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 investigate the current status of pharmaceutical care in medical institutions in China， and provide experience and suggestions for better development of pharmaceutical care. METHODS Questionnaire survey was used to investigate the development of pharmaceutical care in medical institutions in 31 provinces （autonomous regions and municipalities directly） in March 2023， and descriptive analysis and binary logistic regression analysis on the influencing factors of pharmaceutical care were conducted. RESULTS A total of 1 368 questionnaires were sent out， and 1 304 valid questionnaires were collected with the effective recovery rate of 95.32%. Pharmaceutical care was carried out in 671 medical institutions （51.46%）， and the rates of pharmaceutical care in tertiary， secondary， primary and other medical institutions were 74.79%， 27.97% and 7.35%， respectively. The average number of patients receiving pharmaceutical care was 2 638.96 per year， and there were 8.33 pharmacists in each medical institution to carry out pharmaceutical care， among which 93.68% were clinical pharmacists. The main departments covered by pharmaceutical care services included respiratory and critical care medicine， cardiology， intensive care unit， endocrinology， oncology， gastroenterology， obstetrics and gynecology and other departments. There were only 48 medical institutions （7.15%） with additional compensation for pharmaceutical care services. The main experiences of developing pharmaceutical care were to pay attention to talent cultivation and discipline construction， but the main difficulties were serious shortage of staff and qualified talents， low compensation level and low enthusiasm. Grade of medical institutions， the number of pharmacists engaged in clinical pharmacy， the number of qualified clinical pharmacists and the degree of information in the pharmacy department were the main influencing factors for carrying out pharmaceutical care （P＜0.05）. CONCLUSIONS In recent years， pharmaceutical care in Chinese medical institutions has made certain progress， while that of primary medical institutions， secondary medical institutions and other medical institutions should be improved. In the future， it is still necessary to further enhance the implementation of pharmaceutical care， promote personnel training， and attach importance to demonstrating the value of pharmaceutical care， thereby promoting the sustainable and high- quality development of pharmaceutical care.

OBJECTIVE To summarize the implementation experiences of the China Hospital Association’s Clinical Pharmacist Instructor Training Program Reform， and to evaluate the effectiveness of the reform， thus continuously enhancing the quality and standards of clinical pharmacist instructor training. METHODS The study drew on project evaluation methodologies to summarize the main characteristics of the comprehensive system and new model for clinical pharmacist instructor training established through the reform by literature review. The “learning assessment” and “reaction assessment” were conducted by using Kirkpatrick’s four-level model of evaluation in order to evaluate the effectiveness of the clinical pharmacist instructor training reform through statistically processing and analyzing the performance data and teaching evaluation data of the instructor participants. Based on problem and trend analysis， the future development directions were anticipated for the reform of clinical pharmacist instructor training. RESULTS & CONCLUSIONS The latest round of clinical pharmacist instructor training reform initiated by the Chinese Hospital Association had initially established a four-pronged training system encompassing “recruitment， training， assessment， and management”. It had also forged a training 。 model “oriented towards enhancing clinical teaching competency， with practical learning and skill-based assessment conducted on clinical teaching sites as its core”. Following a period of over three years of gradual reform， the new training system and model became increasingly mature. In both 2023 and 2024， the participants achieved relatively high average total scores in their initial completion assessments [with scores of （84.05± 5.83） and （85.82±4.35） points， respectively]. They also reported a strong sense of gain from the training reform [with self- perceived gain scores of （4.80±0.44） and （4.85±0.39） points， respectively]. The operation and implementation effects of the reform were generally satisfactory. In the future， clinical pharmacist instructor training reforms should continue to address the issues remaining from the current phase， while aligning with global trends in pharmacy education and industry development. Additionally， sustained exploration and practice will be carried out around the core objective of “enhancing clinical teaching competence”.

Objective To observe the expression and localization of group Ⅰ metabotropic glutamate receptors (mGluR1/ 5) in rat superior cervical ganglion (SCG) and the effect of chronic intermittent hypoxia (CIH) on mGluR1/ 5 protein level. Methods Twelve male SD rats were randomly divided into control group(Ctrl)and CIH group(CIH), 6 rats in each group. After 6 weeks of modeling, the effect of CIH on mGluR1/ 5 protein level was detected by Western blotting, the expression and distribution of mGluR1/ 5 in SCG were detected by immunohistochemistry and double-immunofluorescent staining. Results mGluR1/ 5 was expressed in rat SCG. mGluR1 was distributed in neurons and small intensely fluorescent (SIF) cells, but not in satellite glial cells (SGCs), nerve fibers and blood vessels, whereas mGluR5 was mainly distributed in nerve fibers and a little in neurons, but not in SGCs, SIF cells and blood vessels. CIH increased the protein levels of mGluR1/ 5 (P<0. 01) in rat SCG. Conclusion Both mGluR1 and mGluR5 are expressed in the rat SCG, but their distribution are different, and the increased protein levels of both may be involved in CIH-induced hypertension.

