ObjectiveTo analyze the research hotspot and future trend of non-invasive brain stimulation (NIBS) in Alzheimer's disease. MethodsRelevant literature on application of NIBS in Alzheimer's disease from January, 2014 to October, 2024 was retrieved from the Web of Science Core Collection database. CiteSpace 6.4.R1 was used to perform a bibliometric analysis and to create knowledge maps, including annual publication volume, countries, institutions, authors, keywords and co-cited references. ResultsA total of 731 articles were included, showing an increasing trend in annual publication volume. The United States was the leading country in publication volume, Harvard University was the most productive institution, and Giacomo Koch was the most prolific author. Brain Stimulation was the most frequently cited journal. Highly focused keywords included cognitive impairment, memory, dementia, transcranial magnetic stimulation and transcranial direct current stimulation. Bursting keywords in the past two years included transcranial alternating current stimulation, functional magnetic resonance imaging, brain-derived neurotrophic factor and oxidative stress. ConclusionResearch interest in NIBS within the field of Alzheimer's disease has been steadily increasing. The research hotspots include the effect and mechanism of NIBS on cognitive function and the impact of stimulating different brain regions on cognitive outcome. Future research may focus on integrating NIBS with techniques such as functional magnetic resonance imaging to achieve individualized and precise stimulation.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective:To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL).Methods:Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis.Results:The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis ( HR=3.09, 95% CI 1.10-8.72), combined relapse ( HR=4.26, 95% CI 1.34-13.52) and CAR-T cell therapy after relapse ( HR=0.15,95% CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions:The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

Objective:To explore the clinical efficacy and safety of CCR (cyclophosphamide+clarithrobin+rituximab) regimen in the treatment of hairy cell leukemia (HCL).Methods:A retrospective case series study was performed. The clinical data of 4 HCL patients who received the treatment of single course CCR regimen in the First Affiliated Hospital of Nanjing Medical University from October 2015 to March 2023 were collected. The short-term efficacy and safety of CCR regimen were summarized, and the survival status of patients was evaluated by using Kaplan-Meier method.Results:All 4 patients were initial-treated classic HCL, including 3 males and 1 female, with a median age of 46 years old (range: 41-66 years old). The median follow-up time of 4 patients was 34.5 months (range: 4-92 months). Four months after the end of treatment, 3 patients achieved complete remission (CR), and 1 patient achieved partial remission (PR); none of 3 CR patients had minimal residual disease. The prognostication of Kaplan-Meier method showed that all 4 patients had progression-free survival and overall survival at 5 years. No serious drug-related adverse events occurred during the treatment process. No infusion response related to rituximab occurred. Two patients developed grade 1 fatigue, 1 patient developed grade 2 pneumonia; 1 patient developed grade 4 granulocytopenia, 3 patients developed grade 4 thrombocytopenia, and no bleeding event occurred; all adverse reactions were controllable.Conclusions:The single course CCR regimen has good efficacy and safety in treating HCL, and it can serve as a new attempt in clinical treatment of HCL.

