1.Regulatory effect of microRNA-544 on liver injury in mice with sepsis and its mechanism
Songmei GUAN ; Peiwu HUANG ; Xiaobao GONG ; Kangqiang LIN ; Shigang DUAN
Journal of Clinical Hepatology 2025;41(9):1861-1867
ObjectiveTo investigate the role and potential mechanism of microRNA-544 (miRNA-544) in lipopolysaccharide (LPS)-induced liver injury in mice with sepsis, and to provide a new target for the treatment of liver injury in sepsis. MethodsA total of 40 C57BL/6J mice were randomly divided into control group (intraperitoneal injection of normal saline), model group (intraperitoneal injection of LPS at a dose of 5 mg/kg), agonist group (intraperitoneal injection of LPS and miR-544 agonist at a dose of 5 mg/kg), and miR-544 inhibitor group (intraperitoneal injection of LPS and miR-544 inhibitor at a dose of 5 mg/kg), with 10 mice in each group. An automatic biochemical analyzer was used to measure the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) in serum and the liver; Western blot was used to measure the expression levels of monocyte chemotactic protein-1 (MCP-1), CD16/32, and proteins associated with the NF-κB signaling pathway in the liver; q-PCR and ELISA were used to measure the expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in serum. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group, the model group of LPS-induced sepsis had a significant reduction in the expression level of miR-544 in serum and liver tissue (P0.01), significant pathological changes of the liver (such as inflammatory cell infiltration and central vein congestion), and significant increases in the levels of liver injury markers (ALT, AST, and TBil) in serum and the liver (all P0.001), the expression levels of inflammatory factors (MCP-1, CD16/32, TNF-α, IL-6, and IL-1β) (all P0.01), and the phosphorylation levels of key proteins of the NF-κB pathway (p-IKK, p-I-NF-κ, and p-p65) (all P0.01). Compared with the model group, the miR-544 inhibitor group had a significant reduction in the expression level of miR-544 in serum and liver tissue (P0.01), aggravated pathological changes of the liver, and significant increases in the levels of liver injury markers and inflammatory factors (ALT, AST, TBil, MCP-1, CD16/32, TNF-α, IL-6, and IL-1) (all P0.05), as well as significant increases in the phosphorylation levels of key proteins of the NF-κB pathway (p-IKK, p-I-κB-α, and p-p65) (all P0.01). On the contrary, the miR-544 agonist group had a significant increase in the expression level of miR-544 in serum and liver tissue (P0.01), significant alleviation of liver pathological changes, and significant reductions in the levels of liver injury markers and inflammatory factors (ALT, AST, TBil, MCP-1, CD16/32, TNF-α, IL-6, and IL-1β) (all P0.05), as well as significant reductions in the phosphorylation levels of key proteins of the NF-κB pathway (p-IKK, p-I-κB-α, and p-p65) (all P0.05). ConclusionThis study shows that miR-544 can alleviate LPS-induced liver injury in mice with sepsis by inhibiting the expression of inflammatory-related proteins and the activation of the NF-κB signaling pathway.
2.Exploration of Predictors to Identify and Screen High Risk Patients With Early Gastric Cancer Submucosal Invasion
Keyan CHEN ; Ye WANG ; Jing ZHANG ; Shigang DING
Chinese Journal of Minimally Invasive Surgery 2024;24(6):401-408
Objective To analyze the clinical,pathological,and endoscopic features of differentiated early gastric cancer,and to study predictors to identify and screen high risk patients with early gastric cancer submucosal infiltration.Methods A total of 172 patients with differentiated early gastric cancer treated by surgical or endoscopic submucosal dissection in our hospital from January 2017 to December 2022 were included,which were divided into the mucosal layer group(144 patients)and submucosal layer group(28 patients)based on postoperative pathology.The clinical,pathological,and white-light endoscopy(WLE)and linked color imaging(LCI)features of the 2 groups were compared.The color difference between the lesion and the surrounding mucosa was evaluated by using the Commission International de L'Eclairage(CIE)L*a*b*system.Indicators with significant differences were included to multifactor logistic stepwise regression analysis(forward method)for the identification and screening of predictors.Results A history of alcohol consumption(P=0.037),a history of smoking(P=0.035),thickening of the gastric wall on enhanced CT(P=0.032),a lesion located in the upper 1/3(P<0.001)or middle 1/3(P=0.009)part of the stomach,depressed macroscopic type(P<0.001),marked margin elevation(P=0.003),presence of fold changes(P=0.006),color difference ≥12.3 under WLE(P=0.003)and≥18.2 under LCI(P=0.002)were associated with submucosal infiltration.Multivariate analysis showed that lesions located in the upper 2/3 portion of the stomach(OR=5.463,95%CI:2.562-11.648,P<0.001),depressed macroscopic type(OR=5.992,95%CI:1.624-22.100,P=0.007),marked margin elevation(OR=4.338,95%CI:1.124-16.747,P=0.033),and color difference ≥18.2 under LCI(OR=4.675,95%CI:1.342-16.288,P=0.015)were independent risk factors for infiltration of submucosal layer of lesions.Conclusion Lesions with depressed macroscopic type,marked elevated margins,located in the upper 2/3 part of the stomach,and having a large color difference from the surrounding mucosa under LCI are high-risk lesions for submucosal infiltration and require more aggressive intervention.
