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.

Depression is a psychiatric disorder whose main symptoms include low mood， loss of interest， anxiety， sleep disturbances， and changes in appetite. Orexin， a neuropeptide located in hypothalamic neurons， has a wide range of projections throughout the central nervous system and is involved in various behavioral modulations related to depression. This study systematically reviewed the effects of orexin and its receptor-related drugs on depression and found that orexin could exert complex regulatory effects on multiple brain regions by binding to related receptors， affecting emotions， sleep， anxiety， etc. The abnormal state of expression of plasma orexin in patients with depression was found. Exogenous orexin-A， selective orexin receptor 1 antagonists （SORA1s）， selective orexin receptor 2 antagonists （SORA2s）， and dual orexin receptor antagonists （DORAs） have demonstrated antidepressant-like effects in various animal models of depression. Among them， clinical trials involving exogenous orexin-A are relatively scarce. Drugs related to SORA1s and SORA2s， such as JNJ-61393215 and Setorexant， have made significant progress in the treatment of depression. DORAs， such as Suvorexant， Lemborexant， and Daridorexant， are primarily used to treat insomnia. Notably， Suvorexant has also shown potential in alleviating symptoms of anxiety and depression.

OBJECTIVE: To observe the clinical efficacy and safety of automatic pressure-controlled pressure cupping in patients with lumbar disc herniation, and compare it with traditional cupping. METHODS: A total of 100 patients diagnosed with lumbar disc herniation from January 2022 to August 2024 were selected and divided into two groups:the automatic pressure-controlled pressure cupping group (controlled pressure cupping group) and the traditional cupping group (control group), 50 cases in each group. In the controlled pressure cupping group, there were 18 males and 32 females, with an age of (51.98±12.69) years;in the control group, there were 16 males and 34 females, with an age of (51.32±12.05) years. The visual analogue scale(VAS), comfort score, and lumbar range of motion were observed before treatment and after the 1st, 3rd, and 7th treatments to evaluate the efficacy and safety. RESULTS: All patients completed the treatment intervention, with complete follow-up data collected. No adverse reactions or complications occurred during treatment and follow-up. After the 3rd treatment, the VAS score of the controlled pressure cupping group was (2.38±0.49), which was lower than that of the control group (2.94±0.68), with a statistically significant difference (P<0.001). In the controlled pressure cupping group, the VAS scores after the 1st, 3rd, and 7th treatments were significantly better than those before treatment (P=0.026);in the control group, the VAS scores after the 3rd and 7th treatments were better than those before treatment, but the difference was not statistically significant(P=0.182). Repeated-measures analysis of variance (ANOVA) on VAS scores at different time points in both groups showed that there were statistically significant differences in inter-group, time, and interaction effects (P<0.05). After the 1st treatment, in the controlled pressure cupping group, 0 patients felt comfortable, 42 patients (84%) felt mild discomfort, and 8 patients (16%) felt moderate discomfort;in the control group, 0 patients felt comfortable, 28 patients (56%) felt mild discomfort, and 22 patients(44%) felt moderate discomfort;the difference between the two groups was statistically significant(P=0.005). After the 3rd treatment, in the controlled pressure cupping group, 30 patients(60%) felt comfortable, 20 patients (40%) felt mild discomfort, and 0 patients felt moderate discomfort; in the control group, 9 patients (18%) felt comfortable, 41 patients (82%) felt mild discomfort, and 0 patients felt moderate discomfort;the difference between the two groups was statistically significant(P<0.001). There was no statistically significant difference in comfort between the two groups after the 7th treatment(P>0.001). There was no statistically significant difference in lumbar range of motion between the two groups before and after treatment(P>0.05);compared with before treatment, the lumbar range of motion of both groups after treatment was significantly improved, with statistically significant differences (P<0.001). CONCLUSION Automatic pressure-controlled pressure cupping can effectively relieve symptoms in patients with lumbar disc herniation, with excellent safety.
Humans ; Female ; Male ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Adult ; Lumbar Vertebrae/physiopathology* ; Cupping Therapy/methods* ; Pressure ; Aged ; Treatment Outcome