Objective:To observe the therapeutic effect of compound Duzhong Jiangu granule on Kashin-Beck disease (KBD), and to provide a new alternative for the treatment of patients with KBD.Methods:According to the principle of random distribution, patients with KBD diagnosed clinically in Linyou County and Yongshou County of Shaanxi Province who meet the inclusion criteria were divided into a traditional Chinese medicine group and a Western medicine group, and they were treated with compound Duzhong Jiangu granule (Chinese medicine group) and ibuprofen sustained release capsule + 21 jinvita + chondroitin sulfate (Western medicine group), respectively, for a duration of one month. Questionnaire survey was conducted to collect the clinical data of all survey respondents before and after medication by using the Joint Dysfunction Index Scale and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scales, for evaluation and analysis. The incidence of adverse reactions of the two groups were recorded.Results:A total of 218 KBD patients that met the inclusion criteria were selected, including 167 patients in the Chinese medicine group and 51 patients in the Western medicine group. There were 94 males and 73 females in the Chinese medicine group, aged (62.93 ± 6.72) years. In the Western medicine group, there were 18 males and 33 females, aged (63.29 ± 7.02) years. There was no statistically significant difference in age between the two groups ( Z = - 0.24, P = 0.813). After taking the compound Duzhong Jiangu granules for treatment of KBD patients in the traditional Chinese medicine group, there were significant changes in the number of patients with joint rest pain, joint movement pain, morning stiffness, maximum walking distance and lower limb mobility in the Joint Dysfunction Scale compared to before treatment. The difference between before and after medication was statistically significant (χ 2 = 37.93, 29.64, 50.40, 13.57, 25.25, P < 0.001). After 1 month of medication, there were 13 cases of significant effect, 64 cases of effectiveness, and 90 cases of ineffectiveness in the traditional Chinese medicine group, with a total effective rate of 46.11%. There were 0 cases of significant improvement, 13 cases of effectiveness, and 38 cases of ineffectiveness in the Western medicine group, with a total effective rate of 25.49%. The difference in total effective rates between the two groups was statistically significant (χ 2 = 8.62, P = 0.013). In addition, there was a statistically significant difference in the improvement of lower limb mobility (difficulty of daily activities) between the Chinese medicine group and the Western medicine group (χ 2 = 8.21, P = 0.017). After taking medication, the joint pain, stiffness, and difficulty of daily activities scores in the WOMAC scale of KBD patients in the Chinese medicine group and the Western medicine group were significantly reduced. The differences in scores before and after medication were statistically significant (Chinese medicine group, Z = - 7.60, - 7.74, - 9.75, P < 0.001; Western medicine group, Z = - 5.20, - 3.81, - 3.93, P < 0.001). There was a significant differences in the improvement degree of daily activity difficulty and total score between the Chinese medicine group and the Western medicine group ( Z = - 3.75, - 3.34, P < 0.01). During the medication period, the incidence of adverse reactions in the traditional Chinese medicine group was lower than that in the western medicine group (Chinese medicine group, 29.34%; Western medicine group, 45.09%, χ 2 = 4.38, P = 0.036). Conclusions:Compound Duzhong Jiangu granule has a good therapeutic effects on KBD, significantly improving joint dysfunction of patients. It has advantages in improving the activity ability of KBD patients and reducing the difficulty of daily activities, and has less adverse reactions else.

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Cohen syndrome. METHODS: A proband who was admitted to Zhengzhou People's Hospital on June 2, 2021 due to intellectual disability and developmental delay, in addition with her younger sister and other family members, were selected as the study subjects. Clinical data of the proband and her younger sister were collected. Genomic DNA was extracted from peripheral venous blood and chorionic villi samples. Chromosomal abnormalities were detected with chromosomal microarray analysis (CMA). Whole exome sequencing (WES) and Sanger sequencing were carried out to detect candidate variants in the proband. With RNA extracted from the peripheral blood samples, VPS13B gene transcripts and expression were analyzed by PCR and real-time quantitative PCR. Prenatal diagnosis was carried out at 12 weeks' gestation. RESULTS: The proband was a 10-year-old female with clinical manifestations including development delay, obesity, severe myopia and peculiar facial features. Her sister was 3 years old with a similar phenotype. CMA revealed no chromosomal abnormality in the proband, while WES results revealed that the proband and her sister had both harbored compound heterozygous variants of the VPS13B gene, namely c.10076_10077delCA (p.T3359fs*29) and c.6940+1G>T, which were respectively inherited from their mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PS4+PM4+PP1; PVS1+PM2_Supporting+PM3+PP1). In vivo splicing assay confirmed that the c.6940+1G>T variant has produced a frameshift transcript with skipping of exon 38. Compared with the control group, the expression of RNA in the peripheral blood of the proband's parents has decreased to 65% ~ 70% (P < 0.01), whilst that in the proband and her sister has decreased to 40% (P < 0.001). Prenatal diagnosis at 12 weeks of gestation has found that the fetus only harbored the heterozygous c.10076_ 10077delCA variant. CONCLUSION The c.10076_10077delCA (p.T3359fs*29) frameshift variant and c.6940+1G>T splicing variant probably underlay the Cohen syndrome in this pedigree. Genetic testing has facilitated the diagnosis of this disease.
