The NOD-like receptor protein 3(NLRP3)inflammasome is essential in innate immune-mediated inflammation,with its overactivation implicated in various autoinflammatory,metabolic,and neurode-generative diseases.Pharmacological inhibition of NLRP3 offers a promising treatment strategy for in-flammatory conditions,although no medications targeting the NLRP3 inflammasome are currently available.This study demonstrates that clioquinol(CQ),a clinical drug with chelating properties,effec-tively inhibits NLRP3 activation,resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages,with a half maximal inhibitory concentration(IC50)of 0.478 μM.Additionally,CQ mitigates experimental acute peritonitis,gouty arthritis,sepsis,and colitis by lowering serum levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Mechanistically,CQ covalently binds to Arginine 335(R335)in the NACHT domain,inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein.Collectively,this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

ObjectiveTo investigate the epidemiological characteristics of hand, foot, and mouth disease (HFMD) in Baoshan District of Shanghai from 2008 to 2023, and to provide scientific evidence for surveillance and standardized management of HFMD. MethodsCase data for HFMD reported in the China Disease Control and Prevention Information System from 2008 to 2023 were collected. Descriptive epidemiological methods were used to analyze the population characteristics, and the Joinpoint regression models were applied to assess the temporal trends of HFMD in Baoshan District. ResultsA total of 43 853 HFMD cases were reported from 2008 to 2023 in Baoshan District, with a male-to-female ratio of 1.50∶1. The majority of cases were children, among which scattered children and preschool children accounted for 54.67% and 36.58%, respectively, with 88.00% occurring in children under 5 years old. The average annual incidence rate was147.22/100 000 individuals. The pathogen detection rate in 2018 was 58.60% (109/186). Prior to 2020, CoxA16 was the predominant strain, while EV71 was not detected after 2019. ConclusionThe incidence of HFMD in Baoshan District of Shanghai was influenced by multiple factors including the inclusion in the notifiable infectious disease surveillance system, the introduction of EV71 vaccination, and the COVID-19 pandemic timeline. Populations characterized by highly mobility and frequent external contacts were at high risk for HFMD in Baoshan District. The predominant circulating strains had shifted sequentially from EV71 and CoxA16 to CoxA6.

Objective To investigate the correlation of the expression levels of serum cyclophilin A （CyPA） and cyclophilin D （CyPD） with the prognosis of patients with acute ischemic stroke （AIS）. Methods A total of 170 patients with first-episode AIS who attended Department of Neurology， The First Affiliated Hospital of Shihezi University， from October 2023 to June 2024 were enrolled as AIS group， and 60 non-AIS patients who were admitted during the same period of time were enrolled as control group. Clinical data were collected， and ELISA was used to measure the serum levels of CyPA and CyPD. For AIS patients， National Institutes of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were used to assess neurological deficits on admission and on day 90 after onset； the Fatigue， Resistance， Ambulation， Illnesses， and Loss of Weight （FRAIL） scale was used to evaluate the status of frailty； the multivariate logistic regression analysis was used to explore the correlation of the serum levels of CyPA and CyPD with neurological dysfunction at 3 months after the onset of AIS. The receiver operating characteristic （ROC） curve was used to assess the value of the serum levels of CyPA and CyPD in predicting neurological dysfunction in AIS patients at 3 months. Results The AIS group had significantly higher serum levels of CyPA and CyPD than the control group （P<0.001）. The Spearman correlation analysis showed that the expression levels of serum CyPA and CyPD were significantly positively correlated with NIHSS score （P<0.001）. The multivariate logistic regression analysis showed that the expression levels of serum CyPA and CyPD were independent influencing factors for neurological deterioration at 3 months after the onset of AIS （P<0.05）. The ROC curve analysis showed that serum CyPA and CyPD used alone or in combination had an area under the ROC curve of 0.875 （95%CI 0.824‒0.926， P<0.001）， 0.790 （95% CI 0.718‒0.862， P<0.001）， and 0.898 （95% CI 0.851‒0.944， P<0.001）， respectively， in predicting short-term adverse prognosis in AIS patients. Conclusion Serum CyPA and CyPD are independent influencing factors for the prognosis of AIS， and their combination has a certain value in predicting the prognosis of AIS.
Prognosis