3.Dual roles of chondrocytes in rheumatoid arthritis
Yanlin ZHOU ; Xiaoli ZHANG ; Zhengwen AI ; Jun CAO ; Shigang LI
Chinese Journal of Pathophysiology 2024;40(5):924-930
Recent studies have found that chondrocytes not only represent the cells targeted by rheumatoid ar-thritis(RA)but may also themselves induce the disease.This dual role indicates the significance of chondrocytes in the pathology of RA.This article summarizes the important roles played by chondrocytes in RA,providing a reference for the pathogenesis and treatment of RA.
4.Study on metabolomics of Xiaoqinglong Decoction Granules in the treatment of chronic persistent cold syndrome of bronchial asthma
Qiuming WANG ; Meng LI ; Wenjing ZHANG ; Xuanhui HE ; Shigang LIU ; Hui LI
International Journal of Traditional Chinese Medicine 2024;46(12):1549-1558
Objective:To evaluate the clinical efficacy of Xiaoqinglong Decoction Granules in the treatment of chronic persistent cold syndrome of bronchial asthma; To explore its treatment mechanism.Methods:A randomized double-blind controlled study was performed. Totally 60 patients from the Respiratory Department of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine from January 2021 to January 2022 were selected as the observation subjects. They were divided into two groups using a random number table method, with 30 cases in each group. The control group was given conventional treatment plus placebo, and the experimental group was given conventional treatment plus Xiaoqinglong Decoction Granules. The treatment for both group lasted for 14d. TCM syndromes and clinical symptoms before and after treatment were scored. Asthma Control Test Questionnaire (ACT) was used to evaluate asthma control status, and the Asthma Quality of Life Questionnaire (Mini AQLQ) was used to evaluate the physiological and psychological effects of asthma on patients; FEV1 was detected using a German Jaeger lung function instrument FEV1/FVC. A exhaled nitric oxide (FeNO) detection instrument was used to observe the changes in FeNO at a flow rate of 50 ml/s, and non-targeted metabolomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS); adverse reactions were observed during treatment and drug safety was evaluated.Results:Eventually 47 cases were included, 24 cases of test group and of 23 cases of control group. Xiaoqinglong Decoction Granules could reduce the TCM syndrome score of patients with chronic duration cold syndrome of asthma ( P<0.05). 2 weeks after treatment, follow up for 4 weeks experimental group clinical symptom score [3.00(1.00,4.00),3.00(0.00,4.00) vs. 3.5(3.00,5.00), Z=8.62], breathing symptom scores [1.00(0.00,1.00),1.00(0.00,1.00) vs. 1.00(0.75,2.00), Z=6.80], cough symptom score [0.50(0.00,1.00),1.00(0.00,1.00) vs. 1.00(0.00,1.25), Z=6.12] were lower than those in the experimental group before treatment in the same group ( P<0.01 or P<0.05). The ACT score of the experimental group at 4 weeks of follow-up was [22.50 (21.00, 24.00) vs. 9.00 (15.00, 21.50), Z=-4.87], Mini AQLQ score (78.5 ± 12.46 vs. 71.27 ± 9.70, t=-2.46) and the control group had an ACT score of [24.00 (19.00, 25.00) vs. 21.5 (8.00, 23.00) Z=-3.18] at 4 weeks of follow-up was higher than before treatment in the same group ( P<0.01 or P<0.05). The experimental group was followed up for 4 weeks with a FEV1 of [2.96 (2.27, 3.49) L vs. 2.60 (2.32, 3.49) L, Z=-3.72], FEV1/FVC [(80.83 ± 6.84)% vs. (77.46 ± 8.15)%, t=-2.32] and FeNO [24.00 (12.50, 31.00) ppb vs. 30.00 (17.00, 91.00) ppb, Z=-3.72] was higher than before treatment in the same group ( P<0.01 or P<0.05). Through LC-MS technique analysis, there were 75 kinds of different metabolites between the experimental group before and after treatment, and 295 kinds of different metabolites between the control group and the experimental group after treatment. Further intersection of differential metabolites showed that they were mainly concentrated in histidine metabolic pathway, phosphonate metabolic pathway and phosphate metabolic pathway. Related metabolites 2-aminoethyl phosphonate and thiomalonic acid were involved. Conclusions:Xiaoqinglong Decoction Granules can effectively improve the TCM syndrome and clinical symptoms of patients with chronic persistent cold syndrome of asthma, especially for wheezing, cough and chest tightness, which can improve the levels of FEV1 and FEV1/FVC in patients and effectively reduce FeNO. Through metabolomics studies, it is speculated that Xiaoqinglong Decoction Granules may play a role in the treatment of asthma by regulating histidine metabolism pathway through thiomalonic acid.