Female ; Humans ; East Asian People ; Intellectual Disability/genetics* ; Mutation ; Myopia/genetics* ; Pedigree ; Vesicular Transport Proteins/genetics* ; Child, Preschool ; Child

Background The safety of drinking water is closely related to people's health. In recent years, relevant studies have identified some health related problems with drinking water in Inner Mongolia Autonomous Region. The complex and diverse natural environment embraced by the vast jurisdiction of the region may lead to uneven drinking water quality across the region. Objective To evaluate eight chemicals including arsenic, cadmium, chromium (hexavalent), lead, mercury, fluoride, trichloromethane, and carbon tetrachloride in urban drinking water in Inner Mongolia Autonomous Region in 2021, and to provide reference for optimizing urban water supply system and ideas for further developing strategies to promote population health. Methods A total of 1228 monitoring sites were set up in urban areas of Inner Mongolia, and water samples were collected once in dry season (May) and once in wet season (August−September). Eight chemicals of interest in drinking water were detected according to the Standard examination methods for drinking water, and assessed for health risks using the health risk assessment model recommended by the United States Environmental Protection Agency (USEPA) and following the Technical guide for environmental health risk assessment of chemical exposure. Mann-Whitney U test was used to compare the concentrations of eight chemicals in urban drinking water by water seasons and water sample types. Results In 2021, a total of 2381 samples of urban drinking water were tested in the Inner Mongolia Autonomous Region, including 1195 samples in wet season and 1186 samples in dry season; 389 samples of finished water and 1992 samples of tap water. The positive rates of arsenic and fluoride were 26.25% and 96.77%, respectively. The positive rates of cadmium, chromium (hexavalent), lead, mercury, trichloromethane, and carbon tetrachloride were 6.22%, 16.63%, 6.09%, 16.67%, 18.98%, and 8.36%, respectively. The exceeding standard rate of fluoride was 4.87%. Trichloromethane and carbon tetrachloride were qualified in all samples. There were statistical differences in the concentrations of arsenic, cadmium, chromium (hexavalent), lead, and carbon tetrachloride in urban drinking water between water seasons (Z=−3.847, P<0.05; Z=2.464, P=0.014; Z=−3.129, P=0.002; Z=4.341, P<0.05; Z=4.342, P<0.05). Only fluoride concentration was found statistically different among different water sample types (Z=−2.287, P=0.022). The non-carcinogenic risks of ingestion and dermal exposure to each chemical in drinking water by water seasons and water sample types were all less than 1, but the P₉₅ total non-carcinogenic risks of oral exposure were greater than 1. The P₉₅ carcinogenic risks of oral exposure to some chemicals in drinking water by water seasons and water sample types were>10⁻⁴, which suggested carcinogenic risks, while the carcinogenic risks of dermal explore to chemicals were all less than 10⁻⁶. Conclusion In 2021, urban drinking water in Inner Mongolia Autonomous Region is generally safe, but arsenic, cadmium, chromium (hexavalent), lead, mercury, and fluoride still exceed the national limits, posing certain health risks.

