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.

Thanks to the application of gene modification technology, the development of new immunosuppressant and the shift towards using pigs as the main organ donors, xenotransplantation has embarked on a new round of "ice-breaking journey". Xenotransplantation demonstrates strong positive value in addressing the imbalance between organ supply and demand, extending the lives of patients with organ failure and enhancing human physical functions. However, xenotransplantation also raises a series of ethical risks, such as safety concerns over health damage and virus transmission, the hollowing out of the principle of informed consent, the impairment of individual identity and independence, and the distribution fairness of access and capability for trials. To address these issues, a mechanism combining prior general consent and specific consent during the process should be established, along with a dynamic and traceable consent procedure to safeguard patient autonomy. A "waterfall-style" regulatory system and a mechanism for aggregating cutting-edge technologies should be created to enhance the safety of xenotransplantation. Distribution and governance rules should be formulated according to different stages and goals of xenotransplantation exploration to improve fairness. A typological approach should be used to determine which groups of people can undergo xenotransplantation under current medical conditions to achieve the minimization of harm.

Objective: To investigate the effects of RING 1 and YY1 binding protein (RYBP), a member of the polycomb group (PcG), on bladder cancer cell proliferation and invasion, as well as the underlying mechanisms involved, so as to provide reference for the prevention and treatment of bladder cancer. Methods: Overexpressing and knocking down of RYBP were achieved in bladder cancer cell lines (T24, UM-UC-3, and 5637) via plasmids or siRNAs.Cell proliferation was assessed via thiazolyl blue (MTT) and colony formation assays, whereas migration was evaluated via scratch and Transwell assays.Changes in epithelial-mesenchymal transition (EMT) markers and other related proteins were examined with Western blotting. Results: RYBP overexpression significantly inhibited bladder cancer cell proliferation, invasion, and migration, whereas RYBP knockdown promoted these behaviors.Western blotting results revealed that RYBP overexpression downregulated the expressions of EMT markers N-cadherin, Vimentin, and Slug, but upregulated the expression of E-cadherin.Conversely, RYBP knockdown upregulated the expressions of N-cadherin, Vimentin, and Slug, while reducing the expression of E-cadherin. Conclusion: RYBP appears to inhibit the proliferation and migration of bladder cancer cells via the EMT pathway, indicating its potential application in bladder cancer therapies.

Objective: To investigate the spatio-temporal clustering characteristics of influenza in Ningxia Hui Autonomous Region from 2014 to 2023, so as to provide the basis for strengthening influenza prevention and control. Methods: Data pertaining to influenza cases reported in Ningxia Hui Autonomous Region from 2014 to 2023 were retrieved from the Infectious Disease Surveillance System of the Chinese Disease Prevention and Control Information System, including age, sex, current residence, onset date, and reporting date. The seasonal incidence of influenza was analyzed using seasonal index. The spatio-temporal clustering characteristics of influenza were identified using spatial autocorrelation analysis and spatio-temporal scan analysis. Results: A total of 20 377 influenza cases were reported in Ningxia Hui Autonomous Region from 2014 to 2023, with a male-to-female ratio of 1.15∶1. The majority were children under 15 years, with 10 950 cases accounting for 53.74%. Influenza was highly prevalent in January, February, March, and December, with seasonal indices of 219.06%, 111.00%, 246.65%, and 366.24%, respectively. The average annual reported incidence was 29.55/100 000, among which Pengyang County, Jinfeng District, Dawukou District, Xiji County, and Litong District had higher average annual reported incidence, at 63.99/100 000, 55.71/100 000, 55.70/100 000, 49.49/100 000, and 49.04/100 000, respectively. Spatial autocorrelation analysis showed that in 2023, there was spatial clustering of influenza cases in Ningxia Hui Autonomous Region (Moran's I=0.333, P<0.05), with a high-high cluster in Jingyuan County, while in other years, the distribution of influenza cases was random (all P>0.05). Spatio-temporal scan analysis showed that from 2014 to 2023, there were four space-time clusters in Ningxia Hui Autonomous Region, including one type Ⅰ cluster in Hongsibao District of Wuzhong City, with the clustering period from January 20 to 26, 2014; and three type Ⅱ clusters, mainly in January, February, March and December, covering one area in Shizuishan City, five areas in Guyuan City, one area in Zhongwei City, three areas in Wuzhong City, and four areas in Yinchuan City. Conclusions From 2014 to 2023, children under 15 years were the primary population affected by influenza in Ningxia Hui Autonomous Region, with distinct spatio-temporal distribution characteristics. The peak incidence occurred during the winter and spring seasons, and the main clustering areas were in the southern regions.

