OBJECTIVE:Neuromuscular exercise is a new comprehensive rehabilitation therapy in recent years,but its effect on knee osteoarthritis is still controversial.The purpose of this paper is to systematically evaluate the efficacy of neuromuscular exercise on knee osteoarthritis pain and function. METHODS:The randomized controlled trials addressing neuromuscular exercise in the treatment of knee osteoarthritis pain and function were retrieved from PubMed,Cochrane Library,Embase,EBSCO,CNKI,Web of Science,China Biomedical Database(CBM),VIP,and WanFang Database.The retrieval time ranged from database inception to October 2023.The neuromuscular training group(experimental group)was given neuromuscular training or neuromuscular training as the main intervention;the control group was a blank group or given conventional rehabilitation.Outcome indicators included the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,walking time,knee stability,and the maximum number of knee flexion in 30 seconds.The risk of bias was evaluated by the Cochrane Collaboration tool and the Physiotherapy Evidence Database.Meta-analysis was performed using RevMan 5.4 software. RESULTS:A total of 11 randomized controlled trials were included,and 628 samples were extracted.The results of Meta-analysis showed that the experimental group was superior to the control group in terms of WOMAC pain score[standardized mean difference(SMD)=0.38,95%confidence interval(CI):0.08-0.69,P=0.01],knee stability(SMD=0.57,95%CI:0.23-0.92,P=0.001),the maximum number of knee joint flexion in 30 seconds(SMD=0.35,95%CI:0.05-0.65,P=0.02),and WOMAC physical function score(SMD=-0.79,95%CI:-1.30 to-0.28,P=0.002).In both groups,walking speed was increased and walking ability was improved in patients with knee osteoarthritis,but there was no significant difference(walking time:SMD=-0.22,95%CI:-0.48-0.03,P=0.09). CONCLUSION:Neuromuscular exercise can effectively improve knee joint pain,enhance the stability of the knee joint,and promote functional recovery in patients with knee osteoarthritis.However,more high-quality randomized controlled trials are still needed to further confirm the research.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Objective: To understand the current situation and influencing factors of comorbidity of depressive and anxiety symptoms among middle school students in Chongqing, so as to provide a scientific basis for formulating a comprehensive strategy for the co prevention of multiple diseases among middle school students. Methods: From September to December 2024, 12 327 middle school students were selected from 6 districts and counties in Chongqing by the combination of stratified cluster sampling and convenience sampling method. The current status of depressive and anxiety symptoms was investigated by using the Center for Epidemiological Survey-Depression Scale (CES-D) and the Generalized Anxiety Disorder-7 (GAD-7). The Chi-squared test was used to compare the differences between groups with comorbidity of depressive and anxiety symptoms, multivariate Logistic regression analysis was used to analyze its related factors, and a nomogram prediction model was drawn. Results: The detection rates of depressive symptoms, anxiety symptoms and comorbidity among middle school students in Chongqing were 26.34%, 34.55% and 21.16%, respectively. Among them, the detection rates of the three types of symptoms in girls (29.80%, 40.99%, 25.15%) were all higher than those in boys (23.22%, 28.73%, 17.55%) ( χ 2=68.61, 204.23, 106.51, all P <0.01). Statistical significance was observed in the distribution of depressive and anxious symptoms among middle school students across different gender, academic stage, school district, family type, physical activity levels, parental discipline, smoking, alcohol consumption, sleep deprivation, excessive screen time, Internet addiction, and bullying ( χ 2=14.49-991.46, all P <0.01). Multivariate Logistic regression analysis showed that compared with junior high school students, ordinary high school students had a higher risk of comorbidity ( OR=2.71, 95% CI = 2.41-3.05); girls ( OR=2.17, 95%CI =1.95-2.40), non-core family ( OR=1.20, 95%CI =1.08-1.32), and good neighborhood ( OR=1.16, 95%CI =1.02-1.30), campus bullying ( OR=4.88, 95%CI =4.32-5.50), Internet addiction ( OR=4.77, 95%CI = 3.41 -6.68), parental beating and scolding ( OR=3.18, 95%CI =2.72-3.71), alcohol consumption ( OR=2.10, 95%CI =1.86- 2.37 ), and insufficient sleep ( OR=1.73, 95%CI =1.54-1.95) had higher risks with comorbidity of depression and anxiety symptoms (all P <0.05). A nomogram prediction model was constructed based on significant variables shows that C-index=0.75 (AUC= 0.75 , 95% CI=0.74-0.76, P <0.05), and the model had good predictive performance. Conclusions The current situation of comorbidity of depressive and anxiety symptoms among middle school students in Chongqing is not optimistic. The nomograms can be used to effectively predict the risk of comorbidity of depressive and anxiety symptoms in middle school students.

