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:Invasive pulmonary mucormycosis(PM)is a rare but highly lethal opportunistic infection.COVID-19 associated mucormycosis(CAM)is difficult to diagnose,often leading to misdiagnosis or missed diagnosis,and has poor treatment outcomes.This study reports a case of successfully treated CAM and explores optimized diagnostic and therapeutic strategies.Methods:A retrospective analysis of the diagnosis and treatment process in a 50-year-old female patient with COVID-19 associated with diabetic ketoacidosis(DKA)and invasive pulmonary mucormycosis was conducted.Combined with a literature review,the therapeutic efficacy of local bronchoscopic instillation in conjunction with systemic treatment using liposomal Amphotericin B(L-AmB)was specifically evaluated.Results:The patient was rapidly diagnosed with Rhizopus microsporus infection through metagenomic next-generation sequencing(mNGS).She subsequently received antifungal treatment with intravenous L-AmB combined with local bronchoscopic instillation.After treatment,the patient was significantly improved,with imaging studies showing gradual absorption of the lesions.Follow-up at six months revealed no recurrence.A literature review suggests that early diagnosis and multimodal therapy are key to improving survival rates in patients with CAM.Conclusion:mNGS can significantly improve the early diagnosis rate of CAM.The combination of local and systemic treatment with L-AmB is valuable in improving prognosis.Early diagnosis,multimodal antifungal therapy,and individualized management are key to increasing the survival rate of patients with CAM.

Objective:To analyze the association of peripheral blood systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR)with disease severity and progno-sis in elderly patients with chronic pulmonary heart disease(CPHD).Methods:A total of 180 elderly CPHD pa-tients admitted in Xuancheng Central Hospital between September 2021 and January 2023 were enrolled as case group.Healthy volunteers who simultaneously underwent physical examinations in our hospital were selected as con-trol group(n=50).According to the 28d prognosis,the case group was divided into death group(n=45)and sur-vival group(n=135).Levels of peripheral blood SII,NLR and PLR were compared among above-mentioned groups;Spearman correlation analysis was used to analyze the association of above indexes with cardiac function class and prognosis in these patients.Multivariate Logistic regression analysis was used to analyze risk factors for death in these patients.The predictive value of SII,NLR,and PLR for death in elderly CPHD patients was ana-lyzed using receiver operating characteristic(ROC)curve.Results:Compared with those in control group,those in the case group had significant higher levels of peripheral blood SII,NLR and PLR(P＜0.001 all).Compared with NYHA class Ⅱ group and class Ⅲ group,those in class Ⅳ group had significant higher levels of peripheral blood SII[(1759.87±179.43)vs.(1148.33±121.57)vs.(1392.44±146.36)],NLR[(8.65±0.89)vs.(7.14±0.75)vs.(7.76±0.81)],PLR[(152.45±16.79)vs.(125.29±13.46)vs.(138.77±13.58)];and levels of peripheral blood SII,NLR,PLR in class Ⅲ group were significantly higher than those of class Ⅱ group(P＜0.001 all).Com-pared with patients in survival group,those in death group had significant higher levels of peripheral blood SII[(1723.86±189.65)vs.(1296.81±142.33)],NLR[(8.24±0.89)vs.(7.63±0.78)],PLR[(148.75±15.26)vs.(134.41±14.58)](P＜0.001 all).Spearman correlation analysis indicated that the levels of peripheral blood SII,NLR and PLR were significant positively correlated with the severity and poor prognosis(r=0.336～0.432,P＜0.05 or＜0.01;r=0.319～0.504,P＜0.05 or＜0.01)in elderly CPHD patients.Multivariate Logistic regression analy-sis indicated that peripheral blood SII,NLR,PLR and smoking were independent risk factors for death(OR=1.024～9.514,P＜0.05 or＜0.01)in elderly CPHD patients.ROC curve indicated that area under curve(AUC)of combination of SII,NLR and PLR predicting death in elderly CPHD patients was 0.979(95％CI 0.946～0.995),significantly higher than those of each single detection[SII:0.847(95％CI 0.786～0.896),NLR:0.832(95％CI 0.769～0.883),PLR:0.881(95％CI 0.825～0.925),Z=3.988,4.386,4.217,P＜0.01 all].The nomogram calibration curve and decision curve showed good consistency and net benefit of the model.Conclusion:Peripheral blood SII,NLR and PLR are associat-ed with the severity and prognosis of elderly CPHD patients,and have certain predictive value for patient's prognosis.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective:To explore the diagnostic efficacy of methylene blue staining combined with light transmission method (termed as light transmission and staining) in endoscopic submucosal dissection (ESD) specimens of early gastric cancer.Methods:A retrospective study was conducted on 75 specimens of early gastric cancer treated with ESD at Beijing Friendship Hospital, Capital Medical University from October 2021 to August 2023. Under a stereomicroscope, magnified observation and transmitted light transmission and staining observation were performed to compare the demarcation line (DL), irregular microvascular pattern (IMVP) and irregular microsurface pattern (IMSP) of the lesion, and the differences among histological types were compared. Furthermore, the false positive rate of surgical margin, the detection rate of undifferentiated cancer and multifocal lesions were compared against the 88 controls processed by traditional method.Results:Using the light transmission and staining method, DL, IMVP and IMSP were detected in 96.0% (72/75), 89.3% (67/75), and 98.7% (74/75), which was higher than 72.0% (54/75), 6.7% (5/75), and 26.7% (20/75) by using the magnified observation ( χ 2=8.036, P<0.001; χ 2=0.640, P<0.001; χ 2=0.369, P<0.001). There was no statistical difference in the coincidence rate of endoscopy and pathology between differentiated type, undifferentiated type and mixed type [92.2% (59/64), 50.0% (1/2), 77.8% (7/9), χ 2=5.145, P=0.055]. Compared to traditional methods, light transmission and staining could increase the detection rate of undifferentiated cancer [14.7% (11/75) VS 4.5% (4/88), χ 2=4.964, P=0.026] and reduce the false positive rate of surgical margins [1.3% (1/75) VS 11.4% (10/88), χ 2=4.585, P=0.032], but showed no statistical difference in the detection rate of multifocal lesions [5.3% (4/75) VS 0.0% (0/88), χ 2=2.841, P=0.094]. Conclusion:Light transmission and staining enhances pathological recognition of DL, IMVP and IMSP during specimen processing, improving detection of undifferentiated cancer and reducing false positive of margin.

