ObjectiveTo investigate the mechanisms by which Jianpi Yangzheng Xiaozheng prescription （JPYZXZ） treats poorly cohesive gastric carcinoma （PC-GC） through regulation of ubiquitin-specific peptidase 51 （USP51）. MethodsIn vitro experiments： Cell viability and proliferation of PC-GC cell lines （MKN-45 and HGC-27） treated with different concentrations of JPYZXZ （2， 4， 6 g·L^-1） were assessed using Cell Counting Kit-8 （CCK-8） and colony formation assays. Cell migration was evaluated by wound healing （scratch） and Transwell assays. The mRNA and protein expression levels of USP51， zinc finger E-box-binding homeobox 1 （ZEB1）， and epithelial-mesenchymal transition （EMT）-related markers （e.g.， E-cadherin） were detected by quantitative real-time PCR （Real-time PCR） and Western blot， respectively. Subsequently， stable MKN-45 and HGC-27 cell lines with USP51 knockdown （sh-USP51） and overexpression （oe-USP51） were constructed. Their migration ability and EMT-related protein expression were further evaluated by scratch assay， Transwell assay， and Western blot. In vivo experiments： A subcutaneous xenograft model of MKN-45 human gastric cancer was established in BALB/c nude mice. Thirty mice were randomly divided into six groups （NC， NC + JPYZXZ， sh-USP51， sh-USP51 + JPYZXZ， oe-USP51， and oe-USP51 + JPYZXZ）， with five mice in each group. After successful modeling， mice in the treatment groups were administered JPYZXZ （30 g·kg^-1） by gavage for 28 days. Body weight and tumor volume were monitored during the experiment. The expression levels of USP51 and EMT-related proteins in tumor tissues were detected by Western blot and immunohistochemistry （IHC）. ResultsCompared with the blank group， the colony formation rate， wound healing rate， and number of migrated cells in MKN-45 and HGC-27 cells were significantly reduced in all JPYZXZ groups and the 5-fluorouracil （5-FU） group （P<0.05）. The mRNA and protein expression levels of USP51 were decreased （P<0.05）. The expression of ZEB1 and mesenchymal phenotype proteins （e.g.， N-cadherin and vimentin） was reduced （P<0.05）， whereas the expression of the epithelial marker E-cadherin was increased （P<0.05）. Compared with the control group， USP51 expression was decreased in the sh-USP51 group and increased in the oe-USP51 group （P<0.05）. Compared with the NC group， USP51 knockdown significantly reduced the migration and proliferation of gastric cancer cells （P<0.01）， decreased the expression of ZEB1 and EMT-related proteins， and increased E-cadherin expression （P<0.05）. In vivo results showed that JPYZXZ significantly inhibited the growth of xenograft tumors in nude mice （P<0.05） and markedly reversed the abnormal expression of EMT-related proteins in tumor tissues （P<0.05）. ConclusionThe therapeutic mechanisms of JPYZXZ in PC-GC may be associated with inhibition of the EMT process via regulation of the USP51-ZEB1 signaling pathway.

