Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Approximately 300 million tons of plastic are produced globally each year,which has a serious impact on human health,marine life and the livestock industry.Microplastics have also been detected in meat and milk samples.Research has shown that nanoplastics(NP)(＜1 μm)and mi-croplastics(MP)(1 μm-5 mm)can affect the digestive,immune and reproductive systems of ani-mals.This experiment aims to investigate whether NP and MP regulate autophagy and damage the nervous system and spatial memory of animals.This experiment was divided into control group,nanoplastic group(PS-NP group,0.1 μm)and microplastic group(PS-MP group,1 μm),with 20 mice in each group.The mice were given 0.5 mL of PS-NP and PS-MP every day for 35 consecutive days,followed by neck amputation and brain analysis.The results showed that NPs and MPs of dif-ferent diameters caused varying degrees of damage to the brains of mice.In the behavioral tests of new object recognition,barnes maze and Y-shaped maze spatial memory,compared with the control group,the PS-NP group and PS-MP group showed a significant decrease in spatial memory ability of mice.HE staining results showed that neuronal cells in the PS-NP and PS-MP groups of mice exhibited shrinkage,decreased cell volume and deepened staining.The number of Nissl bodies de-creased,leading to dissolution and disappearance.RT-PCR and Western blot results showed that compared with the control group,the expression of glutamate receptors NR1,NR2A and NR2B in-creased in mice administered NP and MP orally,while the expression of autophagy related proteins Parkin,LC3B and Beclin1 was inhibited.In summary,this study suggests that nanoplastics and mi-croplastics stimulate glutamate receptors in mice by inhibiting the autophagy pathway,leading to impaired spatial memory.

Objective The clinical characteristics of 21 cases of nocardiosis were reviewed and antimicrobial resistance of Nocardia strains was analyzed in order to improve the accuracy of clinical diagnosis and treatment of nocardiosis.Methods Clinical data of patients diagnosed with nocardiosis in Zhoukou Central Hospital from 2019-2023 and the corresponding results of antimicrobial susceptibility testing were retrospectively analyzed to summarize the clinical characteristics and outcomes of patients.Results Overall,the 21 cases of nocardiosis included 9 males and 12 females,aged 2-91 years.Underlying disease was reported in 15 patients.Most common type of nocardiosis was pulmonary nocardiosis in 15 cases,followed by skin and soft tissue infection,pleurisy,lymphadenitis,and disseminated nocardiosis.Laboratory tests showed increased levels of WBC,neutrophils percentage,erythrocyte sedimentation rate,C-reactive protein,and procalcitonin.The 21 strains of Nocardia included 4 strains of Nocardia cyriacigeorgica,2 strains each of Nocardia brasiliensis,Nocardia abscessus,Nocardia asiatica,Nocardia otitidiscaviarum and Nocardia beijingensis,and 1 strain each of Nocardia puris,Nocardia asteroides,Nocardia farcinica,Nocardia pneumoniae,Nocardia amamiensis,and 2 strains of unclassified Nocardia.All of the Nocardia strains(100％)were susceptible to linezolid,amikacin,and trimethoprim-sulfamethoxazole,followed by various levels of susceptibility to cefotaxime,moxifloxacin,imipenem and ceftriaxone,and lower susceptibility rate to cefepime,minocycline,ciprofloxacin and clarithromycin.Antimicrobial susceptibility of Nocardia strains varied with different Nocardia species.Of the 21 patients,two were referred to other hospitals,another two died,two patients received unknown treatment,and the remaining 15 patients were improved after antibiotic treatment,including sulfonamides combined with other antibiotics in 11 cases,other antibiotics in 4 cases.Conclusions Immunocompromised patients or those with underlying diseases are more susceptible to nocardiosis.The clinical features are complex and diverse.Antimicrobial susceptibility of Nocardia strains varied with different Nocardia species.Accurate identification and antimicrobial susceptibility test are essential for prescribing effective antibiotic treatment.