To compare and analyze the clinical manifestations,laboratory characteristics,imaging findings,and treatment outcomes of patients with acute and chronic brucellosis,a retrospective analysis was conducted on 258 patients with brucellosis(202 in the acute group and 56 in the chronic group)hospitalized in Xinkang Hospital in Dalad Banner,Ordos City,Inner Mongolia Autonomous Region,from November 2023 to November 2024.General data,epidemiological characteristics,clinical presentations,laboratory test results,imaging findings,treatment outcomes,and prognosis were collected.The incidences of fever(51.5%vs 7.1%),fatigue(30.2%vs 12.5%),joint pain(42.9%vs 16.1%),and muscle pain(9.9%vs.1.8%)were significantly higher in the acute phase group(all P<0.05).The incidence of osteoarthritis complications was higher in the chronic brucellosis group(51.8%vs 8.9%,χ2=75.697,P<0.01).Univariate ANOVA analysisshowed that the Serum Agglutination Tests(SAT),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),creatinine(CRE),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),and bone destructionexhibited statistically significant differences between the acute and chronic phases of brucellosis(all P<0.05).Multivariate logistic regression analysis indicated that abnormal ALT(OR=14.18,95%CI:1.11-181.72;P=0.041)and bone destruction(OR=0.16,95%CI:0.04-0.63;P=0.009)were associated with chronic brucellosis.After treatment,all patients experienced have symptom relief in varying degrees,with 157 patients(60.9%)cured and 101 patients(39.1%)symptomatic improved(P<0.01).In conclusion,the incidences of fever,fatigue,and joint pain in patients during the acute phase is significantly higher than that those in patients during the chronic phase,while the incidence of osteoarthritis complications is higher in chronic phase patients.The incidences of abnormal SAT,ALT,AST,TBIL,CRE,CRP,and ESR,and bone destruction varies at different stages of brucellosis.Of those,abnormal ALT and bone destruction show a stronger association with,which can assist the clinical staging of brucellosis.

