Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorate obesity. Our previous studies revealed that (Ex-4)₂-Fc, a long-acting GLP-1RA we developed, depends on the leptin pathway to treat obesity. However, the mechanisms linking (Ex-4)₂-Fc and leptin resistance remain largely unclear. To address this question, we explored the mechanism of GLP-1RAs from the perspective of the gut microbiota, as increasing evidence indicates an important link between the gut microbiota and obesity. This study aimed to explore the potential role of the gut microbiota in the treatment of GLP-1RAs. We found that (Ex-4)₂-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila (Am). In addition, (Ex-4)₂-Fc did not respond well in antibiotic-treated (ATB) Obese mice. Subsequent studies have shown that this defect can be overcome by gavage with Am. In addition, we found that Am enhanced (Ex-4)₂-Fc therapy by producing the metabolite inosine. Inosine regulates the macrophage adenosine A2A receptor (A2A) pathway to indirectly reduce leptin levels in adipocytes Thus, elucidating the role of metabolites in regulating the leptin pathway will provide new insights into GLP-1RAs therapy and may lead to more effective strategies for guiding the clinical use of antidiabetic agents.

Objective:To compare the consistency of lymphoma multigene detection panels based on next-generation sequencing (NGS) with FISH detection of B-cell lymphoma gene rearrangement.Methods:From January 2019 to May 2023, fusion genes detected by lymphoma-related 413 genes that targeted capture sequencing of 489 B-cell lymphoma tissues embedded in paraffin were collected from Henan Cancer Hospital, and the results were compared with simultaneous FISH detection of four break/fusion genes: BCL2, BCL6, MYC, and CCND1. Consistency was defined as both methods yielding positive or negative results for the same sample. The relationship between fusion mutation abundance in NGS and the positivity rate of cells in FISH was also analyzed.Results:Kappa consistency analysis revealed high consistency between NGS and FISH in detecting the four B-cell lymphoma-related gene rearrangement ( P<0.001 for all) ; however, the detection rates of positive individuals differed for the four genes. Compared with FISH, NGS demonstrated a higher detection rate for BCL2 rearrangement, a lower detection rate for BCL6 and MYC rearrangement, and a similar detection rate for CCND1 rearrangement. No correlation was found between fusion mutation abundance in NGS and the positivity rate of cells in FISH. Conclusions:NGS and FISH detection of B-cell lymphoma gene rearrangement demonstrate overall good consistency. NGS is superior to FISH in detecting BCL2 rearrangement, inferior in detecting MYC rearrangement, and comparable in detecting CCND1 rearrangement.

Cell Cycle Proteins ; Microtubule-Associated Proteins

Objective: To investigate the high occupational stress and its influencing factors in traffic police in Shanghai. Methods: 728 traffic police were selected as the study subjects, and the《Occupational Health Questionnaire》was used to investigate and evaluate their job demand-control (JDC) and effort-reward imbalance model (ERI) occupational stress situation respectively. The related influencing factors were analyzed. Results: The prevalence rates of high occupational stress in JDC and ERI models were 74.6% (543/728) and 51.5% (375/728) . The influencing factors of JDC were education, marriage, average weekly hours (χ²=16.82, 10.04, 18.71, P<0.05) , and The influencing factors of ERI were gender, age, marriage, real monthly income level, education, work experience, and average weekly hours (χ²=7.02, 26.18, 6.73, 50.42, 4.75, 26.61, 112.98, 6.19, P<0.05) . The JDC multivariate logistic analysis indicated that the risk of occupational stress of married police was 2.81 times as high as that of Unmarried ones. The risk of occupational stress of traffic police with more education was 1.92 times as high as that of low eduacation, average weekly working 41-50 hours and≥51 hours was 2.53, 3.12 times as high as that of ones with average working 40 hours, respectivly. Meanwhile, the ERI multivariate logistic analysis indicated that high income level is the protective factor of occupational stress. The traffic police with 15-<20 working years were more likely to occur higher occupational stress. The traffic police with the more average weekly hours had greater possibility of higher occupational stress. Conclusion The main influencing factors of JDC and ERI are marriage, real monthly income level, education, work experience, and average weekly hours.

Objective: To observe the effect of nerve growth factor (NGF) and Mecobalamin on chronic peripheral neuropathy in rats induced by 1-bromopropane. Methods: 36 male SD rats were exposed to 1-bromopropane vapor at concentrations of 4 000 mg/m³, 6 hours per day, 5 days per week for 12 weeks. The rats were randomed divided into 4 groups, and treated by Mecobalamin for 300 μg/kg qd, NGF for 40 μg/kg qd, Mecobalamin+NGF with the dose as mentioned above, respecively. The control group were fed in normal condition. The changes of Sciatic nerve conduction velocity (NCV) , electromyography (EMG) and pathology were observed 30 days later. Results: The nerve conduction velocity were decreased in all the rats. Compared with the control group, the motor nerve conduction velocity (MCV) was improved in group Mecobalamin and group Mecobalamin+NGF, The difference was statistically significant, as the sensory nerve conduction velocity (SCV) was improved only in group Mecobalamin+NGF. Sciatic nerve biopsy observed by electron microscope showed that myelinated nerve fibers were obvious swelling, lamellar separation, partial myelin vacuolization, and axonal degeneration. After treatment with exogenous nerve growth factor, the number and severity of damaged nerve fibers were restored. Conclusion Exogenous nerve growth factor contributes to the recovery of peripheral nerve damage induced by 1-bromopropane.

OBJECTIVE: To analyze chromosome damage and its possible influencing factors in patients with occupational chronic benzene poisoning. METHODS: Fifty patients with occupational chronic benzene poisoning were selected as chronic benzene poisoning group,and 53 workers without occupational exposure to benzene and other toxic substances were chosen as control group by using convenience sampling method. Questionnaire and routine blood test were conducted on all study subjects. Micronucleus rate test was performed by micronucleus blocking cytokinesis assay. RESULTS: Peripheral blood tests of chronic benzene poisoning group showed significantly reduced hemoglobin level,counts of red blood cells,white blood cells,platelets,lymphocytes and neutrophils( P < 0. 01),and higher lymphocyte micronucleus rates compared to control group( !: 6. 26‰ vs 3. 91‰,P < 0. 01). The proportion of increased lymphocyte micronucleus rate in chromic benzene poisoning group was also higher than that in control group( 46. 0% vs 5. 7%,P < 0. 01). The multivariate Poisson analysis results indicated that the time after disengagement from benzene exposure was the influencing factor of micronucleus rate in chronic benzene poisoning group( P < 0. 05),after adjusting the confounding factors of gender,age,smoking status,alcohol drinking status and working age of benzene exposure. CONCLUSION: Occupational chronic benzene poisoning leads to increase of chromosome damage in lymphocytes of patients. The time after disengagement from benzene exposure was positively correlated with chromosome damage.

OBJECTIVETo investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients.

METHODSSixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy.

RESULTSPatients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy.

CONCLUSIONIn the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.

Biopsy ; Case-Control Studies ; Complement C3 ; analysis ; Glomerulonephritis, IGA ; blood ; diagnosis ; Humans ; Immunoglobulin A ; blood ; Kidney ; pathology

Objective To investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients. Methods Sixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy. Results Patients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy. Conclusion In the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.

Objective To investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients. Methods Sixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy. Results Patients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy. Conclusion In the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.