Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Objective To investigate the expression levels and clinical significance of type Ⅰ innate lymphoid cells(ILC1s),T-box transcription factor(T-bet),interleukin(IL)-12,IL-18 and interferon-gamma(IFN-γ)in peripheral blood of patients with primary immune thrombocytopenia(ITP).Methods Thirty-five ITP patients with their first episode were selected as the initial treatment group.Thirteen of these patients were followed up after receiving treatment.Additionally,20 healthy individuals underwent routine physical examinations during the same period were recruited as the control group.Peripheral blood samples were collected for analysis.The proportion of ILC1s was determined by flow cytometry.T-bet mRNA expression was measured using quantitative real-time PCR(qRT-PCR).Serum levels of IL-18,IL-12 and IFN-γ were quantified by enzyme-linked immunosorbent assay(ELISA).The differences in ILC1s proportion,T-bet mRNA expression and cytokine levels were compared between groups.Correlations between ILC1s proportion,T-bet mRNA,cytokine levels and platelet(PLT)counts were also analyzed.Results Compared with the control group,the initial treatment group exhibited significantly elevated levels of peripheral ILC1s,T-bet mRNA and serum IL-18,IL-12 and IFN-γ(P＜0.05).Among the 13 patients who were followed up,all these indices decreased significantly after treatment(P＜0.05).Correlation analysis revealed that the proportion of ILC1s in the initial treatment group was positively correlated with IL-12,IL-18,IFN-γ and T-bet mRNA levels(rs=0.666,0.647,0.677,and 0.750,respectively,P＜0.01),and negatively correlated with PLT count(rs=-0.637,P＜0.01).Conclusion Innate immunity may play a role in the pathogenesis and progression of ITP by regulating the expression levels of ILC1s,T-bet,IL-12,IL-18 and IFN-γ.

Objective:To investigate the effects of two anastomosis methods on perioperative and pathological outcomes during totally laparoscopic right hemicolectomy (TLRH).Methods:In a national multicenter snapshot study, 1,854 patients who underwent laparoscopic right hemicolectomy were enrolled from 52 tertiary hospitals across China. The post-hoc analysis based on this study compared the data of 303 patients who underwent TLRH. Patients were divided into the antiperistaltic group (33 cases) and the isoperistaltic group (270 cases) according to type of anastomosis. Due to the significant difference in sample size between the two groups, propensity score matching (PSM) was performed to eliminate the influence of baseline characteristic discrepancies. The matching was based on the following known confounding factors: age, gender, body mass index (BMI), history of abdominal surgery, and history of diabetes, with a caliper value of 0.2. Perioperative and pathological outcomes were compared between the two groups.Results:After PSM, 33 patients were included in the antiperistaltic group and 65 patients in the isoperistaltic group. There were no statistically significant differences in baseline data between the two groups (all P>0.05). No significant differences were observed between the two groups in terms of operation time, blood loss, time to first defecation, time to first oral intake, or the incidence and grading of complications either (all P>0.05). However, length of postoperative hospital stay in the isoperistaltic group was significantly shorter than that in the antiperistaltic group, however (7.0 [6.0, 9.0] days vs. 8.0 [7.0, 10.5] days, P=0.049). In terms of pathological outcomes, there were also no statistically significant differences between the two groups in the number of harvested lymph nodes or the number of positive lymph nodes (all P>0.05). Conclusions:The two digestive tract reconstruction modalities, antiperistaltic and isoperistaltic anastomosis, have comparable perioperative safety and efficacy in TLRH. The isoperistaltic group had better outcomes in terms of postoperative hospital stay.

Objective To investigate the expression levels and clinical significance of type Ⅰ innate lymphoid cells(ILC1s),T-box transcription factor(T-bet),interleukin(IL)-12,IL-18 and interferon-gamma(IFN-γ)in peripheral blood of patients with primary immune thrombocytopenia(ITP).Methods Thirty-five ITP patients with their first episode were selected as the initial treatment group.Thirteen of these patients were followed up after receiving treatment.Additionally,20 healthy individuals underwent routine physical examinations during the same period were recruited as the control group.Peripheral blood samples were collected for analysis.The proportion of ILC1s was determined by flow cytometry.T-bet mRNA expression was measured using quantitative real-time PCR(qRT-PCR).Serum levels of IL-18,IL-12 and IFN-γ were quantified by enzyme-linked immunosorbent assay(ELISA).The differences in ILC1s proportion,T-bet mRNA expression and cytokine levels were compared between groups.Correlations between ILC1s proportion,T-bet mRNA,cytokine levels and platelet(PLT)counts were also analyzed.Results Compared with the control group,the initial treatment group exhibited significantly elevated levels of peripheral ILC1s,T-bet mRNA and serum IL-18,IL-12 and IFN-γ(P＜0.05).Among the 13 patients who were followed up,all these indices decreased significantly after treatment(P＜0.05).Correlation analysis revealed that the proportion of ILC1s in the initial treatment group was positively correlated with IL-12,IL-18,IFN-γ and T-bet mRNA levels(rs=0.666,0.647,0.677,and 0.750,respectively,P＜0.01),and negatively correlated with PLT count(rs=-0.637,P＜0.01).Conclusion Innate immunity may play a role in the pathogenesis and progression of ITP by regulating the expression levels of ILC1s,T-bet,IL-12,IL-18 and IFN-γ.