The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

BACKGROUND:Compared with conventional repetitive transcranial magnetic stimulation,Theta burst transcranial magnetic stimulation(TBS)has attracted extensive attention from scholars in various fields due to its advantages of short stimulation time,high efficiency,good safety and long-lasting effect,and the research popularity continues to rise.OBJECTIVE:Through the visual bibliometrics analysis of international TBS research in the past 20 years,to sort out the development context of TBS research,summarize the research status,reveal research hotspots and development trends,and provide reference for subsequent research.METHODS:Relevant studies on TBS from January 2005 to June 2024 were searched in the Web of Science Core Collection database.CiteSpace software was used to perform annual publication volume analysis,co-occurrence analysis of countries,institutions and authors,and co-citation analysis of references,journals and authors,keywords co-occurrence,clustering,time evolution and emergence analysis,and so on,and draw the visual knowledge map.RESULTS AND CONCLUSION:(1)After screening,a total of 1914 papers were included in the study,and the amount of TBS research has shown an overall increasing trend over the past 20 years,and it is expected to continue to be a hot topic of research in the future.(2)The top three countries in terms of number of publications are the United States,China and Italy,and the top three institutions are the University of Toronto,the University of London and Harvard Medical School.Pascual-leone Alvaro from Harvard Medical School has the most research achievements,and HUANG YZ from Chang Gung University has the most citations.NEURON is the most influential core journal.(3)Analyses of high-frequency keywords,highly cited references and clustering topics showed that the research hotspots of TBS in the past 20 years mainly focus on the mechanism of TBS on synaptic plasticity and neurophysiological activity,the effect of TBS on stimulating targets in different brain regions(including the motor cortex,dorsolateral prefrontal cortex,anterior cingulate cortex and cerebellum,etc.),and the therapeutic effect of TBS on neurological and psychiatric diseases(including depression,Parkinson's disease movement disorder,post-stroke movement disorder and cognitive impairment,and Alzheimer's disease memory disorders).(4)Keyword burst,literature emergence and keyword temporal evolution analyses showed that"major depression,application guidelines,rating scale,efficacy,disorder,refractory depression,meta-analysis,etc."are not only current research hotspots,but also future research trends.(5)In the future,TBS research should strengthen the regional cooperation of core authors and institutions,explore the clinical application in the treatment of refractory diseases,and realize the precision,personalization and optimization of TBS application by combining cutting-edge technologies and optimizing stimulus parameters,so as to solve more clinical problems.

