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.

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*

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.

Abstract To investigate the effects of exercise on gut microbiota(GM) among children with autism spectrum disorder(ASD)，the review provides an in depth summary of the three core biological pathways through which exercise modulates the GM: repairing the integrity of the intestinal barrier to inhibit lipopolysaccharide mediated neuroinflammation; optimizing key metabolites, such as short chain fatty acids, to reshape gut-brain communication; synergistically regulating the tryptophan-kynurenine metabolic pathway and vagus nerve signaling to balance neurotransmitters. These interconnected pathways not only alleviate gastrointestinal discomfort but also provide a solid biological foundation for improving the core behavioral symptoms of ASD, such as social deficits and repetitive behaviors. Future research should focus on establishing standardized exercise intervention protocols, validating the efficacy of these key biological pathways using multi omics approaches, and exploring combined intervention strategies. The results of corollary studies will provide a more robust scientific basis for precision rehabilitation of children with ASD.

BACKGROUND:Parkinson's disease has the main pathological changes in the midbrain,especially in the dense substantia nigra,leading to impaired motor and non-motor function in patients.At present,research is limited by cellular heterogeneity,and its pathogenesis still needs to be further elucidated.In recent years,single-cell RNA sequencing(scRNA-seq)has gradually been applied in neurodegenerative diseases,which is of great significance for understanding intercellular heterogeneity,disease development mechanisms,and treatment strategies. OBJECTIVE:To review the research progress of scRNA-seq technology applied to Parkinson's disease in recent years,providing a theoretical basis for the application of scRNA-seq in the treatment and diagnosis of Parkinson's disease. METHODS:The first author used a computer system to search for relevant literature in the CNKI,WanFang,PubMed,and Web of Science databases,with the Chinese search terms"single-cell RNA sequencing,Parkinson's disease,cell heterogeneity,cell subtypes,dopaminergic neurons,glial cells"and English search terms"single-cell RNA seq,Parkinson disease,heterogenicity,subtypes,dopaminergic neurons,glial cells."71 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:(1)scRNA-seq is a high-throughput experimental technique that utilizes RNA sequencing at the single-cell level to quantify gene expression profiles in specific cell populations,revealing cellular mysteries at the molecular level.Compared with traditional sequencing techniques,scRNA-seq technology is used to reveal the diversity of cell types and changes in specific gene expression in complex tissues under various physiological and pathological conditions through automatic clustering analysis of cell transcriptome.(2)By using scRNA-seq,the development process of dopaminergic neurons and the unique functional characteristics of various cell subtypes are elucidated,in order to better understand potential therapeutic molecular targets.(3)The use of scRNA-seq analysis has improved our understanding of the response of Parkinson's disease glial cells,enabling us to comprehensively map and characterize different cell type populations,identify specific glial cell subpopulations related to neurodegeneration,and draw valuable single cell maps as reference data for future research.(4)The application of scRNA-seq to detect embryonic mice and stem cells will help improve the in vitro differentiation protocol and quality control of cell therapy,as well as evaluate the overall cell quality and developmental stage of dopaminergic neurons derived from stem cells.

Objective:To evaluate the long-term clinical efficacy and the influence on anal function of surgery combined with ustekinumab (UST) in active Crohn's disease (CD) patients with perianal fistula.Methods:A retrospective cohort study was conducted. Clinical data of active CD patients with perianal fistula undergoing surgery combined with UST at Longhua Hospital of Shanghai University of Traditional Chinese Medicine from August 2020 to December 2022 were collected. The primary endpoints were clinical healing rate, Wexner score, and anorectal manometry values at week 52 of treatment. Secondary endpoints included the Crohn's disease activity index (CDAI), perianal Crohn's disease activity index (PDAI), laboratory indicators [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC) ], endoscopic remission rate, Van Assche score, and radiographic healing rate at week 52 of treatment.Results:A total of 28 patients were included, with 22 males (78.6%) and 6 females (21.4%) ; age (25.2 ± 7.7) (16.0-52.0) years. There was 1 patient (3.6%) of simple anal fistula. There were 27 patients (96.4%) of complex anal fistulas, including 12 of high intersphincteric type, 15 of high transsphincteric type, in which 15 with branched tracts (or ≥2 fistula tracts). The pre-treatment CDAI was 187.0 (156.0, 245.0), and the PDAI was 10.0 (9.0, 12.0). Among the 28 patients, 23 (82.1%) underwent fistulotomy, 1 (3.6%) underwent transanal opening of intersphincteric space (TROPIS), and 4 (14.3%) underwent video-assisted anal fistula treatment (VAAFT) combined with fistula-tract laser closure (FiLaC). All the patients received UST treatment postoperatively, without concurrent use of immunosuppressants or corticosteroid therapy. At week 52 of treatment, 28 (100%) patients achieved clinical healing. Compared to pre-treatment, Wexner score of patients at week 52 of treatment was significantly lower [0 (0, 0) vs. 1.0 (0, 3.0), P < 0.001], maximum anal sphincter pressure increased [ (137.6±40.9) mmHg vs. (105.1±29.2) mmHg, P < 0.001], maximum anal sphincter contraction time extended [9.0 (5.0, 15.0) s vs. 4.0 (2.0, 6.0) s, P < 0.001], and there was no significant decrease in anal resting pressure ( P > 0.05). Compared to pre-treatment, CDAI, PDAI, Van Assche scores, and simple endoscopic score for Crohn's disease (SES-CD) of patients at week 52 of treatment all significantly decreased (all P < 0.001), and CRP, ESR, and FC all decreased (all P < 0.05), with statistically significant differences. The radiographic healing rate at week 52 of treatment was 75.0% (21/28), and the radiographic remission rate was 92.9% (26/28). The endoscopic remission rate was 57.1% (16/28), and the endoscopic response rate was 82.1% (23/28) . Conclusion:The long-term clinical healing rate of active CD patients with perianal fistula receiving surgery combined with UST is high, and the anal function can be improved significantly.

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.