Surgical site infection(SSI)is a significant type of hospital-associated infection,with varying incidence rates across different regions and surgical procedures.SSI not only increases the burden on the healthcare system but also poses serious threats to patient safety and quality of life.China has established a multi-level and multi-di-mensional management framework,including laws,industry standards and guidelines,to regulate prevention and control behaviors through various documents such as the"Measures for the Management of Hospital-associated In-fection"and the"Technical Guidelines for the Prevention and Control of Surgical Site Infection".In recent years,with the development of international and domestic cooperation,the formulation of professional guidelines and consensuses and the implementation of evidence-based research,China has achieved certain results in SSI preven-tion and control.However,problems such as differences in awareness and implementation across regions,inade-quate data sharing and integration and lack of long-term follow-up still exist.In the future,it is necessary to create an AI-assisted personalized prevention and control model,establish an interdisciplinary collaborative prevention and control system and promote the implementation of administrative management and professionalization to con-tinuously optimize the SSI prevention and control system and improve medical quality and patient safety.

Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy. METHODS: To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated. RESULTS: OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression. CONCLUSION Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans ; ErbB Receptors/metabolism* ; Mouth Neoplasms/metabolism* ; Cell Line, Tumor ; Animals ; Drug Resistance, Neoplasm/genetics* ; Cadherins/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Mutation/genetics* ; Mice, Nude ; Protein Kinase Inhibitors/therapeutic use* ; Cetuximab/pharmacology* ; Afatinib/therapeutic use* ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects*

Adenosine triphosphate(ATP),as a rich energy currency in cells,is released into the extracellular space through a variety of regulatory mechanisms.The role of extracellular ATP(eATP)and related purine and pyrimidine nucleotides as extracellu-lar signal molecules regulating immune cell function has been reported as evidence of purine signal transduction and has become the focus of attention as a therapeutic target for various diseases.Mast cells(MC)are distributed in tissues that come into contact with the external environment and are the first immune cells to respond to non-microbial environmental antigens.Although eATP is considered to be an activator of MC,the details remain to be further elucidated.This article describes the role of purine receptor signaling in MC degranulation.It expands the further understanding of the mechanism of allergic diseases,and further provides ideas for finding new targets for the treatment of allergic diseases and formulating new treatment strategies.

BACKGROUND:Observations from several clinical studies suggest a close relationship between hypertension and osteoporosis,but the causal relationship between hypertension and osteoporosis is unclear. OBJECTIVE:To determine whether there is a causal relationship between hypertension and osteoporosis,multisite bone mineral density and osteoporosis with fractures in Asian and European populations,respectively,using a comprehensive two-sample Mendelian randomized analysis. METHODS:Data of osteoporosis in Asian populations were obtained through Japan biological bank. Data of osteoporosis in European populations were obtained from UK Biobank,a British biological bank. Data of hypertension,multisite bone mineral density and osteoporosis with fractures were all from FinnGen R10 database. Inverse variance weighted method,MR-Egger regression method,weighted median method,weighted model method and simple model method were used to study the causal relationship between hypertension and osteoporosis,multisite bone mineral density and osteoporosis with fracture in Asian and European populations. Comprehensive sensitivity analysis was used to verify the robustness,heterogeneity and level pleiotropy of the results. Stsiger test was used to determine whether there was a reverse causal relationship between osteoporosis and hypertension. RESULTS AND CONCLUSION:In Asian populations,there was no significant genetic predictive causal relationship between hypertension and osteoporosis,and there was a positive causal relationship between hypertension and calcaneal bone mineral density. In European populations,hypertension had a negative causal relationship with osteoporosis,and there was no significant causal relationship between hypertension and systemic bone mineral density,calcaneal bone mineral density,forearm bone mineral density and osteoporosis with fracture. According to the stsiger test,there was no reverse causal relationship between osteoporosis,multiplesite bone mineral density,osteoporosis with fracture and hypertension in Asian and European populations. These results indicate that there is a causal relationship between hypertension and osteoporosis,that is,in Asian populations,hypertension and calcaneal bone mineral density show a positive causal relationship;in European populations,hypertension and osteoporosis show a negative causal relationship,but no reverse causal relationship.

