ObjectiveTo investigate molecular alterations in tumor cells of multiple myeloma （MM） before and after B-cell maturation antigen （BCMA）-directed chimeric antigen receptor T-cell （CAR-T） therapy， with a focus on changes in invariant chain （CD74） expression and its potential association with macrophage migration inhibitory factor （MIF）. MethodsPaired bone marrow samples collected before BCMA CAR-T infusion and at ≥3 months after infusion were analyzed. Differential gene expression， functional enrichment， and cell-cell communication analyses were performed in malignant plasma cell-related populations. In vitro coculture experiments and MIF stimulation assays were conducted using the U266 cell line， and cell proliferation was assessed by CCK-8 and EdU incorporation assays. ResultsCD74 expression was upregulated in MM cells at ≥3 months after BCMA CAR-T therapy， and CD74 expression was consistently higher in post-treatment samples than in paired pre-treatment samples across all four cases. Genes upregulated after treatment were mainly enriched in antigen processing and presentation， cell adhesion， and immune-related processes. Cell-cell communication analysis revealed prominent interaction signals involving MIF-related pathways. In vitro experiments showed that coculture conditions induced changes in membrane CD74 expression in tumor cells， and MIF stimulation promoted proliferation of U266 cells. ConclusionCD74 expression is upregulated in tumor-associated MM cells following BCMA CAR-T therapy and is accompanied by the activation of the MIF-CD74 axis， suggesting a potential role in post-treatment adaptive changes and warranting further investigation into its therapeutic relevance.

ObjectiveTo explore the effect of Polygonati Odorati Rhizoma polysaccharides on hyperlipidemia in mice by modulating the gut microbiota. MethodsNinety male C57BL/6J mice were randomized into the following groups （n=15）： control， model， simvastatin， low- （100 mg·kg^-1）， medium- （200 mg·kg^-1）， and high-dose （400 mg·kg^-1） Polygonati Odorati Rhizoma polysaccharides groups. Other groups except the control group were fed with a high-fat diet for the modeling of hyperlipidemia， and drug interventions lasted for 12 weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by an automatic biochemical analyzer. The pathological changes in the liver and epididymal fat were observed by hematoxylin-eosin staining， and lipid accumulation in the liver was assessed by oil red O staining. The gut microbiota was analyzed by 16S rRNA gene sequencing. ResultsCompared with the control group， the model group exhibited an increase in body weight （P<0.01）， along with marked elevations in serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）. Furthermore， the model group showcased increase in the liver index and epididymal fat coefficient （P<0.05）， increased liver fat accumulation， enlargement of adipocytes in the epididymal fat， decreases in both alpha and beta diversity of the gut microbiota， and an increase in the relative abundance of Allobaculum （P<0.01）. Compared with the model group， Polygonati Odorati Rhizoma polysaccharides suppressed the increase in body weight （P<0.01）， lowered the serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）， reduced the liver index and epididymal fat coefficient （P<0.05）， alleviated liver fat accumulation， and decreased the size of adipocytes in the epididymal fat. Furthermore， it enhanced the alpha and beta diversity of the gut microbiota in mice， reduced the relative abundance of Allobaculum， Erysipelotrichaceae， and Clostridium （P<0.01）， and increased the relative abundance of Akkermansia and Blautia （P<0.01）. ConclusionPolygonati Odorati Rhizoma polysaccharides can ameliorate hyperlipidemia induced by a high-fat diet in mice by regulating the diversity and composition of the gut microbiota.

The menopausal age is one of the important menopausal factors, and women of different menopausal ages have different risks of diabetes. This study reviewed the evidence from prospective studies on the association between the age at natural menopause and diabetes risk, both domestically and internationally, and presented its research design and main findings. Advanced menopause, especially premature and early menopause, will increase the risk of diabetes in postmenopausal women. The research on the influence of delayed menopause on the incidence of diabetes is still insufficient. Many factors may modify the association between menopausal age and the risk of diabetes.

