Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

OBJECTIVE To analyze the investigation and handling process of a suspected outbreak of hospital-ac-quired Serratia marcescens infection in the Neonatal Intensive Care Unit(NICU)of a certain hospital,and to pro-vide valuable reference for the prevention and control of hospital-acquired infections.METHODS An epidemiologi-cal investigation was conducted on three S.marcescens-positive neonates admitted to the NICU of the Affiliated Hospital of Guizhou Medical University from Oct.12 to 18,2024.Environmental hygiene sampling was carried out on the surfaces of the ward.The homology of the strains was analyzed,and effective intervention measures were taken.RESULTS The incidence of S.marcescens sepsis in the NICU from Oct.12 to 18,2024 was 2.20％(2/91)compared to 2.35％in the same period of 2023(2/85),no significant difference was found between the two time periods(P=0.946).Among the three S.marcescens-positive NICU neonates,one was considered com-munity-acquired,while the other two were diagnosed with S.marcescens sepsis.A total of 59 environmental hy-giene samples were collected,with one sample detecting S.marcescens in the bedside infusion pump slot of case 1.The homology analysis results showed high homology among the four S.marcescens strains but not completely homologous.After effective preventive and control measures were implemented,suspected S.marcescens cluste-ring events didn't further occurred.CONCLUSION The occurrence of this incident may be attributed to inadequate cleaning and disinfection of environmental surfaces and improper hand hygiene practices by some medical staff.

Objective:Based on multi-source databases,the changes in the current status and structure of China's basic medical insurance participation are analyzed to identify the characteristics of the uninsured and the reasons for their non-participation,and provide decision-making references for China to improve the coverage rate in the process of modernization.Methods:Survey data from several national public databases are selected as reference comparisons,including the China Family Survey,the China Household Finance Survey,and the Chinese Social Survey,to carry out a descriptive analysis of the current status of basic medical insurance participation and changes in the structure of participation.Results:In 2022,4.7%of China's population,nearly 66 million residents,were still not be covered by the basic medical insurance system.In terms of the participation structure,employee health insurance shows that the growth rate of the number of retirees exceeds the growth rate of the number of contributors,and the participation rate of the flexibly employed people is still low,while the participation rate of newborn babies,migrant minors,college students,and elderly people over 75 years old is low in the resident health insurance.At the same time,there is a large scale of selective enrollment in the adult population.Conclusion:Individual voluntary enrollment,household registration restrictions,and information barriers are the reasons for basic medical insurance has not yet achieved universal coverage.It is recommended to expand the coverage by actively recruiting flexibly employed people to participate in the employee health insurance scheme,improve innovative mechanisms for special groups to participate in the scheme,realize cross-region and cross-sectoral mobility of participation data,and strengthen policy publicity.

OBJECTIVE To optimize the risk matrix assessment model for management of hospital-associated infec-tion based on analytic hierarchy process(AHP)and evaluate the application effect of the model after optimization.METHODS By means of AHP,the model was optimized by constructing the quantitative evaluation indexes weight system for consequence severity induced by hospital-associated infection from Feb.2023 to Jul.2023.Taken The Affiliated Hospital of Guizhou Medical University as an example,the risk for occurrence of hospital-associated in-fection in 20 internal medicine departments was evaluated,the risk grades were determined,and the application effect of the risk assessment model was evaluated after the optimization.RESULTS The weight system indexes for severity of consequences due to hospital-associated infection included surgical site infection(18.03％),treatment outcomes(49.50％),increased length of hospital stay(11.52％),increased hospitalization cost(6.43％)and variable coefficient of monthly morbidity(14.53％).Ward 2 of emergency internal medicine department,neurolo-gy department,Ward 1 of emergency internal medicine department and hematopoietic stem cell transplantation de-partment were the extremely high risk departments acquired by the risk assessment model.The risk assessment was carried out for the extremely high risk departments,and the Ward 1 of emergency internal medicine depart-ment was determined as the department that the risk coping strategies were taken in priority after the risk value was adjusted.CONCLUSION The risk matrix assessment model can be optimized by establishing the weight sys-tem of quantitative indexes for risk assessment based on AHP,the model achieves remarkable application effect,and the result of risk assessment is reliable and has significance for clinical guidance.

