Objective: To assess the association between the metabolic score for insulin resistance index (METS-IR) and overactive bladder (OAB) in the US population，so as to explore the potential of METS-IR as a predictive tool for OAB risk and to provide insights for early screening and intervention strategies. Methods: Based on the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018，a cross-sectional design was employed，and multivariate logistic regression models were used to analyze the association between METS-IR and OAB. METS-IR was analyzed both as a continuous variable and categorized into quartiles. To further validate the association between METS-IR and OAB across diverse populations，subgroup analyses were conducted in participants stratified by clinical characteristics. Smooth curve fitting was employed to test the linearity of the METS-IR-OAB relationship. Results: Elevated METS-IR was associated with an increased risk of OAB (P<0.001)，and this positive correlation remained stable when METS-IR was categorized into quartiles (P<0.001). Subgroup analyses revealed that the association between METS-IR and OAB was more pronounced in females，participants younger than 55 years，and non-diabetic individuals (P<0.05). Furthermore，smooth curve fitting confirmed a linear positive correlation between METS-IR and OAB，with this linear relationship observed in both diabetic and non-diabetic groups. Conclusion: This study，based on the NHANES 2005-2018 database，found a linear positive correlation between METS-IR and OAB.

The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Objective Evaluate the performance of the encephalon state index(ESI)in depth of anesthesia monitoring during clinical surgery,compared with the bispectral index(BIS).Methods ESI and BIS data were collected from 60 patients in a single-center clinical trial to compare their efficacy in measuring the depth of anesthesia.Results Consistency analysis revealed mean differences and standard deviations of-0.18±5.42 and-0.11±6.51 between ESI and BIS for awake and anesthetized states,respectively.Correlation analysis showed a correlation coefficient of 0.92 throughout the operative period.Prediction probability analysis indicated that both ESI and BIS had prediction probabilities of 0.97,effectively predicting anesthesia status.Conclusion ESI and BIS show good equivalence in monitoring depth of anesthesia during clinical surgery,which meet the requirements of clinical anesthesia.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

This experiment aims to screen and isolate bacteria for the domestication of macrophages and to identify their domestication effector molecules.Bacteria were isolated and purified from cow and sheep feces.The procedures included preparing fermentation supernatant and conducting ex-periments with a mouse peritoneal macrophage model.Nitric oxide(NO)levels were measured,tumor necrosis factor-alpha(TNF-α)was analyzed using ELISA,the domestication activity was e-valuated by mouse peritoneal macrophage model.The activated bacteria were subjected to 16S rRNA gene sequences identification,growth curves determination,and saturated ammonium sul-fate precipitation for NO assay and ELISA analysis of TNF-α to assess the phagocytic capability of domesticated macrophages against Staphylococcus aureus.One strain,ED-8,with immunomodula-tory polarizing properties was successfully isolated.Alignment of its 16S rRNA gene sequence showed 99.86％similarity with Streptococcus zooepidemicus,classifying it as such species.The fermentation supernatant significantly stimulated NO and TNF-a secretion in macrophages.The phagocytic capability against Staphylococcus aureus of macrophages polarized by ED-8 also en-hanced.This effect was retained after crude extraction,indicating the presence of immunomodula-tory activity.In this study,multiple animal chain streptococcus ED-8 was successfully isolated.Its secreted products were shown to induce the trained immunity of macrophages,enhancing their phagocytic activity.

Objective To investigate the changes and clinical significance of plasminogen activator inhibi-tor-1(PAI-1),transforming growth factor-β(TGF-β),vascular endothelial growth factor(VEGF),and inter-leukin-6(IL-6)in patients with tuberculous pleurisy and pleural fibrosis.Methods A total of 103 patients with tuberculous pleurisy and pleural fibrosis who were treated in a hospital from July 2020 to July 2023 were selected as the research subjects.After 2 weeks of treatment,they were divided into a significant effect group and a non-significant effect group based on the therapeutic efficacy of glucocorticoid treatment.The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion were compared before treatment,after 1 and 2 weeks of treatment.The correlation between the levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion and the therapeutic efficacy was analyzed by Spearman correlation analysis.Pearson correlation analy-sis was used to analyze the correlation between the levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleu-ral effusion and the levels of these indicators in pleural effusion after 2 weeks of treatment.A receiver operat-ing characteristic curve was drawn to analyze the predictive value of the levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion for the efficacy of tuberculous pleurisy and pleural fibrosis patients after 1 and 2 weeks of treatment.Results The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion after 1 and 2 weeks of treatment in both groups were lower than those before treatment,and the levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion after 1 and 2 weeks of treatment in the significant effect group were lower than those in the non-significant effect group,with statistically significant differences(P＜0.05).The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion after 1 and 2 weeks of treatment were negatively correlated with the efficacy(P＜0.05).The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion after 2 weeks of treatment were positively correlated(r=0.761,0.783,0.812,0.741,all P＜0.05).The area under the curve(AUC)of combined detection of serum and pleural effusion in-dicators after 1 and 2 weeks of treatment was greater than the AUC of individual indicators(P＜0.05).Con-clusion The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion of patients with tubercu-lous pleurisy and pleural fibrosis are related to the efficacy of treatment.The combined detection of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion has good predictive value and can provide reference for clinical intervention.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.