Objective To explore the prognostic factor and its predictive value of patients with Wilson disease-related acute-on-chronic liver failure(WD-ACLF).Methods The clinical data of 70 patients diagnosed as WD-ACLF admitted to the Department of Encephalopathy of the First Affiliated Hospital of Anhui University of Chinese Medicine from January 1,2017 to January 1,2022 were retrospectively collected.According to the 12-week prognosis,patients were divided into survival group(n=36)and death group(n=34).The data of the two groups were analyzed by univariate and multivariate logistic analysis to screen the prognostic risk factors and evaluate their predictive value.The model coefficient is omnibus tested,and the model-fitting degree is evaluated by the Hosmer-Lemeshow test.ROC curve was used to analyze the prognostic value for WD-ACLF between the new model and chronic liver failure-sequential organ failure assessment(CLIF-SOFA)score,model for end-stage liver disease(MELD)score and Child-Turcotte-Pugh(CTP)score.Results A total of 70 WD-ACLF patients were enrolled in present study,including 36 cases in survival group[22 males and 14 females with median age of 30.0(17.3,40.0)]and 34 cases in death group[25 males and 9 females with median age of 34.0(28.8,41.0)].Univariate analysis showed that the course of disease,prothrombin time(PT),activated partial thromboplastin time(APTT)were shorter in survival group than that in death group,the white blood cells(WBC),international normalized ratio(INR),aspartate transaminase(AST),total bilirubin(TBIL),blood urea nitrogen(BUN),creatinine(Cre)and ceruloplasmin(CER)levels and the proportion of infection,ascites,and upper gastrointestinal bleeding were lower in survival group than those in death group,however,the proportion of infection,ascites and upper digestive bleeding in the survival group were lower than those in the death group.Meanwhile,the red blood cells(RBC),hemoglobin(Hb),Na+ and total cholesterol(TC)level in the survival group were higher than those in the death group(P<0.05 or P<0.01).The results of multivariate logistic regression analysis showed that disease course(OR=1.176,95%CI 1.043-1.325),INR(OR=7.635,95%CI 1.767-32.980),TBIL(OR=1.012,95%CI 1.003-1.021),and upper gastrointestinal bleeding(OR=11.654,95%CI 1.029-131.980)were independent risk factors affecting the prognosis of WD-ACLF(P<0.05).Based on the results of logistic regression analysis,a joint model for predicting the prognosis of WD-ACLF was established.The AUC of the model for evaluating the prognosis of WD-ACLF was 0.941,which was greater than the CLIF-SOFA score(AUC=0.802),MELD score(AUC=0.897),and CTP score(AUC=0.722).Conclusions The course of disease,TBIL,INR,and upper gastrointestinal bleeding are risk factors that affect the prognosis of WD-ACLF.The prognosis model established based on this can more accurately predict the prognosis of WD-ACLF patients,and its predictive value is superior to CLIF-SOFA score,MELD score,and CTP score.

BACKGROUND:Previous literature reported that the fusion cage moved more than 2 mm from its original position,which means that the fusion cage moved backward.At present,clinical observation has found that the factors leading to the displacement of the fusion cage are complex,and the relationship between these factors and the cage retropulsion is not clear. OBJECTIVE:To explore the risk factors related to cage retropulsion after lumbar interbody fusion. METHODS:Retrospective analysis was conducted in 200 patients who underwent transforaminal lumbar interbody fusion surgery with a polyetheretherketone interbody fusion from February 2020 to February 2022.According to the distance from the posterior edge of the vertebral fusion cage to the posterior edge of the vertebral body after the operation(the second day after the removal of the drainage tube)and 1,3,6 and 12 months after the operation,patients were divided into cage retropulsion group(≥2 mm)and cage non-retropulsion group(<2 mm).The factors that may affect cage retropulsion,such as age,gender,body mass index,bone mineral density,operation time,bleeding,endplate injury,preoperative and postoperative interbody height,cage implantation depth,cage size,and segmental anterior convexity angle,were analyzed by univariate and logistic regression analysis. RESULTS AND CONCLUSION:(1)Posterior displacement of the fusion cage occurred in 15 cases(15/200).The differences in basic information such as age and body mass index between the two groups were not statistically significant.(2)The results of the univariate analysis were that gap height difference,time to wear a brace,segmental anterior convexity angle difference,bone mineral density,and age were related to posterior migration of the cage.(3)The results of logistic regression analysis were that cage size,endplate injury condition,and depth of cage implantation were risk factors for cage retropulsion.(4)These findings suggest that cage retropulsion after lumbar interbody fusion is caused by multiple factors,including segmental anterior convexity angle difference,bone mineral density,cage size,endplate damage,time to wear a brace,and depth of cage implantation.

