BACKGROUND:Ammonia poisoning is considered to be the main hypothesis for the pathogenesis of hepatic encephalopathy.Ammonia can lead to psychiatric and cognitive behavioral disorders,although the specific pathological molecular mechanisms remain unclear.OBJECTIVE:To investigate the effects of ammonia poisoning on cognitive behavior and hippocampal neuronal synapses in mice.METHODS:Thirty-two C57BL/6J mice were randomly divided into a normal control group and an ammonium chloride group,with 16 mice in each group.Normal saline was injected intraperitoneally in the control group,and ammonium chloride(10 mmol/kg)was injected intraperitoneally in the ammonium chloride group to construct a model of ammonia poisoning,once a day.After 7 days of ammonium chloride intervention,blood samples were collected from the hearts of six mice in each group for blood ammonia concentration detection.Behavioral experiments,including the open field test,novel object recognition test,and Y-maze test,were performed to assess mental and cognitive-behavioral changes in mice.Finally,hippocampal tissues were extracted for western blot analysis to detect the expression levels of synaptophysin and postsynaptic density protein-95 in hippocampal neurons.RESULTS AND CONCLUSION:The blood ammonia concentration was significantly elevated in the ammonium chloride group compared with the control group(P＜0.05).Mice in the ammonium chloride group showed anxiety-like behavior and disinhibition phenomenon,and a significant decrease in recognition memory and working memory ability.Western blot results revealed that the expression of synaptophysin and postsynaptic density protein-95 protein in hippocampal neurons in the ammonium chloride group was lower than that in the control group(P＜0.05).To conclude,ammonia poisoning can induce hippocampal neuronal synaptic damage,leading to psychiatric and cognitive behavioral abnormalities in mice.

BACKGROUND:Ammonia poisoning is considered to be the main hypothesis for the pathogenesis of hepatic encephalopathy.Ammonia can lead to psychiatric and cognitive behavioral disorders,although the specific pathological molecular mechanisms remain unclear.OBJECTIVE:To investigate the effects of ammonia poisoning on cognitive behavior and hippocampal neuronal synapses in mice.METHODS:Thirty-two C57BL/6J mice were randomly divided into a normal control group and an ammonium chloride group,with 16 mice in each group.Normal saline was injected intraperitoneally in the control group,and ammonium chloride(10 mmol/kg)was injected intraperitoneally in the ammonium chloride group to construct a model of ammonia poisoning,once a day.After 7 days of ammonium chloride intervention,blood samples were collected from the hearts of six mice in each group for blood ammonia concentration detection.Behavioral experiments,including the open field test,novel object recognition test,and Y-maze test,were performed to assess mental and cognitive-behavioral changes in mice.Finally,hippocampal tissues were extracted for western blot analysis to detect the expression levels of synaptophysin and postsynaptic density protein-95 in hippocampal neurons.RESULTS AND CONCLUSION:The blood ammonia concentration was significantly elevated in the ammonium chloride group compared with the control group(P＜0.05).Mice in the ammonium chloride group showed anxiety-like behavior and disinhibition phenomenon,and a significant decrease in recognition memory and working memory ability.Western blot results revealed that the expression of synaptophysin and postsynaptic density protein-95 protein in hippocampal neurons in the ammonium chloride group was lower than that in the control group(P＜0.05).To conclude,ammonia poisoning can induce hippocampal neuronal synaptic damage,leading to psychiatric and cognitive behavioral abnormalities in mice.

To analyze the distribution of serotypes and antimicrobial resistance of clinical Salmonella isolates from multiple centers across China.

Objective　To analyze the epidemiological characteristics and infection sources of six human Streptococcus suis infection outbreaks in Shenzhen in 2023, and to provide a reference for effective prevention and control of the epidemic. Methods　Field epidemiological methods were used to investigate the disease onset and medical consultation process, exposure history of household and farmer market pork stalls, and other relevant factors. Data on patient demographics, clinical profiles, epidemiological characteristics, and common exposure cases were collected. Blood, cerebrospinal fluid, and environmental samples were collected for pathogen detection and genotyping. Spatial-geographical analysis of infection characteristics was performed using the professional mapping software ArcMap. Results　In 2023, a total of six cases were reported in Shenzhen, all of which were severe hospitalized cases with no deaths. Among them, five cases were of the meningitis type, and one was of the common type. All patients improved and were discharged after treatment. All six cases were male, with a median age of 47.5 years, and all had a history of direct exposure to raw pork through hand-skin wounds. Two cases were engaged in raw pork sales, while four were non-occupationally exposed individuals. Of the six cases, four were identified as Streptococcus suis serotype 2, and two were serotype 14. The positive rate of raw pork and environmental samples was 8.45% (6/71). Field epidemiological investigation found these six outbreaks were mainly directed toward three slaughterhouses in Guangming District, Bao'an District, and Longgang District. However, different genetic typing results suggested sporadic cases. Conclusions　These six outbreaks in Shenzhen in 2023 were all sporadic individual cases, showing characteristics such as multiple-point sporadic occurrences, diversified case composition, and primarily meningitis-type clinical manifestations. Although the genetic typing of the samples varied, the epidemiological investigation indicated three slaughterhouses as potential sources, providing a scientific basis for source control. In infectious disease epidemic source tracing, gene sequencing combined with field epidemiological surveys is more conducive to determining the source of infection and the relationship between transmission.