5.Study on the long-term clinical efficacy of endoscopic submucosal dissection in colorectal mucosal lesions
Yuxin ZHANG ; Xun LIU ; Fang GU ; Shigang DING
Chinese Journal of Digestion 2024;44(5):321-329
Objective:To evaluate the long-term clinical efficacy of endoscopic submucosal dissection (ESD) in the treatment of early colorectal cancer and precancerous lesions, and to explore the risk factors of local recurrence after operation.Methods:From January 1, 2011 to December 31, 2022, the clinical and endoscopic follow-up data of 1 095 patients (1 186 lesions) who underwent ESD at Peking University Third Hospital and were pathologically diagnosed as early colorectal cancer or precancerous lesions after ESD were retrospectively analyzed. The long-term efficacy of ESD was evaluated, which included 5-year overall survival rate, disease-specific survival rate, local recurrence rate, and recurrence-free survival rate. The Kaplan-Meier method was used for survival analysis. Multivariate Cox proportional hazards regression models were performed to analyze local recurrence related clinical pathological factors.Results:After ESD, 1 067 patients were followed up, and the median follow-up period was 44.4 (20.3, 62.1) months. There were 734 patients having endoscopic follow-up (798 lesions, the follow-up rate was 67.0%). During the follow-up period, 26 patients died, and the 5-year overall survival rate and disease-specific survival rate were 96.0% and 100.0%, respectively. During the follow-up period, local recurrence was observed in 17 lesions, with a recurrence rate of 2.1%(17/798) and a median time of recurrence after ESD was 11.8 (4.9, 21.4) months. The 5-year cumulative recurrence rate was 3.4%, and the 5-year recurrence-free survival rate was 94.0%. The results of multivariate Cox regression analysis showed that lesions located in the rectum ( HR=2.64, 95% confidence interval (95% CI) 1.00 to 6.94, P=0.049), histologically incomplete resection ( HR = 4.40, 95% CI 1.62 to 11.94, P=0.004), and positive vertical margin ( HR=10.27, 95% CI 2.95 to 35.77, P<0.001) were independent risk factors for local recurrence after ESD in the treatment of colorectal mucosal lesions. Conclusions:Long-term efficacy of ESD in the treatment of colorectal mucosal lesions are favorable. Lesions located in the rectum, histologically incomplete resection, and positive vertical margin are independent risk factors for local recurrence after ESD in the treatment of colorectal mucosal lesions.
6. Progress in Research on Helicobacter pylori Thioredoxin
Xin GUAN ; Jing NING ; Jing ZHANG ; Shigang DING
Chinese Journal of Gastroenterology 2023;27(5):311-315
Helicobacter pylori (Hp) infection is one of the main causes of gastric cancer. The virulence factors of Hp, cytotoxin⁃associated gene A (CagA) and vacuolating cytotoxin A (VacA), are closely related to the pathogenicity of Hp in European and American countries. However, the positivity rate of CagA is as high as 90% in East Asian countries, indicating that the above⁃mentioned virulence factors could not fully explain the differences in pathogenicity of Hp, and other pathogenic factors might be speculated. In our previous studies, thioredoxin⁃1 (Trx1) was found to be a virulence factor of highly pathogenic Hp, and a series of studies were conducted on Hp Trx1 in cytology, zoology and human histology. This article reviewed the progress in research on Hp Trx1.
