The therapeutic effects of Yueju Pills on depression and cardiovascular diseases have been widely recognized. Previous studies have shown that the drug can significantly improve depressive-like behaviors induced by chronic unpredictable mild stress(CUMS) combined with atherosclerosis(AS). Given the complex pathogenesis of psychocardiac diseases, this study integrated metabolomics and network pharmacology to systematically elucidate the mechanism of Yueju Pills in alleviating depressive symptoms in psychocardiac diseases. The results demonstrate that, after Yueju Pill intervention, the levels of 9 abnormal metabolites in the hippocampus restore to normal ranges, primarily involving key pathways or signaling pathways, including the cyclic adenosine monophosphate(cAMP), mammalian target of rapamycin(mTOR), glycine/serine/threonine metabolism, and aminoacyl-tRNA biosynthesis. In a high-fat diet-induced CUMS ApoE~(-/-) mouse model, Yueju Pills significantly increases adenosine monophosphate(AMP) levels and decreases L-alanine and D-glyceric acid levels in the hippocampus. In conclusion, Yueju Pills exert antidepressant effects by regulating multiple metabolic axes, including glycine/serine/threonine metabolism and the cAMP, mTOR signaling pathways. Network pharmacology predictions reveal that the treatment of CUMS combined with AS by its core active components may be realized through modulating pathways concerning neuroinflammation and synaptic plasticity, including serine/threonine-protein kinase 1(AKT1), mitogen-activated protein kinase 1(MAPK1), and prostaglandin-endoperoxide synthase 2(PTGS2). This study provides a theoretical reference for the clinical application of Yueju Pills in alleviating the depressive symptoms of psychocardiac diseases.
Animals ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Male ; Depression/genetics* ; Humans ; Hippocampus/drug effects* ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Objective To explore the protective effect and underlying mechanism of roxadustat(FG-4592),hypoxia-inducible factor-α(HIF-α)prolyl hydroxylase inhibitor,on brain injury caused by heat stroke(HS).Methods A total of 140 male C57BL/6J mice(6～8 weeks old,weighing 18～22 g)were subjected,and 40 of them were randomly divided into HS group,and low-,medium-and high-dose roxadustat groups(LD,MD and HD groups,5,10 and 20 mg/kg),with 10 mice in each group.The 24-hour survival rate was observed to determine the optimal dosage of roxadustat after modeling.Additionally,the remaining 100mice were randomly allocated to normal control(Control)group,roxadustat(FG-4592)group,HS group,and roxadustat+HS(FG-4592+HS)group,with 25 mice in each.Heat shock was inflicted to establish mouse model of HS.Modified neurological severity score(mNSS)was used to assess neurological function.HE staining of brain sections was performed to examine pathological damage,and Fluoro-Jade C staining was applied to observe neuronal degeneration.The activity of total superoxide dismutase(SOD)and content of malondialdehyde(MDA)in brain tissue were measured to assess oxidative stress.Transmission electron microscopy was employed to visualize mitochondrial damage.Western blotting was performed to assess the protein levels of Caspase-3,Cleaved Caspase-3,Mfn1,Mfn2,Opa1,Fis1,HIF-1α,HO-1 and p-Drp1(Ser616)/Drp1 ratio in the cerebral cortex.Results Compared to the HS group,FG-4592 significantly improved the survival rate of HS mice within 24 h,with the MD group showing the highest survival rate.Compared to the Control group,the HS group showed an increase in mNSS score(P＜0.05),an elevation in the MDA content in the cerebral cortex(P＜0.05),and a decrease in total SOD activity in the cerebral cortex(P＜0.05);HE staining revealed pathological damage in the cerebral cortex,and Fluoro-Jade C staining displayed obvious neuronal degeneration in the cerebral cortex;Electron microscopy revealed obvious mitochondrial structural damage in the cerebral cortex tissue;The protein expression of Caspase-3,Cleaved Caspase-3,Fis1,HIF-1α,HO-1 and p-Drp1(Ser616)/Drp1 ratio was