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Objective To analyze the differences in bone serum protein between patients with osteoporosis accompanied by obstructive sleep apnea syndrome(OSAS)and those with osteoporosis only using proteomics.Methods A total of 80 osteoporosis patients who attended our hospital between June 2022 and June 2024 were enrolled.Based on their polysomnography results,the participants were divided into an OSAS and osteoporosis comorbidity(OSAS-osteoporosis)group(n=42)and an osteoporosis only group(n=38).Propensity score matching was applied to incorporate covariates in logistic regression so that the individual characteristics of the two groups of patients were generally balanced.Following the matching procedure,a final cohort of 20 matched pairs was obtained and subsequently utilized for further analysis.The mass spectrum was obtained using laser desorption ionization mass spectrometry.Principal component analysis(PCA)was performed to assess differences in metabolic patterns between groups.Partial least squares discriminant analysis(PLS-DA)and orthogonal PLS-DA(OPLS-DA)were employed for further data analysis.Variable importance in projection(VIP)scores of each substance were calculated with OPLS-DA to screen the metabolites showing inter-group differences.Heatmaps were generated to visualize metabolic profile differences between the OSAS-osteoporosis group and the osteoporosis group.Enrichment pathway analysis was conducted on the differential identified metabolites.Results After propensity score matching,individual characteristics between the groups were well balanced.Mass spectrometry revealed significant differences between the OSAS-osteoporosis and osteoporosis groups.In the PCA score plot,the separation trend of the two groups was not significant.The PLS-DA score plot showed a discernible separation trend,with R2 and Q2 lower than those of the corresponding results of the real model,confirming the reliability of the model.OPLS-DA showed that the total R2X of the model was 0.635,R2Y was 0.879,and O2Y was 0.728,showing obvious separation trends between the two groups.A total of 16 differential metabolites were identified,including stearyl-oleyl-glycerol phosphate choline,phosphate choline,L-histidine,erucamide,2'-deoxyuridine,1-palmitoyl glycerol,thymine,tyramine,L-pyroglutamic acid,L-glutamic acid,myristate,glycerol-3-phosphate,caprylic acid,pregnenolone,L-arginine,D-4-hydroxyphenylglycine,and isobutyric acid.Heatmaps showed significant differences in metabolic profiles between the OSAS-osteoporosis group and the osteoporosis group.Pathway enrichment analysis showed that 27 metabolic pathways were involved.27 metabolic pathways.Under the conditions of P<0.05 and pathway impact>0.2,the three most significant metabolic pathways identified included mainly alanine,aspartate,and glutamate metabolism,arginine biosynthesis,and histidine metabolism.Conclusion Significant differences were observed in the metabolic profiles between patients with both OSAS and osteoporosis and those with osteoporosis alone.

Objective:To explore the effect of Swanson theory combined with hand touch on the existential distress of patients with advanced lung cancer, in order to provide reference for clinical humanistic care.Methods:A non synchronous controlled study was conducted using convenience sampling to select advanced lung cancer patients admitted to the Oncology Department of the First People's Hospital of Yongkang City, Zhejiang Province from October 2023 to March 2024 as the control group, and advanced lung cancer patients admitted from April to October 2024 as the experimental group. The control group received routine care, while the experimental group received Swanson theory combined with hand touch intervention on the basis of routine care. The Existential Distress Scale (EDS) and Functional Assessment of Cancer Therapy- General (FACT-G) scores of the two groups were compared before and 2 weeks after intervention.Results:During the study period, there were 3 dropouts in the experimental group and 2 dropouts in the control group. Finally, 37 cases were included in the experimental group, including 16 males and 21 females, with an age of (62.35 ± 12.13) years. There were 38 cases in the control group, including 25 males and 13 females, with an age of (65.68 ± 13.46) years. After 2 weeks of intervention, the EDS score of the experimental group patients was (6.65 ± 2.89) points, while that of the control group was (8.16 ± 2.27) points. The difference between the two groups was statistically significant ( t = 2.52, P<0.05). After intervention, the social/family status dimension, emotional status dimension, and total score of FACT-G in the experimental group were (15.35 ± 4.18), (19.27 ± 3.54), and (57.46 ± 14.69) points, respectively, which were better than the control group's (13.08 ± 3.77), (16.53 ± 3.88), and (50.58 ± 11.86) points. The difference between the two groups was statistically significant ( t = - 2.47, - 3.20, - 2.24, all P<0.05). Conclusions:The combination of Swanson theory and hand touch can effectively reduce the existential distress of patients with advanced lung cancer, improve their quality of life, and embody the concept of nursing humanistic care into simple and safe intervention measures, providing reference for clinical humanistic care.