OBJECTIVE To optimize the risk matrix assessment model for management of hospital-associated infec-tion based on analytic hierarchy process(AHP)and evaluate the application effect of the model after optimization.METHODS By means of AHP,the model was optimized by constructing the quantitative evaluation indexes weight system for consequence severity induced by hospital-associated infection from Feb.2023 to Jul.2023.Taken The Affiliated Hospital of Guizhou Medical University as an example,the risk for occurrence of hospital-associated in-fection in 20 internal medicine departments was evaluated,the risk grades were determined,and the application effect of the risk assessment model was evaluated after the optimization.RESULTS The weight system indexes for severity of consequences due to hospital-associated infection included surgical site infection(18.03％),treatment outcomes(49.50％),increased length of hospital stay(11.52％),increased hospitalization cost(6.43％)and variable coefficient of monthly morbidity(14.53％).Ward 2 of emergency internal medicine department,neurolo-gy department,Ward 1 of emergency internal medicine department and hematopoietic stem cell transplantation de-partment were the extremely high risk departments acquired by the risk assessment model.The risk assessment was carried out for the extremely high risk departments,and the Ward 1 of emergency internal medicine depart-ment was determined as the department that the risk coping strategies were taken in priority after the risk value was adjusted.CONCLUSION The risk matrix assessment model can be optimized by establishing the weight sys-tem of quantitative indexes for risk assessment based on AHP,the model achieves remarkable application effect,and the result of risk assessment is reliable and has significance for clinical guidance.

Objective:Based on multi-source databases,the changes in the current status and structure of China's basic medical insurance participation are analyzed to identify the characteristics of the uninsured and the reasons for their non-participation,and provide decision-making references for China to improve the coverage rate in the process of modernization.Methods:Survey data from several national public databases are selected as reference comparisons,including the China Family Survey,the China Household Finance Survey,and the Chinese Social Survey,to carry out a descriptive analysis of the current status of basic medical insurance participation and changes in the structure of participation.Results:In 2022,4.7%of China's population,nearly 66 million residents,were still not be covered by the basic medical insurance system.In terms of the participation structure,employee health insurance shows that the growth rate of the number of retirees exceeds the growth rate of the number of contributors,and the participation rate of the flexibly employed people is still low,while the participation rate of newborn babies,migrant minors,college students,and elderly people over 75 years old is low in the resident health insurance.At the same time,there is a large scale of selective enrollment in the adult population.Conclusion:Individual voluntary enrollment,household registration restrictions,and information barriers are the reasons for basic medical insurance has not yet achieved universal coverage.It is recommended to expand the coverage by actively recruiting flexibly employed people to participate in the employee health insurance scheme,improve innovative mechanisms for special groups to participate in the scheme,realize cross-region and cross-sectoral mobility of participation data,and strengthen policy publicity.

OBJECTIVE To analyze the investigation and handling process of a suspected outbreak of hospital-ac-quired Serratia marcescens infection in the Neonatal Intensive Care Unit(NICU)of a certain hospital,and to pro-vide valuable reference for the prevention and control of hospital-acquired infections.METHODS An epidemiologi-cal investigation was conducted on three S.marcescens-positive neonates admitted to the NICU of the Affiliated Hospital of Guizhou Medical University from Oct.12 to 18,2024.Environmental hygiene sampling was carried out on the surfaces of the ward.The homology of the strains was analyzed,and effective intervention measures were taken.RESULTS The incidence of S.marcescens sepsis in the NICU from Oct.12 to 18,2024 was 2.20％(2/91)compared to 2.35％in the same period of 2023(2/85),no significant difference was found between the two time periods(P=0.946).Among the three S.marcescens-positive NICU neonates,one was considered com-munity-acquired,while the other two were diagnosed with S.marcescens sepsis.A total of 59 environmental hy-giene samples were collected,with one sample detecting S.marcescens in the bedside infusion pump slot of case 1.The homology analysis results showed high homology among the four S.marcescens strains but not completely homologous.After effective preventive and control measures were implemented,suspected S.marcescens cluste-ring events didn't further occurred.CONCLUSION The occurrence of this incident may be attributed to inadequate cleaning and disinfection of environmental surfaces and improper hand hygiene practices by some medical staff.

