ObjectiveTo assess the cost-effectiveness of human immunodeficiency virus (HIV) prevention and control strategies across different high-risk populations, investment levels, and allocation proportions in an area, thereby providing a reference for optimizing resource allocation in acquired immunodeficiency syndrome (AIDS) prevention and control. MethodsDemographic, epidemiological, and clinical progression data of the target population in an area from 2018 to 2024 were collected, along with the input costs and intervention coverage of HIV-related projects. The Optima HIV model was utilized to perform fitting and prediction, whereby the allocation of resources to optimized target populations and program interventions was modeled under varying future investment scenarios to predict the impacts on the reduction of new HIV infections and HIV-related deaths. ResultsUnder the scenario of maintaining the current level of intervention input for HIV key populations, new HIV infections and related deaths in the region were predicted to be controlled at a low level by 2030. In terms of intervention input for HIV key populations, it is suggested that appropriately increasing the intervention input for key HIV populations will further reduce new HIV infections and HIV-related deaths in the region. However, when the total input increases to 1.75 times the baseline level, the marginal effect of input will be saturated. Regarding structural adjustments in investment and considering both the current total investment scenario and 1.75 times the total investment scenario, it is predicted that further reductions in regional HIV new infections and HIV-related deaths can be achieved, provided that the intervention input for key populations (including men who have sex with men, MSM) is increased, while concurrently intensifying the proportion of intervention measures such as condom promotion to form optimized intervention portfolios. ConclusionIn the field of HIV/ AIDS prevention and control, sustained commitment to intervention investment, with a strategic focus on interventions for key populations and intensified implementation of critical intervention measures, will effectively improve the epidemiological impacts of HIV/AIDS prevention and control efforts.

OBJECTIVE: To investigate the effects of acupuncture on the neurotransmitter levels and gut microbiota in a mouse model of Tourette syndrome (TS). METHODS: Thirty-six male C57/BL6 mice were randomly divided into 4 groups using a random number table method: 3,3'-iminodipropionitrile (IDPN) group, control group, acupuncture group, and tiapride group, with 9 mice in each group. In the IDPN group, acupuncture group, and tiapride group, mice received daily intraperitoneal injections of IDPN (300 mg/kg body weight) for 7 consecutive days to induce stereotyped behaviors. Subsequently, in the acupuncture intervention group, standardized acupuncture treatment was administered for 14 consecutive days to IDPN-induced TS model mice. The selected acupoints included Baihui (DU 20), Yintang (DU 29), Waiguan (SJ 5), and Zulinqi (GB 41). In the tiapride group, mice were administered tiapride (50 mg/kg body weight) via oral gavage daily for 14 consecutive days. The control group, IDPN group, and acupuncture group received the same volume of saline orally for 14 consecutive days. Stereotypic behaviors were quantified through behavioral assessments. Neurotransmitter levels, including dopamine (DA), glutamate (Glu), and aspartate (ASP) in striatal tissue were measured using enzyme-linked immunosorbent assay. Dopamine transporter (DAT) expression levels were additionally quantified through quantitative polymerase chain reaction (qPCR). Gut microbial composition was analyzed through 16S ribosomal RNA gene sequencing, while metabolic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Acupuncture administration significantly attenuated stereotypic behaviors, concurrently reducing striatal levels of DA, Glu and ASP concentrations while upregulating DAT expression compared with untreated TS controls (P<0.05 or P<0.01). Comparative analysis identified significant differences in Muribaculaceae (P=0.001), Oscillospiraceae (P=0.049), Desulfovibrionaceae (P=0.001), and Marinifilaceae (P=0.014) following acupuncture intervention. Metabolomic profiling revealed alterations in 7 metabolites and 18 metabolic pathways when compared to the TS mice, which involved various amino acid metabolisms associated with DA, Glu, and ASP. CONCLUSIONS Acupuncture demonstrates significant modulatory effects on both central neurotransmitter systems and gut microbial ecology, thereby highlighting its dual therapeutic potential for TS management through gut-brain axis regulation.
Animals ; Tourette Syndrome/metabolism* ; Gastrointestinal Microbiome ; Neurotransmitter Agents/metabolism* ; Acupuncture Therapy ; Male ; Mice, Inbred C57BL ; Mice

G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in eukaryotes, with nearly 800 genes coding for these proteins. They are involved in many physiological processes, such as light perception, taste and smell, neurotransmitter, metabolism, endocrine and exocrine, cell growth and migration. Importantly, GPCRs and their ligands are the targets of approximately one third of all marketed drugs. GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane. However, emerging evidence suggests that GPCRs are also localized on mitochondria, where they play critical roles in modulating mitochondrial functions. These mitochondrial GPCRs (mGPCRs) can influence processes such as mitochondrial respiration, apoptosis, and reactive oxygen species (ROS) production. By interacting with mitochondrial signaling pathways, mGPCRs contribute to the regulation of energy metabolism and cell survival. Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling, highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction. This expanding understanding of mGPCR function on mitochondria opens new avenues for research, particularly in the context of diseases where mitochondrial dysfunction plays a key role. Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease, diabetes, obesity and Alzheimer's disease. In this review, we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases. We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease, and to underscore their potential as therapeutic targets in the treatment of these conditions.