7.Cronkhite-Canada Syndrome:Clinical Analysis of 9 Cases
Chinese Journal of Gastroenterology 2023;28(7):385-389
Background:Cronkhite Canada syndrome(CCS)is a rare non hereditary disease of unknown etiology,there are still challenges in its diagnosis and treatment.Aims:To explore the clinical characteristics and treatment responses of CCS in Chinese population,and to improve the understanding of its diagnosis and treatment.Method:Retrospective analysis and summary of clinical data of CCS patients at Peking University Third Hospital from 2012 to 2022.Results:From the clinical data of a total of 9 cases,the patients'average age was 63.89 years,and the male to female ratio was 1.25.all patients presented with multiple gastrointestinal polyps,non-specific gastrointestinal symptoms and at least one ectodermal manifestation.Laboratory tests for fecal occult blood were positive,and iron deficiency anemia and hypoalbuminemia were common.Histological manifestations were hyperplastic polyps and adenomatous polyps,with commonly found eosinophil infiltration.Patients'conditions could be complicated with severe osteoporosis and fractures,intestinal bacterial overgrowth,asthma,membranous nephropathy,and nodular goiter.Most patients obtained positive currative effect with glucocorticoids therapy,but recurrence of the disease may occur during or after hormone reduction.Azathioprine treatment was attempted in one patient,but the effect was poor.Conclusions:The etiology and pathogenesis of CCS are unclear,and glucocorticoids therapy is still the main treatment method.However,there are still challenges for patients with glucocorticoids resistance and contraindications to glucocorticoids therapy.
8.Predictive value of lipoprotein-associated phospholipase A2 combine with systemic immune-inflammation index for coronary heart disease risk in patients with type 2 diabetes mellitus
Shigang WEI ; Yali WANG ; Qian PENG ; Fangfang WANG
Chinese Journal of Postgraduates of Medicine 2023;46(9):838-843
Objective:To explore the predictive value of lipoprotein-associated phospholipase A2 (Lp-PLA2) combined with systemic immune-inflammation index (SII) for coronary heart disease risk in patients with type 2 diabetes mellitus.Methods:A prospective study was performed, 130 patients with type 2 diabetes mellitus from May 2018 to May 2021 in the People′s Hospital of Pengzhou were selected. All patients underwent coronary angiography examination, and 49 cases were complicated with coronary heart disease (coronary heart disease group), 81 cases were not complicated with coronary heart disease (non-coronary heart disease group). The clinical data were recorded; the white blood cell, monocyte, platelet, neutrophils, lymphocyte, hemoglobin, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose, C-reactive protein (CRP), glycated hemoglobin and Lp-PLA2 were detected; and the SII was calculated. Multivariate Logistic regression analysis was used to analyze the independent risk factors of coronary heart disease in patients with type 2 diabetes mellitus; the efficacy of Lp-PLA2 and SII in predicting the coronary heart disease in patients with type 2 diabetes mellitus was evaluated using the receiver operating characteristics (ROC) curve.Results:There were no statistical differences in white blood cell, hemoglobin, TC, TG, LDL-C, fasting blood glucose, glycated hemoglobin and CRP between two groups ( P>0.05); the monocyte, platelet, neutrophils, Lp-PLA2 and SII in coronary heart disease group were significantly higher than those in the non-coronary heart disease group: (0.55 ± 0.22) × 10 9/L vs. (0.40 ± 0.11) × 10 9/L, (227.84 ± 40.76) × 10 9/L vs. (205.81 ± 39.04) × 10 9/L, (6.78 ± 1.45) × 10 9/L vs. (6.30 ± 1.18) × 10 9/L, (240.67 ± 41.48) μg/L vs. (214.83 ± 36.35) μg/L and 1 245.76 ± 383.08 vs. 929.84 ± 260.27, the lymphocyte and HDL-C were significantly lower than those in the non-coronary heart disease group: (1.26 ± 0.17) × 10 9/L vs. (1.41 ± 0.19) × 10 9/L and (1.15 ± 0.14) mmol/L vs. (1.23 ± 0.21) mmol/L, and there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that monocyte, HDL-C, Lp-PLA2 and SII were the independent risk factors of coronary heart disease in patients with type 2 diabetes mellitus ( OR = 1.812, 1.013, 1.013 and 2.004; 95% CI 4.430 to 6.801, 0.992 to 1.013, 1.001 to 1.026 and 0.004 to 0.855; P<0.01 ore <0.05). ROC curve analysis result showed that the area under the curve of Lp-PLA2 combined with SII to predict the coronary heart disease in patients with type 2 diabetes mellitus was significantly larger than Lp-PLA2 and SII alone: 0.783 (95% CI 0.702 to 0.851) vs. 0.681 (95% CI 0.593 to 0.760) and 0.744 (95% CI 0.660 to 0.816), and there was statistical difference ( P<0.05). Conclusions:Lp-PLA2 and SII are independent risk factors for coronary heart disease in patients with type 2 diabetes mellitus, and their combined detection can improve the predictive value of coronary heart disease.