Objective:To explore the genetic and clinical characteristics of Guizhou patients with enlarged vestibular aqueduct（EVA） syndrome through combined SLC26A4 variant analysis and clinical phenotype analysis. Methods:Seventy-two EVA patients underwent comprehensive genetic testing using a multiplex PCR-based deafness gene panel and next-generation sequencing（NGS）. The audiological and temporal bone imaging characteristics were compared across mutation subtypes. Results:A total of 27 pathogenic loci of SLC26A4 were detected in 72 patients, including c.919-2A>G in 79.2%（57/72）. A novel deletion（c.1703_1707+6del） was discovered. Among 65 cases, truncated mutations were 89.2%（58/65）, 52.3%（34/65）, 28（43.1%） and 7（10.8%）. No significant differences were observed in the midpoint diameter of the vestibular aqueduct and the incidence of incomplete partitioning typeⅡ（IP-Ⅱ） of the cochlea among the three groups of patients. Moreover, there was no difference in the midpoint diameter of different vestibular pipes or the combination with IP-Ⅱ. Conclusion:The most common mutation site of SLC26A4 in EVA patients in Guizhou is c.919-2A>G, though genotype-phenotype correlations remain elusive. The detection of 27 mutation sites and the discovery of new mutation sites suggested the precise diagnostic significance of NGS technology in EVA patients in Guizhou.
Humans ; Sulfate Transporters ; Vestibular Aqueduct/abnormalities* ; Mutation ; Membrane Transport Proteins/genetics* ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Adult ; Young Adult ; Phenotype ; High-Throughput Nucleotide Sequencing

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

There is a certain correlation and interaction between circulating tumor cells and recurrence-metastasis of colorectal cancer. The circulating tumor cells hidden in the human body can lead to the recurrence and metastasis of colorectal cancer， and the recurrence and metastasis of colorectal cancer can in turn cause a sharp increase in the number of circulating tumor cells， which is consistent with the characteristics of latent pathogens in traditional Chinese medicine leading to diseases. Starting from the theory of latent pathogens， this article summarized the etiology and disease mechanism of recurrence-metastasis of colorectal cancer as harmed healthy qi， latent pathogenic qi， prolonged latent pathogens， and triggering healthy qi deficiency. This article also proposes four major treatment methods as reinforcing healthy qi， assisting yang， opening the exterior， and expelling pathogen， in order to provide ideas and methods for the prevention and treatment of recurrence and metastasis of colorectal cancer.

ObjectiveTo evaluate the effect of transcranial direct current stimulation (tDCS) on the cognitive function and quality of life in patients with Parkinson's disease. MethodsRandomized controlled trials (RCTs) on tDCS for Parkinson's disease were searched in PubMed, Web of Science, Embase, Cochrane Library, CNKI, CBM, VIP and Wanfang Data from the inception to September, 2023. Control group was administered standard Parkinson's medications or placebo, physical therapy, and cognitive rehabilitation, while treatment group received tDCS additionally. The quality of the researches was evaluated using the Cochrane Risk of Bias Tool. Data synthesis and analysis were performed using RevMan 5.4 and Stata 17.0, with heterogeneity and sensitivity analyses. ResultsEight articles were included. tDCS significantly improved the scores of Montreal Cognitive Assessment (MD = 2.00, 95%CI 1.13 to 2.87, P < 0.001). However, there was no significant difference in the scores of Parkinson's Disease Questionnaire (MD = 0.73, 95%CI -5.78 to 7.23, P = 0.830), Beck Depression Inventory-Ⅱ(MD = -0.77, 95%CI -7.14 to 5.60, P = 0.810), and Unified Parkinson Disease Rating Scale-Ⅲ (MD = 1.60, 95%CI -0.77 to 3.97, P = 0.190). ConclusiontDCS may improve cognitive function of patients with Parkinson's disease.