OBJECTIVE: To construct an integrated management model for early screening and diagnosis of PCa based on the Innovative Care for Chronic Conditions Framework (ICCC) and the 1+1 contract-based tiered diagnosis and treatment system (TDTS) in China. METHODS: Based on the 1+1 contract-based TDTS platform, we conducted PCa screening for the male residents aged 60 years and above during health check-ups in Pujin Community Health Center from January 1, 2023 to December 31, 2023. For those with abnormal total prostate-specific antigen (tPSA) ≥ 4 μg/L, we promptly referred them to higher-level hospitals for further diagnosis and treatment via the two-way referral green channel platform and information sharing service using the 1+1 contract model. We further analyzed the relevant data on screening and diagnosis. RESULTS: A total of 4 080 males aged 71.39±5.059 years received PCa screening from January to December 2023. PSA screening was performed in 43.96% of the male residents, revealing 654 cases of PSA abnormality, with a PSA positivity rate of 16.03%, which was higher than that found in the previous large-scale PCa screenings in other regions of China. Among the males with PSA abnormality, 292 (44.65%) expressed their willingness for medical referral, while the others did not seek further medical attention for reasons of being asymptomatic, low awareness of the disease, no accompany for medical visits, and concerns about further costs of diagnosis and treatment. Prostate biopsy was recommended to 154 cases after further examinations, which was accepted by 92 (59.74%). Fifty-eight cases were diagnosed with Pa, and thedetection rate reached 63.04%. CONCLUSION The integrated management model for PSA examination-based early screening and diagnosis of PCa using the 1+1 contract-based TDTS platform is plays a significant role in enhancing people's awareness and knowledge of PCa and improving the early detection rate of the malignancy.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Early Detection of Cancer ; Prostate-Specific Antigen/blood* ; Aged ; China ; Mass Screening ; Middle Aged ; Chronic Disease

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

Objective To assess the blood pressure control and its influencing factors among hypertensive patients in communities in different time periods by 24 h ambulatory blood pressure monitoring(24 h ABPM)and provide reference for optimizing the health management services for hypertension in communities. Methods A total of 765 hypertensive patients registered in the hypertension management project of national essential public health services in Sanxiang Town,Zhongshan City from October 2022 to September 2023 were identified as target subjects.The 24 h ABPM devices were distributed for blood pressure monitoring and a questionnaire survey was conducted to analyze the influencing factors of blood pressure control. Results Of all the participants,16.5% did not monitor blood pressure regularly,and 59.2% monitored blood pressure 1-2 times per week.The patients who were not on night shifts/staying up late had higher mean rates of achieving the target blood pressure and the circadian rhythm of blood pressure during 24 h,nighttime,and early morning than those who were on night shifts/staying up late(all P<0.05).The patients who never drank alcohol had higher rate of achieving the target blood pressure in early morning than those who drank alcohol(P=0.012).The average blood pressure during daytime,nighttime,and 24 h were different by sex(all P<0.05).The average blood pressure during nighttime was different by age and job types(all P<0.05).The average blood pressure during daytime,nighttime,and 24 h were different in patients with different body weight types(all P<0.05).The results of the multivariate logistic regression analysis showed that uncontrolled blood pressure during daytime was more likely to occur in male patients(OR=1.394,95%CI=1.045-1.858,P=0.024),and that during nighttime was more likely to be associated with male patients(OR=1.573,95%CI=1.088-2.275,P=0.016)and night shifts(OR=2.467,95%CI=1.198-5.077,P=0.014).It was difficult to achieve blood pressure control in early morning for the patients who drank alcohol for more than three times per week(OR=4.567,95%CI=1.629-12.807,P=0.004),woke up at night(OR=1.800,95%CI=1.125-2.878,P=0.014),and had night shifts(OR=1.579,95%CI=1.102-2.465,P=0.044).The patients on night shifts were more likely to have abnormal circadian rhythm of blood pressure(OR=1.753,95%CI:1.018-3.018,P=0.043). Conclusions The personal characteristics and lifestyle of hypertensive patients significantly affect the blood pressure control in different time periods(daytime,nighttime,and early morning)and the circadian rhythm of blood pressure.The family doctor team of community healthcare institutions can implement targeted and precise intervention measures for hypertensive patients according to the influencing factors of blood pressure control in different time periods,so as to achieve better management effects.
Humans ; Blood Pressure Monitoring, Ambulatory ; Hypertension/physiopathology* ; Male ; Female ; Middle Aged ; Circadian Rhythm ; Blood Pressure ; Surveys and Questionnaires ; Adult ; Aged ; Time Factors