Objective:To investigate the effects of two anastomosis methods on perioperative and pathological outcomes during totally laparoscopic right hemicolectomy (TLRH).Methods:In a national multicenter snapshot study, 1,854 patients who underwent laparoscopic right hemicolectomy were enrolled from 52 tertiary hospitals across China. The post-hoc analysis based on this study compared the data of 303 patients who underwent TLRH. Patients were divided into the antiperistaltic group (33 cases) and the isoperistaltic group (270 cases) according to type of anastomosis. Due to the significant difference in sample size between the two groups, propensity score matching (PSM) was performed to eliminate the influence of baseline characteristic discrepancies. The matching was based on the following known confounding factors: age, gender, body mass index (BMI), history of abdominal surgery, and history of diabetes, with a caliper value of 0.2. Perioperative and pathological outcomes were compared between the two groups.Results:After PSM, 33 patients were included in the antiperistaltic group and 65 patients in the isoperistaltic group. There were no statistically significant differences in baseline data between the two groups (all P>0.05). No significant differences were observed between the two groups in terms of operation time, blood loss, time to first defecation, time to first oral intake, or the incidence and grading of complications either (all P>0.05). However, length of postoperative hospital stay in the isoperistaltic group was significantly shorter than that in the antiperistaltic group, however (7.0 [6.0, 9.0] days vs. 8.0 [7.0, 10.5] days, P=0.049). In terms of pathological outcomes, there were also no statistically significant differences between the two groups in the number of harvested lymph nodes or the number of positive lymph nodes (all P>0.05). Conclusions:The two digestive tract reconstruction modalities, antiperistaltic and isoperistaltic anastomosis, have comparable perioperative safety and efficacy in TLRH. The isoperistaltic group had better outcomes in terms of postoperative hospital stay.

Objective·To explore the correlation among perceived social support,rehabilitation self-efficacy and rehabilitation exercise adherence of in-patients after hip/knee arthroplasty,and examine the mediating role of rehabilitation self-efficacy in the correlation between perceived social support and rehabilitation exercise adherence.Methods·A convenience sampling method was used,and 141 post-total hip/knee arthroplasty inpatients in the bone and joint ward of the First Affiliated Hospital of Naval Medical University(Shanghai Changhai Hospital)from October 2021 to February 2023 were selected as the study subjects.The general demographic data,such as age and gender,and the information of disease and operation were assessed by using General Data Questionnaire.The adherence to rehabilitation exercise in patients after hip/knee arthroplasty was assessed by using the Rehabilitation Exercise Adherence Scale(REAS);the self-efficacy of rehabilitation exercise was assessed by using the Self-Efficacy for Rehabilitation Outcome Scale(SER);the social support level of individual subjective feelings of the patients was assessed by using the Perceived Social Support Scale(PSSS).Pearson's correlation analysis was used to test the correlation between the variables,and Bootstrap method was used to investigate the mediating role of rehabilitation self-efficacy in the correlation between perceived social support and rehabilitation exercise adherence.Results·A total of 167 questionnaires were distributed and 141 valid questionnaires were recovered,with a valid recovery rate of 84.4%.The age range of the 141 patients after hip/knee arthroplasty was 26?84 years old,and the average age was(64.75±10.74)years old.The total score of SER of the patients after hip/knee arthroplasty was(100.45±21.71),the total score of PSSS was(68.29±10.89),and the total score of REAS was(11.93±2.29).Pearson's correlation analysis results showed that there was a significant correlation between SER score and PSSS score,SER score and REAS score,and PSSS score and REAS score in patients after hip/knee arthroplasty.The mediation effect analysis showed that the indirect effect of perceived social support on rehabilitation exercise adherence was significant(effect value 0.033,95%CI 0.017?0.058,P<0.05),and the direct effect of perceived social support on rehabilitation exercise adherence was not significant(effect value 0.027,95%CI-0.008 ? 0.065,P>0.05).Conclusion·Perceived social support positively predicts rehabilitation exercise adherence,and rehabilitation self-efficacy fully mediates the correlation.Direct intervention in rehabilitation self-efficacy is superior to moderating the level of perceived social support.

Chemokines and their receptors play crucial roles in nervous system diseases,among which the CXC chemokine receptor 3(CXCR3)is an important mediator of intercellular communication.CXCR3 not only participates in inflammatory chemotaxis and malignant behaviors of tumor cells but also regulates the neurologic diseases.CXCR3 and its ligands directly or indirectly contribute to neuroinflammation and neuroimmunity,and potentially serve as therapeutic targets for diseases like multiple sclerosis,Alzheimer's disease,and glioma and so on.This review discusses the expression and impact of CXCR3 and its ligands in neurological diseases such as multiple sclerosis,neurologic tumors,neurodegenerative diseases,and neuropathic pain,as well as their associations with CXCR3 ligands.Understanding the mechanisms linking CXCR3 to these diseases could facilitate its potential as an early diagnostic biomarker and a target for drug intervention,and provide the basis of studying the occurrence and developmant of nervous system disease.