Objective To understand the willingness of general practitioner(GP) to enhance working competence in community healthcare centers in Shanghai and provide a basis for the competence training of GPs in community healthcare centers. Methods In August 2023,GPs were selected from some community healthcare centers in Shanghai and their willingness to enhance working competence were studied by a questionnaire survey.The survey included 39 secondary indicators in three dimensions:general practice theory,skills,and humanity. Results A total of 1 192 GPs completed the questionnaire,with an effective rate of 100%.The total score of GPs' willingness to enhance their working competence was 258.45±80.93,and the mean score of the three dimensions was 6.63±2.08.The score for the general practice theory was the highest (6.92±1.95),while that for general practice humanity was the lowest (6.44±2.34) among the three dimensions.The score of willingness to enhance working efficiency differed across different age ranges (P<0.001),professional titles (P<0.001),years of work (P<0.001),and educational backgrounds of GPs (P=0.039).Those with the age younger than 30 years old,junior professional titles,less than 5 years of work experience,and a college degree or below had the highest willingness score to enhance their working competence.Among the top three secondary indicators of willingness score in each dimension,the top three methods of working competence enhancement were community general practice and specialized healthcare services combined with outpatient learning,flexible further training,and continuing education courses.Conclusions There is an urgent need for young GPs in community healthcare centers in Shanghai to enhance their working competence.Targeted enhancement plans can be provided to different groups of GPs with different characteristics through community general practice and specialized healthcare services combined with outpatient learning,flexible further training,and continuing education courses,which can further enhance the ability and quality of the GP team.
Humans ; China ; General Practitioners/psychology* ; Surveys and Questionnaires ; Community Health Centers ; Clinical Competence ; Female ; Adult ; Male ; Attitude of Health Personnel ; Middle Aged

As palliative care practice gradually undertakes important missions in both the medical field and the society,it has become an emerging disciplinary area that meets the needs of the times.At the same time,the discipline construction of palliative medicine has become a crucial issue that urgently needs to be addressed in the cause of palliative care in China.In this article,we trace the origin of the concept of palliative care and classify,sort out,and expound the research objects,research contents,research methods,etc.of palliative medicine by combining the methods of literature analysis and focus group interviews.According to the development context and evolution process of palliative care,we put forward the proposition of building a discipline of palliative medicine,with the aim of helping the academic community distinguish the connotation and denotation of the disciplinary definition and laying a foundation for the work of discipline construction.
Palliative Medicine ; Palliative Care ; Humans