The research progress in key technologies for dynamic perception of battlefield casualties was reviewed,including unmanned equipment dynamic mapping,dynamic environment semantic segmentation and casualty detection and identification.The discussion also covered the current state of research on casualty dynamic perception equipment in aerial and ground domains.The development trends of key technologies and equipment for dynamic perception of battlefield casualties were pointed out,and references were provided for enhancing the efficacy of battlefield casualty care and improving medical service support capabilities.[Chinese Medical Equipment Journal,2024,45(9):95-108]

Objective To explore medium and long term efficacy of oblique lateral interbody fusion(OLIF)in treating lumbar specific infection.Methods From October 2017 to January 2021,24 patients with lumbar specific infection were treated by OLIF combined with vertebral screw internal fixation,including 15 males and 9 females,aged from 27 to 61 years old with an average of(43.0±15.0)years old;the courses of disease ranged from 6 to 24 months with an average of(14.0±7.0)months;7 patients with L2-L3,12 patients with L3-L4 and 5 patients with L4-L5;19 patients with tuberculosis infection and 5 patients with brucella infection.The amount of intraoperative blood loss,operative time and complications were recorded,and erythro-cyte sedimentation rate(ESR),C-reactive protein(CRP),visual analogue scale(VAS),Japanese Orthopaedic Association(JOA)score and American Spinal Injury Association(ASIA)rating were compared before and one month after opertaion.Re-sults All patients were followed up from 9 to 24 months with an average of(13.0±6.0)months.Operative time was(132.5±21.4)min,and intraoperative blood loss was(227.3±43.1)ml.ESR and CRP were decreased from(82.34±18.62)mmol·h-1 and(53.08±21.84)mg·L-1 before operation to(33.52±17.31)mmol·h-1 and(15.48±8.36)mg·L-1 at one month after opera-tion,respectively(P＜0.05).VAS was decreased from(7.52±1.36)before opertaion to(1.74±0.87)at one month after opera-tion(P＜0.05).JOA was increased from(17.86±3.95)before operation to(24.72±3.19)at one month after operation(P＜0.05).Four patients had neurological symptoms before operation,and were classified to grade D according to ASIA classifica-tion,who were recovered to grade E at 1 month after operation.One patient was suffered from psoas major muscle injury after operation,and returned to normal at 3 weeks.One patient was suffered from abdominal distension and difficulty in defecation,and relieved after gastrointestinal decompression and enema.No complications such as abdominal organ injury and poor wound healing occurred in all patients.Conclusion OLIF combined with vertebral screw internal fixation is a new minimally invasive surgical method for the treatment of lumbar specific infection,especially the lesion located on the middle lumbar vertebra.It has advantages of less trauma,short operation time,less blood loss,convenient operation,complete removal of the lesion,safety and effectiveness,and has good medium-and long-term efficacy for lumbar specific infection.

To understand the pathogenicity,virulence genes,drug resistance genes,and drug resistance of Staphylococcus aureus isolated from yaks in some areas of Lhasa and Nagqu City,55 yak nasal swab samples were analyzed for S.aureus in this study.The cocci were isolated and identified,and the carriage of virulence genes and drug resistance genes,as well as the pathogenicity and drug sensitivity of the isolated S.aureus strains,were detected with PCR,artificially infected mice,and the K-B drug susceptibility disk method.Seven strains of S.aureus were isolated from the 55 yak nasal swab samples,with an iso-lation rate of 12.73％.The isolated strains were all pathogenic to mice,with a fatality rate exceeding 60％.These seven strains of S.aureus carried three drug resistance genes(tetM,tet,and mecA)and six virulence genes(seb,sec,clfA,hla,hlb,and nuc).The detection rate of the three drug resistance genes was 100％,whereas the detection rate of the six virulence genes in the isolates ranged from 83.33％to 100％.The resistance rates of the isolated strains to penicillin,ampicillin,and cotrimox-azole reached 85.71％-100％,whereas the resistance rates to tetracycline and ceftazidime were both 28.57％.Thus,yaks in Lhasa and Nagqu cities were found to be infected by S.aureus strains carrying various drug-resistance genes and virulence genes.These strains were highly pathogenic and showed sensi-tivity to most antibacterial drugs.These findings may serve as a reference for treating S.aureus infection in yaks in the cities of Lhasa and Nagqu.

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.