9.Classification of main pancreatic duct and treatment strategy after linear stapler closure of pancreatic neck in laparoscopic pancreaticoduodenectomy
Xiangtao WANG ; Jian KONG ; Jun GAO ; Xinliang KONG ; Shan KE ; Qiang WANG ; Shaohong WANG ; Chunmin NING ; Shigang GUO ; Shuying DONG ; Liqiang MI ; Wenxiao LI ; Shuangxi HAN ; Jinglong LI ; Wenbing SUN
International Journal of Surgery 2023;50(6):390-393
Objective:To investigate the classification of main pancreatic duct and treatment strategy after linear stapler closure of pancreatic neck in laparoscopic pancreaticoduodenectomy (LPD).Methods:The records of 51 consecutive patients with LPD who were treated by linear staple closure technique of pancreatic neck from February to December 2022 from Binzhou Second People′s Hospital, Shijingshan Campus, Beijing Chaoyang Hospital, Capital Medical University, Rizhao Hepatobiliary-Pancreatic-Splenic Surgery Research Institute, Chaoyang Central Hospital, Shandong Juxian People′s Hospital, Weihai Municipal Hospital, Binzhou Central Hospital, and Affiliated Hospital of Chifeng University were retrospectively reviewed. According to the visibility, position and diameter of the main pancreatic duct at the stump of the pancreas, the type of main pancreatic duct was divided into type I, type Ⅱ, type Ⅲa and type Ⅲb. The number of cases in each main pancreatic duct classification and the corresponding treatment strategies were examined.Results:A total of 51 cases of LPD were successfully completed. Of these patients, the males comprised 56.9%(29/51), and females comprised 43.1%(22/51), with age ranging from 31 to 88 years old. The type of the main pancreatic duct at the stump of the pancreas included 7 cases (13.7%) of type Ⅰ, 39 cases (76.5%) of type Ⅱ, 2 cases (3.9%) of type Ⅲa, and 3 cases (5.9%) of type Ⅲb. Corresponding treatment strategies were adopted according to different main pancreatic duct types, the main pancreatic duct was successfully found, and a support drainage tube was inserted.Conclusion:After linear stapler closure of pancreatic neck, corresponding treatment strategies should be adopted according to the classification of the main pancreatic duct, which would help to improve the success rate of finding the main pancreatic duct and placing a support drainage tube.
10.Research progress on the mechanism of Chinese medicine and active components against cartilage destruction of rheumatoid arthritis
Zhihao DUAN ; You ZHOU ; Shigang LI ; Can JIN ; Ying DENG ; Jinlang LIU ; Shuai MA
China Pharmacy 2023;34(7):892-896
Rheumatoid arthritis (RA) is a systemic chronic auto-inflammatory disease, characterized by infiltration of inflammatory cells, pannus formation, articular cartilage destruction, and bone matrix destruction. Therefore, improving articular cartilage destruction has an important impact on the treatment of RA. Chinese medicine has a good application effect in improving cartilage destruction of RA due to its characteristics of multiple components, multiple targets, high activity and low side effects. Based on this, the author reviewed relevant literature to summarize the relevant research and mechanism of Chinese medicine and its active components in improving RA cartilage destruction. The results showed that Chinese medicine and its active components can improve RA cartilage destruction by regulating inflammatory factors, phosphatidylinositol 3-kinase/protein kinase B, Wnt/β- catenin, nuclear factor-κB, mitogen-activated protein kinase, Janus kinase 2/signal transduction and activator of transcription 3/ vascular endothelial growth factor, microRNAs, fibroblastic synovial cells.

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