Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Objective: To summarize strategies for improving childhood hypertension, so as to provide evidencebased recommendations for poliymaking and practice childhood hypertension management in China. Methods: From March to April 2024, child health stakeholders from five districts in Hangzhou were selected using a combination of stratified and convenience sampling methods. Data were analyzed using a groundedtheory approach. During the indepth interview phase, six policymakers were interviewed. Focus group discussions were conducted with school administrators, healthcare providers, and parents, comprising a total of 62 participants. Results: Through threelevel coding, 116 initial categories were identified(e.g., "trend of younger age" "difficulty in behavior change"), 35 main categories (e.g., "higher incidence compared to the past" "caused by comprehensive influencing factors"), and 12 core categories (e.g., "epidemic status" "influencing factors"). Finally, the cognitive status, problem analysis, and management strategies of children hypertension were constructed. Conclusion Effective prevention and control of childhood hypertension requires coordinated efforts among governments, schools, families, and society to establish a comprehensive management system, with dynamic monitoring and evaluation to optimize policy implementation.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

Humans ; Gastrointestinal Microbiome ; Constipation/therapy* ; Probiotics/therapeutic use* ; Patients

Objective To observe the clinical efficacy of joint needling method combined with ultrasound in the treatment of qi stagnation and blood stasis type of patellofemoral pain syndrome(PFPS).Methods Eighty-six patients with qi stagnation and blood stasis type of PFPS were randomly divided into observation group and control group,with 43 cases in each group.The control group was given western medicine conventional treatment combined with functional exercise,and the observation group was given joint needling method combined with ultrasound treatment on the basis of the control group.Both groups were treated for 2 consecutive weeks.After 2 weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Visual Analogue Scale(VAS)scores of knee pain and the Kujala scale scores of the two groups were observed before and after treatment.The changes in active range of motion(AROM)of the affected knee joint were compared before and after treatment between the two groups.Results(1)After treatment,the VAS scores of the two groups of patients were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the level of VAS scores,and the difference was statistically significant(P＜0.05).(2)After treatment,the Kujala scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the level of Kujala scores,and the difference was statistically significant(P＜0.05).(3)After treatment,the AROM of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the level of AROM,and the difference was statistically significant(P＜0.05).(4)The total effective rate was 95.35%(41/43)in the observation group and 81.40%(35/43)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The joint needling method combined with ultrasound can significantly relieve the pain symptoms of patients with PFPS and promote the recovery of knee joint function,and the clinical efficacy is remarkable.

Objective To investigate the viability and safety of laparoscopic sleeve gastrectomy(LSG)based on the TJ point at the junction of the posterior gastric wall and the apex of the medial edge of the left diaphragm.Methods A retrospective analysis of 135 patients with obesity or obesity with metabolic syndrome who underwent LSG from January 2019 to January 2022 were divided into two groups according to the different free modes of fundogastric body.68 patients underwent surgery using the TPOL model LSG.A control group of 67 patients was treated with conventional LSG surgery.To analyze and compare the duration of operation,gastric fundus free time,intraoperative blood loss time,hospital stay time,postoperative gastric fistula,bleeding rate,and occurrence of gastroesophageal reflux disease(GERD)between the two groups.Results All patients successfully completed LSG surgery and were safely discharged.They were followed for a period of 12 to 36 months.the duration of operation for the study group was(56.13±10.56)minutes,while for the control group it was(62.45±12.74)minutes.The gastric fundus was freed in(6.34±4.16)minutes for the study group and(12.58±6.37)minutes for the control group.The duration of hospitalization was(3.84±0.42)days for the study group and(4.06±0.69)days for the control group.The intraoperative blood loss was(10.87±1.28)ml for the study group and(15.56±3.39)ml for the control group.The incidence of postoperative GERD was 5(7.35％)for the study group and 13(19.40％)for the control group.The differences between the two groups were statistically significant(P＜0.05).The decrease in excess weight at 12 months after surgery,as well as complications such as bleeding and gastric fistula,were not statistically significant(P＞0.05).Conclusion LSG(TPOL model)extends from the TJ point(the Tri-junction point where the gastric left mesangium,gastric posterior mesangium,and pancreatic mesangium meet)to the apex of the medial foot edge of the left diaphragm.LSG(TPOL model)can be efficiently and safely achieve tension-free anastomosis,resulting in a complete free gastric fundus.This method is feasible,and has clinical value for the standardized free gastric fundus of LSG.

