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.

The writing of pharmacist-managed clinics documents （hereinafter referred to as “outpatient medication record”） is a necessary part of pharmacist-managed clinics service. Outpatient medication record is an important carrier to reflect the quality of pharmacist-managed clinics service. The Chinese Hospital Association Pharmaceutical Specialized Committee was entrusted by the Pharmaceutical Administration Department of the National Health Commission to lead the formulation of the Guidelines for the Pharmacist-managed Clinics Service and Document Writing and Usage （Reference） （hereinafter referred to as Guidelines） according to the compilation method of group standards and the technical route of “documentation combing→framework establishment→draft writing→opinion collection→Guidelines formation”. The Guidelines standardizes the basic requirements of pharmacist-managed clinics record management and the basic content of record， and provides a general template and two specialized templates including pregnant and lactating pharmacist-managed clinics record template and cough and asthma pharmacist-managed clinics record template， which provides a reference for medical institutions to write pharmacist-managed clinics record. This paper introduces the formulation process of Guidelines and analyzes the key contents of Guidelines， which is helpful for the application practice of Guidelines and further improves the quality of pharmacist-managed clinics work.

The prevalence of overweight and obesity has been on rising steadily, posing a major challenge to public health. Focusing on changing systems, a new strategy for overweight and obesity prevention and control, this article elaborates on five pillars: government-led efforts to cultivate a sense of shared responsibility among four stakeholders, scientific weight management advocating multi-disciplinary collaborative diagnosis and treatment, precision management covering the entire population throughout the life cycle, policy incentives to optimize obesity-prone environments, and digital and intelligent empowerment to reshape the paradigm of weight management. However, overweight and obesity prevention and control face persistent challenges, including the difficulty of sustaining individual behavior change, the lack of supportive social environments, and the obstacles to implementing precise interventions. It is recommended to begin by shifting societal perceptions, collaborate across multiple sectors to implement a multi-pronged strategy, and promote highly effective and cost-efficient interventions.

Ganoderma lucidum is one of the widely-used traditional Chinese medicines.Ganoderma lucidum extract and Ganoderma spore powder are also widely used in foods,health care and cosmetics,and are highly favored by consumers.Ganoderic acid A is one of the main effective components of Ganoderma lucidum triterpenoids.In recent years,a large number of studies have proved that ganoderic acid A has anti-tumor,anti-inflammatory,hepatoprotection,hypolipidemic,renoprotective properties,and has therapeutic potential in psychiatric and neurological disorders.,which has high medicinal value and good prospects for development.Based on review of domestic and foreign literatures in recent years,the new research progress in pharmacology of ganoderic acid A is summarized in this paper in order to provide references for its further development and clinical applications.

Objective To analyze the factors affecting the prognosis of patients with knee osteoarthritis,and to construct a nomogram prediction model in conjunction with multi-dimensional clinical indicators.Methods The clinical data of 234 pa-tients with knee osteoarthritis who were treated in our hospital from January 2015 to June 2021 were retrospectively analyzed,including 126 males and 108 females;age more than 60 years old for 135 cases,age less than 60 years old for 99 cases.Lysholm knee function score was used to evaluate the prognosis of the patients,and the patients were divided into good progno-sis group for 155 patients and poor prognosis group for 79 patients according to the prognosis.The clinical data of the subjects in the experimental cohort were analyzed by single factor and multiple factors.The patients were divided into experimental co-hort and verification cohort,the results of the multiple factor analysis were visualized to obtain a nomogram prediction model,the receiver operating characteristic curve(ROC),calibration curve and decision curve were used to evaluate the model's dis-crimination,accuracy and clinical benefit rate.Results The results of multivariate analysis showed that smoking,pre-treatment K-L grades of Ⅲto Ⅳ,and high levels of interleukin 6(IL-6)and matrix metallo proteinase-3(MMP-3)were risk factors for the prognosis of patients with knee osteoarthritis.ROC test results showed that the area under the curve of the nomogram model in the experimental cohort and validation cohort was 0.806[95％CI(0.742,0.866)]and 0.786[(95％CI(0.678,0.893)],re-spectively.The results of the calibration curve showed that the Brier values of the experimental cohort and verification cohort were 0.151 points and 0.134 points,respectively.When the threshold probability value in the decision curve was set to 31％,the clinical benefit rates of the experimental cohort and validation cohort were 51％and 56％,respectively.Conclusion The prognostic model of patients with knee osteoarthritis constructed based on multi-dimensional clinical data has both theoretical and practical significance,and can provide a reference for taking targeted measures to improve the prognosis of patients.