Background and objective Radiation therapy is one of the most common treatments for non-small cell lung cancer(NSCLC).However,the insensitivity of some tumor cells to radiation is one of the major reasons for the poor efficacy of radiotherapy and the poor prognosis of patients,and exploring the underlying mechanisms behind radioresistance is the key to solving this clinical challenge.This study aimed to identify the molecules associated with radioresistance in lung ad-enocarcinoma(LUAD),identified thyroid hormone receptor interactor 13(TRIP13)as the main target initially,and explored whether TRIP 13 is related to radioresistance in LUAD and the specific mechanism,with the aim of providing theoretical basis and potential targets for the combination therapy of LUAD patients receiving radiotherapy in the clinic.Methods Three data-sets,GSE18842,GSE19188 and GSE33532,were selected from the Gene Expression Omnibus(GEO)database and screened for differentially expressed genes(|log FC|＞1.5,P＜0.05)in each of the three datasets using the R 4.1.3 software,and then Venn diagram was used to find out the differentially expressed genes common to the three datasets.The screened differential genes were then subjected to protein-protein interaction(PPI)analysis and module analysis with the help of STRING online tool and Cytoscape software,and survival prognosis analysis was performed for each gene with the help of Kaplan-Meier Plotter database,and the TRIP13 gene was identified as the main molecule for subsequent studies.Subsequently,the human LUAD cell line H292 was irradiated with multiple X-rays using a sub-lethal dose irradiation method to construct a radioresistant cell line,H292DR.The radioresistance of H292DR cells was verified using cell counting kit-8(CCK-8)assay and clone formation assay.The expression levels of TRIP 13 in H292 and H292DR cells were measured by Western blot.Small interfering RNA(siRNA)was used to silence the expression of TRIP 13 in H292DR cells and Western blot assay was performed.The clone formation ability and migration ability of H292DR cells were observed after TRIP13 silencing,followed by the detection of changes in the expression levels of proteins closely related to homologous recombination,such as ataxia telangiectasia mutated(ATM)protein.Results Screening of multiple GEO datasets,validation of external datasets and survival analysis revealed that TRIP 13 was highly expressed in LUAD and was associated with poor prognosis in LUAD patients who had received radiation therapy.And the results of gene set enrichment analysis(GSEA)of TRIP13 suggested that TRIP13 might be closely associated with LUAD radioresistance by promoting homologous recombination repair after radiation therapy.Experimentally,TRIP13 expression was found to be upregulated in H292DR,and silencing of TRIP13 was able to increase the sensitivity of H292DR cells to radiation.Conclusion TRIP13 is associated with poor prognosis in LUAD patients treated with radiation,possibly by promoting a homologous recombination repair pathway to mediate resistance of LUAD cells to radiation.

Objective To analyze the effects of massage therapy on the inflammatory state and lung function of pediatric refractory Mycoplasma pneumonia (RMPP). Methods A total of 320 children with RMPP treated in Hebei Seventh People′s Hospital from September 2022 to August 2023 were selected in the study. According to different treatment methods, they were divided into two groups, with 160 cases in each group. The western medicine group was given conventional anti-inflammatory and other symptomatic treatment, while the massage group was given dialectical massage treatment based on the western medicine group. The clinical efficacy, duration of disappearance of clinical symptoms, pulmonary function indexes, serum inflammatory factors, immune function indexes and total incidence of adverse reactions were compared between the two groups. Results The total effective rate of massage group was higher than that of control group (P < 0.05). The disappearance time of fever, cough, sputum and lung moist rales in observation group was shorter than that in control group (P < 0.05). After treatment, the peak expiratory flow (PEF), maximum mid-expiratory flow (MMEF) and forced vital capacity (FVC) in the massage group were higher than those in the control group (P < 0.05). The levels of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the massage group were lower than those in the control group after treatment (P < 0.05). After treatment, CD3⁺, CD4⁺, CD4⁺/CD8⁺ in the massage group were higher than those in the control group (P < 0.05), and CD8⁺ was lower than that in the control group (P < 0.05). There was nosignificant difference in the total incidence of adverse reactions between the massage group and the western medicine group (P>0.05). Conclusion Massage based on syndrome differentiation combined with western medicine can effectively relieve fever, cough and other symptoms of RMPP children, reduce inflammatory response, improve lung function and immune function, and has less adverse reactions.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair