BACKGROUND:Parkinson's disease has the main pathological changes in the midbrain,especially in the dense substantia nigra,leading to impaired motor and non-motor function in patients.At present,research is limited by cellular heterogeneity,and its pathogenesis still needs to be further elucidated.In recent years,single-cell RNA sequencing(scRNA-seq)has gradually been applied in neurodegenerative diseases,which is of great significance for understanding intercellular heterogeneity,disease development mechanisms,and treatment strategies. OBJECTIVE:To review the research progress of scRNA-seq technology applied to Parkinson's disease in recent years,providing a theoretical basis for the application of scRNA-seq in the treatment and diagnosis of Parkinson's disease. METHODS:The first author used a computer system to search for relevant literature in the CNKI,WanFang,PubMed,and Web of Science databases,with the Chinese search terms"single-cell RNA sequencing,Parkinson's disease,cell heterogeneity,cell subtypes,dopaminergic neurons,glial cells"and English search terms"single-cell RNA seq,Parkinson disease,heterogenicity,subtypes,dopaminergic neurons,glial cells."71 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:(1)scRNA-seq is a high-throughput experimental technique that utilizes RNA sequencing at the single-cell level to quantify gene expression profiles in specific cell populations,revealing cellular mysteries at the molecular level.Compared with traditional sequencing techniques,scRNA-seq technology is used to reveal the diversity of cell types and changes in specific gene expression in complex tissues under various physiological and pathological conditions through automatic clustering analysis of cell transcriptome.(2)By using scRNA-seq,the development process of dopaminergic neurons and the unique functional characteristics of various cell subtypes are elucidated,in order to better understand potential therapeutic molecular targets.(3)The use of scRNA-seq analysis has improved our understanding of the response of Parkinson's disease glial cells,enabling us to comprehensively map and characterize different cell type populations,identify specific glial cell subpopulations related to neurodegeneration,and draw valuable single cell maps as reference data for future research.(4)The application of scRNA-seq to detect embryonic mice and stem cells will help improve the in vitro differentiation protocol and quality control of cell therapy,as well as evaluate the overall cell quality and developmental stage of dopaminergic neurons derived from stem cells.

Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Abstract To investigate the effects of exercise on gut microbiota(GM) among children with autism spectrum disorder(ASD)，the review provides an in depth summary of the three core biological pathways through which exercise modulates the GM: repairing the integrity of the intestinal barrier to inhibit lipopolysaccharide mediated neuroinflammation; optimizing key metabolites, such as short chain fatty acids, to reshape gut-brain communication; synergistically regulating the tryptophan-kynurenine metabolic pathway and vagus nerve signaling to balance neurotransmitters. These interconnected pathways not only alleviate gastrointestinal discomfort but also provide a solid biological foundation for improving the core behavioral symptoms of ASD, such as social deficits and repetitive behaviors. Future research should focus on establishing standardized exercise intervention protocols, validating the efficacy of these key biological pathways using multi omics approaches, and exploring combined intervention strategies. The results of corollary studies will provide a more robust scientific basis for precision rehabilitation of children with ASD.

BACKGROUND: Meningeal metastasis (MM) is a form of malignant metastasis where tumor cells spread from the primary site to the pia mater, dura mater, arachnoid, subarachnoid space, and other cerebrospinal fluid compartments. Lung cancer is one of the most common malignant tumor types with MM. MM not only signifies that the lung cancer has progressed to an advanced stage but also leads to a range of severe clinical symptoms due to meningeal involvement. Currently, the risk factors associated with the development of MM are not fully elucidated. The aim of this study was to investigate the risk factors for MM in patients with lung adenocarcinoma (LUAD) who underwent non-surgical interventions, in order to identify LUAD patients at high risk for MM. METHODS: This retrospective study analyzed the clinical data of patients diagnosed with LUAD at the First Affiliated Hospital of Zhengzhou University from January 2020 to July 2024. Missing data were imputed using multiple imputation methods, and risk factors were identified through LASSO, univariate, and multivariate Logistic regression analyses. RESULTS: A total of 170 patients with LUAD were included in this study and divided into two groups: 87 patients with MM and 83 patients without MM. Univariate and multivariate Logistic regression analyses revealed that younger age at diagnosis (P=0.004), presence of the epidermal growth factor receptor (EGFR) L858R gene mutation (P=0.008), and concurrent liver metastasis at baseline (P=0.004) were independent risk factors for developing MM in LUAD patients who did not undergo surgical intervention. Conversely, higher baseline globulin levels (P=0.039) and the presence of the anaplastic lymphoma kinase (ALK) gene mutation (P=0.040) were associated with a reduced risk of MM development. CONCLUSIONS Age at diagnosis, EGFR L858R mutation status, ALK gene mutation status, concurrent liver metastasis, globulin levels at baseline were significantly associated with the risk of developing MM in patients with LUAD patients who did not undergo surgical intervention. For patients diagnosed at a younger age, carrying the EGFR L858R mutation, or presenting with baseline liver metastasis, early implementation of tertiary prevention strategies for MM is crucial. Regular monitoring of MM status should be conducted in these high-risk groups.
Humans ; Male ; Adenocarcinoma of Lung/therapy* ; Female ; Middle Aged ; Risk Factors ; Lung Neoplasms/therapy* ; Retrospective Studies ; Aged ; Meningeal Neoplasms/genetics* ; Adult

Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored. Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD's direct target. ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 via the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD's therapeutic efficacy against METH addiction. Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO-A1R signaling pathway.