Objective To establish an epirubicin (EPI)-resistant murine triple-negative breast cancer (TNBC) (4T1/EPI) cell line and evaluate its biological characteristics and drug resistance. Methods The EPI-resistant cell line 4T1/EPI was developed through intermittent induction with gradually increasing EPI concentrations in vitro. Morphological changes were observed under an inverted microscope. Drug resistance index (MTT assay), cell doubling time (CCK-8 assay), and migration ability (wound healing assay) were evaluated. Western blot was used to detect the expression of drug resistance-related proteins. Transcriptome sequencing and KEGG pathway enrichment analysis were performed to identify the pathways and targets involved in EPI resistance, followed by experimental validation. Results The 4T1 cells eventually grew normally in a medium containing 100 ng/mL EPI, confirming the establishment of the 4T1/EPI resistant cell line. After stable resistance was acquired, morphological alterations were observed. Compared with their parental 4T1 cells, 4T1/EPI cells showed significantly prolonged doubling time (P<0.01) and enhanced migration ability (P<0.05). Expression levels of drug resistance-related proteins MDR1, MRP1 (P<0.01), and ABCG2 (P<0.05) were elevated in 4T1/EPI cells. In vivo models also demonstrated significant EPI resistance in 4T1/EPI tumors in terms of tumor weight and volume. Transcriptome sequencing highlighted the involvement of the PI3K/Akt signaling pathway and ABC transporter pathway. Validation experiments showed the upregulation of Erbb3, Egfr, PI3K, and Akt (P<0.05) and significant downregulation of Fgfr1 (P<0.01) in 4T1/EPI cells. Conclusion The EPI-resistant TNBC cell line 4T1/EPI was successfully established, exhibiting significant resistance in vitro and in vivo. The mechanism may involve the EPI-induced upregulation of Egfr and Erbb3, activating the PI3K/Akt pathway and subsequently enhancing ABC transporter expression.

Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO₂), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO₂ plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.

Objective To elucidate the mechanisms of trauma-induced coagulopathy(TIC),clarify the specific pathogenic factors and pathophysiological processes,and discover the effective diagnostic indicators and therapeutic targets.Methods Transcriptomic data of traumatic hemorrhagic shock patients were obtained from the Gene Expression Omnibus(GEO)to identify differentially expressed genes(DEGs).Coagulation-related genes(CRGs)from the Kyoto Encyclopedia of Genes and Genomes(KEGG)were intersected with DEGs.Machine learning algorithms,including least absolute shrinkage and selection operator(LASSO)and random forest(RF),were applied to identify key genes.The CIBERSORT algorithm was used to analyze the correlation between key genes and immune cell infiltration.Through consensus clustering,subtype analysis was conducted on trauma patients to compare the infiltration of immune cells.A rat model of traumatic hemorrhagic shock was established to validate coagulation function and the expression of key genes.Results The dataset included samples from 17 healthy controls and 478 patients with traumatic hemorrhagic shock.A total of 6 315 DEGs were identified under the screening criterion of corrected P<0.05.Gene set enrichment analysis(GSEA)showed that the up-regulated DEGs were significantly enriched in the glucose metabolism pathway,while the down-regulated DEGs were enriched in the immune reaction-related pathways.Through cross-analysis of DEGs and CRGs,a total of 65 differentially expressed coagulation-related genes(DE-CRGs)were screened out.GO functional enrichment showed that these genes were mainly located in secreting granular membranes and platelet α-granules,and were involved in physiological processes such as blood coagulation,regulation of body fluid levels,and wound healing.KEGG pathway analysis revealed that these genes were significantly enriched in pathways such as platelet activation,complement and coagulation cascade reactions,Rap1 signaling pathway,and human cytomegalovirus infection.Six key DE-CRGs were identified through machine learning.Receiver operating characteristic(ROC)curve analysis indicated that these genes had good diagnostic efficacy.CIBERSORT analysis revealed a significant correlation between key genes and immune cell infiltration.Patients were classified into two subtypes based on the six key genes:subtype A was rich in CD8+T cells and activated NK cells,presented an immune-active state;subtype B was mainly composed of monocytes and resting NK cells,with insufficient activation of immune pathways.Animal experiments on rats showed that hemorrhagic shock can lead to coagulation dysfunction.The results of qRT-PCR further confirmed that the expression trend of key genes was consistent with the results of bioinformatics analysis.Conclusion In this study,through transcriptomics and machine learning methods,six key genes closely related to TIC were systematically screened out,namely GNA13,PIK3R3,ITGAM,MAPK14,PPP1CC and LYN,and their close connections with coagulation function and immune infiltration were revealed.Animal experiments have further verified the value of these genes as potential diagnostic and therapeutic targets.