Objective:To investigate the effects of massive blood transfusion on serum electrolyte balance and serum levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in patients with severe trauma.Methods:A total of 83 patients with severe trauma who received treatment in Eastern District of LiHuili Hospital, Ningbo Medical Center between July 2019 and December 2020 were included in this study. All of them underwent blood transfusion. They were divided into massive blood transfusion group ( n = 29) and general blood transfusion group ( n = 54) according to the volume of blood transfused. Changes in coagulation function, electrolyte, liver-kidney function and inflammatory factor levels pre- and post-blood transfusion were compared between massive blood transfusion and general blood transfusion groups. Results:At 1 day after blood transfusion, activated partial thromboplastin time (APTT) and prothrombin time (PT) in the massive blood transfusion group were (45.64 ± 2.78) seconds and (17.71 ± 2.08) seconds, respectively, which were significantly longer than those in the general blood transfusion group [(41.02 ± 2.80) seconds, (15.35 ± 1.72) seconds, t = 5.53, 7.18, P < 0.05). At 1 day after blood transfusion, levels of tumor necrosis factor-α, interleukin-6 and C-reaction protein in the massive blood transfusion group were (1.84 ± 0.32) μg/L, (113.72 ± 13.34) ng/L, (28.94 ± 4.22) mg/L, respectively, which were significantly increased compared with those measured before blood transfusion [(1.28 ± 0.29) μg/L, (95.18 ± 10.64) ng/L, (16.48 ± 3.37) mg/L, t = 6.98, 5.85, 12.42, all P < 0.05]. Levels of tumor necrosis factor-α, interleukin-6 and C-reaction protein in the general blood transfusion group were (1.34 ± 0.27) μg/L, (98.54 ± 9.62) ng/L, (20.05 ± 3.30) mg/L, respectively at 1 day after blood transfusion, which were significantly increased compared with those measured before blood transfusion [(1.23 ± 0.26) μg/L, (94.22 ± 8.82) ng/L, (16.16 ± 3.39) mg/L, t = 2.15, 2.43, 6.04, all P < 0.05]. At 1 day after blood transfusion, serum levels of tumor necrosis factor-α and C-reaction protein in the massive blood transfusion group were significantly higher than those in the general blood transfusion group ( t = 7.53, 10.59, both P < 0.05). At 1 day after blood transfusion, serum levels of K + and Ca 2+ in the massive blood transfusion group were (3.56 ± 0.54) mmol/L and (1.87 ± 0.28) mmol/L, respectively, which were significantly lower than those in the general blood transfusion group [(4.27 ± 0.34) mmol/L, (2.26 ± 0.24) mmol/L, t = 7.34, 6.65, both P < 0.05]. Serum levels of alanine aminotransferase and aspartate aminotransferase in the massive blood transfusion group were (52.46 ± 20.27) U/L, (82.37 ± 31.15) U/L, respectively, which were significantly higher than those in the general blood transfusion group [(37.57 ± 10.31) U/L, (49.35 ± 10.14) U/L, t = 4.44, 7.14, both P < 0.05)]. The incidence of abnormal liver function in the massive blood transfusion group was significantly higher than that in the general blood transfusion group [62.07% (18/29) vs. 29.63% (16/54), χ2 = 10.13, P < 0.05)]. Conclusion:The internal environment of patients with severe trauma will change after massive blood transfusion. Their coagulation function, inflammatory factors, liver function and electrolyte balance should be monitored in time.

Objective:To explore the effects of continuous nursing based on Siebens domain management model (SDMM) in patients with severe cerebral hemorrhage.Methods:A total of 284 patients with severe cerebral hemorrhage admitted to the Department of Neurology of Zhumadian Central Hospital from July 2019 to June 2020 were selected and randomly divided into control group and observation group, with 142 cases in each group. Patients in the control group were treated with conventional continuous nursing intervention, while patients in the observation group were treated with continuous nursing based on SDMM. Both groups were intervented for 3 mouths. The National Institutes of Health Stroke Scale (NIHSS) and the MOS 36-Item Short-Form Health Survey (SF-36) were used to compare the neurological function and quality of life of the two groups before and after the intervention.Results:The NIHSS scores of the two groups of patients after the intervention were lower than those before the intervention, and the NIHSS score of the observation group was lower than that of the control group after the intervention, with statistically significant differences ( P< 0.01) . After the intervention, the SF-36 scores of physiological function, energy, general health and mental health in the observation group were higher than those in the control group, and the differences were statistically significant ( P< 0.01) . Conclusions:Continuous nursing based on SDMM can effectively improve neurological function and quality of life in neurological patients with severe cerebral hemorrhage, which is worth promoting in clinical practice.