Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Objective To analyze the metabolic changes of myocardial tissue in rats under acute exposure to macleaya cordata by gas chromatography mass spectrometry(GC-MS),explore forensic identifications of its characteristic metabolites,and verify its toxicological mechanism in poisoning cases.Methods The rats in the exposure group were given 382 mg/kg macleaya extract solution by gavage,and the rats in the control group were given the same dose of solvent.The myocardial samples were analyzed by GC-MS,and pattern recognition was conducted through partial least squares discriminant analysis(PLSDA).The differential metabolites with characteristic changes were identified by variable importance projection(VIP value＞1)and Student's t test(P＜0.01).Results Compared with the control group,21 potential characteristic metabolites were identified.Through KEGG pathway enrichment analysis,it was found that these metabolites were mainly involved in the pathways of glycine,serine and threonine metabolism;pyruvate metabolism and glycerolipid metabolism.Conclusion Through the study of myocardial metabolism in rats exposed to macleaya cordata,we found the information on metabolites closely related to poisoning,which provides new insight and reference for studies on the mechanisms of macleaya cordata poisoning in the field of forensic medicine.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To assess the effects of repeated mild traumatic brain injury(rmTBI)in the parietal cortex on neuronal morphology and synaptic plasticity in the medulla oblongata of mice.Methods Thirty-two male ICR mice were randomly divided into sham operation group(n=8)and rmTBI group(n=24).The mice in the latter group were subjected to repeated mild impact injury of the parietal cortex by a free-falling object.The mice surviving the injuries were evaluated for neurological deficits using neurological severity scores(NSS),righting reflex test and forced swimming test,and pathological changes of the neuronal cells in the medulla oblongata were observed with HE and Nissl staining.Western blotting and immunofluorescence staining were used to detect the expressions of neuroligin 1(NLG-1)and postsynaptic density protein 95(PSD-95)in the medulla oblongata of the mice that either survived rmTBI or not.Results None of the mice in the sham-operated group died,while the mortality rate was 41.67%in rmTBI group.The mice surviving rmTBI showed significantly reduced NSS,delayed recovery of righting reflex,increased immobility time in forced swimming test(P<0.05),and loss of Nissl bodies;swelling and necrosis were observed in a large number of neurons in the medulla oblongata,where the expression levels of NLG-1 and PSD-95 were significantly downregulated(P<0.05).The mice that did not survive rmTBI showed distorted and swelling nerve fibers and decreased density of neurons in the medulla oblongina with lowered expression levels of NLG-1 and PSD-95 compared with the mice surviving the injuries(P<0.01).Conclusion The structural and functional anomalies of the synapses in the medulla oblongata may contribute to death and neurological impairment following rmTBI in mice.

NLRP3 can recruit proteins such as ASC and pro-caspase1 to form NLRP3 inflammasomes after being stimulated by pathogen and danger signals in vivo,and then induce pyropto-sis and promote the inflammatory reactions to maintain the home-ostasis.However,the overactivation of NLRP3 inflammasomes is closely related to many inflammatory and autoimmune diseases in humans.Targeted inhibition of NLRP3 inflammasomes can sig-nificantly inhibit inflammation and alleviate the relative symp-toms.Therefore,it is an important research direction for treating diseases of NLRP3 inflammasome that searching for effective in-hibitors targeting NLRP3 inflammasome activation and achieving clinical transformation.This review summarizes the latest re-search progress based on the sources of NLRP3 inflammasome inhibitors.

Objective To assess the effects of repeated mild traumatic brain injury(rmTBI)in the parietal cortex on neuronal morphology and synaptic plasticity in the medulla oblongata of mice.Methods Thirty-two male ICR mice were randomly divided into sham operation group(n=8)and rmTBI group(n=24).The mice in the latter group were subjected to repeated mild impact injury of the parietal cortex by a free-falling object.The mice surviving the injuries were evaluated for neurological deficits using neurological severity scores(NSS),righting reflex test and forced swimming test,and pathological changes of the neuronal cells in the medulla oblongata were observed with HE and Nissl staining.Western blotting and immunofluorescence staining were used to detect the expressions of neuroligin 1(NLG-1)and postsynaptic density protein 95(PSD-95)in the medulla oblongata of the mice that either survived rmTBI or not.Results None of the mice in the sham-operated group died,while the mortality rate was 41.67%in rmTBI group.The mice surviving rmTBI showed significantly reduced NSS,delayed recovery of righting reflex,increased immobility time in forced swimming test(P<0.05),and loss of Nissl bodies;swelling and necrosis were observed in a large number of neurons in the medulla oblongata,where the expression levels of NLG-1 and PSD-95 were significantly downregulated(P<0.05).The mice that did not survive rmTBI showed distorted and swelling nerve fibers and decreased density of neurons in the medulla oblongina with lowered expression levels of NLG-1 and PSD-95 compared with the mice surviving the injuries(P<0.01).Conclusion The structural and functional anomalies of the synapses in the medulla oblongata may contribute to death and neurological impairment following rmTBI in mice.

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

This study assessed and explored the pharmacological effects and mechanisms of action of IMMH002 {2-amino-2-(2-(4ʹ-(2-ethyloxazol-4-yl)-[1,1ʹ-biphenyl]-4-yl)ethyl)propane-1,3-dio}, a selective sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator, in a concanavalin A (ConA)-induced autoimmune hepatitis (AIH) mouse model. The experimental protocol strictly adhered to the guidelines of the Ethics Committee for Animal Research of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No.: 00004046). Male ICR mice were pre-treated with the drug for four days, followed by induction of AIH through tail vein injection of ConA protein. Liver function, hepatic tissue pathology, peripheral blood parameters, as well as immunoglobulin G (IgG), inflammatory cytokines, T cell distribution, and inflammatory pathways were evaluated in mice. Results demonstrated that IMMH002 significantly reduced liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated hepatic tissue inflammation and necrotic damage, decreased serum IgG levels, and lowered the expression of inflammatory mediators including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). Additionally, it facilitated T lymphocyte homing, downregulated the phosphorylation of nuclear factor kappa-B (NF-κB), IκB kinase β (IKKβ) and nuclear factor inhibitor protein-α (IκBα) proteins in hepatic tissue and cellular inflammation models. Collectively, IMMH002 effectively ameliorated ConA-induced autoimmune hepatitis in mice, exhibiting extensive anti-inflammatory and anti-necrotic effects, thereby laying a theoretical foundation for AIH clinical treatment.