OBJECTIVES: To investigate the etiological characteristics of bacterial meningitis (BM) in infants aged <90 days. METHODS: A retrospective analysis was conducted on the etiology and outcomes of BM in infants aged <90 days admitted to five collaborating hospitals between January 2007 and December 2021. The overall etiological profile was described, and pathogen distributions were compared across different age groups, regions, and years. The prognosis of BM caused by common pathogens was also evaluated. RESULTS: A total of 197 infants with bacteriologically confirmed BM were included. The most common pathogens were Escherichia coli (E. coli) (72 cases, 36.5%), group B Streptococcus (GBS) (49 cases, 24.9%), and Listeria monocytogenes (LM) (11 cases, 5.6%). The detection rate of E. coli was significantly higher in the neonatal group than in the infant group (40.2% vs 18.2%, P<0.05). E. coli was the predominant pathogen in Beijing (31.7%) and Kunming (54.1%), while GBS and E. coli were equally prevalent in Shenzhen (33.3%). From 2018 to 2021, the detection rates of E. coli were 46.4%, 47.2%, 45.2%, and 36.8%, respectively, whereas those of GBS were 25.0%, 27.8%, 22.6%, and 31.6%. No significant difference was observed in the overall complication rates among BM cases caused by E. coli, GBS, and LM (P>0.05). However, ventriculitis and hydrocephalus were more frequent in LM meningitis than in GBS meningitis (P<0.017). CONCLUSIONS E. coli is the most common pathogen in BM among young infants, particularly neonates. GBS is predominant in Shenzhen, with an increasing trend. LM meningitis accounts for a notable proportion of cases and is associated with poorer outcomes.
Humans ; Meningitis, Bacterial/microbiology* ; Infant ; Retrospective Studies ; Infant, Newborn ; Male ; Female

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective: To understand the current situation of academic burnout among primary and middle school students and to explore its associated factors, so as to provide a scientific guidance and preventing and amelioration academic burnout among primary and middle school students. Methods: Between September and October 2023, a total of 10 474 primary and middle school students residing in Wuxi City participated in a questionnaire survey and physical examination conducted through stratified cluster random sampling. Latent profile analysis was used to classify academic burnout among primary and middle school students. Furthermore, differences in the types of academic burnout among children and adolescents with varying characteristics were examined using the Chi square test. Additionally, multinomial Logistic regression analysis was utilized to identify the associated factors for academic burnout. Results: The academic burnout of primary and middle school students was divided into 4 categories:no/light academic burnout group(43.6%),physical and mental exhaustion group (32.9%), low achievement group(15.0%), high physical and mental exhaustion/high academic burnout group(8.5%). Middle and high school students, boys, not living with parents, smoking, daily screen time ≥2 hours, suffering from campus bullying, sometimes/often subjected to cyber attacks, abused by parents were more likely to have high physical and mental exhaustion/high academic alienation among primary and middle school students ( OR=1.70, 1.42, 1.56, 1.56, 2.31, 1.48, 2.94, 3.03, 5.94, 2.08, P <0.01). Conclusions The phenomenon of academic burnout among primary and middle school students is prominent. And targeted intervention measures shoould be actively taken to prevent and reduce the occurrence of academic burnout among primary and middle school students.