Objective To observe the value of machine learning(ML)model based on chest non-contrast CT(NCCT)radiomics for diagnosing metabolic syndrome(MetS)in males.Methods A total of 792 males who would undergo chest NCCT and bone density CT examination for physical check-up were prospectively enrolled and divided into training set(n=554,including 171 cases of MetS)and validation set(n=238,including 70 cases of MetS)at the ratio of 7∶3.Chest NCCT was performed,ROI of liver,intra-abdominal fat and skeletal muscle were delineated,and visceral fat area(VFA)at L2-3 intervertebral disc level was measured.Then radiomic signature(RS)of liver,intra-abdominal fat and skeletal muscle were established,and ML models were constructed using logistic regression(LR),random forests(RF)and extreme gradient boosting(XGBoost)algorithms,respectively,and their diagnostic performance were observed.Results Significant difference of age was found between MetS and non-MetS males in training set(P=0.010),while of RS scores were noticed in both training set and validation set(all P＜0.001).Combined ML models were constructed with age and RS.The area under the curve(AUC)of combined LR,RF and XGBoost models for diagnosing male MetS in training set was 0.899,0.996 and 0.943,while that in validation set was 0.861,0.860 and 0.876,respectively.Combined XGBoost model had the best performance.Conclusion XGBoost model based on chest NCCT radiomics was helpful for diagnosing male MetS.Combining with age could further improve its efficacy.

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Objective To investigate the clinical efficacy of the"dynamic and static combination"approach in the treatment of Hepple Ⅰ-Ⅲ type osteochondral lesions of the talus(OLT),utilizing external ankle shaking,pulling,and poking manipulations in conjunction with ankle brace fixation.Methods A total of 82 patients diagnosed with OLT,who sought treatment at four hospitals between June 2022 and December 2023,were included in the study.Both the experimental and control groups received ankle immobilization using braces through-out the treatment period.The control group was administered Voltaren Emulgel topically twice daily(morning and evening),with each treatment course lasting 30 days,for a total of one course.The experimental group received additional therapeutic intervention involving shaking,pulling,and poking manipulations,conducted twice weekly,with the same duration and number of treatment courses as the control group.Follow-up assessments were scheduled at 2 weeks,4 weeks,and 2 months post-treatment.Outcome measures included the pain rating index(PRI),visual analogue scale(VAS)for pain intensity,current pain intensity(PPI),American Orthopaedic Foot & Ankle Society(AOFAS)ankle and hindfoot scores,proprioceptive function,and the size of OLT.Results During the longitudinal assessment conducted at 2-week,4-week,and follow-up intervals,the experimental group exhibited superior clinical outcomes compared to the control group,with statistically significant decreases in PRI,PPI,and AOFAS scores(all P＜0.05).VAS scores showed progressive improvement over time,with significant intergroup differences observed at both the 4-week and follow-up assessments(P＜0.05).Biomechanical analysis performed post-intervention indicated improved kinematic repositioning accuracy in the experimental group,as reflected by significantly reduced active-passive error angles(P＜0.05).Importantly,measurements of OLT area revealed notable therapeutic effects in the experimental group(P＜0.05),whereas no statistically significant changes were observed in the control group throughout the study period(all P＞0.05).Conclusions Under the guidance of the"dynamic and static combination"concept,the integration of shaking,pulling,and poking manipu-lation with conventional Western medicine-based conservative treatment for OLT demonstrates more pronounced advantages in alleviating pain,improving ankle joint function,restoring proprioception,facilitating lesion recovery,and enhancing overall quality of life.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective To explore the risk factors associated with the occurrence of dampness syndrome based on peripheral blood multiple laboratory indicators,construct predictive model and validate it.Methods A retrospective analysis was conducted on 180 patients who visited the Preventive Treatment Center of Guangdong Provincial Hospital of Chinese Medicine from May 2022 to December 2023.They were divided into two groups according to the diagnostic criteria:the damp syndrome of TCM group(n=118)and the balanced yin-yang constitution group(n=62),with the latter serving as the"non-syndrome"control group for dampness syndrome.Serum biochemical indicators were detected by electrochemiluminescence(ECL),immune cell subsets were analyzed through flow cytometer,and routine blood parameters were assessed using an automatic hematology analyzed.Logistic regression analysis was employed to screen risk factors and develop a predictive model.The Bootstrap method was used for data resampling to draw the receiver operating characteristic(ROC)curve,calibration curve,and clinical decision curve analysis(DCA)to evaluate the predictive value,consistency,and clinical efficacy of the model.Results Compared with the balanced yin-yang constitution group,the damp syndrome of TCM group showed increased levels of insulin(INS),non-high-density lipoprotein cholesterol(non HDL-C),red blood cells(RBC)and the proportion of CD4+T cells,the proportion of triglyceride(TG)>1.70 mmol/L,total cholesterol(TC)>5.20 mmol/L,low-density lipoprotein cholesterol(LDL-C)>3.37 mmol/L,and high-density lipoprotein cholesterol(HDL-C)≤1.15 mmol/L were also significantly higher,with statistical significance(U/t/χ2=-2.900～4 626,all P＜0.05).Logistic regression analysis showed that INS,TC>5.20 mmol/L,HDL-C≤1.15 mmol/L,and the proportion of CD4+T cells were independent risk factors for the occurrence of damp syndrome of TCM(all P＜0.05).Based on the screened risk factors,a forecasting model was established and a nomogram was plotted.The model had an area under the ROC curve area under curve(AUC)of 0.747(95%CI=0.672～0.822),a Brier score of 0.184 for the calibration curve,and demonstrated clinical net benefit at threshold probabilities ranging from 0.30 to 1.00.Conclusion The forecasting model constructed based on INS,TC>5.20 mmol/L,HDL-C≤1.15 mmol/L,and CD4+T cells ratio has a high predictive value for damp syndrome of TCM.

