OBJECTIVE To investigate the potential mechanism of berberine improving diabetes mellitus type 2 （T2DM） combined with metabolic-associated fatty liver disease （MAFLD） by regulating ceramide. METHODS Thirty-two db/db mice with blood glucose levels＞11.1 mmol/L （T2DM model） were divided into four groups： model group， berberine low- and high-dose groups [100， 200 mg/（kg·d）] and metformin group [300 mg/（kg·d）]， with 8 mice in each group. Additionally， 8 wt/wt mice were selected as the normal control group. Mice in each group were administered the corresponding drug solution or water by gavage once daily for a continuous period of 6 weeks. During the experiment， the body weight of the mice was monitored， and the differences in final body weight were analyzed. After the last administration， the body shape of the mice in each group was observed， and their fasting blood glucose （FBG） and the lipid indicators [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] were measured. Fasting serum insulin （FINS） levels were also measured， and the insulin resistance index HOMA-IR） and insulin sensitivity index （ISI） were calculated. Liver weight， liver index and serum liver function indicators [alanine transaminase （ALT）， aspartate transaminase（AST）] were assessed， and hepatic histopathological changes were observed. Additionally， the expression of fatty acid synthesis-related proteins [sterol regulatory element-binding protein 1 （SREBP1）， fatty acid synthase （FASN）， acetyl-CoA carboxylase 1 （ACC1）] in liver tissue was examined. Serum samples from the normal control group， model group， and berberine high-dose group were collected for non-targeted lipidomics analysis and validation. RESULTS Compared with the model group， the pathological changes， including disordered liver tissue cell arrangement and lipid vacuoles， were significantly improved in the berberine low- and high-dose groups. The significant decreases or down-regulations were observed in body weight in the last week， as well as FBG， TC， TG， and LDL-C levels， HOMA-IR （except for the berberine low-dose group）， liver weight， liver index， AST and ALT levels， and protein expressions of SREBP1， FASN and ACC1. Additionally， HDL-C levels， FINS （except for the berberine high-dose group）， and ISI （except for the berberine low-dose group） were significantly increased （P＜0.05）. A total of 21 potential differential metabolites， including multiple types of ceramides， were identified； these metabolites were primarily enriched in sphingolipid metabolism and glycerophospholipid metabolism pathways. Verification experiments confirmed that high-dose berberine significantly reduced the serum content of ceramide in model mice （P＜0.05）. CONCLUSIONS Berberine reduces insulin resistance， improves liver damage and lipid accumulation in the T2DM combined with MAFLD mice， and these effects may be related to the reduction of ceramide content.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Objective To investigate the mechanism of inducing macrophage polarization induced by acupoint effect of electroacupuncture to promote the repair of acute skeletal muscle injury.Methods 45 SD rats were randomly divided into blank group,model group,electroacupuncture group(EA group),sodium chrominate group (DSCG group) and electroacupuncture+sodium chrominate group (hereinafter referred to as EA+DSCG group),with 9 rats in each group. The rats in the EA group and the EA+DSCG group were subjected to EA intervention at the right "Chengshan" (BL57) and "Yanglingquan"(GB34),with a frequency of 2 Hz/100 Hz. The gait changes of rats were recorded by animal gait analyzer. The morphological changes of the right gastrocnemius were observed by HE staining. The changes of mast cell aggregation and degranulation in local skin muscles of "chengshan" point were observed by toluidine blue staining. The expressions of Pax7,MyoD and skin mast cells and 5-HT in the right gastrocnemius were detected by immunofluorescence method. The positive expressions of CD68 and CD206 in right gastrocnemius macrophage was observed by immunohistochemical staining.Results Compared with blank group,the wiggle time of the right hind leg in model group and DSCG group increased,stride length decreased,HE staining showed inflammatory cell infiltration,myocyte enlargement,degeneration and necrosis. The degranulation rate of local skin mast cells in "Chengshan" (BL57) area increased,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD,CD68 and CD206 increased (P<0.05). Compared with model group,the wiggle time of the right hind leg in EA group and EA+DSCG group decreased,stride length increased,HE staining showed that inflammatory cell infiltration was reduced,muscle cells were uniform in size and arranged neatly. Mast cell degranulation rate increased significantly in EA group,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased (P<0.05). Compared with EA+DSCG group,the degranulation rate of mast cells and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased in EA group (P<0.05). Conclusion EA "Chengshan" (BL57) and "Yanglingquan" (GB34) can stimulate acupuncture points to locally induce mast cell degranulation,promote the polarization of macrophages,and then activate muscle satellite cells to play the regulatory process of repairing skeletal muscle injury.

Objective To explore the associations between risk factors for cardiovascular disease and breast cancer. Methods A total of 300 patients with breast cancer and 300 with benign breast diseases diagnosed by postoperative pathology were included in the Department of Breast Surgery, Huangpu Branch of the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from January 2023 to June 2023. The main cardiovascular risk factors in patients between the two groups were compared. Stratification was performed according to menstrual status, and the main cardiovascular risk factors in patients with different menstrual status between the two groups were compared. The logistic regression correlation analysis was used to analyze the risk factors related to cardiovascular disease for breast cancer. Results There were statistically significant differences in clinical data and laboratory indicators between the two groups (P＜0.01) . Multivariate logistic regression analysis showed that age (OR=1.03, P=0.029), triglyceride (TG; OR=1.94, P=0.025), C-reactive protein (CRP; OR=2.73, P＜0.001), D-dimer (OR=61.19, P＜0.001), and homocysteine (Hcy; OR=2.10, P＜0.001) were independently associated with breast cancer. The stratified analysis showed age, TG, CRP, D-dimer, and Hcy were independently associated with breast cancer in both premenopausal and postmenopausal patients (P＜0.05). Conclusions Among risk factors for cardiovascular disease, advanced age, increased TG, CRP, D-dimer, and Hcy might increase breast cancer risk, which are helpful of screening high-risk individuals for breast cancer.

Humans ; Carcinoma, Hepatocellular ; Liver Neoplasms ; Ribonucleoproteins ; Eukaryotic Initiation Factor-4E

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.
Adult ; Female ; Humans ; Male ; Alcohol Drinking ; Diseases in Twins/genetics* ; Hypertension/genetics* ; Twins, Dizygotic/genetics* ; Twins, Monozygotic/genetics*

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with complicated pathogenesis and diverse clinical manifestations. The current recommendations of the Chinese Rheumatology Association are based on a comprehensive investigation of evidence based medicine, domestic and international guidelines for SLE, and experts' proposals, and aim to provide a more scientific and authoritative reference for the diagnosis and management of SLE. The recommendations focus on four aspects; clinical manifestations, laboratory evaluation, diagnosis and disease assessment, and disease treatment and monitoring. The goal of the recommendations is to standardize the diagnosis and treatment of SLE in China so as to improve the prognosis of SLE patients.
Humans ; Lupus Erythematosus, Systemic/complications* ; Prognosis ; Rheumatology ; China ; Severity of Illness Index

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Male ; Humans ; Penis ; Granuloma/etiology* ; Pelvis ; Iatrogenic Disease

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*