Objective:To explore therapeutic effect of sacubitril valsartan sodium combined with Wenxin granule in the treatment of hypertension complicated with paroxysmal atrial fibrillation(AF)and its effect on cardiac electro-physiological structure.Methods:A total of 116 patients with hypertension and paroxysmal atrial fibrillation treated in our hospital from Oct 2021 to Nov 2022 were consecutively selected.According to random number table,they were divided into Wenxin granule group(received Wenxin granule treatment based on routine antihypertensive ther-apy)and combined treatment group(received sacubitril valsartan sodium combined Wenxin granule therapy based on routine antihypertensive therapy)with 58 cases in each group,and both groups were consecutively treated for six months.Clinical symptom score,AF burden,P wave duration,P wave dispersion,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDd)and left ventricular ejection fraction(LVEF)were compared between two groups before and after treatment.Results:After treatment,compared with Wenxin granule group,there were significant reductions in clinical symptom score[(1.66±0.69)scores vs.(1.40±0.53)scores],AF burden[4.43(1.65)％vs.1.62(3.50)％],P wave duration[(112.17±6.46)ms vs.(109.29±8.59)ms],P wave dispersion[(32.47±8.11)ms vs.(29.02±7.49)ms]and LAD[(34.83±3.41)mm vs.(33.40±3.74)mm]in combined treatment group(P＜0.05 or＜0.01).There were no significant difference in LVEDd and LVEF between two groups,P＞0.05 both.Conclusion:Sacubitril valsartan sodium combined with Wenxin granule can significantly im-prove clinical symptoms and atrial fibrillation burden,reduce the susceptibility to atrial fibrillation,and inhibit atrial electrical remodeling and structural remodeling in patients with hypertension complicated with paroxysmal atrial fi-brillation.

OBJECTIVE To investigate the current situation of pharmaceutical clinic service in medical institutions in China and provide experience and suggestions for promoting the development of pharmaceutical clinics. METHODS Questionnaire survey was used to investigate the development of pharmaceutical clinics in medical institutions of 31 provinces （autonomous regions and municipalities directly under the central government） in March to April 2023， and the descriptive analysis was conducted. The regression analysis was carried out for the influential factors of pharmaceutical clinic service. RESULTS A total of 1 368 questionnaires were distributed in this survey and 1 304 valid questionnaires were collected with the effective response rate of 95.32%. A total of 463 medical institutions carried out pharmaceutical clinic service， the rate of which was 35.51% （463/1 304）； the rates of pharmaceutical clinics in tertiary， secondary， primary and other medical institutions were 52.80%， 17.18% and 5.88%， respectively. The frequency of opening pharmaceutical clinics was 3.17 days per week on average， with an average of 5.99 visiting pharmacists in each medical institution. Among the visiting pharmacists， clinical pharmacists accounted for the vast majority （88.68%， 2 459/2 773）. There were various categories of pharmaceutical clinics， including joint clinics and pharmacist-independent clinics； among pharmacist-independent clinics， pharmaceutical specialty/specialty disease clinics were the main ones， accounting for 89.72% of the total number of pharmaceutical clinics. The value of pharmacists in pharmaceutical clinics was manifested in various forms， among which the proportion of medical institutions charging pharmaceutical clinics was 10.80%. The main experiences in developing pharmaceutical clinics were to attach importance to discipline construction and personnel training. The main difficulties in developing pharmaceutical clinics were low compensation levels and a shortage of talent.The number of clinical pharmacists， the number of visiting pharmacists in pharmaceutical clinics and additional compensation were positively correlated with the amount of pharmaceutical clinic services（P＜0.05）. CONCLUSIONS In recent years， pharmaceutical clinics have made significant progress； in the future， it is still necessary to further strengthen discipline construction and talent cultivation， pay attention to the value embodiment of pharmacists， to promote the healthy development of pharmaceutical clinics.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Chronic bronchitis （CB） is a common respiratory system disease that is classified as a lung disease in traditional Chinese medicine （TCM） and is closely related to lung dysfunction. Lung Yang is the Yang Qi of the lungs，which drives the physiological activities within the lungs. It has physiological functions such as warming the lung system，regulating lung fluid，and dispersing the protective Yang. It can be distributed on the surface of the airway's Yin skin through sweat pores in the form of airflow and fluid，playing a protective and nourishing role. If the protective Yang fails to guard the Yin skin or if the lung fluid cannot nourish the Yin skin，the structural integrity of the airway's Yin skin may be compromised. This may weaken lung Yang's functions， such as clearing phlegm turbidity，dispersing lung fluid，and resisting external pathogens. Consequently， the retention of phlegm turbidity，insufficient nourishment of the Yin skin，and invasion by external pathogens all damage the lung Yang，burn the lung fluid，and exacerbate the pathological state of Yin skin unprotected，forming a vicious cycle that ultimately results in lung Yang asthenia and then the onset of CB. Based on the intrinsic connection between "Yin skin unprotected" and "lung Yang asthenia"，this paper interprets the etiology and pathogenesis of CB. It proposes that "Yin skin unprotected" in the airway is the basic cause of CB and "lung Yang asthenia" caused by "Yin skin unprotected" is the core pathogenesis of CB. By integrating micro differentiation indicators with macro differentiation syndromes， the study explores its modern biological basis. Guided by the theory of "warming the lung Yang and protecting the Yin skin" and based on modern pharmacology research，this study further explores the scientific connotation of single TCM and compound formulations for treating TCM by warming the lung Yang and protecting the Yin skin. Furthermore， it proposes methods for dispelling pathogenic factors and protecting the Yin skin during the acute exacerbation phase，as well as nourishing and warming lung Yang during the remission phase，in order to provide new ideas for the early prevention and treatment of TCM.