,and NeuN proteins were significantly increased(P<0.05);the serum levels of IL-17 and IL-22 were significantly decreased(P<0.05),and the level of IL-10 was significantly increased(P<0.05);the percentage of Th17 cells in peripheral blood was significantly decreased(P<0.05),the percentage of Treg cells was significantly increased(P<0.05),and the Th17/Treg ratio was significantly decreased(P<0.05).Conclusion:Xuebijing injection can improve BBB injury,regulate Th17/Treg balance,and thereby alleviate the neurological functional damage in anti-NMDAR encephalitis.
4.Healthy Lifestyle and the Risk of Metabolic Dysfunction-Associated Fatty Liver Disease: A Large Prospective Cohort Study
Qing CHANG ; Yixiao ZHANG ; Tingjing ZHANG ; Zuyun LIU ; Limin CAO ; Qing ZHANG ; Li LIU ; Shaomei SUN ; Xing WANG ; Ming ZHOU ; Qiyu JIA ; Kun SONG ; Yang DING ; Yuhong ZHAO ; Kaijun NIU ; Yang XIA
Diabetes & Metabolism Journal 2024;48(5):971-982
Background:
The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD.
Methods:
A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors.
Results:
The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle.
Conclusion
Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.
5.Effect of CTRP13 regulates high glucose-induced autophagy dysfunction of primary rat liver sinusoidal endothelial cells through the AMPK/mTOR pathway
Jing YU ; Qi ZHANG ; Jing LIU ; Zibing QIAN ; Limin TIAN ; Peiyun ZENG ; Ruixia YANG ; Jie YANG ; Rui CUI ; Zhengping CHANG
Chinese Journal of Diabetes 2023;31(12):929-937
Objective To investigate the effect of C1q/tumor necrosis factor-related protein 13 protein(CTRP13)on the autophagy function of primary rat liver sinusoidal endothelial cells(rLSECs)induced by high glucose through AMP-activated protein kinase/mammalian target of rapamycin complex(AMPK/mTOR)pathway.Methods After isolation,identification and culture,original rat liver sinusoid endothelial cells(rrLSECs)were divided into normal control(NC)group,high glucose(HG)group,HG +LV-CTRP13 group,HG+ lentiviral empty vector(LV-Con)group(HG+LV-Con).CTRP13 lentivirus over expression vector(LV-CTRP13)and lentivirus empty vector(LV-Con)were constructed and transfected into rrLSECs.According to the intervention methods of AMPK inhibitor Compound C,mTOR inhibitor Torin1 and autophagy inhibitor 3MA,the transfected cell were divided into normal control(NC)group,high glucose(HG)group,HG+LV-CTRP13 group,HG+lentiviral empty vector(LV-Con)group(HG+ LV-Con).qRT-PCR and western blot were used to detect the mRNA and protein expression levels of CTRP13,autophagy related protein Beclin1,human microtubule-associated protein light chain 3II(LC3II),human plasma membrane membrane vesicle association proteins(PLVAP)and p-AMPK and p-MTOR in rat rLSECs of each group.Results Compared with NC group,the number of autophagosome was decreased in HG and HG+LV-CTRP13 group(P<0.05).Compared with HG group,the number of autophagosome bodies was increased in HG +LV-CTRP13 group(P<0.05).The CTRP13 mRNA and protein expression was higher in NC and HG + LV-CTRP13 groups than in HG and HG + LV-Con groups(P<0.05).In HG+LC-CTRP13 group,Beclin1,LC3II,p-AMPK,and AMPK mRNA,Beclin1,LC3II/LC3I protein expression were higher than HG and HG + LV-Con group(P<0.05),PLVAP,p-mTOR,mTOR mRNA,and PLVAP protein expression were lower than HG and HG+LV-Con group(P<0.05).Comparison with HG + LV-CTRP13,p-mTOR protein expression in HG+LV-CTRP13+Compound C group increased(P<0.05),while expressions of CTRP13,Beclin1 and LC3II/LC3I protein decreased(P<0.05);the protein expressions of p-AMPK,Beclin1 and LC3II/LC3I were increased in HG+LV+ CTRP13+Torin1 group(P<0.05),while CTRP13 and p-mTOR protein expression was decreased(P<0.05);protein expressions of p-AMPK,p-mTOR and LC3II/LC3I were higher in HG+LV-CTRP13 + 3MA group(P<0.05),while LC3II/LC3I protein expression was lower(P<0.05).Conclusion CTRP13 overexpression activates AMPK/mTOR-autophagy signaling pathway,which may play a protective role in the function of rLSECs anddelay liver sinusoid capillarization.