Objectives:To investigate the association between social determinants of health(SDOH)and incident stroke and analyze the main risk factors for stroke among resident with different SDOH levels. Methods:From 2012 to 2015,30 036 residents(≥35 years old)from 30 districts in 14 provincial-level administrative divisions in China were enrolled this study based on stratified multi-stage-random-sampling method.The prevalence of cardiovascular diseases and related risk factors were investigated,and stroke events were followed up in 2018 to 2019.Principal component analysis was performed to establish SDOH scores based on 9 indicators related to socioeconomic and healthcare resources,participants were divided into low SDOH group(n=8 343)when it was≥-2.01 to<-1.14,middle SDOH group(n=7 257)when it was≥-1.14 to<0.10,and high SDOH group(n=8 457)when it was≥0.10 to≤5.79.Multivariate Cox regression was applied to estimate the association of SDOH levels with incident stroke.The random survival forest method was used to analyze the major risk factors in different SDOH levels. Results:A total of 24 057 participants were finally included,669(2.8%)participants developed stroke during a mean of(4.7±0.8)years follow-up.The incidence densities of stroke in the low,medium,and high SDOH groups were 468.39,628.85,and 700.39/100 000 person-years,respectively(Pdifference<0.05,Ptrend=0.01).Compared with individuals with low SDOH level group,fully HR for incident stroke among those with medium and high were 1.91(95%CI:1.54-2.36)and 1.59(95%CI:1.30-1.95),respectively(Ptrend<0.001).Advanced age is the primary risk factor for stroke in the population,especially in districts with high SDOH level.In districts with medium SDOH level,diabetes is an important risk factor for stroke.High blood pressure and alcohol consumption are important modifiable risk factors in low SDOH level districts. Conclusions:Present study shows that higher levels of SDOH are associated with increased risk of stroke.The main risk factors for stroke differ among participants with different SDOH level districts.Targeted interventions should be implemented to improve the prevention and treatment of stroke in populations with different levels of SDOH.

AIM To explore the effects of Yupingfeng Powder on the binding of programmed death receptor 1(PD-1)and programmed death ligand 1(PD-L1),and the growth of lung cancer cells in vitro and in vivo.METHODS Yupingfeng Powder extract had its effect on the growth of Lewis lung carcinoma(LLC)cells in mice detected by MTT assay;its effect on eliminating target cells in the co-culture of T cells and LCC cells detected by lactate dehydrogenase(LDH)release test;its effect on blocking the combination of PD-1 and PD-L1,and its influence on the levels of interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α)release detected by enzyme-linked immunosorbent assay(ELISA);its inhibitory effect on the growth of LLC cells in vivo analyzed by homologous tumor model;its effect on the infiltration of CD4+T cells and CD8+T cells in tumor tissues investigated by immunohistochemical staining.RESULTS Yupingfeng Powder inhibited the growth of LLC cells and the expression of endogenous PD-L1 protein in a dose-dependent manner(P＜0.05,P＜0.01),competitively blocked the combination of PD-1 and PD-L1(P＜0.05,P＜0.01),and promoted the release of IFN-γ and TNF-α from T cells(P＜0.05,P＜0.01).Yupingfeng Powder inhibited the growth of LLC tumor(P＜0.01),and increased the infiltration of CD4+T and CD8+T cells(P＜0.01).CONCLUSION Yupingfeng Powder exhibits its in vitro capability in blocking the PD-L1 inhibition on T cells,and its in vivo anti-tumor effect in terms of the improvement of CD4+T cells and CD8+T cells in this homologous mouse tumor model.