increased(P＜0.05),while that of Mfn1,Mfn2,and Opa1 was decreased(P＜0.05).Pretreatment with FG-4592 significantly reduced the mNSS score in HS mice(P＜0.05),decreased MDA content(P＜0.05),and enhanced total SOD activity(P＜0.05).Additionally,FG-4592 pretreatment improved pathological damage in the cerebral cortex,reduced neuronal degeneration,and mitigated mitochondrial structural damage.Furthermore,it decreased the protein levels of Caspase-3,Cleaved Caspase-3,Fis1 and p-Drp1(Ser616)/Drp1 ratio(P＜0.05),while increased the levels of Mfn1,Mfn2,Opa1,HIF-1α,and HO-1(P＜0.05).Conclusion Roxadustat regulates the balance between mitochondrial fission and fusion,reduces mitochondrial structural damage,oxidative stress and apoptosis,and alleviates heat stroke-induced brain injury.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Objective:To analyze the clinical characteristics of ulcerative colitis (UC) in Han and Uyghur patients in Xinjiang Uygur Autonomous Region.Method:Data of UC patients hospitalized at the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2015 to June 2023 were retrospectively collected, with a focus on the differences in basic information, extraintestinal manifestations and biochemical laboratory indicators between Han and Uyghur patients.Results:A total of 315 UC patients were included, with 172 Han cases (54.6%) and 143 Uyghur cases (45.4%) . Compared to the Han group, the Uyghur group had a higher proportion of females, a lower average age, and lower rates of smoking and alcohol consumption (all P<0.05) . The Uyghur group showed a higher prevalence of hepatobiliary diseases and joint injuries as extraintestinal manifestations, although the differences were not statistically significant ( P all>0.05) . The Han group had a statistically significant higher level of intraepithelial neoplasia (χ 2 = 5.075, P<0.05) . The Uyghur group exhibited significantly higher levels of white blood cell count, platelet count, neutrophils, lymphocyte count, globulin, C-reactive protein, erythrocyte sedimentation rate, highly sensitive C-reactive protein, anti-neutrophil cytoplasmic antibodies, and H.pylori antibodies compared to the Han group (all P<0.05) . Both Han and Uyghur UC patients achieved satisfactory clinical efficacy. Conclusion:Uyghur UC patients have distinct characteristics, including a younger age of onset and more severe disease course, yet appropriate treatment can lead to satisfactory clinical outcomes.

Objective:To analyze the clinical characteristics of ulcerative colitis (UC) in Han and Uyghur patients in Xinjiang Uygur Autonomous Region.Method:Data of UC patients hospitalized at the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2015 to June 2023 were retrospectively collected, with a focus on the differences in basic information, extraintestinal manifestations and biochemical laboratory indicators between Han and Uyghur patients.Results:A total of 315 UC patients were included, with 172 Han cases (54.6%) and 143 Uyghur cases (45.4%) . Compared to the Han group, the Uyghur group had a higher proportion of females, a lower average age, and lower rates of smoking and alcohol consumption (all P<0.05) . The Uyghur group showed a higher prevalence of hepatobiliary diseases and joint injuries as extraintestinal manifestations, although the differences were not statistically significant ( P all>0.05) . The Han group had a statistically significant higher level of intraepithelial neoplasia (χ 2 = 5.075, P<0.05) . The Uyghur group exhibited significantly higher levels of white blood cell count, platelet count, neutrophils, lymphocyte count, globulin, C-reactive protein, erythrocyte sedimentation rate, highly sensitive C-reactive protein, anti-neutrophil cytoplasmic antibodies, and H.pylori antibodies compared to the Han group (all P<0.05) . Both Han and Uyghur UC patients achieved satisfactory clinical efficacy. Conclusion:Uyghur UC patients have distinct characteristics, including a younger age of onset and more severe disease course, yet appropriate treatment can lead to satisfactory clinical outcomes.

