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.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

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.

Objective:To investigate the status of leisure crafting and post competence and their correlation among anesthesia specialist nurses.Methods:A convenience sampling method was used to conducted a questionnaire survey on 280 anesthesia specialist nurses at grade A tertiary hospitals in 19 provinces of China. Data were collected using a general information questionnaire, the Chinese version of Leisure Crafting Scale, and the Post Competency Scale for Anesthesia Specialist Nurses. SPSS 24.0 was used for t test and one-way analysis of variance. A Pearson correlation analysis was used to assess relationships between variables. Results:The total score of leisure crafting was (30.41±6.69) and the average score was (3.38±0.74). The total score of post competency was (141.76±21.76) and the average score was (3.73±0.57). A positive correlation was observed between leisure crafting and post competency ( r=0.215, P<0.01). Conclusions:Managers should encourage anesthesia specialist nurses to actively engage in leisure crafting and provide diverse opportunities for leisure crafting to improve their post competence and ultimately the quality of anesthesia nursing.

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.

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.