BACKGROUND: Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China. METHODS: Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate. RESULTS: Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P  <0.05). CONCLUSIONS: This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics. REGISTRATION ClinicalTrials.gov , NCT03484806.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Heart Valve Diseases/therapy* ; Kaplan-Meier Estimate ; Tertiary Care Centers ; Treatment Outcome

Objective:To perform adenovirus detection and genetic evolutionary analysis on specimens from a fever outbreak in Kunming city.Methods:Pharyngeal swabs from typical febrile patients were collected and tested for nucleic acids of 30 common respiratory pathogens using TaqMan Array Card technology. The full-length sequences of three important genes of adenovirus, Penton base, Hexon and Fiber, were amplified, sequenced and typed using Nanopore high-throughput sequencing. A phylogenetic tree was constructed. Molecular variations and genetic evolution of the three genes were analyzed.Results:Five specimens were collected and all of them tested positive for adenovirus and Haemophilus influenzae. The sequences of the full-length coding regions of the Penton base, Hexon and Fiber genes were obtained by Nanopore sequencing. The homology of the three gene sequences in the five specimens was 100.0%, 99.9%-100.0% and 100.0% in nucleotide sequences, and 100.0% in amino acid sequences. The three genes in the specimens had the highest homology with those of the reference strain of human adenovirus type 3 (HAdV3, accession number: AY599834) in nucleotide sequences, which was 98.6%, 98.7% and 98.9%, respectively. Results of the phylogenetic analysis of the three genes were basically consistent. These Kunming strains were clustered into an independent clade with the reference HAdV3 strain and had a distant relationship with the strains isolated in foreign countries and Taiwan, China in the early years. They were closely related to the domestic and foreign strains in recent years and highly homologous to the 2019 Japanese strain (accession: LC703523) and the Guangzhou strain (accession: MZ540961). Compared with the reference strain, these Kunming strains had five amino acid variations in Penton base, 10 in Hexon and 11 in Fiber. Conclusions:All of the adenovirus strains isolated in this outbreak belong to P3H3F3 type based on the full-length sequences of Penton base, Hexon and Fiber genes. They share high homology with the domestic and foreign HAdV3 strains, including the reference strain. Compared with the reference strain, several amino acid mutations are identified in these Kunming strains, and most of them are in the high variability region or functional regions. M7L in the Hexon protein is an unique amino acid mutation site of Kunming strains.

Objective:To analyze the clinical characteristics, treatment, and prognosis of ectopic bronchogenic cysts in children.Methods:A retrospective analysis was conducted on the data including the clinical characteristics, auxiliary examination and treatment of 21 children with ectopic bronchogenic cysts diagnosed pathologically at Children′s Hospital Affiliated to Zhengzhou University from July 2015 to December 2023. There were 16 males and 5 females, with a male-female ratio of 3.2∶1, and the age ranged from 4 days to 8 years old (median age 2 years and 8 months).Results:Among the 21 cases of ectopic bronchogenic cysts, 11 cases were found in the pharynx, with symptoms including dyspnea (4 cases), snoring during sleep (3 cases), and choking on milk(4 cases).Ten cases were found in the head, neck or anterior chest, 5 of these cases had infection history, and 5 showed progressive mass growth.Imaging and endoscopy showed 9 patients underwent preoperative color ultrasonography revealed cystic masses with well-defined boundaries. CT examination was performed on 13 patients, which showed round or nearly round masses with homogeneous density, smooth margins, and regular cyst walls. CT attenuation values ranged from 2 to 52 Hounsfield Units (HU). Four cystic lesions were assessed via MRI, 3 cases demonstrated long T1 and long T2 signals, while 1 case had a slight short T1 and long T2 signal, with high signal intensity on fat-suppressed images. Eleven cases of pharyngopharyngeal cysts were examined by electronic nasopharyngoscopy. The cysts appeared as spherical or ovoid masses with smooth surfaces, close to or slightly light in color with the surrounding tissue, with one cyst presenting with a bluish blue in the oropharynx. All 11 pharyngeal cysts were excised using low-temperature plasma under general anesthesia and intubation assisted by a nasal endoscope. The cysts were pulled and excised as completely as possible.Ten cases of neck and anterior chest cysts were completely excised. Postoperative histopathology confirmed bronchogenic cyst. Twenty-one children were followed up postoperatively for 4 months to 7 years without recurrence, except for 1 patient who was lost to follow-up.Conclusions:Ectopic bronchogenic cysts are uncommon and lack of typical imaging and clinical features.Combination of ultrasonography, CT and MRI is recommended for cases occuered in neck and anterior chest, while electronic nasopharyngoscopy complements pharyngeal evaluations. Surgical intervention is the preferred treatment choice for this disease.