BACKGROUND:The relationship between rheumatoid arthritis and coronary atherosclerosis has received extensive attention.Inflammation is related to rheumatoid arthritis and coronary atherosclerosis,indicating that there may be a common pathophysiological pathway between the two diseases.However,observational studies have not yet clarified the causal relationship.OBJECTIVE:To explore whether there is a causal relationship between rheumatoid arthritis and coronary atherosclerosis,as well as the potential causal relationship with 1 400 serum metabolites and 91 inflammatory factors through a Mendelian randomization analysis.METHODS:Coronary atherosclerosis data are from Finngen database,rheumatoid arthritis data are from IEU OpenGWAS database,serum metabolites data are from Canadian Longitudinal Study on Aging,Augsburg Cooperative Health Research and British Twin Project Research,and data of 91 inflammatory proteins are from research published in Nature Immunology in 2023.Mendelian randomization analysis was performed using data from genome-wide association studies,and causal effects were evaluated using inverse variance weighting,MR-Egger regression,weighted median,weighted model,and simple model methods,with inverse variance weighting being the primary analysis method.To enhance robustness,Cochran's Q-test MR-Egger intercept was used for sensitivity analysis.RESULTS AND CONCLUSION:(1)Inverse variance weighting results showed that rheumatoid arthritis was positively correlated with the increased relative risk of coronary atherosclerosis(odds ratio=1.002,95％confidence interval=1.001-1.003,P=0.003).There was no reverse causal relationship between coronary atherosclerosis and rheumatoid arthritis.In addition,96 serum metabolites and 9 inflammatory factors were found to have causal relationships with coronary atherosclerosis.There was a causal relationship between 51 serum metabolites and 7 inflammatory factors and rheumatoid arthritis.(2)This study provided epidemiological evidence between rheumatoid arthritis and coronary atherosclerosis,and emphasized the potential role of serum metabolites and inflammatory factors in the pathogenesis of these diseases.These findings may contribute to the development of new treatment strategies.Due to the limited inclusion of data from Asian populations,most contemporary studies used international databases and European population analyses.By collecting and analyzing the health data of European populations,it is conducive to a better understanding of the effects and potential role of Chinese medicine in Europe,and to further promote the practice of modern integration of Western and Chinese medicine.Meanwhile,through the comparative study with the European databases,it is possible to reveal the genetic differences and susceptibility to diseases among different populations,providing more dimensions and perspectives for global health research.

Objective To investigate the mechanisms by which Porphyromonas gingivalis(P.gingivalis)promotes the malignant progression of oral squamous cell carcinoma(OSCC)through the recruitment of chemokine receptor 6-positive(CCR6+)regulatory T cells(Treg)in the tumor microenvironment(TME).Methods The Cancer Genome Atlas(TCGA)database was used to analyze the correlation between chemokine ligand 20(CCL20),CCR6,and Treg.The Treg enrichment index and the expression levels of interleukin(IL)-10 and tumor necrosis factor β1(TGF-β1)were assessed in the high CCR6 expression group of OSCC patients.C57BL/6 mice were randomly assigned to a control group and an experimental group(n=6 in each group).The control group received a single injection of 100 μL SCC7,a mice head and neck squamous carcinoma cell line,while the experimental group received a single injection of 100 μL mixture of SCC7 cells and P.gingivalis in the cheek.After two weeks,the mice were sacrificed,and immunohistochemistry was performed to assess the expression levels of CCR6 and forkhead box protein 3(FOXP3)in OSCC.Flow cytometry was performed to analyze the effects of P.gingivalis on OSCC malignant biological behavior,CCR6+Treg cells,and the immune microenvironment.Results Bioinformatics analysis revealed a correlation between CCL20,CCR6,and Treg(r=0.373,P＜0.0001).OSCC patients with high CCR6 expression showed higher Treg enrichment scores and increased IL-10 expression.Animal experiments showed that P.gingivalis promoted the increase in the tumor volume(mm3)(0.294±0.105 in the control group and 0.526±0.101 in the experimental group,P＜0.01)and mass(mg)(206.200±53.950 in the control group and 376.000±119.200 in the experimental group,P＜0.01)in mice with OSCC.Immunohistochemistry confirmed a correlation between CCR6 and FOXP3(r=0.659,P＜0.05),and P.gingivalis promoted the expression of CCR6 and FOXP3.Flow cytometry analysis showed that P.gingivalis increased the proportion of CCR6+Treg(％)(13.780±1.506 in the control group and 18.260±2.257 in the experimental group,P＜0.01)and decreased the proportion of CD8+T cells(％)(27.120±1.647 in the control group and 21.060±3.148 in the experimental group,P＜0.01)in OSCC,thereby promoting the formation of a immunosuppressive microenvironment.Conclusion P.gingivalis promotes the malignant progression of OSCC by recruiting CCR6+Treg cells to form an immunosuppressive TME.

