Objective: To explore the impact of household tobacco smoke exposure on adolescents attempted smoking behavior, so as to provide a reference for tobacco control policy formulation and evaluation. Methods: From September to November 2023, a stratified cluster random sampling method was employed to select 7 841 middle and high school students from 10 monitoring sites (districts/counties) in Beijing for a questionnaire survey. Rao-Scott Chi square test was used to assess differences in proportions across subgroups, and complex sampling design based multivariate Logistic regression analysis was conducted to explore the influence of parental smoking and secondhand smoke (SHS) exposure at home on adolescents attempted smoking behavior. Results: About 47.17% of adolescents reported to have at least one parent smoked, with 42.36% reported of having only the father smoked, 0.73% reported of having only the mother smoked, and 4.08% reported of having both parents smoked. About 34.66% of middle and high school students were reported SHS exposure at home in the past 7 days, with 10.98%, 4.79% and 18.89% reported SHS exposure for 1-2, 3-4 and 5-7 days. Compared to adolescents with non smoking parents, those with a smoking father or both smoking parents had higher rates of attempted smoking [ OR (95% CI )=1.45(1.06-1.98), 3.73(2.18-6.37), P < 0.05 ]. Compared to adolescents without SHS exposure at home in the past 7 days, those exposed for 3-4 or 5- 7 days had higher rates of attempted smoking [ OR (95% CI )=2.21(1.27- 3.84 ), 2.46(1.58-3.83), P <0.01]. Conclusions Household tobacco smoke exposure is associated with adolescent attempted smoking behavior. Parents should quit smoking and prohibit smoking at home to create a smoke free environment for adolescents.

Objective:To systematically evaluate the effect of singing therapy on patients with chronic obstructive pulmonary disease.Methods:Randomized controlled trials on the effect of singing therapy in patients with chronic obstructive pulmonary disease were searched by computer from PubMed, Web of Science, Cochrane Library, CINAHL, Embase, China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, and VIP. The search period was from the establishment of databases to June 30, 2023. Two researchers independently screened literature, performed a literature quality assessment, and extracted data. Meta-analysis was performed using RevMan 5.4 software.Results:A total of 11 articles were included. Meta-analysis showed that singing therapy for 10 weeks or more could improved anxiety ( MD=-5.01, 95% CI: -5.76~-4.25, P<0.001), and depression ( MD=-4.73, 95% CI: -8.82~-0.64, P=0.020). Singing therapy with a duration of less than 60 min per session and/or five interventions per week or more could improve FEV 1% predicted values ( MD=9.46, 95% CI: 7.66~11.26, P<0.001) in patients with chronic obstructive pulmonary disease. Conclusions:Singing therapy is best achieved at least five times a week, with each session lasting less than 60 minutes and lasting for at least ten weeks. However, more high-quality, multicenter and large sample studies are still needed for further validation.

Objective:To investigate regulatory effect and mechanism of protein kinase C(PKC)δ/θ-dual functional oxidase 1(Duox1)-reactive oxygen species(ROS)signaling pathway on human airway mucin(MUC)5AC,to provide a new target for treatment of high secretion of airway mucus.Methods:Human airway epithelial cells 16HBE were pretreated with PKC and its subunit PKCδ/θ inhibitor,Duox1 inhibitor or free radical scavenger DMTU,respectively,and then human neutrophil elastase(HNE)stimulation to establish an in vitro airway inflammatory cell model.Generation level of ROS in each group of cells was determined by kit,mRNA levels of Duox1 and MUC5AC were detected by real-time fluorescent quantitative PCR,influence of interfering factors of each group of cells on Duox1 protein level was determined by Western blot,and protein expression of MUC5AC in each group of cells was detected by ELISA and immunofluorescence.Results:Compared with control group,ROS production in HNE group was increased significantly,expressions of Duox1 and MUC5AC mRNA and protein were also increased(P<0.05).After administration of Duox1 inhibitors,free radical scavengers or PKC inhibitors and PKCδ/θ inhibitors,ROS production was significantly inhibited,Duox1 and MUC5AC mRNA and protein expressions were decreased(P<0.05),while after giving PKCα/β,ROS generation,Duox1 and MUC5AC mRNA and pro-tein expressions were not significantly changed compared with HNE group(P>0.05).Conclusion:HNE can mediate high expression of MUC5AC through PKCδ/θ-Duox1-ROS,which plays an important role in development of high secretion of airway mucus in vitro cell model experiment.

Objective:To retrieve, evaluate, and summarize relevant evidence on remote pulmonary rehabilitation programs for patients with Chronic Obstructive Pulmonary Disease (COPD) .Methods:Following the 6S Pyramid Evidence Model, domestic and international guideline websites, evidence-based databases, association websites, and original databases were systematically searched for literature related to remote pulmonary rehabilitation for patients with COPD, including guidelines, expert consensus, evidence summaries, clinical decisions, practice recommendations, systematic reviews, and randomized controlled trials. The search was conducted from the databases' inception to July 31, 2023. Quality assessment and data extraction were independently conducted by two researchers.Results:A total of 27 articles were included, including five guidelines, one clinical decision, four evidence summaries, one expert consensus, 14 systematic reviews, and two randomized controlled trials. A total of 27 best evidence recommendations were synthesized across seven aspects, including setting, target population, pre-intervention preparation, communication devices, remote pulmonary rehabilitation programs, maintenance exercise plans, and remote health monitoring.Conclusions:The process of forming the best evidence for remote pulmonary rehabilitation programs for patients with COPD is comprehensive and scientific. Healthcare professionals should integrate evidence-based practice with patient preferences to develop personalized remote pulmonary rehabilitation programs according to individual circumstances.

Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

Objective:To explore the application of 18F-flurodeoxyglucose positron emission tomo-graphy/computed tomography(18F-FDG PET/CT)in rheumatic diseases,to compare these different ima-ging features,and to describe the current PET/CT imaging status in clinical practice.Methods:A total of 486 cases in our department from January 2012 to December 2018 were enrolled in this study,and 18 F-FDG PET/CT examination was performed in all the patients.The clinical use of 18F-FDG PET/CT was retrospectively analyzed to discuss the clinical application and its imaging characteristics of rheumatic diseases.Categorical data were used to ascertain prevalence statistics,whereas continuous data were used to delineate means and standard deviations.Independent sample t test,Chi square test and Mann-Whit-ney U test were used for statistical analysis.A P-value of＜0.05 was considered significant.Results:(1)From 2012 to 2018,totally 486 patients in the Department of Rheumatology and Immunology under-went18F-FDG PET/CT examination,accounting for 5.30％of the total number of PET/CT examinations in the whole hospital.In this study,304 of the 486 patient were female(62.55％),182 of them were male(37.45％),the average age of the patients was(53.21±18.81)years,and the proportion of the patients aged 45-65(227/486,46.71％)was the highest group.(2)Three leading purposes of the PET/CT examination in our department were to exclude cancers(55.56％),assist in diagnosis(24.60％)and evaluate the disease activity(19.84％).(3)Of the 486 patients who underwent 18F-FDG PET/CT,327 cases might indicate a differential diagnosis of rheumatic disease,of which,292 ca-ses were highly suggestive of diagnosis,including 61 cases of myositis,60 cases of vasculitis,37 cases of adult still's disease,32 cases of IgG4 related diseases,30 cases of rheumatoid arthritis,22 cases of Sj?gren's syndrome,22 cases of systemic lupus erythematosus,and 9 cases of rheumatic polymyalgia;the remaining 35 cases only prompted the possibility of autoimmune disease.Of the 486 patients,74 ca-ses suggested the diagnosis of cancers,25 cases indicated the diagnosis of infectious diseases,while 60 cases could not show any diagnostic values.Ten patients with rheumatic disease were followed up with a post-treatment repeat PET/CT,and the findings in remission showed reduced 18F-FDG metabolic activity as well as a reduction in the extent of metabolic hypertrophic lesions.Conclusion:There are some typi-cal sign of 18F-FDG PET/CT for diffuse connective tissue diseases,therefore 18F-FDG PET/CT has auxi-liary effect on the classification diagnosis of rheumatic diseases,especially for the exclusion of cancers.

Objective:To discuss the damage effect of vesicular stomatitis virus(VSV)on the vascular endothelial(VE)barrier,and to clarify its mechanism.Methods:The canine kidney cells were used to amplify VSV.The half tissue culture infective dose(TCID50)of VSV was determined using mouse brain endothelial tumor bEnd.3 cells,and subsequent experiment was conducted using 300 times the TCID50.The bEnd.3 cells were divided into infection 0 h group,infection 4 h group,infection 8 h group,and infection 12 h group for VE barrier damage experiments due to VSV infection.The bEnd.3 cells were also divided into control group,infection group,and correction group for experiments to inhibit the VSV replication and restore the VE barrier.The bEnd.3 cells were inoculated into Transwell chambers to construct an in vitro VE barrier model.Cell voltage resistance meter was used to detect the transepithelial resistance(TER)in various groups after the bEnd.3 cells were infected with VSV at different time points;fluorescein isothiocyanate-dextran leakage assay was used to detect the permeability coefficients of the cells in various groups;immunofluorescence staining was used to observe the localization changes of VE-cadherin,β-catenin,and phosphorylated β-catenin(p-β-catenin)in cytoskeleton and adherens junctions(AJs)of the bEnd.3 cells after VSV infection;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Wnt and β-catenin mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Wnt,β-catenin,and p-β-catenin proteins in the cells in various groups.Results:The TCID50 of VSV was 10-4.5·100 μL-1.TheTranswell chamber experiment results showed that compared with infection 0 h group,the TERs in the cells in the other groups were significantly decreased(P＜0.05),and the permeability coefficients were significantly increased(P＜0.05).The immunofluorescence staining results showed that compared with control group,the cytoskeleton of the bEnd.3 cells in infection group was disordered,the cell gaps was increased,the linear index of AJs was significantly decreased(P＜0.05),and β-catenin and p-β-catenin translocated from the cell membrane to the perinuclear area.The RT-qPCR results showed that compared with infection 0 h group,the expression levels of Wnt mRNA in the cells in the other groups were significantly decreased(P＜0.05),while the expression levels of β-catenin mRNA showed no statistically significant difference(P＞0.05).The Western blotting results showed that compared with infection 0 h group,the expression levels of Wnt protein in the cells in the other groups were significantly decreased(P＜0.05),the expression levels of β-catenin showed no statistically significant differences(P＞0.05),and the expression levels of p-β-catenin were significantly increased(P＜0.05).After inhibiting the VSV replication and correcting the low density lipoprotein receptor(LDLR)abnormalities,the Transwell chamber experiment results showed that compared with infection group,the TER in the cells in correction group was significantly increased(P＜0.05),and the permeability coefficient was significantly decreased(P＜0.05).The immunofluorescence staining results showed that compared with infection group,the gaps in the cells in correction group were reduced,and the perinuclear aggregation of β-catenin and p-β-catenin in the cells was restrained.The RT-qPCR results showed that compared with infection group,the expression level of Wnt mRNA in the cells in correction group was significantly increased(P＜0.05).The Western blotting results showed that compared with infection group,the expression level of Wnt protein in the cells in correction group was significantly increased(P＜0.05),the expression level of β-catenin showed no statistically significant difference(P＞0.05),and the expression level of p-P-catenin was significantly decreased(P＜0.05).Conclusion:VSV infection can cause the LDLR inactivation,reduce the expression level of Wnt protein,increase the phosphorylation level of β-catenin and cause its internalization,disrupt the stability of AJs,and ultimately lead to VE barrier damage.