BACKGROUND:Superior lower limb mobility is regarded as one of the prerequisites for winning competitions.Wearable resistance training can effectively overcome the deficiency in the transfer efficiency of traditional strength training in enhancing lower limb mobility.Considering that the impact of wearable resistance training based on different body parts on lower limb mobility may have significant differentiated characteristics,it is particularly important to review and summarize the specific application strategies and acute and chronic intervention effects. OBJECTIVE:To comb and analyze acute and chronic intervention effects of wearable resistance training based on different body parts on lower limb mobility,in order to provide insightful and methodological references for optimizing application strategies for lower limb movement ability. METHODS:A literature search was conducted in CNKI,Wanfang,VIP,Web of Science,Medline,SPORTDiscus,and PubMed databases for publications up to October 2023.Chinese and English search terms were"arm,forearm,limb,leg,lower extremity,vest,trunk,resist,weight,load,sprint,agility,change of direction".A total of 60 articles were ultimately included for review after screening the retrieval results. RESULTS AND CONCLUSION:(1)Trunk loading of 6-20%of body mass is suitable for optimizing acceleration in sprinting,while trunk loading of≤6%body mass is suitable for optimizing high-speed running.A trunk load of 5%body mass is applicable for optimizing change-of-direction movement;forearm,calf,or thigh loading often uses 1%or 2%body mass.(2)Trunk loading optimizes the functional performance of the lower limb stretch-shortening cycle by increasing vertical load.This enhances the efficiency of ground reaction force utilization and strengthens the coordinated stability control of the whole body musculature.Forearm loading effectively enhances the driving force of the upper limb swing,improves the propulsive force of the lower limb sprint,and optimizes the efficiency of inter-limb coordination.Calf loading can impose restrictions on the function of the hip joint,thereby leading to localized load stimulation and compensatory functional enhancement in the knee or ankle joint.Thigh loading partially restricts the peak extension angle and speed of the knee joint,creates specific load stimulation at the hip joint,and significantly improves its rotational kinetic energy output.(3)During larger-angle change-of-direction movements,the impact of calf loading is more significant than thigh loading.Thigh loading stimulation helps to enhance power output,while calf loading stimulation aids in improving stability control and directional change.(4)Currently,wearable resistance training has been proven to be an effective way to improve sprint and change-of-direction performance.The methodological strategies to improve sprint performance are relatively mature,but the optimal application scheme to improve change-of-direction performance needs to be further refined and optimized.Further research is recommended to supplement this area.

Objective To analyze the factors associated with pain after arthroscopic rotator cuff bridge suture.Methods According to the inclusion and exclusion criteria,the data of 112 patients with unilateral rotator cuff injury who received arthroscopic bridge suture in our department were collected and were investigated in the form of telephone follow-up.In this study,SPSS 23.0 was used to input data and conduct statistical analysis.Logistic regression analysis was used to analyze the correlation between the above influencing factors and postoperative pain.Results A total of 112 patients were included for statistical analysis,single factor analysis revealed,including course of disease,smoking history,preoperative University of California,Los Angeles(UCLA)score,Constant score,numeric rating scale(NRS),size of rotator cuff tear,whether it was full-thickness tear and degree of tendon retraction might be related to postoperative pain(P<0.05).The age,gender,body mass index(BMI),drinking history,diabetes and hypertension were not related to postoperative pain(P>0.05).Multiple linear regression analysis concluded that there were four factors related to postoperative pain,and the correlation degree was preoperative NRS,preoperative UCLA score,tear size and smoking history.Conclusion The causes of postoperative pain after arthroscopic rotator cauff repair are complex and diverse.Analyzing the cause of postoperative pain can effectively reduce the pain of patients and promote the recovery of shoulder joint function.

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.