To effectively carry out community health education and prevention and control of chronic obstructive pulmonary disease(COPD),we conducted a questionnaire survey on the awareness of COPD knowledge among residents aged 40 and above in Jiading District of Shanghai by using two-stage sampling method.We included 1 783 permanent residents in 4 districts and collected 1 666 valid questionnaires.The awareness rates of COPD name,pulmonary function test and related knowledge were 15.9%,11.9%and 17.2%,respectively.For the main symptoms of COPD,the awareness rate of sputum was the lowest(65.2%),of shortness of breath and dyspnea was the highest(78.4%).For the risk factors,the awareness rate of severe respiratory tract infection in childhood was the lowest(67.3%),of smoking was the highest(86.8%).Multiple response analysis showed that mobile phones and computers accounted for the highest proportion of acquiring knowledge of COPD(66.7%).Multivariate logistic regression analysis showed that low educational level,low monthly income,engaged in production and manufacturing,never or less exercise,no use of indoor air improvement measures,no wearing of masks in public places and no vaccination of influenza vaccine per year were associated with lower awareness rate of COPD.The community should improve the way and ability of health science popularization,and carry out health education for key groups.

Objective To explore the effect of bionic electrical stimulation(BES)combined with resistance tightening leg training on postpartum pelvic floor dysfunction(PFD).Methods A total of 205 patients with PFD were divided into the BES group(n=102)and the combined group(n=103)by random number table method.All subjects received routine pelvic floor muscle training.In addition,the BES group was treated with BES intervention,and the combined group was treated with BES combined with resistance tightening leg training,with 8 weeks of treatment.The classification of pelvic floor muscle strength,electrophysiological indexes of pelvic floor function,urodynamics and stress urinary incontinence(SUI)classification/pelvic organ prolapse(POP)degree were compared between the two groups before and after treatment.Results After treatment,the pelvic floor muscle strength classification,SUI classification and POP degree in the combined group were significantly better than those in the BES group(P<0.05).After treatment,ClassⅠ/ClassⅡmuscle fiber fatigue,vaginal dynamic pressure and maximal electromyography(EMG)value of fast muscle in the combined group were(-1.20±0.35)%,(-0.90±0.30)%,(76.30±5.51)cmH2 O,(43.00±5.82)μV,respectively,which were all significantly higher than those in the BES group(P<0.05).After treatment,the indexes of urodynamics in both groups were significantly improved,and the combined group was better than the BES group(P<0.05).Conclusions BES combined with resistance tightening leg training can significantly improve pelvic floor muscle strength,muscle fiber fatigue and urodynamics in patients with PFD,thus alleviating SUI/POP symptoms.

OBJECTIVE To explore the effectiveness and possible mechanism of Shangke Lengtong Patch in treating knee osteo-arthritis with cold-dampness arthralgia obstruction.METHODS A total of 70 patients who met the inclusion criteria of knee osteoar-thritis with cold-dampness arthralgia obstruction in the Orthopedics Department of Affiliated Hospital of Nanjing University of Chinese Medicine from November to December 2024 were randomly divided into an experimental group and a control group,with 35 cases in each group.During the treatment,1 case dropped out of the experimental group,3 cases dropped out of the control group,and 1 case was discontinued.The experimental group was treated with Shangke Lengtong Patch,and the control group was treated with Compound Nanxing Zhitong Ointment.The WOMAC scores and TCM syndrome scores of the two groups before and after treatment were compared to comprehensively evaluate the clinical efficacy.The changes in the expression levels of CGRP,substance P,HMGB1,IL-1β,CX-CL12,and CXCR4 in the serum of the two groups were detected by ELISA.RESULTS After 3,7,and 14 d of treatment,the WOMAC scores and TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score of aggrava-ted cold in the experimental group was better than that in the control group at 7 d of treatment(P<0.05);after 14 d of treatment,the expression levels of CGRP,substance P,HMGB1,IL-1β,CXCL12,and CXCR4 in the serum of the two groups were significantly re-duced(P<0.05),and there was no statistical difference between the two groups.CONCLUSION Shangke Lengtong Patch can sig-nificantly relieve the pain symptoms of knee osteoarthritis patients with cold-dampness arthralgia obstruction and improve the joint func-tion of patients.It may improve synovial inflammation by inhibiting the HMGB1/CXCL12/CXCR4 pathway,thereby exerting a thera-peutic effect.