Objective To investigate the effect and mechanism of miR-155-5p targeting suppressor of cytokine signaling 1(SOCS1)in regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcrip-tion 3(STAT3)signaling pathway in renal injury associated with lupus nephritis(LN).Methods Thirty female MRL-faslpr lupus model mice were randomly divided into five groups(n=6 per group):the model group,the antagomir NC group,the miR-155-5p antagomir group,the miR-155-5p antagomir+shRNA control group,and the miR-155-5p antagomir+SOCS1 shRNA group.The mice were treated with adeno-associated virus vectors carrying miR-155-5p antagomir,antagomir NC,SOCS1 shRNA,or shRNA control.Additionally,six age-matched C57BL/6 mice served as a control group and received an equivalent volume of saline.Serum blood urea nitrogen(BUN)and creatinine(Scr)levels,renal histopathological changes,and the expression levels of miR-155-5p,SOCS1,phosphorylated JAK2(p-JAK2),and phosphorylated STAT3(p-STAT3)in renal tissues were evaluated.Results Compared with the normal group,the model group exhibited significantly elevated levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins in the kidneys(P<0.01),while the expression level of SOCS1 was markedly reduced(P<0.01).Compared with both the model group and the antagomir NC group,the miR-155-5p antagomir group showed decreased levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins(P<0.01),along with a significant increase in SOCS1 expression(P<0.01).Similarly,compared with the miR-155-5p antagomir group and the miR-155-5p antagomir+shRNA control group,the miR-155-5p antagomir+SOCS1 shRNA group demon-strated significantly higher levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins(P<0.01),while SOCS1 expression was notably decreased(P<0.01).Renal pathology analysis revealed that,compared to the normal group,the model group exhibited glomerular atrophy,extensive infiltration of inflammatory cells in the renal tubulointerstitial region,and partial renal tubular necrosis.In contrast,the miR-155-5p antagomir group showed marked improvements in glomerular atrophy,tubular necrosis,and inflammatory cell infiltration compared with the model group and antagomir NC group.Furthermore,compared with the miR-155-5p antagomir group and the miR-155-5p antagomir+shRNA control group,the miR-155-5p antagomir+SOCS1 shRNA group exhibited more severe glomerular atrophy,tubular necrosis,and inflammatory cell infiltration.Conclusion MiR-155-5p exacerbates renal damage in MRL-faslpr lupus model mice by targeting SOCS1,potentially through the activation of the JAK2/STAT3 signaling pathway.

This study aims to innovate a homogeneous outpatient service management system across multiple hospital campuses to enhance service quality.Based on the practical experience of a tertiary general hospital in Guangdong Province and in accordance with the"Interim Regulations on Outpatient Quality Management in Healthcare Institutions,"we constructed a"6+1"homogeneous outpatient service management system.This system includes:① a multi-stakeholder co-governance outpa-tient management system,②a vertical and cross-hierarchical management network,③ a democratic-centralized clinical coordina-tion strategy,④ a guidance-encouragement performance evaluation standard,⑤a collaborative dynamic supervision mechanism,⑥a spiral retrospective evaluation and improvement method,and ⑦ an integrated outpatient diagnosis and treatment system.Af-ter over two years of implementation,the hospital's outpatient volume has grown by an average of over 15％annually,patient waiting time after appointment has been reduced to 20 minutes,and patient satisfaction in the tertiary public hospital performance evaluation achieved full marks.The electronic medical record system functionality reached Level 6,significantly improving healthcare service efficiency and quality while enhancing homogeneous management across campuses.