The overuse of antibiotics in animal husbandry has resulted in escalating animal safety con-cerns,highlighting the urgent need for a safe and effective alternative to traditional acidifiers.necessita-ting the development of safe and effective alternatives to traditional acidifiers.This study investigates the antibacterial activity and underlying mechanisms of rare-earth organic acid complexes (Re-SOA),a promising alternative to traditional acidifiers,against three common poultry and livestock pathogens:Escherichia coli,Staphylococcus aureus,and Salmonella.A series of Re-SOA were synthesized via a liq-uid-phase method.Structural characterization using infrared spectroscopy,X-ray photoelectron spectros-copy,and Raman spectroscopy confirmed successful complexation.The minimum inhibitory concentration (MIC) and minimum sterilization concentration (MBC) were determined using the Oxford cup method and agar dilution method,respectively.The results indicated a synergistic antibacterial effect of the Re-SOA complexes,demonstrating significantly enhanced antibacterial activity compared to organic acids (SOA) and rare-earth ions (Re3+) alone.The antibacterial activity of the Re-SOA complexes followed the order:Yb-SOA>Gd-SOA>La-SOA,with Yb-Ac (Ac:acetic acid) exhibiting MIC values of 0.27,0.53,and 0.53 mmol·L-1,and MBC values of 0.53,0.53,and 0.53 mmol·L-1 against the three path-ogenic bacteria,respectively.Further investigation into the cellular mechanisms of action using field e-mission scanning electron microscopy (FESEM),transmission electron microscopy (TEM),and tran-scriptome sequencing revealed that Re-SOA effectively inhibits bacterial growth by targeting key metabolic pathways,including carbohydrate metabolism,energy metabolism,amino acid metabolism,and biofilm formation.Re-SOA,as a novel antibacterial agent,exhibits high efficacy and safety.This research pro-vides a promising approach for developing novel antibacterial agents and offers a potential solution to the critical issue of antibiotic resistance in animal husbandry.

The overuse of antibiotics in animal husbandry has resulted in escalating animal safety con-cerns,highlighting the urgent need for a safe and effective alternative to traditional acidifiers.necessita-ting the development of safe and effective alternatives to traditional acidifiers.This study investigates the antibacterial activity and underlying mechanisms of rare-earth organic acid complexes (Re-SOA),a promising alternative to traditional acidifiers,against three common poultry and livestock pathogens:Escherichia coli,Staphylococcus aureus,and Salmonella.A series of Re-SOA were synthesized via a liq-uid-phase method.Structural characterization using infrared spectroscopy,X-ray photoelectron spectros-copy,and Raman spectroscopy confirmed successful complexation.The minimum inhibitory concentration (MIC) and minimum sterilization concentration (MBC) were determined using the Oxford cup method and agar dilution method,respectively.The results indicated a synergistic antibacterial effect of the Re-SOA complexes,demonstrating significantly enhanced antibacterial activity compared to organic acids (SOA) and rare-earth ions (Re3+) alone.The antibacterial activity of the Re-SOA complexes followed the order:Yb-SOA>Gd-SOA>La-SOA,with Yb-Ac (Ac:acetic acid) exhibiting MIC values of 0.27,0.53,and 0.53 mmol·L-1,and MBC values of 0.53,0.53,and 0.53 mmol·L-1 against the three path-ogenic bacteria,respectively.Further investigation into the cellular mechanisms of action using field e-mission scanning electron microscopy (FESEM),transmission electron microscopy (TEM),and tran-scriptome sequencing revealed that Re-SOA effectively inhibits bacterial growth by targeting key metabolic pathways,including carbohydrate metabolism,energy metabolism,amino acid metabolism,and biofilm formation.Re-SOA,as a novel antibacterial agent,exhibits high efficacy and safety.This research pro-vides a promising approach for developing novel antibacterial agents and offers a potential solution to the critical issue of antibiotic resistance in animal husbandry.