ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

Objective:To investigate the trajectory of frailty in elderly patients on maintenance hemodialysis(MHD)following SARS-CoV-2 infection and its associated risk factors.Methods:This prospective cohort study focused on elderly patients who underwent baseline frailty assessment(T0)during hemodialysis treatment at Beijing Friendship Hospital for over 3 months between December 1st, 2022, and December 31th, 2022, and were diagnosed with SARS-CoV-2 infection.The Fried Frailty Phenotype was evaluated at 1 month(T1), 3 months(T2), and 6 months(T3)post-infection.Frailty trajectory after infection was analyzed using repeated measurement ANOVA.Patients were divided into stable/improvement or exacerbation groups based on their frailty status at T0 and T3, with logistic regression analysis employed to identify risk factors for different frailty trajectories.Results:A total of 130 elderly maintenance hemodialysis patients, with a median age of 66 years(range: 63-71 years)and 62 males(47.7%), were included in the study.Six months after the infection, a majority of surviving patients saw their frailty scores return to baseline levels.Specifically, 72 patients(55.4%)either maintained or improved to robust or pre-frail states, while 9 patients(6.9%)progressed to a pre-frail state, 18 patients(13.8%)progressed to a frail state, and 31 patients(23.8%)remained in a frail state.Results from multivariate logistic regression analysis indicated that low grip strength( OR: 6.30, 95% CI: 1.48-26.73)and all-cause hospitalization( OR: 5.01, 95% CI: 1.19-21.03)were identified as risk factors for non-frail patients transitioning to frailty( P<0.05). Conclusions:The majority of elderly maintenance hemodialysis patients who survived SARS-CoV-2 infection returned to their baseline level of frailty or showed improvement within 6 months.Non-frail patients with low grip strength or those who were hospitalized were more likely to deteriorate towards frailty.

Aim To explore the possible regulatory effect of leptin on acyl-CoA synthetase long chain fami-ly member ACSL5 and their effect on migration and in-vasion of breast cancer cell,and to explore the underly-ing mechanism.Methods The expression of leptin receptor was detected by immunofluorescence assay.The migration and invasion ability of MCF-7 cells were detected by wound healing assay and Transwell assay respectively.The downstream target gene of leptin was analyzed by PCR microarray data.The expression of ACSL5 in breast cancer and its correlation with the staging and prognosis of breast cancer patients were as-sessed uing bioinformatics methods.The expression of ACSL5 in MCF-7 cells treated with different concentra-tions of leptin was detected using real time fluorescence quantitative polymerase chain reaction(RT-qPCR).Overexpressing ACSL5 was constructed by lentiviral transfection;the expressions of EMT related proteins,AMPK-α and p-AMPK-α were detected by Western blot.Results Leptin promoted breast cancer cell mi-gration and invasion and EMT.ACSL5 was significant-ly low expressed in breast cancer and related to progno-sis.Leptin downregulated the expression of ACSL5 through OBR.Leptin activated AMPK pathway to downregulate ACSL5 and promote migration,invasion and EMT of breast cancer cells.Conclusions Leptin may promote the migration,invasion and EMT of breast cancer by downregulating ACSL5 through activating AMPK pathway.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Articular cartilage is a crucial tissue structure in humans.With ongoing exploration of joint tissue structure and the emergence of innovative biotechnological organoids,various sources of stem cells can be selected for induction to differentiate into articular cartilaginous organoids based on the articular cartilage tissue structure,which can be applied to the treatment of cartilage defects,drug testing,and precision medicine and biological development.This article presents a review of the research progress concerning articular cartilaginous organoids,in order to provide a reference for clinical practice.

Articular cartilage is a crucial tissue structure in humans.With ongoing exploration of joint tissue structure and the emergence of innovative biotechnological organoids,various sources of stem cells can be selected for induction to differentiate into articular cartilaginous organoids based on the articular cartilage tissue structure,which can be applied to the treatment of cartilage defects,drug testing,and precision medicine and biological development.This article presents a review of the research progress concerning articular cartilaginous organoids,in order to provide a reference for clinical practice.

Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of patients with adrenal diffuse large B-cell lymphoma(DLBCL).Methods·From March 2002 to December 2022,a total of 105 patients with adrenal DLBCL admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival outcomes,and prognostic factors.Patients'gene mutation profiles were evaluated by targeted sequencing of 152 lymphoma-related genes.Results·The median age of the patients was 62(15?82)years and the male-to-female ratio was 2.3∶1.Among them,63 patients(60.0%)were over 60 years old,22 patients(21.0%)had an Eastern Cooperative Oncology Group(ECOG)performance status of two or higher,87 patients(82.9%)were staged Ann Arbor Ⅲ?Ⅳ,92 patients(87.6%)had elevated serum lactate dehydrogenase(LDH)levels(above the upper limit of reference),84 patients(80.0%)had extranodal invasion in at least two organs,67 patients(63.8%)were of non-germinal center B-cell(non-GCB)origin,and 95 patients(90.5%)had an international prognosis index(IPI)scored over 2.With a median follow-up of 28.3(0.7?191.9)months,the estimated 2-year overall survival(OS)rate and progression-free survival(PFS)rate were 68.3%and 53.1%,respectively.The estimated 5-year OS rate and PFS rate were 52.6%and 44.0%,respectively.Among 93 patients who could be evaluated for clinical outcomes,62(66.7%)got a complete response(CR).Univariate analysis and multivariate Cox analysis revealed that age over 60 years was an adverse prognostic factor for PFS,and ECOG performance status of two or higher was an adverse prognostic factor for both OS and PFS.Targeted gene sequencing in 46 adrenal diffuse DLBCL patients showed high mutation frequencies in lysine methyltransferase 2D(KMT2D;n=17,37%),Pim-1 proto-oncogene,serine/threonine kinase(PIM1;n=17,37%),MYD88 innate immune signal transduction adaptor(MYD88;n=15,33%),CD79b molecule(CD79B;n=13,28%),and BTG anti-proliferation factor 2(BTG2;n=10,22%).Conclusion·Age over 60 years is an adverse prognostic factor for PFS,and ECOG performance status of two or higher is an adverse prognostic factor for both OS and PFS in patients with adrenal DLBCL.Patients exhibited high frequencies of KMT2D,PIM1,MYD88,CD79B,and BTG2 mutations,as well as an increased proportion of the MCD-like subtype.

Objective·To investigate the clinicopathologic features,gene mutation profile,and real-world survival prognosis of diffuse large B-cell lymphoma(DLBCL)with pulmonary involvement.Methods·The clinical data of 110 patients with newly diagnosed,pathologically confirmed DLBCL and pulmonary involvement at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,between August 2003 and December 2022 were retrospectively collected and analyzed.Evaluation of the efficacy of treatment,survival analyses,and univariate and multivariate analyses were performed in 88 patients who received a first-line regimen based on rituximab in combination with cyclophosphamide,doxorubicin/epirubicine,vincristine,and prednisone(R-CHOP).A total of 74 patients underwent targeted DNA sequencing of 55 lymphoma-related genes and were evaluated for mutations.Results·Among the 110 patients,72(65.5%)were>60 years old,52(47.3%)were female,92(83.6%)presented with Ann Arbor stage Ⅲ?Ⅳ,20(18.2%)had ECOG scores≥2,75(68.2%)had elevated lactate dehydrogenase(LDH)levels,79(71.8%)had≥2 extranodal involvements,32(31.4%)were classified as germinal center B-cell subtype,22(26.8%)were diagnosed with double expressor lymphoma,and 4(4.6%)with double-hit lymphoma.Among the patients treated with R-CHOP-based first-line regimens,the objective response rate(ORR)was 68.2%,the 5-year progression-free survival(PFS)rate was 43.7%,and the 5-year overall survival(OS)rate was 65.4%.Univariate analysis showed that elevated LDH and ECOG score≥2 were poor prognostic factors for PFS and OS,and mutations in PIM1 and CD79B were poor prognostic factors for PFS among high-frequency mutations.Multivariate analysis showed that elevated LDH was an independent adverse prognostic factor for PFS(HR=2.47,95%CI 1.28?4.77)and OS(HR=2.71,95%CI 1.21 ? 6.07).Targeted sequencing results showed that PIM1(25.7%),MYD88(24.3%),TP53(18.9%),CD79B(17.6%),KMT2D(17.6%),and TNFAIP3(16.2%)were the high-frequency mutations with mutation rates over 15%.Conclusion·Elevated LDH is an independent adverse prognostic factor for PFS and OS in DLBCL with pulmonary involvement.Mutations in PIM1,MYD88,TP53,CD79B,KMT2D,and TNFAIP3 are frequently observed in this population.

Aim To explore the possible regulatory effect of leptin on acyl-CoA synthetase long chain fami-ly member ACSL5 and their effect on migration and in-vasion of breast cancer cell,and to explore the underly-ing mechanism.Methods The expression of leptin receptor was detected by immunofluorescence assay.The migration and invasion ability of MCF-7 cells were detected by wound healing assay and Transwell assay respectively.The downstream target gene of leptin was analyzed by PCR microarray data.The expression of ACSL5 in breast cancer and its correlation with the staging and prognosis of breast cancer patients were as-sessed uing bioinformatics methods.The expression of ACSL5 in MCF-7 cells treated with different concentra-tions of leptin was detected using real time fluorescence quantitative polymerase chain reaction(RT-qPCR).Overexpressing ACSL5 was constructed by lentiviral transfection;the expressions of EMT related proteins,AMPK-α and p-AMPK-α were detected by Western blot.Results Leptin promoted breast cancer cell mi-gration and invasion and EMT.ACSL5 was significant-ly low expressed in breast cancer and related to progno-sis.Leptin downregulated the expression of ACSL5 through OBR.Leptin activated AMPK pathway to downregulate ACSL5 and promote migration,invasion and EMT of breast cancer cells.Conclusions Leptin may promote the migration,invasion and EMT of breast cancer by downregulating ACSL5 through activating AMPK pathway.