Objective: To investigate the mechanism of cathepsin L(CTSL)-mediated kidney injury in trichloroethene(TCE)-sensitized mice. Methods: 41 BALB/C mice were randomly divided into blank group(n=5), solvent group(n=5), TCE treatment group(n=15) and TCE+CTSLi treatment group(n=16). TCE percutaneous sensitization mouse model was established, and the mice were evaluated as positive group and negative group according to skin sensitization score. The renal pathology of mice was observed by electron microscopy and HE staining, the renal function level of mice was assessed by serum urea nitrogen(BUN). The expression of CTSL was detected by immunofluorescence, the apoptosis of renal cells was assessed by TUNEL staining, and the activation of renal protein kinase C(PKC) signal molecule was detected by Western blot. Results: The sensitization rates of TCE treatment group and TCE+CTSLi treatment group were 53.3%(8/15) and 50.0%(8/16), respectively, and there was no statistical difference in sensitization rates(P>0.05). Pathological results showed that TCE sensitized-mice showed edema and vacuolar degeneration of renal tubular cells, thickening of glomerular basement membrane, fusion of podocytes and mitochondria vacuolar degeneration. The results of renal function showed that the serum BUN level of TCE sensitized mice was higher than that of other groups. Immunofluorescence results showed that the expression level of CTSL in the kidney of TCE-sensitized positive mice increased(P<0.05,F=82.438), and the apoptosis level of renal structure cells was also higher than that of other groups(P<0.05). Western blot showed that the phosphorylation of PKC protein in the kidney of TCE-sensitized mice increased, while the expression of PKC protein in TCE+CTSLi sensitized mice was down-regulated after CTSLi pretreatment(P<0.05,F=35.686), the level of renal cell apoptosis decreased, and renal damage was improved. Conclusion CTSL might aggravate renal damage via activation of PKC signaling in TCE-sensitized mouse.

There are many abnormal signaling pathways in the occurrence, development and microenvironment of liver cancer. The abnormal activation or inhibition of cell signaling pathway can regulate cell proliferation, apoptosis and migration, and then affect inflammation, angiogenesis and tumor migration. Experimental studies have shown that Traditional Chinese medicine (TCM) can prevent and treat hepatocellular carcinoma by intervention with the transduction of related signaling pathways, which mainly includes hedgehog signaling pathway, IL-6/STAT3 signaling pathway, NF-κB signaling pathway, PI3K/Akt/mTOR signaling pathway, MAPK signaling pathway, toll-like receptor signaling pathway and Wnt signaling pathway. At present stage, TCM has a definite effect on the prevention and treatment of liver cancer, but the specific mechanism has not been fully elucidated, and the regulation of TCM on liver cancer related signaling pathways still needs further exploration.

Objective:To compare the efficacy and safety of endoscopic mucosal resection (EMR), EMR with pre-cutting (EMR-P), endoscopic submucosal dissection (ESD) and ESD with snare (ESD-S) for the treatment of colorectal laterally spreading tumors (LSTs).Methods:Between January 2016 and March 2018, a total of 146 patients with 146 colorectal LSTs undergone endoscopic resection at the first medical center of PLA General Hospital. Data of demographics, treatment information, pathology and follow-up results were retrospectively analyzed.Results:Among the 146 patients, EMR, EMR-P, ESD, and ESD-S were performed in 23, 29, 50 and 44 tumors, respectively. Median tumor diameter was 2.5 cm (ranged 1.2-10.0 cm). The en bloc resection rate of EMR, EMR-P, ESD and ESD-S were 73.9% (17/23), 72.4% (21/29), 96.0% (48/50), and 65.9% (29/44), respectively, with statistical difference ( P<0.001). And the R0 resection rate were 65.2% (15/23), 69.0% (20/29), 94.0% (47/50), and 63.6% (28/44), respectively, with statistical difference ( P=0.002). The en bloc resection rate and R0 resection rate of the ESD group were significantly higher than those of the other three groups (all P<0.05). The difference was not statistically significant in terms of perforation rate [0, 0, 6.0% (3/50), and 9.1% (4/44), respectively, P=0.269] and delayed hemorrhage rate [4.3% (1/23), 0, 2.0% (1/50), and 2.3% (1/44), respectively, P=0.768] among the four groups. Follow-up endoscopy was performed in 117 cases (80.1%) with a median period of 10.0 months (ranged 3.0-26.0 months), and local recurrence was identified in 7 (6.0%) cases. Conclusion:ESD could be the optimal method for the resection of colorectal LSTs, while LSTs smaller than 20 mm can be resected by EMR. EMR-P and ESD-S as modified methods have their respective advantages for the treatment of LSTs.