BACKGROUND:The analgesic effect of stagnant moving needle on myofascial pain syndrome is remarkable,but the analgesic mechanism is still unclear.OBJECTIVE:To investigate the analgesic mechanism of stagnant moving needle acupuncture in the treatment of myofascial pain syndrome.METHODS:Fifty-four SD rats were randomly divided into a blank group(n=16)and a modeling group(n=38).The models of leftmyofascial pain syndrome in the modeling group were prepared by using the method of"striking combined with centrifugal movement".Twelve weeks after modeling,six mice were randomly selected to verify the success of the modeling.The rest of the 32 rats were randomly divided into the model group and the stagnant moving needle group,with 16 rats in each group.The stagnant needle moving group was treated by stagnant moving needle into the local excitation point nodule of the left medial vastus muscle fascia in rats,twice a week,for 4 weeks.The mechanical foot contraction reflex threshold of the leftfoot were measured weekly in the pre/post modeling and post-intervention groups of rats.At 4 weeks after treatment,hematoxylin-eosin staining was used to observe the morphological changes in the muscle tissue of the leftmedial femoral muscle of rats,ELISA was used to detect the levels of substance P and β-endorphin in the serum and the gray matter around the midbrain aqueduct.Immunohistochemistry was used to detect positive expression of microglia markers(Iba-1)and c-fos in the gray matter around the midbrain aqueduct.Western blot assay was used to detect the expression level of brain-derived neurotrophic factor protein in the periaqueductal gray.RESULTS AND CONCLUSION:Compared with the blank group,the mechanical pain threshold of the rats in the model group and the stagnant moving needle group decreased after modeling(P<0.05).After 4 weeks of treatment,the mechanical pain threshold of the rats in the stagnant moving needle group was higher than that in the model group(P<0.05).Hematoxylin-eosin staining results showed that in the model group,the muscle fibers of the leftlower limb medial femoral muscle of rats were disorganized,unequal in thickness,myocytes were enlarged,with inward movement of the nucleus,rounded contracture nodules and tension bands;whereas in the stagnant moving needle group,the muscle fibers were arranged in a neat way,the myocytes were angular,and the contracture nodules were occasionally seen.Compared with the blank group,the expression of substance P in the serum of the model group was significantly higher(P<0.05),while the levels of β-endorphin in serum and substance P and β-endorphin in brain were decreased(P<0.01).Compared with the model group,the level of serum substance P in the stagnant moving needle group was decreased(P<0.05),and the levels of serum β-endorphin and brain substance P and β-endorphin were increased(P<0.05).Compared with the blank group,the positive expression of c-fos and Iba-1 and the protein of brain-derived neurotrophic factor in the model group were increased(P<0.05).Compared with the model group,the positive expression of c-fos in the stagnant moving needle group was increased(P<0.05),and the positive expression of Iba-1 and the protein of brain-derived neurotrophic factor were decreased(P<0.05).These findings suggest that stagnant moving needle may indirectly promote the release of β-endorphin by microglia polarized to the M2 phenotype and increase the excitability of c-fos neurons by inhibiting the activity of microglia in the gray matter around the periaqueductal gray and downregulating the expression of brain-derived neurotrophic factor protein,thereby reducing the degree of central sensitization and effectively relieving myofascial pain syndrome.

Objective:To investigate depressive symptoms and associated factors among precariously em-ployed individuals(PEI).Methods:A total of 11 031 residents were selected by a combination of stratified sam-pling and quota sampling from 120 cities nationwide according to the proportion of the seventh national population census in 2021,including 1 829 PEI.New general self-efficacy scale,short-form of family health scale,12-item short-form health literacy questionnaire,Patient Health Questionaire-9items used to evaluate self-efficacy,family health,health literacy and depressive symptoms.among people with precarious employment.Results:The prevalence of depressive symptoms in PEI was 21.0％.Male gender(OR=1.30)was risk factors for depressive symptoms in PEI.Age 46 to 55 years(OR=0.39),junior middle school graduate(OR=0.46),and high family health(OR=0.90)were protective factors for depressive symptoms in PEI.The structural equation model showed that the family health scores were negatively correlated with the depression scores(β=-0.13,P＜0.001),while family health scores were positively correlated with health literacy scores(β=0.10,P＜0.01)and self-efficacy scores(β=0.66,P＜0.001).The self-efficacy scores were negatively correlated with the depression scores(β=-0.11,P＜0.001).Conclusion:The prevalence of depressive symptoms in PEI is high.Young age,male gender,high educa-tional level and lower family health are the risk factors of depression,while health literacy and self-efficacy play protective roles.

The clinical diagnosis and treatment of urinary tract infection has long faced the challenges of insufficient standardization of diagnosis and treatment pathways,irrational use of antimicrobial drugs and high recurrence rate.How to optimize the hierarchical diagnosis and treatment pathway of urinary tract infection,standardize the use of antimicrobial drugs,and reduce the recurrence rate have always been the focus of clinical attention.There is significant heterogeneity in the existing diagnostic criteria for urinary tract infection,which seriously affects the comparability and evidence integration of clinical and research studies.In order to solve the above problems,a consensus on global multidisciplinary diagnostic criteria for urinary tract infection has been formed by international multidisciplinary experts after three rounds of Delphi method.Breaking through the traditional classification framework,the consensus innovatively established a four-dimensional quantitative scoring system including local symptoms and signs,systemic inflammatory response,quantitative analysis of pyuria and urine culture results,and established a hierarchical standard for stepwise urinary tract diagnosis according to the scoring threshold.Based on the key citations related to the consensus,this paper interprets in detail the basis for the selection of core indicators and the establishment of thresholds for the diagnosis of urinary tract infection in the consensus,and focuses on the key issues and implementation paths of the consensus in localization practice.This consensus provides a unified standard for standardizing the clinical diagnosis and treatment of urinary tract infection,improving the homogeneity of clinical research through standardized diagnostic processes,and promoting the standardization of UTI drug research and development and the rational use of antibiotics and precision.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.