Objective The clinical characteristics of 21 cases of nocardiosis were reviewed and antimicrobial resistance of Nocardia strains was analyzed in order to improve the accuracy of clinical diagnosis and treatment of nocardiosis.Methods Clinical data of patients diagnosed with nocardiosis in Zhoukou Central Hospital from 2019-2023 and the corresponding results of antimicrobial susceptibility testing were retrospectively analyzed to summarize the clinical characteristics and outcomes of patients.Results Overall,the 21 cases of nocardiosis included 9 males and 12 females,aged 2-91 years.Underlying disease was reported in 15 patients.Most common type of nocardiosis was pulmonary nocardiosis in 15 cases,followed by skin and soft tissue infection,pleurisy,lymphadenitis,and disseminated nocardiosis.Laboratory tests showed increased levels of WBC,neutrophils percentage,erythrocyte sedimentation rate,C-reactive protein,and procalcitonin.The 21 strains of Nocardia included 4 strains of Nocardia cyriacigeorgica,2 strains each of Nocardia brasiliensis,Nocardia abscessus,Nocardia asiatica,Nocardia otitidiscaviarum and Nocardia beijingensis,and 1 strain each of Nocardia puris,Nocardia asteroides,Nocardia farcinica,Nocardia pneumoniae,Nocardia amamiensis,and 2 strains of unclassified Nocardia.All of the Nocardia strains(100％)were susceptible to linezolid,amikacin,and trimethoprim-sulfamethoxazole,followed by various levels of susceptibility to cefotaxime,moxifloxacin,imipenem and ceftriaxone,and lower susceptibility rate to cefepime,minocycline,ciprofloxacin and clarithromycin.Antimicrobial susceptibility of Nocardia strains varied with different Nocardia species.Of the 21 patients,two were referred to other hospitals,another two died,two patients received unknown treatment,and the remaining 15 patients were improved after antibiotic treatment,including sulfonamides combined with other antibiotics in 11 cases,other antibiotics in 4 cases.Conclusions Immunocompromised patients or those with underlying diseases are more susceptible to nocardiosis.The clinical features are complex and diverse.Antimicrobial susceptibility of Nocardia strains varied with different Nocardia species.Accurate identification and antimicrobial susceptibility test are essential for prescribing effective antibiotic treatment.

Approximately 300 million tons of plastic are produced globally each year,which has a serious impact on human health,marine life and the livestock industry.Microplastics have also been detected in meat and milk samples.Research has shown that nanoplastics(NP)(＜1 μm)and mi-croplastics(MP)(1 μm-5 mm)can affect the digestive,immune and reproductive systems of ani-mals.This experiment aims to investigate whether NP and MP regulate autophagy and damage the nervous system and spatial memory of animals.This experiment was divided into control group,nanoplastic group(PS-NP group,0.1 μm)and microplastic group(PS-MP group,1 μm),with 20 mice in each group.The mice were given 0.5 mL of PS-NP and PS-MP every day for 35 consecutive days,followed by neck amputation and brain analysis.The results showed that NPs and MPs of dif-ferent diameters caused varying degrees of damage to the brains of mice.In the behavioral tests of new object recognition,barnes maze and Y-shaped maze spatial memory,compared with the control group,the PS-NP group and PS-MP group showed a significant decrease in spatial memory ability of mice.HE staining results showed that neuronal cells in the PS-NP and PS-MP groups of mice exhibited shrinkage,decreased cell volume and deepened staining.The number of Nissl bodies de-creased,leading to dissolution and disappearance.RT-PCR and Western blot results showed that compared with the control group,the expression of glutamate receptors NR1,NR2A and NR2B in-creased in mice administered NP and MP orally,while the expression of autophagy related proteins Parkin,LC3B and Beclin1 was inhibited.In summary,this study suggests that nanoplastics and mi-croplastics stimulate glutamate receptors in mice by inhibiting the autophagy pathway,leading to impaired spatial memory.

Objective To understand the real experience of kinesiophobia in patients after bone transport technique,providing references for taking targeted nursing interventions to alleviate kinesiophobia of patients.Methods Purposive sampling method was employed to select 15 patients who underwent bone transport technique in the Department of Traumatic Orthopedics in a tertiary A hospital in Guangdong Province from October to December 2023 as the research subjects.Phenomenological research method was utilized to conduct semi-structured interviews with the patients,and Colaizzi 7-step analysis method was applied for data analysis and theme extraction.Results A total of 3 themes and 11 sub-themes were extracted,including the existence of negative psychological experience(fear and concern regarding exercise,excessive alarm in response to pain,helplessness and sadness about the change of life,persistent reflection on past experiences,anxiety and confusion about the future),facing the dilemma of physiological symptoms(pain and discomfort,fatigue and disturbed sleep),taking diversified coping approaches(selecting avoidance strategies,conducting self-adjustment,seeking kinesiophobia related knowledge and exercise guidance,acquiring social support).Conclusion The experience of kinesiophobia in patients after bone transport technique is complex and varied.Medical and nursing staff should prioritize the psychological relief of patients after bone transport technique,pay attention to the assessment and management of kinesiophobia related symptom,provide professional guidance and assist with multi-dimensional support to help patients reduce the experience of kinesiophobia and promote recovery of patients.