Chemoimmunotherapy has been approved as standard treatment for triple-negative breast cancer (TNBC), but the clinical outcomes remain unsatisfied. Abnormal epigenetic regulation is associated with acquired drug resistance and T cell exhaustion, which is a critical factor for the poor response to chemoimmunotherapy in TNBC. Herein, macrophage-camouflaged nanoinducers co-loaded with paclitaxel (PTX) and decitabine (DAC) (P/D-mMSNs) were prepared in combination with PD-1 blockade therapy, hoping to improve the efficacy of chemoimmunotherapy through the demethylation of tumor tissue. Camouflage of macrophage vesicle confers P/D-mMSNs with tumor-homing properties. First, DAC can achieve demethylation of tumor tissue and enhance the sensitivity of tumor cells to PTX. Subsequently, PTX induces immunogenic death of tumor cells, promotes phagocytosis of dead cells by dendritic cells, and recruits cytotoxic T cells to infiltrate tumors. Finally, DAC reverses T cell depletion and facilitates immune checkpoint blockade therapy. P/D-mMSNs may be a promising candidate for future drug delivery design and cancer combination therapy in TNBC.

Objective:To investigate the relationship between metabolic syndrome and 1-year poor outcome in elderly patients with acute cerebral infarction (ACI).Methods:The clinical data of elderly patients with ACI admitted to Renqiu Kangjixintu Hospital from January 2014 to November 2018 were selected and divided into metabolic syndrome group (931 cases) and non-metabolic syndrome group (1 851 cases). The clinical data of the two groups of elderly patients with ACI were compared, and the effect of metabolic syndrome on poor outcome (modified Rankin scale>2 scores) of elderly patients with ACI in 1 year was analyzed by multivariate Logistic regression.Results:The proportion of female, hypertension, diabetes, hyperlipidemia, coronary heart disease, smoking, excessive alcohol consumption and antiplatelet drug use in the metabolic syndrome group were higher than those in the non-metabolic syndrome group: 52.74%(491/931) vs. 32.58%(603/1 851), 79.16%(737/931) vs. 64.29% (1 190/1 851), 42.32% (394/931) vs. 6.43% (119/1 851), 17.19% (160/931) vs. 11.62% (215/1 851), 18.90% (176/931) vs. 14.10% (261/1 851), 62.73% (584/931) vs. 50.89% (942/1 851), 3.73% (69/931) vs. 1.61% (15/1 851), 19.23% (179/931) vs. 15.51% (287/1 851), the levels of body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), fasting plasma glucose (TG), total cholesterol (TC), platelet (PLT), fibrinogen (FIB), fall score were higher than those in non-metabolic syndrome group: 26.67 (25.31, 28.60) kg/m 2 vs. 23.30 (21.48, 24.91) kg/m 2, (167.17 ± 22.96) mmHg (1 mmHg = 0.133 kPa) vs. (164.21 ± 24.90) mmHg, (87.06 ± 13.10) mmHg vs. (85.76 ± 12.99) mmHg, (7.33 ± 2.64) mmol/L vs. (5.35 ± 1.38) mmol/L, (2.12 ± 1.51) mmol/L vs. (1.13 ± 0.78) mmol/L, (4.97 ± 1.31) mmol/L vs. (4.65 ± 0.99) mmol/L, 213.00 (179.00, 256.00) × 10 9/L vs. 203.00 (172.00, 241.00) × 10 9/L, 3.07 (2.63, 3.52) g/L vs. 2.94 (2.55, 3.37) g/L, (6.12 ± 1.70) scores vs. (5.93±1.74) scores, the levels of age, high density lipoprotein cholesterol (HDL-C), homocysteine (Hcy) and pressure ulcer score were lower than those of non-metabolic syndrome group: (69.29 ± 6.96) years vs. (71.28 ± 7.66) years, (0.98 ± 0.34) mmol/L vs. (1.31 ± 0.88) mmol/L, (18.93 ± 13.07) mmol/L vs. (21.66 ± 16.39) mmol/L, (18.55 ± 2.42) vs. (19.02 ± 2.43), with statistical significance ( P<0.05). After 1-year follow-up, the proportion of poor outcomes in the metabolic syndrome group was higher than that in the non-metabolic syndrome group: 21.70%(202/931) vs. 18.69% (346/1 851), with statistical significance ( P<0.05). Multivariate Logistic regression analysis showed that age, stroke, national institutes of health stroke scale (NIHSS) score at admission, systolic blood pressure, Hcy, pressure ulcer score, fall score, metabolic syndrome were independent risk factors for poor outcome of ACI in 1 year ( OR = 1.056, 1.309, 1.138, 1.005, 1.006, 0.882, 1.076 and 1.285; 95% CI 1.040 to 1.072, 1.037 to 1.652, 1.097 to 1.180, 1.000 to 1.010, 1.000 to 1.013, 0.834 to 0.933, 1.004 to 1.152 and 1.001 to 1.657; P<0.05). Conclusions:Multiple risk factors for stroke are closely related to poor outcome of ACI in the elderly. And metabolic syndrome is an independent risk factor for poor outcome of ACI in the elderly in 1 year.