ObjectiveTo analyze the epidemiological and clinical characteristics of pertussis in Baoshan District, Shanghai from 2017 to 2024, so as to provide an evidence-based reference for optimizing prevention and control strategies. MethodsData on pertussis cases were collected from the China Disease Prevention and Control Information System, Shanghai Integrated Management and Immunization Service Information System, and follow-up epidemiological investigations. Descriptive epidemiological analyses were performed to analyze the epidemiological characteristics, clinical manifestations, and vaccine effectiveness. Joinpoint regression analyses were used to examine the temporal trends in incidence rates, and a Poisson model was constructed for spatiotemporal scan analyses. ResultsA total of 1 634 pertussis cases were reported in Baoshan District from 2017 to 2024, with a male-to-female ratio of 1.08∶1. More cases were observed in males than in females, with the age ranged from 20 days to 81 years. Among them, 59.92% were in the 6‒<11 years age group, and 63.34% were students. Low-level sporadic incidence persisted during 2017‒2023, followed by a sharp increase in 2024 (71.37/100 000). Starting in January 2024, the incidence rate showed an upward trend, peaking in May before declining. The majority of cases occurred between April and June. The trend in reported pertussis incidence rates in Baoshan District from 2017 to 2023 showed no statistically significant change (APC=10.039%, t=2.586, P=0.150). Incidence rate rose from January 2024, peaked in May (APC=133.641%, t=3.841, P=0.006), then declined significantly (APC=-47.816%, t=2.586, P<0.001). The 12 subdistricts of Baoshan District were divided into low, medium, and high population density areas, with an average annual reported incidence rate of 6.09/100 000, 8.19/100 000 and 11.96/100 000, respectively. The reported incidence rate increased with an increase in population density. Spatiotemporal scan analyses showed that cases clustered in the southwest and northeast of Baoshan District. Epidemiological follow-up investigations of 1 520 cases revealed that the main clinical symptoms were cough (97.63%) and sputum production (41.58%), and 98.13% of the cases were confirmed by positive nucleic-acid test results. Among the 1 475 cases with immunization records, 83.53% had completed the four-dose pertussis vaccine before onset. The complication incidence rates, from high to low, were in the 0-dose vaccination group, 1‒3-dose vaccination group and 4-dose vaccination group. The duration of cough, from long to short, was observed in the the 0-dose vaccination group, 1‒3-dose vaccination group and 4-dose vaccination group, correspondingly. ConclusionIt is recommended to improve the pertussis surveillance system in medical institutions and establish an active monitoring network, prioritizing deployment in school settings and areas with high population density. Enhancing diphtheria-tetanus-pertussis (DTP) vaccination coverage among 6-year-old children and further optimizing the pertussis immunization strategies are essential to prevent and reduce the risk of pertussis among school-aged children.

Objective:To preliminarily investigate the safety and efficacy of programmed death-1(PD-1)inhibitor combined with cord blood-derived natural killer cells(NK cells)in the treatment of advanced malignant solid tumors in an exploratory clinical trial.Methods:Three patients with advanced solid tumors treated at the Second Affiliated Hospital of Xi'an Medical University from December 2019 to December 2021 were enrolled.According to tumor type and CSCO guidelines,patients received multiple treatment cycles(21 days per cycle)consisting of standard chemotherapy,targeted therapy,or bevacizumab combined with PD-1 inhibitor.Umbilical cord blood-derived NK cells(8×107 cells per infusion)were infused at appropriate intervals during the treatment course.Target lesion size,tumor markers,levels of 12 peripheral blood cytokines,and lymphocyte subsets were assessed in each treatment cycle.Adverse events were also monitored throughout the treatment.Results:Following the treatment with PD-1 inhibitor combined with cord blood NK cells,2 patients achieved stable disease(SD,per RECIST 1.1 criteria),with durations of 118 days and 92 days,respectively.After NK cell infusion,patient#1 exhibited a marked decrease in the tumor marker CA199 to normal range and sustained for three follow-up periods;patient#2 showed significant reductions in tumor markers CA199,CA242,and CA724.Conclusion:The combination of NK cells with chemotherapy and PD-1 inhibitor demonstrates potential therapeutic efficacy for solid tumors.No severe immune-related adverse reactions were observed in the three patients enrolled in this study.