Pyroptosis is a programmed death of inflammatory cells triggered by pathogen invasion,dependent on caspase activation,through both classical and non-classical pyroptosis pathways.Cell pyroptosis is related to the occurrence and development of a variety of animal infectious diseases caused by microbial infection.After microorganisms invading,cells are stimulated by pathology-re-lated molecular patterns,causing strong immune response,stimulating inflammatory signaling pathways,and then activating inflammasome,leading to pyroptosis.The immune system has e-volved multiple mechanisms to fight microbial infections and regulate inflammatory responses.The innate immune system,by recognizing microbial molecules in pathogens and responding quickly by producing inflammasome and activating pyroptosis,helps clear pathogens to prevent infection and maintain the normal functioning of the body.A thorough study of the pathogenesis and immune es-cape mechanism of cell pyroptosis in animal infectious diseases will provide a new direction for the treatment of animal infectious diseases.

Objective:To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021.Methods:The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis.Results:A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M ( Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m 2 and baseline CD4 +T lymphocyte (CD4) counts <200 cells/μl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m 2 and baseline CD4 counts ≥200 cells/μl were more likely to have complete immune reconstitution. Conclusions:In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.

BackgroundPatients with schizophrenia are at high risk of suffering from metabolic syndrome. Most previous studies on the influencing factors of metabolic syndrome focused on the inpatients and limited ones on patients dwelling in community. ObjectiveTo explore the influencing factors at different risk levels of metabolic syndrome in community-dwelling patients with schizophrenia in Guangzhou， so as to provide references for future interventions on metabolic syndrome in this patient population. MethodsIn November 2021， 3 339 patients with schizophrenia who were registered in and administered by Guangzhou Mental Health Information System were included. All these patients had finished the physical examination in 2020， and whether they had metabolic syndrome was assessed basing on Guideline for the prevention and treatment of type 2 diabetes mellitus in China （2020 edition）. Patients were divided into high-risk group （n=423）， critical group （n=1 524） and metabolic syndrome group （n=1 392） according to the Chinese expert consensus on the management of metabolic syndrome in patients with schizophrenia. Multiple logistic regression analysis were performed on the risk factors of metabolic syndrome in community-dwelling patients with schizophrenia. ResultsThe prevalence rate of metabolic syndrome in community-dwelling patients with schizophrenia was 41.69%. Univariate analysis showed that the results in gender （χ²=44.610）， age （χ²=55.992）， marriage status （χ²=30.755）， illness course （χ²=25.913） and body mass index （χ²=829.265） were significantly different among the three groups （P<0.01）. Kruskal-Wallis H test showed that the levels of waist circumference （H=920.331）， systolic blood pressure （H=436.673）， diastolic blood pressure （H=393.337）， fasting blood glucose （H=807.304）， triglyceride （H=1 134.125） and high-density lipoprotein cholesterol （H=593.615） among the three groups were significantly different （P<0.01）. Logistic regression analysis showed that age ≥50 （OR=1.761， 95% CI： 1.087~2.853）， overweight （OR=2.418， 95% CI： 1.862~3.140） and obesity （OR=57.903， 95% CI： 14.340~233.802） were risk factors contributing to high-risk patients becoming critical population （P<0.05 or 0.01）. Female gender （OR=1.295， 95% CI： 1.034~1.622）， aged 40~49 （OR=2.597， 95% CI： 1.582~4.263）， age ≥50 （OR=4.392， 95% CI： 2.609~7.395）， overweight （OR=7.844， 95% CI： 6.018~10.223） and obesity （OR=426.785， 95% CI： 105.724~1 722.839） were risk factors for high-risk patients developing into metabolic syndrome population （P<0.05 or 0.01）. ConclusionThe prevalence rate of metabolic syndrome is higher in community-dwelling patients with schizophrenia. Female gender， older age， overweight and obesity would increase the risk of metabolic syndrome in schizophrenic patients. ［Funded by Health Science and Technology Project in Guangzhou （number， 20221A010028）］