Objective To characterize the clinical features of the group of gout patients to facilitate earlier identifi-cation,and optimize the diagnosis and treatment of the condition.Methods The retrospective study analyzed 24 gout patients with shoulder joint(s)involved and consulted by physicians of Peking Union Medical College Hospital from March 2021 to April 2025,while 70 outpatient gout patients matched by clinical course duration and sex were enrolled as control group.Clinical data including medical history,laboratory tests,therapeutic interventions.Prog-nosis was systematically collected to delineate the distinctive clinical manifestations of the patients.Results All 24 gout patients with shoulder joints involved were male,aged(43.16±13.13)years and had an average BMI of 27.70±4.63.The duration of gout was 8(5,12)years while of those patients had an early onset before 30 years old.The maximal serum uric acid concentration was(754.15±175.79)μmol/L.It was shown by case review that 16.67％of the patients were asymptomatic,and 79.17％suffered from shoulder pain.A quarter of the patients developed subcutaneous tophi.All the patients affected(P＜0.05).The affected joints ascended from lower extremities to the upper averagely took 4.72±2.80 years and had heavier burden of hyperuricemia(P＜0.05),while no significant difference was found in renal function and inflammation level.Conclusions Gout patients with shoulder joints involvement are older and have atypical manifestation.The diagnosis needs support of imaging or ar-throcentesis.

Objective Chronic gouty arthritis(CGA)can lead to severe bone erosion resulting in joint destruction,which significantly decreases the life quality and prognosis of CGA patients.Osteoclasts play an important role in this course.We aim to investigate the effect of interleukin-17A(IL-17A)on osteoclast formation in vitro in patients with chronic gouty arthritis(CGA)and its potential mechanism.Methods Osteoclasts induced in vitro from pe-ripheral blood mononuclear cells(PBMC)of healthy controls(HC)and CGA patients were studied.CGA-derived osteoclasts were divided into four groups:untreated group,IL-17A-treated group,carbonyl cyanide 3-chlorophenyl-hydrazone(CCCP)group,and mitochondrial division inhibitor-1(Mdivi-1)group.Tartrate-resistant acid phospha-tase(TRAP)staining was used to observe and compare osteoclastogenesis between HC and the untreated group.Western blot was performed to detect mitophagy levels and the expression of key osteoclast differentiation factors.Results Compared with healthy controls,CGA patients showed higher osteoclastogenesis(P＜0.01).Compared with the untreated group,the IL-17A-treated group showed up-regulated expression of key osteoclast transcription factors and decreased mitophagy levels(P＜0.05).Intervention with 10 nmol/L and 15 nmol/L Mdivi-1 significantly promoted the expression of key osteoclast transcription factors(P＜0.01).Conclusions IL-17A promotes osteoclast formation in vitro in CGA patients,and its mechanism may be related to decreased mitophagy levels.

Objective To determine the intrahepatic portal blood flow distribution by using dynamic contrast-enhanced CT(DCE-CT)scan,and to evaluate its application value in preventing overt hepatic encephalopathy(OHE)after transjugular intrahepatic portosystemic shunt(TIPS).Methods The clinical data of 110 patients with digestive tract hemorrhage due to cirrhotic portal hypertension,who received TIPS at Henan Provincial Hospital of Traditional Chinese Medicine of China from July 2017 to November 2023,were retrospectively analyzed.Preoperative DCE-CT was performed to evaluate the type of intrahepatic portal blood flow distribution.In patients with different types of intrahepatic portal blood flow distribution,the incidence of post-TIPS OHE was compared between the patients receiving portal vein left branch shunting and the patients receiving portal vein right branch shunting.Results In patients with the right splenic vein type,the incidences of post-TIPS OHE in left portal branch shunting and right portal branch shunting were 58.3％and 21.1％respectively,and the difference was statistically significant(P=0.022).In patients with the left splenic vein type and the diffuse distribution type,there was no statistically significant difference in the incidence of post-TIPS OHE between left portal branch shunting and right portal branch shunting(P=0.246 and 0.846 respectively).Further subgroup analysis results showed that the incidences of OHE in patients receiving splenic vein dominant branch shunting and in patients receiving superior mesenteric vein dominant branch shunting were 20.8％and 57.9％respectively,and the difference was statistically significant(P=0.008).Conclusion Pre-TIPS DCE-CT evaluation of intrahepatic portal blood flow distribution and intraoperative selective portal vein branch shunting can reduce the risk of postoperative OHE to a certain extent.