This study aims to investigate the therapeutic effect and mechanism of Daotan Xixin Decoction on APP/PS1 mice. Twelve APP/PS1 male mice were randomized into four groups: APP/PS1 and low-, medium-, and high-dose Daotan Xixin Decoction. Three C57BL/6 wild-type mice were used as the control group. The learning and memory abilities of mice in each group were examined by the Morris water maze test. The pathological changes of hippocampal nerve cells were observed by hematoxylin-eosin staining and Nissl staining. Immunohistochemistry was employed to detect the expression of β-amyloid(Aβ)_(1-42) in the hippocampal tissue. The high-dose Daotan Xixin Decoction group with significant therapeutic effects and the model group were selected for high-throughput sequencing. The differentially expressed gene(DEG) analysis, Gene Ontology(GO) analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and Gene Set Variation Analysis(GSVA) were performed on the sequencing results. RT-qPCR and Western blot were conducted to determine the mRNA and protein levels, respectively, of some DEGs. Compared with the APP/PS1 group, Daotan Xixin Decoction at different doses significantly improved the learning and memory abilities of APP/PS1 mice, ameliorated the neuropathological damage in the CA1 region of the hippocampus, increased the number of neurons, and decreased the deposition of Aβ_(1-42) in the brain. A total of 1 240 DEGs were screened out, including 634 genes with up-regulated expression and 606 genes with down-regulated expression. The GO analysis predicted the biological processes including RNA splicing and protein folding, the cellular components including spliceosome complexes and nuclear spots, and the molecular functions including unfolded protein binding and heat shock protein binding. The KEGG pathway enrichment analysis revealed the involvement of neurodegenerative disease pathways, amyotrophic lateral sclerosis, and splicing complexes. Further GSVA pathway enrichment analysis showed that the down-regulated pathways involved nuclear factor-κB(NF-κB)-mediated tumor necrosis factor-α(TNF-α) signaling pathway, UV response, and unfolded protein response, while the up-regulated pathways involved the Wnt/β-catenin signaling pathway. The results of RT-qPCR and Western blot showed that compared with the APP/PS1 group, Daotan Xixin Decoction at different doses down-regulated the mRNA and protein levels of signal transducer and activator of transcription 3(STAT3), NF-κB, and interleukin-6(IL-6) in the hippocampus. In conclusion, Daotan Xixin Decoction can improve the learning and memory abilities of APP/PS1 mice by regulating the STAT3/NF-κB/IL-6 signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Male ; Alzheimer Disease/metabolism* ; Computational Biology ; Mice, Inbred C57BL ; High-Throughput Nucleotide Sequencing ; Amyloid beta-Protein Precursor/metabolism* ; Hippocampus/metabolism* ; Mice, Transgenic ; Presenilin-1/metabolism* ; Humans ; Memory/drug effects* ; Maze Learning/drug effects* ; Amyloid beta-Peptides/genetics* ; Disease Models, Animal

As a physical treatment technique, modified electro-convulsive therapy (MECT) is used to treat mental and certain neurological disorders by causing seizures with short, suitable electrical currents applied to the brain while the patient is under general anesthesia and muscle relaxants. MECT is recognized for its therapeutic efficacy and clinical safety, rendering it one of the most prevalent interventions in psychiatric care. To enhance clinical outcomes and minimize adverse effects, this consensus document delineates the indications, therapeutic parameters, therapeutic procedures, potential adverse effects, and associated management strategies for MECT. These guidelines are informed by the latest clinical research and expert consensus, integrating evidence-based medicine methodologies. The objective is to furnish clinicians with precise operational guidelines and to advance the standardization of MECT practices in clinical settings.

Objective:To investigate the relationship among seminal oxidation-reduction potential(nORP),sperm DNA frag-mentation(DFI)and semen parameters in patients with varicocele.Methods:Clinical data of 522 patients treated in the reproduc-tive andrology clinic of the Northern Theater General Hospital from November 2023 to December 2023 were retrospectively analyzed,in-cluding 435 men of childbearing age and 87 men of infertile age.The patients were divided into the varicocele group(n=116)and non-varicocele group(n=406)according to clinical diagnosis.The differences of seminal plasma nORP,DFI,sperm high DNA stain ability(HDS)and semen parameters were analyzed between the two groups.The relationship among general clinical data,seminal plasma nORP,semen parameters,DFI and HDS in patients with varicocele were further analyzed.According to the severity of varico-cele,the patients were divided into three groups,including mild,moderate and severe.And the differences of seminal plasma nORP and semen parameters,DFI and HDS among all groups were analyzed.The differences of seminal plasma nORP,semen parameters,DFI and HDS were compared between the varicocele and non-varicocele groups.Results:The total sperm count,sperm concentra-tion,progressive motility sperm percentage(PR％)and normal sperm morphology rate(NSMR)in patients with varicocele were sig-nificantly lower than those in control group(P＜0.05).And seminal plasma nORP,DFI and HDS in patients with varicocele were sig-nificantly higher than those in control group(P＜0.05).Seminal plasma nORP in patients with varicocele was significantly negatively correlated with total sperm,sperm concentration and NSMR(P＜0.05),and significantly positively correlated with DFI and HDS(P＜0.05).There were significant differences in nORP,total sperm count,sperm concentration,PR％,DFI and HDS among mild,moderate and severe varicocele groups(P＜0.05).Seminal plasma nORP,sperm concentration,PR％and DFI in severe group were significantly lower than those in mild and moderate groups(P＜0.05).Sperm count and HDS in severe group were significantly lower than those in mild group(P＜0.05).In infertile patients,seminal plasma nORP,DFI and HDS in varicocele group were significantly higher than those in control group(P＜0.05).And PR％in varicocele group was significantly lower than that in control group(P＜0.05).Conclusions:Seminal plasma nORP in patients with varicocele may be an important marker of oxidative stress affecting DFI and semen parameters.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all mar-keted drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respi-ration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Ab-normalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alz-heimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.