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

In the face of DNA damage caused by various factors, cells have a set of response and repair mechanisms. Cell cycle arrest plays an important role in the DNA damage repair, which provides enough time for repairing damaged DNA. Research on cell cycle regulation focuses on cyclin-dependent protein kinases (CDKs) and cell cycle checkpoints. In the process of DNA damage repair, phosphatidylinositol-3-kinase like kinases (PIKKs) which are recruited to the DNA damage sites can activate cell cycle checkpoint-related proteins to halt cell cycle. In the common DNA damage repair pathways, such as base excision repair (BER), nucleotide excision repair (NER) , mismatch repair (MMR) , and DNA double-strand break repair, the recruitment of repair-related proteins also plays a role in the cell cycle regulation. In this paper, the relationship between the main forms of DNA damage repair and cell cycle arrest and relevant research progress were reviewed.

Objective: To investigate the molecular genetic and clinicopathologic characteristics, immunophenotypes, diagnostic and differential diagnostic features of myxoid angiomatoid fibrous histiocytoma (MAFH). Methods: Three cases of MAFH were collected from the archives of Zhejiang Provincial People′s Hospital between January 2015 to August 2018. The clinical and radiologic features, histomorphology, immunohistochemistry, molecular genetics and prognosis were analyzed. Results: Patients consisted of 2 women and 1 man aged 37 years, 46 years, and 57 years, respectively. The clinical manifestations of 3 patients were presented as a painless, slowly-enlarged mass with a duration ranging of 2 weeks, 2 months and 50 years. These tumors were located at the deep somatic soft tissue of extremities or limbs (right hip, left forearm, left wrist, respectively) and 2 were preoperatively considered as ganglion cyst or giant cell tumor of tendon sheath by imaging examinations. The diameter of circumscribed mass lesion was ranged from 3.0 to 7.5 cm, which exhibited a gray white to tan and gelatinous cut surface. Extensive hemorrhage and cystic changes were observed in 2 cases. Under low magnification, all tumors showed a dense fibrous pseudo-capsule with a peritumoral lymphoplasmacytic cuff and a multi-nodular growth pattern. Blood-filled cystic spaces were observed in 2 tumors. The myxoid stroma occupied 60.0%, 80.0% and 90.0% area of the entire tumor, respectively. Within the myxoid areas, tumor cells were oval to stellate and arranged in cord-like, microcystic and reticular growth patterns. Transitions of myxoid tumor components to more solid areas with typical histology of angiomatoid fibrous histiocytoma (AFH) were observed at least focally in all the three cases. The tumor cells exhibited minimal atypia and scarce mitoses (1 to 2/50 HPF) without necrosis, and prominently focal intracytoplasmic vacuoles were identified in one case. The results of immunohistochemistry staining showed that, 2/3 cases focally expressed desmin, 2/3 focally expressed epithelial membrane antigen (EMA), and 1/3 focally expressed CD99. The positive index of Ki67 was approximately 1% to 5%. Fluorescence in situ hybridization analysis showed that EWSR1 gene rearrangement occurred in all of the three cases. During the period of follow-up, one case showed local recurrence at 15 months, one case showed postoperative recurrence at 24 months, and the recurrent tumor slowly grew for 120 months until the second resection, without recurrence at the following 2 months. The left case showed a disease-free survival at 32 months. Conclusions MAFH is a rare subtype of AFH with a low-grade behavior and may lead to diagnostic confusions. Carefully searching for the typical AFH histomorphology and combining with EWSR1 gene rearrangement test can help to distinguish MAFH from other mimickers.