AIM To study the effects of Liangxue Heying Formula on vascular inflammatory injury in a rat model of thromboangiitis obliterans(TAO).METHODS The rats were randomly divided into the sham operation group,the model group and the low,medium and high dose Liangxue Heying Formula groups(2.25,4.5,9 g/kg).With the rat TAO model successfully established by injection of 0.1 mL sodium laurate(10 mg/mL)into the femoral artery of hind limbs,corresponding doses of drugs by gavage were administered upon the rats.Subsequently,the rats had their morphological changes of the affected limbs observed and assessed;their changes of blood flow in hind limbs scanned by laser Doppler flowmetry;their plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1 detected by ELISA;their histopathological changes of femoral artery and vein observed by HE staining;and their protein expressions of TNF-α,IL-6,JAK2,p-JAK2,STAT3,p-STAT3,ICAM-1 and VCAM-1 in femoral artery detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased morphological score of the affected limb(P＜0.01);decreased blood perfusion ratio of the affected side/healthy side(P＜0.01);increased plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1(P＜0.01);more existence of thrombotic infiltration containing a larger number of inflammatory cells in femoral artery and femoral vein tissue,and increased protein expressions of TNF-α,IL-6,p-JAK2,p-STAT3,ICAM-1 and VCAM-1 in femoral artery(P＜0.01).Compared with the model group,the medium and high dose Liangxue Heying Formula groups demonstrated decreased morphological score of the affected limb(P＜0.01);increased blood perfusion ratio of the affected side/healthy side(P＜0.01);reduced infiltration of thrombus and inflammatory cells in femoral artery and femoral vein tissue,and decreased protein expressions of IL-6 and p-STAT3 in femoral artery tissue(P＜0.01).All Liangxue Heying Formula groups shared decreased plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1(P＜0.05,P＜0.01);and reduced protein expressions of TNF-α,ICAM-1,VCAM-1 and p-JAK2 in femoral artery(P＜0.01).CONCLUSION Liangxue Heying Formula can improve the systemic inflammatory state of TAO rats by inhibiting the activation of endothelial cells and reducing vascular inflammatory injury possibly due to the mechanism associated with the regulation of the JAK2/STAT3 signaling pathway.

Objective To explore the effectiveness of transperineal tension-free repair of rectal seromuscular layer in the treatment of acquired rectovestibular fistula.Methods Clinical data of 97 girls with acquired rectovestibular fistula from May 2016 to November 2023 were enrolled.The surgical age ranged from 6 months to 11 years old(median,3 years old).The fistula was disconnected and resected via the perineal approach.The anterior wall of the rectum was fully disconnected.Then the fistula was repaired with horizontal continuous tension-free suture of rectal plasmomuscular layer with 5-0 PDS sutures.After continuous suture reinforcement,the perineal muscle layer and skin were longitudinally continuously sutured.The internal fistula opening was exposured with an anal dilator or small hook,and the mucosal layer was continuously sutured with 5-0 PDS sutures.Postoperatively,the anal tube and urinary tube were retained for 5-7 d and antibiotics was administered for treatment.Results The mean operation time was(60.5±9.0)min,the mean fistula diameter was(5.2±2.1)mm,and the mean hospital stay was(7.4±1.9)d.The follow-ups time was 4.5 months to 8.5 years(median,4.25 years).Primary healing was achieved in 92 cases(94.8％),with satisfactory perineal appearance,smooth stool passage,and regular defecation.Fistula recurred within 5-10 d after operation in 5 cases(5.2％),2 of which healed after 3 weeks of sitz baths by using 3％boric acid or Kangfuxin solution,2 of which healed after second operation,and 1 of which experienced recurrence after secondary fistula repair.Conclusion Transperineal tension-free rectal seromuscular layer repair is a simple,safe,and effective surgical method for the treatment of acquired rectovestibular fistula in girls.

Objective To summarize the experience of laparoscopic appendectomy in children with retrocecal appendicitis.Methods Between October 2019 and February 2024,57 children with retrocecal appendicitis were confirmed in three-port laparoscopic appendectomy operations in this department.A 5 mm trocar and a 30°observation laparoscope were inserted through the umbilical midline incision.A 5 mm trocar and operating forceps were inserted through the midline above the bladder in the lower abdomen and the outer edge of the left rectus abdominis muscle 3-5 cm below the umbilicus,respectively.The laparoscopic forceps were inserted into the abdomen cavity to search and ligate the root of the appendix.An electric hook was used to detach the blind end and body of the appendix with combination of forward and reverse cutting.If the appendix was located outside of retroperitoneum,the electric hook was used to open retroperitoneum aiming to expose the appendix,followed by releasing,detaching and cutting the appendix.Results The operations were successfully completed in all the 57 cases.The operating time was 65-120 min(mean,85.0±10.5 min).All the patients got out of bed and moved around at 8-12 h after surgery and passed flatus and took liquid diet at 0.5-2 d after surgery.The postoperative hospital stay was 3-7 d(mean,5.5 d).The follow-ups time ranged from 1 to 18 months(mean,5.7 months).No complications were noted,including wound infection,adhesive intestinal obstruction,appendiceal stump inflammation or pelvic abscess.Conclusions The retrocecal appendix is closely attached to the cecal wall,leading to a relatively long surgical time.During the operation,the root of the appendix should be ligated firstly,and the appendix be detached closely to the appendix wall.The combination of forward and backward appendectomy during the surgery should be emphasized.In case the appendix is located outside of the retroperitoneum,the lateral retroperitoneum should be opened with an electric hook to expose the appendix,and the appendix should be removed by combining forward and reverse cutting.