Objective To explore the effect of bionic electrical stimulation(BES)combined with resistance tightening leg training on postpartum pelvic floor dysfunction(PFD).Methods A total of 205 patients with PFD were divided into the BES group(n=102)and the combined group(n=103)by random number table method.All subjects received routine pelvic floor muscle training.In addition,the BES group was treated with BES intervention,and the combined group was treated with BES combined with resistance tightening leg training,with 8 weeks of treatment.The classification of pelvic floor muscle strength,electrophysiological indexes of pelvic floor function,urodynamics and stress urinary incontinence(SUI)classification/pelvic organ prolapse(POP)degree were compared between the two groups before and after treatment.Results After treatment,the pelvic floor muscle strength classification,SUI classification and POP degree in the combined group were significantly better than those in the BES group(P<0.05).After treatment,ClassⅠ/ClassⅡmuscle fiber fatigue,vaginal dynamic pressure and maximal electromyography(EMG)value of fast muscle in the combined group were(-1.20±0.35)%,(-0.90±0.30)%,(76.30±5.51)cmH2 O,(43.00±5.82)μV,respectively,which were all significantly higher than those in the BES group(P<0.05).After treatment,the indexes of urodynamics in both groups were significantly improved,and the combined group was better than the BES group(P<0.05).Conclusions BES combined with resistance tightening leg training can significantly improve pelvic floor muscle strength,muscle fiber fatigue and urodynamics in patients with PFD,thus alleviating SUI/POP symptoms.

Objective To explore the protective effect and mechanism of Xinkang Granules-containing serum in adriamycin-induced injury of cardiomyocytes H9C2 based on cGAS-STING signaling axis.Methods Adriamycin was used to induce the H9C2 cells injury model.The cells were divided into normal group,model group,Xinkang Granules group and inhibitor group.After 24 hours of intervention,the CCK-8 method was used to detect cell survival rate,the DCFH-DA fluorescent probe was used to detect the content of cell reactive oxygen species(ROS),cell apoptosis rate was detected by flow cytometry,ELISA was used to detect the content of tumor necrosis factor-α(TNF-α)in cell supernatant,colorimetry was used to detect lactate dehydrogenase(LDH)in cells,RT-qPCR was used to detect the expression of mitochondrial transcription factor A(TFAM),cyclic guanosine-adenylate synthetase(cGAS),stimulator of interferon genes(STING)and TNF-α mRNA,Western blot and immunofluorescence were used to detect the protein expressions of cGAS and STING.Results Compared with the normal group,cell survival rate in the model group was significantly reduced(P<0.01),the ROS content was significantly increased(P<0.01),the apoptosis rate significantly increased(P<0.01),the content of TNF-α in the supernatant significantly increased(P<0.01),the activity of LDH significantly increased(P<0.01),the expression of TFAM mRNA significantly decreased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expression of cGAS and STING significantly increased(P<0.01).Compared with the model group,cell survival rate in Xinkang Granules group and inhibitor group significantly increased(P<0.01),the ROS content significantly decreased(P<0.01),the apoptosis rate significantly decreased(P<0.01),the content of TNF-α in supernatant significantly decreased(P<0.01),the activity of LDH significantly decreased(P<0.01),the expression of TFAM mRNA significantly increased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expressions of cGAS and STING significantly decreased(P<0.05,P<0.01).Conclusion Xinkang Granules have a protective effect on adriamycin-induced H9C2 cardiomyocytes,which may be related to the inhibition of cGAS/STING axis activation and the secretion of inflammatory factors.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.