Objective:To explore the influencing factors of left ventricular thrombus (LVT) in patients with non-ischemic heart failure (NIHF) and to construct a nomogram prediction model for NIHF patients with LVT.Methods:This study was a case-control study. A total of 2 592 patients with NIHF hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2018 to July 2022 were selected. Fifty-one patients with LVT identified by echocardiography and cardiac magnetic resonance were classified into LVT group. One hundred and sixty patients were selected as the non-LVT group using a 1∶3 propensity score matching based on age and gender. Multivariate logistic regression analysis was used to explore the influencing factors of LVT in patients with NIHF. A nomogram prediction model was constructed, and the area under (AUC) the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive effect of the model.Results:A total of 211 patients were enrolled, with a median age of 40 years old and 160 males (76%). Compared with non-LVT group, LVT group had lower systolic blood pressure ((112±20) mmHg vs. (120±19) mmHg; 1 mmHg=0.133 kPa), lower left ventricular ejection fraction (LVEF; (27±12)% vs. (39±14)% ), lower proportion of patients with history of hypertension (28% (14/51) vs. 44% (70/160)) and atrial fibrillation (8% (4/51)vs.39% (62/160)), higher proportion of patients with New York Heart Association functional class Ⅲ to Ⅳ (class Ⅲ: 59% (30/51) vs. 41% (66/160); class Ⅳ: 28% (14/51) vs. 19% (31/160)), and larger left ventricular end-systolic diameter (LVESD; (56±14) mm vs. (50±15) mm). The levels of hemoglobin ((152±23) g/L vs. (142±30) g/L), D-dimer (508 (300, 1 105) μg/L vs. 158 (68, 379) μg/L), and N-terminal pro-brain natriuretic peptide (3 429 (2 462, 4 734) ng/L vs. 1 288 (422, 2 544) ng/L) were higher in LVT group than in non-LVT group ( P all<0.05). LVT group had a higher proportion of patients using beta-blockers (92% (47/51) vs. 78% (124/160)), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (88% (45/51) vs. 72% (115/160)), and anticoagulant drugs (98% (50/51) vs. 32% (51/160)) than non-LVT group (all P <0.05). Multivariate logistic regression showed that reduced LVEF ( OR=1.08, 95% CI 1.02-1.15, P=0.008), decreased LVESD ( OR=1.07, 95% CI 1.01-1.12, P=0.013), and increased D-dimer levels ( OR=5.40, 95% CI 1.98-14.74, P=0.001) were independent influencing factors for LVT in patients with NIHF. The ROC curve showed that the AUC of the nomogram for predicting LVT in patients with NIHF was 0.793 (95% CI 0.710-0.876, P<0.001). Conclusion:Reduced LVEF, decreased LVESD, and elevated D-dimer are associated with LVT in NIHF patients. The predictive model developed based on the above indicators has certain value in predicting LVT in NIHF patients.

Objective To evaluate the effect of acupuncture at Yin Wei point on postoperative nausea and vomiting(PONV)in female patients undergoing abdominal surgery.The clinical efficacy of postoperative nausea and vomiting(PONV)and its impact on gut microbiota.Methods This study included 184 patients who underwent gynecological laparoscopic surgery in Jinhua Central Hospital from January 2021 to April 2024.They were randomly divided into control group(n=93)and acupuncture group(n=91)using a random number method.At the completion of surgery,the control group received intravenous injection of 5mg of tropisetron hydrochloride.In acupuncture group,on the basis of control group,intervention was performed by needling the palmar Yin Wei points of both forearms for 30 minutes before surgery.The incidence and severity of PONV were compared between two groups of patients.In addition,fecal samples were collected from two groups of patients before and after surgery,and differential analysis of gut microbiota community structure was performed using 16S amplicon absolute quantitative sequencing technology.Results In the 0-24 hours after surgery,40 cases of the acupuncture group and 56 cases of control group experienced PONV.The acupuncture group's PONV incidence was lower than control group's(P＜0.05).The nausea severity of acupuncture group after surgery was significantly lower than that of control groups.The proportion of patients taking antiemetic drugs after surgery in acupuncture group was also significantly lower than that in control group(P＜0.05).Before surgery,the two groups have no significant difference regarding Chao1,ACE,Shannon,and Simpson indices(P＞0.05).After surgery,the acupuncture group's Chao1,ACE,and Shannon indices were significantly higher than control group's(P＜0.05).The Simpson scores of two groups of patients were compared after surgery,and no significant difference was found(P＞0.05).The Observed,Chao1,ACE,and Shannon indices were significantly higher in the acupuncture group after surgery than before(P＜0.05).The incidence of adverse reactions in acupuncture group and control group were 8.8％and 8.6％,respectively,and there was no statistical significance(P＞0.05).Conclusion Acupuncture at Yin Wei point combined with intravenous injection of tropisetron can reduce the incidence of PONV in patients undergoing gynecological laparoscopic surgery.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.