6.Role of STING signaling pathway in CORM-3-induced reduction of hepatocyte pyroptosis and apoptosis in a rat model of hepatic ischemia-reperfusion
Weichao ZHENG ; Yulin CHANG ; Yue XIN ; Yan LI ; Jing BAI ; Manman QI ; Limin ZHANG
Chinese Journal of Anesthesiology 2022;42(10):1197-1201
Objective:To evaluate the role of stimulator of interferon genes (STING) signaling pathway in carbon monoxide (CO)-releasing molecule-3 (CORM-3)-induced reduction of hepatocyte pyroptosis and apoptosis in a rat model of hepatic ischemia-reperfusion.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 9-11 weeks, weighing 320-380 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), ischemia-reperfusion group (IR group), CORM-3 group (C group) and STING agonist ADU-S100 group (A group).Hepatic ischemia-reperfusion injury models were developed by reversible ligation of left middle hepatic artery, portal vein and bile duct branches for 45 min, followed by reperfusion in anesthetized animals in IR, C and A groups.In group C, CORM-3 4 mg/kg was injected into the femoral vein immediately after reperfusion.The equal volume of normal saline containing dimethyl sulfoxide was injected into the femoral vein in S, IR and A groups.At 1.5 h after injection into the femoral vein, ADU-S100 10 mg/kg was intraperitoneally injected in A group, and the equal volume of normal saline was given instead in S, IR and C groups.The serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations were determined at 3 h of reperfusion.The rats were sacrificed at 12 h of reperfusion, and liver tissues were collected for determination of the content of CO (by colorimetry), expression of interleukin-1beta (IL-1β), IL-18, Bcl-2, Bax, interferon regulatory factor 3 (IRF3), phosphorylated IRF3 (p-IRF3), STING, NOD-like receptor protein 3 (NLRP3), aspirin D (GSDMD) and activated caspase-1 (by Western blot), and pyroptosis and apoptosis rates of hepatocytes (by immunofluorescence staining).The liver injury was scored. Results:Compared with group S, the serum ALT and AST concentrations, liver injury score, CO content, and pyroptosis and apoptosis rates of hepatocytes were significantly increased, and the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was up-regulated, and the Bcl-2/Bax ratio was decreased in group IR ( P<0.05).Compared with group IR, the serum ALT and AST concentrations, liver injury score, and pyroptosis and apoptosis rates of hepatocytes were significantly decreased, the CO content was increased, the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was down-regulated, and the Bcl-2/Bax ratio was increased in group C ( P<0.05).Compared with group C, the serum ALT and AST concentrations, liver injury score, and pyroptosis and apoptosis rates of hepatocytes were significantly increased, the CO content was decreased, the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was up-regulated, and the Bcl-2/Bax ratio was decreased in group A ( P<0.05). Conclusions:The mechanism by which CORM-3 attenuates hepatocyte pyroptosis and apoptosis may be related to the inhibition of activation of STING signaling pathway in a rat model of hepatic ischemia-reperfusion.
7.Infix plus cannulated screws for the treatment of pelvic injuries caused by pubic symphysis separation in middle-aged and elderly patients
Tonglin CHEN ; Xuanlin ZHENG ; Shuolei WANG ; Liangyuan WEN ; Xianjun LV ; Limin CHANG ; Tao LI ; Bao ZHU ; Haili ZHAO
Chinese Journal of Geriatrics 2022;41(7):780-784
Objective:To investigate the clinical effect of Infix combined with hollow screws for the treatment of pelvic injuries with pubic symphysis separation in middle-aged and elderly patients.Methods:Data of 8 middle-aged and elderly patients with pelvic injuries due to pubic symphysis separation undergone treatment from January 2017 to December 2020 were retrospectively analyzed.Results:The average operating time of 8 patients was (46.0±6.2)min(range: 40-62min); the average intraoperative blood loss was (32.0±5.6)ml(range: 25-50 ml); the average length of incisions at the iliac screw was(2.6±0.4)cm(range: 2.0-3.5 cm); the average length of incisions at the hollow screw was (1.1±0.3)cm(range: 0.8-1.5 cm); and the average times of fluoroscopy were (36.0±6.0)times(range: 28-52 times). Postoperative X-ray and CT examinations showed that the reduction of the pubic symphysis was good, the inserted iliac screws and cannulated screws were positioned accurately, and the incision healed well.Based on Matta's criteria, postoperative radiological outcomes were evaluated, with 7 cases rated as excellent and 1 as good, giving an excellent to good rate of 100%(8/8). The average followed up time for all 8 patients was (15.0±4.2)months(range: 6-24 months). Pelvic X-ray and CT examinations at the last follow-up showed that the fractures healed well and the pubic symphysis reduction did not fail.Infix and cannulated screws in the pubic symphysis were removed 10-12 weeks after surgery[average: (10.5±0.5)weeks]. According to the Majeed Pelvic Score, 5 cases were rated as excellent, 2 cases as good and 1 as fair, with an excellent to good rate of 87.5%(7/8). One patient had symptoms related to the lateral femoral cutaneous nerve that disappeared after 3 months.One patient developed deep venous thrombosis after surgery, and the filter was placed and removed 10 weeks later.Conclusions:Using Infix plus cannulated screws for the treatment of pelvic injuries in middle-aged and elderly patients with pubic symphysis separation has the advantages of limited trauma and intraoperative blood loss, good fixation and few complications.