Objective To analyze differences of purified water,softened water,and concentrated softened water on the decontamination effects for surgical instruments,so as to provide a reliable reference for the selection of cleaning water for surgical instruments.Methods The physical and chemical indexes and components of concentrated softened water,softened water,and purified water were detected,and their cleaning effects for instrument were compared.The decontamination cleaning experiment was conducted in three hospitals with different types of cleaning water using mini cleaning machines,and the differences in the decontamination time were analyzed.The cleaning and decontamination experiments on contaminated instruments was performed using a spray cleaning and disinfection device,and the cleaning effects of instruments with different types of cleaning water were analyzed.Results Calcium content and hardness of the three types of cleaning water were all at a low level,which can avoid scale adhesion for cleaning surgical instruments.There were statistically significant differences in the pH value,conductivity,and contents of calcium,sodium and chloride among the three cleaning waters(P<0.05).The purified water was weakly acidic,and its conductivity,hardness,and contents of calcium,sodium and chloride were all at low levels.The softened water and concentrated softened water were weakly alkaline,with high levels of conductivity and sodium content and low level of chloride.There were statistically significant differences in the decontamination time of the purified water,softened water and concentrated softened water among hospitals(P<0.05).Under the same contamination condition of surgical instruments,there was a statistically significant difference in the qualified rate of instruments cleaning in the upper and lower cleaning baskets with different cleaning waters(P<0.05).Conclusion Concentrated softened water and softened water have high sodium content,and their decontamination and cleaning abilities are significantly stronger than those of the purified water.Purified water has poorer effects in instruments cleaning for its deionized property.Using concentrated softened water or softened water in the surgical instrument cleaning process can achieve effects of reducing consumption and increasing efficiency,which is conducive to improving cleaning efficiency and quality.

Objective To investigate the clinical efficacy of the traditional Chinese medicine(TCM)throat opening and brightening method in treating unilateral vocal cord paralysis(UVCP).Methods Sixty patients with UVCP were prospectively collected and randomly assigned to two groups:the Chinese herbal medicine group(trea-ted with Buyang Huanwu Decoction,n=30)and the throat opening and brightening method group(treated with TCM throat opening and brightening method,n=30).The clinical studies that had utilized injection laryngoplasty for the treatment of UVCP(historical control group).Evaluation indicators included the voice handicap index-10(VHI-10),GRBAS-G,objective acoustic measurements of voice(vocal intensity,F0,shimmer,jitter,HNR),and aerodynamic measurements(maximum phonation time,MPT).Results Before treatment,no significant differences were observed between the two groups in all the evaluation indicators(P＞0.05).Post-treatment,the throat open-ing and brightening method group demonstrated significant improvements in VHI-10,GRBAS-G,shimmer,jitter,HNR,and MPT compared to pre-treatment values(P＜0.01),and these improvements were superior to those in the Chinese herbal medicine group.Pre-treatment VHI-10,GRBAS-G,and shimmer scores in the throat opening and brightening method group were significantly higher than those in the historical literature group(P＜0.01).Af-ter treatment,no significant differences were noted in any assessed parameters between the two groups(P＞0.05).Conclusion The TCM throat opening and brightening method significantly enhances phonatory function and quality of life in patients with UVCP,showing comparable efficacy to injection laryngoplasty.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

To compare and analyze the clinical manifestations,laboratory characteristics,imaging findings,and treatment outcomes of patients with acute and chronic brucellosis,a retrospective analysis was conducted on 258 patients with brucellosis(202 in the acute group and 56 in the chronic group)hospitalized in Xinkang Hospital in Dalad Banner,Ordos City,Inner Mongolia Autonomous Region,from November 2023 to November 2024.General data,epidemiological characteristics,clinical presentations,laboratory test results,imaging findings,treatment outcomes,and prognosis were collected.The incidences of fever(51.5%vs 7.1%),fatigue(30.2%vs 12.5%),joint pain(42.9%vs 16.1%),and muscle pain(9.9%vs.1.8%)were significantly higher in the acute phase group(all P<0.05).The incidence of osteoarthritis complications was higher in the chronic brucellosis group(51.8%vs 8.9%,χ2=75.697,P<0.01).Univariate ANOVA analysisshowed that the Serum Agglutination Tests(SAT),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),creatinine(CRE),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),and bone destructionexhibited statistically significant differences between the acute and chronic phases of brucellosis(all P<0.05).Multivariate logistic regression analysis indicated that abnormal ALT(OR=14.18,95%CI:1.11-181.72;P=0.041)and bone destruction(OR=0.16,95%CI:0.04-0.63;P=0.009)were associated with chronic brucellosis.After treatment,all patients experienced have symptom relief in varying degrees,with 157 patients(60.9%)cured and 101 patients(39.1%)symptomatic improved(P<0.01).In conclusion,the incidences of fever,fatigue,and joint pain in patients during the acute phase is significantly higher than that those in patients during the chronic phase,while the incidence of osteoarthritis complications is higher in chronic phase patients.The incidences of abnormal SAT,ALT,AST,TBIL,CRE,CRP,and ESR,and bone destruction varies at different stages of brucellosis.Of those,abnormal ALT and bone destruction show a stronger association with,which can assist the clinical staging of brucellosis.