BACKGROUND:Compared with conventional repetitive transcranial magnetic stimulation,Theta burst transcranial magnetic stimulation(TBS)has attracted extensive attention from scholars in various fields due to its advantages of short stimulation time,high efficiency,good safety and long-lasting effect,and the research popularity continues to rise.OBJECTIVE:Through the visual bibliometrics analysis of international TBS research in the past 20 years,to sort out the development context of TBS research,summarize the research status,reveal research hotspots and development trends,and provide reference for subsequent research.METHODS:Relevant studies on TBS from January 2005 to June 2024 were searched in the Web of Science Core Collection database.CiteSpace software was used to perform annual publication volume analysis,co-occurrence analysis of countries,institutions and authors,and co-citation analysis of references,journals and authors,keywords co-occurrence,clustering,time evolution and emergence analysis,and so on,and draw the visual knowledge map.RESULTS AND CONCLUSION:(1)After screening,a total of 1914 papers were included in the study,and the amount of TBS research has shown an overall increasing trend over the past 20 years,and it is expected to continue to be a hot topic of research in the future.(2)The top three countries in terms of number of publications are the United States,China and Italy,and the top three institutions are the University of Toronto,the University of London and Harvard Medical School.Pascual-leone Alvaro from Harvard Medical School has the most research achievements,and HUANG YZ from Chang Gung University has the most citations.NEURON is the most influential core journal.(3)Analyses of high-frequency keywords,highly cited references and clustering topics showed that the research hotspots of TBS in the past 20 years mainly focus on the mechanism of TBS on synaptic plasticity and neurophysiological activity,the effect of TBS on stimulating targets in different brain regions(including the motor cortex,dorsolateral prefrontal cortex,anterior cingulate cortex and cerebellum,etc.),and the therapeutic effect of TBS on neurological and psychiatric diseases(including depression,Parkinson's disease movement disorder,post-stroke movement disorder and cognitive impairment,and Alzheimer's disease memory disorders).(4)Keyword burst,literature emergence and keyword temporal evolution analyses showed that"major depression,application guidelines,rating scale,efficacy,disorder,refractory depression,meta-analysis,etc."are not only current research hotspots,but also future research trends.(5)In the future,TBS research should strengthen the regional cooperation of core authors and institutions,explore the clinical application in the treatment of refractory diseases,and realize the precision,personalization and optimization of TBS application by combining cutting-edge technologies and optimizing stimulus parameters,so as to solve more clinical problems.

ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism. MethodMale SD rats were randomized into sham operation， model， low- and high -dose （3.5 g·kg^-1 and 7 g·kg^-1） Rehmannia Radix Praeparata， and nimodipine （0.01 g·kg^-1） groups. The rat model of middle cerebral artery occlusion （MCAO） was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile， the serum levels of lactate dehydrogenase （LDH）， oxidative stress-related indicators superoxide dismutase （SOD）， glutathione peroxidase 4 （GPX4）， and malondialdehyde （MDA）， and the iron （Fe） content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats， Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector （beclin-1）， microtubule-associated protein light chain 3 （LC3B）， and ubiquitin-binding protein p62 （p62）. The ferroptosis-associated proteins included transferrin （TF）， transferrin receptor 1 （TFR1）， ferritin heavy chain 1 （FTH1）， and ferropotin （FPN1）. The neurological function injury-associated proteins included brain-derived neurotrophic factor （BDNF） and tyrosine kinase receptor B （TrkB）. ResultCompared with the sham operation group， the model group showed increased neurological function score， cerebral infarction volume， and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition， the model group presented elevated levels of LDH， MDA， and Fe （P<0.01） and lowered levels of SOD and GPX4 （P<0.01）. Compared with the model group， Rehmanniae Radix Praeparata decreased the content of LDH， MDA， and Fe （P<0.05， P<0.01） and elevated the levels of SOD and GPX4 （P<0.05， P<0.01）. Compared with the sham operation group， the modeling promoted the expression of beclin-1，LC3B Ⅱ/Ⅰ， TF， and TFR1 and inhibited the expression of p62， FTH1， FPN1， BDNF， and TrkB （P<0.01）. The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata. ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.

Objective:To calculate the scale of China's mental health treatment costs,analyze its financing structure,and provide a decision-making basis for optimizing China's mental health disease financing,prevention and control policies.Methods:System of Health Account 2011 was employed to calculate mental disorders(MDs)curative expenditure,and analyze the expenditure by health function,health provider and financing schemes.Results:In 2018,MDs curative expenditure in China was 87.17 billion yuan.Of MDs curative expenditure,over 84%occurred in hospitals,and over 66%was spent on inpatient care.31.80%of MDs curative expenditure was financed by Out-of-Pocket(OOP).Conclusion:China's mental health and mental disorders treatment costs are developing rapidly,the existing resource allocation is unreasonable,and there is an urgent need to optimize the function and institutional configuration.MDs patients and their families bare a high burden on MDs curative expenditure,and the financing policy needs to be further improved.