8.Correlation between corneal neuropathy and ocular surface flora in type 2 diabetes
Tian CHANG ; Limin WANG ; Shanjun GAO ; Pingping WANG ; Huijuan YUAN
Chinese Journal of Endocrinology and Metabolism 2021;37(6):534-541
Objective:To explore the changes of corneal neuropathy and ocular surface flora in patients with type 2 diabetes, and the correlation between corneal neuropathy and ocular surface flora changes.Methods:According to the results of fundus fluorescein angiography, 65 patients with type 2 diabetes (130 eyes in total) who were treated with insulin alone and without comorbid retinopathy in the Department of Endocrinology, Henan People′s Hospital from March to June 2019 were selected. Sixty-five age-matched normal glucose tolerance subjects (130 eyes in total) were also enrolled. Confocal microscopy was performed and conjunctival sac secretions were collected. Through 16S rRNA analysis and sequencing and PICRUSt bacterial gene function prediction, the relationship between patients with type 2 diabetes and the difference in the degree of corneal neuropathy and the composition of ocular surface flora and function prediction in healthy people were explored, and the correlation between corneal neuropathy and ocular surface flora was analyzed as well.Results:Compared with healthy people, patients with type 2 diabetes have more severe corneal neuropathy, and it was related to the changes in ocular surface flora. Brevibacillus and paenibacillus were significantly positively correlated with the degree of corneal neuropathy ( P<0.05), and enhydrobacter and proteobacteria were significantly negatively correlated with the degree of corneal neuropathy ( P<0.05). PICRUSt analysis showed that the degree of enrichment of metabolism-related genes in the ocular surface flora of patients with type 2 diabetes was significantly changed compared with healthy people. Conclusion:Patients with type 2 diabetes present with more severe corneal neuropathy. The diversity of ocular surface flora and metabolic function have significant changes. The degree of severity corneal neuropathy is related to brevibacillus, paenibacillus, enhydrobacter, and proteobacteria.
9.Combined lumbar pelvic fixator for treatment of unstable vertical fracture and dislocation of old posterior pelvic ring
Tonglin CHEN ; Shuolei WANG ; Caili SUN ; Hongtao BAI ; Limin CHANG ; Xianjun LYU ; Tao LI ; Bao ZHU ; Yuanyuan LI ; Xuanlin ZHENG ; Weidou JIA
Chinese Journal of Orthopaedics 2021;41(20):1493-1499
Objective:To investigate the clinical effect of using combined lumbar pelvis fixation device in the treatment of old vertical unstable fracture dislocation of posterior pelvic ring.Methods:Data of 7 patients with old vertical unstable fracture dislocation of posterior pelvic ring admitted and followed up from January 2017 to April 2020 were retrospectively analyzed, including 4 males and 3 females with an average age of 42.4 years old (range, 22-73 years old). There were 3 cases of traffic injury, 3 cases of falling injury and 1 case of tumble injury. According to Tile classification for pelvic fractures, there were 5 cases of type C1, 1 case of type C2 and 1 case of type C3. The average time from fracture to surgery was 5.4 weeks (range, 3-10 weeks). Among the 7 patients, 4 patients' posterior ring fractures were fixed by combined lumbar pelvic triangle fixation, and 3 patients' posterior ring fracture were fixed by combined lumbar pelvic fixation. 4 patients' anterior ring injury were not treated, 2 patients' anterior ring injury were treated by closed cannulated screw and internal fixation, and 1 patient's anterior ring injury was fixed by INFIX and cannulated screw. Every patient's operating time, intraoperative blood loss, length of incision and times of X-ray fluoroscopy were recorded. Pelvic X-ray and CT scan were taken postoperatively to observe the condition of reduction and screw position. Postoperative fracture reduction quality was assessed by Matta radiological criteria and Majeed criteria was used at the final follow-ups to evaluate the degree of functional recovery after pelvic fracture.Results:The average operating time of 7 patients was 143 min (range, 96-205 min); the intraoperative average blood loss was 579 ml (range, 300-1 650 ml); the average length of incisions was 12.9 cm (range, 9-15 cm) and the average time of X-ray fluoroscopy was 27 times (range, 15-52 times). Postoperative X-ray and CT scan showed that the displacements of the posterior rings were reset well and all the hollow screws were located accurately and firmly. Postoperative radiation quality was evaluated according to Matta radiological criteria, and there were 4 cases of excellent, 2 cases of good and 1 case of fair, with an excellent and good rate of 85.7% (6/7). Seven patients had good fracture union. The average followed up time for all 7 patients was 12 months (range, 6-16 months). At the last follow-up, imaging examination showed good reduction of the sacroiliac joint, and the reduction of anterior and posterior rings were not lost. The healing time was 14.2 weeks (range, 12-20 weeks). Majeed score: postoperative 4.90±6.64 points (range, 48-58 points), postoperative 3 months 71.40±7.32 points (range, 67-75 points), postoperative 6 months 84.90±8.14 points (range, 68-96 points), the difference was statistically significant ( F=0.614, P=0.004). Majeed score 6 months after operation showed that 5 cases were excellent, 1 case was good and 1 case was fair, and the excellent and good rate was 85.7% (6/7). Conclusion:Using combined lumbar pelvis fixation device in the treatment of old vertical unstable fracture dislocation of posterior pelvic ring has good reduction quality, high fixed strength and good postoperative effect.

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