Objective To investigate the reliability and validity of the assessment tools of Brief ICF Core Sets for Arthroplasty of Knee Osteoarthritis in Perioperative Period(ICSAKOPP). Methods From May,2022 to April,2023,320 patients undergoing knee arthroplasty were selected in Peking University Third Hospital,China-Japan Friendship Hospital,Peking University First Hospital and Chinese PLA General Hospital.Trained assessors used Brief ICSAKOPP to evaluate all enrolled patients before arthroplasty,three days(±one day)after arthroplasty,three weeks(±one week)after arthroplasty,and three months(±one month)after ar-throplasty.Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores were recorded at the same time.Five professionals were asked to score all the items of Brief ICSAKOPP,and the content validity index(CVI)was caculated. Results A total of 64 cases were dropped down.CVI of all the items of the Brief ICSAKOPP were above 0.8,with a av-erage CVI of the scale of 0.938.The Cronbach's α coefficient of the Brief ICSAKOPP was 0.813.There was a moderate correlation(r=0.681,P<0.001)between the overall Brief ICSAKOPP and WOMAC scores,as well as body functional dimension score(r=0.668,P<0.001)and activities and participation dimension score(r=0.657,P<0.001). Conclusion Brief ICSAKOPP is good in content validity,internal consistency reliability and criterion validity.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the mechanism by which lectin-like oxidized low density lipoprotein receptor-1(LOX-1)regulates hyperglycemic-induced myocardial fibroblast(CFs)fibrosis through the glycogen synthase kinase-3β(GSK-3β)/signal transducer and activator of transcription 3(STAT3)pathway.Methods CFs were isolated,cultured and identified.LOX-1 RNAi lentiviral vector was constructed and infected CFs.The experimental groups were as follows:Normal control(NC)group,High glucose(HG)group,LV-LOX-1,LV-Con group,Hypertonic(HPG)group.After LV-LOX-1 and LV-Con were infected with CFs,adding 25 mmol/L glucose to culture CFs for 24 h,they were denoted as HG+LV-LOX-1 group and HG+LV-Con group.Cells in HG+LV-LOX-1 group and HG+LV-Con group were treated with 10 μ mol/L SB216763 and 10 μ mol/L STATTIC for 24 h,respectively,and then they were recorded as HG+LV-LOX-1+SB216763 group,HG+LV-Con+SB216763 group,HG+LV-LOX-1+STATTIC group and HG+LV-Con+STATTIC group.CCK-8 was used to detect the activity of CFs,and the expression levels of mRAN and protein of LOX-1,collagen type I(COL-I),thioredoxin 5(TXNDC5),GSK-3β,STAT3,p-GSK-3β and p-STAT3 were detected by qRT-PCR and Western blot.Results CFs infected with LOX-1 RNAi lentiviral vector were obtained,which showed green under fluorescence microscopy.Compared with HG and HG+LV-Con groups,the mRNA expressions of LOX-1,COL-I and TXNDC5 were decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,mRNA expressions of COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Compared with HG and HG+LV-Con groups,p-GSK-3β protein expression was increased in HG+LV-LOX-1 group(P<0.05),while LOX-1,p-STAT3,COL-I,TXNDC5 protein expression was decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,p-GSK-3β protein expression was increased in HG+LV-LOX-1+SB216763 group(P<0.05),while the protein expressions of p-STAT3,COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Conclusion LOX-1,GSK-3β,STAT3,TXNDC5,and COL-I are involved in high glucose induced CFs fibrosis.LOX-1 promotes the expression of TXNDC5 and COL-I through GSK-3β/STAT3 pathway,and inhibition of LOX-1 can inhibit high glucose induced CFs fibrosis.

ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of different concentration of rutin （3.125， 6.25， 12.5， 25， 50， 100， 200 μmol·L^-1） on 3T3-L1 cell activity， and Western blot to examine the effect of rutin （12.5， 25， 50 μmol·L^-1） on the expression of thermogenesis-associated proteins uncoupling protein 1 （UCP1）， PR domain containing 16 （PRDM16） and peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） in adipocytes. After the optimal concentration of rutin was determined， the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining， and the expression of nuclear respiratory factor 1 （NRF1）， nuclear respiratory factor 2 （NRF2） and mitochondrial transcription factor A （TFAM）， which were the landmark proteins of mitochondrial biosynthesis， was detected by Western blot. ResultCompared with the blank group， 200 μmol·L^-1 rutin inhibited 3T3-L1 cell activity （P<0.01）. Compared with the blank group， at the concentration of 12.5， 25， 50 μmol·L^-1 rutin significantly promoted the expression of thermogenesis-associated proteins （UCP1， PRDM16， and PGC-1α） （P<0.01）， which was determined as the optimal concentration. Compared with the blank group， 50 μmol·L^-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells （P<0.01） and the expression of the markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM） （P<0.01）. In addition， 50 μmol·L^-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes （P<0.01）. ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins （UCP1， PRDM16， and PGC-1α） and markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM）， thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.

ObjectiveTo explore the effects of after-school tutoring for school-age children on their emotions and behaviors， and to provide a basis for developing after-school tutoring and psychological support strategies for school-age children. MethodsFour elementary schools in a district of Shanghai were selected by simple random sampling method. Whole group sampling was conducted by class， and parents of students were surveyed by general questionnaire and the scale of strengths and difficulties. Information was collected on the basic conditions of children and families and the results were compared and analyzed. ResultsThis study showed that 88.26% of children attended extracurricular classes， of which 26.16% attended 3 or more classes， 42.5% attended cultural classes， 28.3% attended sports classes， and 59.8% attended art classes. Children who did not attend classes had higher pro-social scores. Children who attended reading class had lower scores for emotional problems that was a protective factor for emotional problems. Children who chose extracurricular programs in sports and reading also had lower overall scores for difficulties. Excessive use of electronic devices by school-age children on weekdays or weekends had a negative effect on emotional and conduct problem scores regardless of whether they chose extracurricular programs. It appeared that the choice of cultural programs， art programs and different levels of exercise intensity had no effect on children's emotions and behaviors. ConclusionFor children with low pro-social level， extracurricular classes should be carefully selected. For extracurricular classes， more reading and sports-related courses can be considered， which have positive effects on school-age children’s emotions and behaviors. Regardless of the choice of extracurricular classes， try to avoid excessive online classes.

The aberrant activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 （NLRP3） inflammasome as an essential component of the innate system is implicated in the pathogenesis of several human inflammatory diseases. Studies have confirmed its association with digestive system diseases such as ulcerative colitis， Crohn's disease， and acute pancreatitis， suggesting that the NLRP3 inflammasome plays a role in the initiation and progression of these diseases. Based on the mechanism of NLRP3 inflammasome activation and the pathways that mediate the inflammatory response， this article introduced the relationship between the NLRP3 inflammasome and the pathogenesis of multiple digestive system diseases and the Chinese and western medical therapies. Traditional Chinese medicine （TCM） has demonstrated definite effects on the NLRP3 inflammasome-mediated digestive system diseases. Some single Chinese medicines or TCM prescriptions can treat digestive system diseases by activating or inhibiting NLRP3 inflammasome activation. NLRP3 inflammasome can receive a variety of endogenous and exogenous stimulatory signals， which can initiate， activate， and mediate inflammatory responses. The inflammasome formation and downstream inflammatory cytokines are involved in not only the inflammatory responses but also the development and progression of multiple digestive system diseases. Therefore， the NLRP3 inflammasome can serve as an ideal target for disease treatment. The future rediscovery and in-depth studies of multiple inflammasomes will shed new light on the treatment of multiple digestive system diseases.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).