Objective:To explore the effect of Swanson theory combined with hand touch on the existential distress of patients with advanced lung cancer, in order to provide reference for clinical humanistic care.Methods:A non synchronous controlled study was conducted using convenience sampling to select advanced lung cancer patients admitted to the Oncology Department of the First People's Hospital of Yongkang City, Zhejiang Province from October 2023 to March 2024 as the control group, and advanced lung cancer patients admitted from April to October 2024 as the experimental group. The control group received routine care, while the experimental group received Swanson theory combined with hand touch intervention on the basis of routine care. The Existential Distress Scale (EDS) and Functional Assessment of Cancer Therapy- General (FACT-G) scores of the two groups were compared before and 2 weeks after intervention.Results:During the study period, there were 3 dropouts in the experimental group and 2 dropouts in the control group. Finally, 37 cases were included in the experimental group, including 16 males and 21 females, with an age of (62.35 ± 12.13) years. There were 38 cases in the control group, including 25 males and 13 females, with an age of (65.68 ± 13.46) years. After 2 weeks of intervention, the EDS score of the experimental group patients was (6.65 ± 2.89) points, while that of the control group was (8.16 ± 2.27) points. The difference between the two groups was statistically significant ( t = 2.52, P<0.05). After intervention, the social/family status dimension, emotional status dimension, and total score of FACT-G in the experimental group were (15.35 ± 4.18), (19.27 ± 3.54), and (57.46 ± 14.69) points, respectively, which were better than the control group's (13.08 ± 3.77), (16.53 ± 3.88), and (50.58 ± 11.86) points. The difference between the two groups was statistically significant ( t = - 2.47, - 3.20, - 2.24, all P<0.05). Conclusions:The combination of Swanson theory and hand touch can effectively reduce the existential distress of patients with advanced lung cancer, improve their quality of life, and embody the concept of nursing humanistic care into simple and safe intervention measures, providing reference for clinical humanistic care.

Social behaviors are fundamental and intricate functions in both humans and animals, governed by the interplay of social cognition and emotions. A noteworthy feature of several neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia (SCZ), is a pronounced deficit in social functioning. Despite a burgeoning body of research on social behaviors, the precise neural circuit mechanisms underpinning these phenomena remain to be elucidated. In this paper, we review the pivotal role of the prefrontal cortex (PFC) in modulating social behaviors, as well as its functional alteration in social disorders in ASD or SCZ. We posit that PFC dysfunction may represent a critical hub in the pathogenesis of psychiatric disorders characterized by shared social deficits. Furthermore, we delve into the intricate connectivity of the medial PFC (mPFC) with other cortical areas and subcortical brain regions in rodents, which exerts a profound influence on social behaviors. Notably, a substantial body of evidence underscores the role of N-methyl-D-aspartate receptors (NMDARs) and the proper functioning of parvalbumin-positive interneurons within the mPFC for social regulation. Our overarching goal is to furnish a comprehensive understanding of these intricate circuits and thereby contribute to the enhancement of both research endeavors and clinical practices concerning social behavior deficits.
Prefrontal Cortex/physiopathology* ; Humans ; Social Behavior ; Animals ; Autism Spectrum Disorder/physiopathology* ; Schizophrenia/physiopathology* ; Receptors, N-Methyl-D-Aspartate/physiology* ; Interneurons/physiology*

With reference to the teaching reform of standardized training cases based on organ systems, a teaching case writing team has been established, integrating the teaching experts in basic medicine, clinical medicine, humanities medicine, and other fields. Through collective lesson preparation and discussion, non-fictional comprehensive scenario writing techniques have been used based on organ systems and oriented by competency development, and the teaching cases for postgraduate students were written on the basis of real cases, which lays a solid foundation for the hierarchical and progressive cultivation and improvement of the quality of competency cultivation for postgraduate students through case teaching based on organ systems.