ObjectiveTo investigate and manage an imported dengue fever (DF) outbreak in Shanghai in 2024, to summarize the experience and lessons learned from the on-site management, and to provide a reference basis for future prevention and control of DF. MethodsEpidemiological investigation and case search were carried out for an imported DF outbreak in Shanghai, 2024. Real-time fluorescence polymerase chain reaction (RT-PCR) was used to detect dengue virus nucleic acid in the serum samples from cases. Meanwhile, emergency vector surveillance and mosquito control measures were carried out in the affected areas, and the effectiveness of the management was evaluated. ResultsAccording to the epidemiological investigation, it was confirmed that this epidemic was a family cluster of imported DF, with both cases infected in Thailand and developed symptoms successively after returning to Shanghai. Laboratory testing identified the pathogens as dengue virus serotype-3 (DENV-3). In the core and precautionary area, ultra-low-volume space spraying and residual spraying were combined to kill adult mosquitoes, and at the same time, comprehensive cleaning and elimination of mosquito breeding sites was carried out. After 2 weeks, the Breteau Index (BI) in the core area decreased from 20 to 5, and the mosquito net trap index decreased from 2 mosquitoes (net·hour)^-1 to 0.67 mosquitoes (net·hour)^-1. Continuous implementation of mosquito control measures kept the BI and net trap index below the safety thresholds [BI<5 and mosquito net trap index <2 mosquitoes (net·hour)^-1] both in the core and precautionary area. ConclusionEarly diagnosis and isolation of patients, combined with rapid suppression of the density of vector Aedes mosquitoes, are the key measures to prevent the transmission of imported DF cases.

Objective To use multiple model integration to predict the potential distribution of suitable areas for Hedysari Radix in China and the main environmental factors affecting its distribution.Methods Based on 119 geographical distribution points obtained from species distribution databases,and incorporating 19 bioclimatic and topographic factors,a species distribution model was constructed using the Biomod2 software package 3.5-1 version ensemble modeling platform,integrating six algorithms including generalized linear model,gradient boosting machine,random forest,and others.Geographic information system spatial analysis methods were used to quantitatively assess the distribution characteristics of suitable habitats of Hedysari Radix under current climate conditions and under future climate scenarios,while identifying the primary environmental drivers of its distribution.Results The ensemble model showed significantly superior predictive performance.TSS value and AUC value were 0.924 and 0.992,respectively.Key environmental factors significantly influencing the distribution of Hedysari Radix included slope,aspect,daily average temperature difference,isothermity,seasonal variation coefficient of temperature,lowest temperature in the coldest month,annual precipitation,driest month precipitation,and seasonal variation coefficient of precipitation.Under current climate conditions,suitable habitats for Hedysari Radix were primarily concentrated in the regions of Longnan and Dingxi in Gansu Province,covering an area of approximately 26.17×104 km2.Under future climate scenarios,suitable habitats will gradually shift toward the northwest into lower temperature zones,with a significant reduction in area.Conclusion The habitat suitability model developed in this study provides a basis for the conservation and sustainable utilization of Hedysari Radix genetic resources,while also offering a methodological reference for ecological adaptability studies of medicinal plants.

Objective To use multiple model integration to predict the potential distribution of suitable areas for Hedysari Radix in China and the main environmental factors affecting its distribution.Methods Based on 119 geographical distribution points obtained from species distribution databases,and incorporating 19 bioclimatic and topographic factors,a species distribution model was constructed using the Biomod2 software package 3.5-1 version ensemble modeling platform,integrating six algorithms including generalized linear model,gradient boosting machine,random forest,and others.Geographic information system spatial analysis methods were used to quantitatively assess the distribution characteristics of suitable habitats of Hedysari Radix under current climate conditions and under future climate scenarios,while identifying the primary environmental drivers of its distribution.Results The ensemble model showed significantly superior predictive performance.TSS value and AUC value were 0.924 and 0.992,respectively.Key environmental factors significantly influencing the distribution of Hedysari Radix included slope,aspect,daily average temperature difference,isothermity,seasonal variation coefficient of temperature,lowest temperature in the coldest month,annual precipitation,driest month precipitation,and seasonal variation coefficient of precipitation.Under current climate conditions,suitable habitats for Hedysari Radix were primarily concentrated in the regions of Longnan and Dingxi in Gansu Province,covering an area of approximately 26.17×104 km2.Under future climate scenarios,suitable habitats will gradually shift toward the northwest into lower temperature zones,with a significant reduction in area.Conclusion The habitat suitability model developed in this study provides a basis for the conservation and sustainable utilization of Hedysari Radix genetic resources,while also offering a methodological reference for ecological adaptability studies of medicinal plants.

Objective:To explore the impact and biological relevance of E3 ubiquitin ligase MARCH2 on the degradation of low-density lipoprotein receptor(LDLR)in hepatic cell lines.Methods:The ubiquitin ligase of the MARCH family involved in LDLR degradation was predicted using databases, and their binding sites were predicted through molecular docking.The association between MARCH2 and cholesterol levels was screened through a literature search.Various experiments including real-time quantitative PCR, immunoblotting, cycloheximide tracing assay, immunoprecipitation, were conducted in hepatic cell lines to investigate the impact of MARCH2 on the ubiquitination degradation of LDLR.Additionally, DiⅠ-labeled low-density lipoprotein(DiⅠ-LDL)uptake assays were performed to examine the effect of MARCH2 overexpression on LDL uptake in hepatocytes.Results:Real-time quantitative PCR, immunoblotting, and cycloheximide tracing experiments illustrated that MARCH2 facilitates the degradation of LDLR at the protein level rather than the transcriptional level.MARCH2 degraded 13% to 33% of LDLR protein within 24 hours, Following serum starvation and subsqnent serum refeeding, the degradation level significantly increased( t=2.280, P=0.046).This degradation process was unaffected by the proteasome pathway inhibitor MG132 but was hindered by the lysosome inhibitor chloroquine.Immunoprecipitation experiments validated the interaction between MARCH2 and LDLR.DiⅠ-LDL uptake experiments showed that MARCH2 overexpression decreased LDL uptake by hepatocytes from 4 039.8±16.2 to 2 630.3±185.9 at 3 hours, indicating a 34.9% reduction( t=16.89, P<0.001). Conclusions:MARCH2 facilitates the degradation of LDLR via the ubiquitin-dependent lysosome pathway, thereby decreasing the uptake of LDL by hepatic cells.

Objective:To explore the impact and biological relevance of E3 ubiquitin ligase MARCH2 on the degradation of low-density lipoprotein receptor(LDLR)in hepatic cell lines.Methods:The ubiquitin ligase of the MARCH family involved in LDLR degradation was predicted using databases, and their binding sites were predicted through molecular docking.The association between MARCH2 and cholesterol levels was screened through a literature search.Various experiments including real-time quantitative PCR, immunoblotting, cycloheximide tracing assay, immunoprecipitation, were conducted in hepatic cell lines to investigate the impact of MARCH2 on the ubiquitination degradation of LDLR.Additionally, DiⅠ-labeled low-density lipoprotein(DiⅠ-LDL)uptake assays were performed to examine the effect of MARCH2 overexpression on LDL uptake in hepatocytes.Results:Real-time quantitative PCR, immunoblotting, and cycloheximide tracing experiments illustrated that MARCH2 facilitates the degradation of LDLR at the protein level rather than the transcriptional level.MARCH2 degraded 13% to 33% of LDLR protein within 24 hours, Following serum starvation and subsqnent serum refeeding, the degradation level significantly increased( t=2.280, P=0.046).This degradation process was unaffected by the proteasome pathway inhibitor MG132 but was hindered by the lysosome inhibitor chloroquine.Immunoprecipitation experiments validated the interaction between MARCH2 and LDLR.DiⅠ-LDL uptake experiments showed that MARCH2 overexpression decreased LDL uptake by hepatocytes from 4 039.8±16.2 to 2 630.3±185.9 at 3 hours, indicating a 34.9% reduction( t=16.89, P<0.001). Conclusions:MARCH2 facilitates the degradation of LDLR via the ubiquitin-dependent lysosome pathway, thereby decreasing the uptake of LDL by hepatic cells.

Vibrio parahaemolyticus, the main pathogen causing seafood related food poisoning worldwide, has strong biofilm formation ability. ToxR is a membrane binding regulatory protein, which has regulatory effect on biofilm formation of V. parahaemolyticus, but the specific mechanism has not been reported. c-di-GMP is an important second messenger in bacteria and is involved in regulating a variety of bacterial behaviors including biofilm formation. In this study, we investigated the regulation of ToxR on c-di-GMP metabolism in V. parahaemolyticus. Intracellular c-di-GMP in the wild type (WT) and toxR mutant (ΔtoxR) strains were extracted by ultrasonication, and the concentrations of c-di-GMP were then determined by enzyme linked immunosorbent assay (ELISA). Three c-di-GMP metabolism-related genes scrA, scrG and vpa0198 were selected as the target genes. Quantitative real-time PCR (q-PCR) was employed to calculate the transcriptional variation of each target gene between WT and ΔtoxR strains. The regulatory DNA region of each target gene was cloned into the pHR309 plasmid harboring a promoterless lacZ gene. The recombinant plasmid was subsequently transferred into WT and ΔtoxR strains to detect the β-galactosidase activity in the cellular extracts. The recombinant lacZ plasmid containing each of the target gene was also transferred into E. coli 100λpir strain harboring the pBAD33 plasmid or the recombinant pBAD33-toxR to test whether ToxR could regulate the expression of the target gene in a heterologous host. The regulatory DNA region of each target gene was amplified by PCR, and the over-expressed His-ToxR was purified. The electrophoretic mobility shift assay (EMSA) was applied to verify whether His-ToxR directly bound to the target promoter region. ELISA results showed that the intracellular c-di-GMP level significantly enhanced in ΔtoxR strain relative to that in WT strain, suggesting that ToxR inhibited the production of c-di-GMP in V. parahaemolyticus. qPCR results showed that the mRNA levels of scrA, scrG and vpa0198 significantly increased in ΔtoxR strain relative to those in WT strain, suggesting that ToxR repressed the transcription of scrA, scrG and vpa0198. lacZ fusion assay showed that ToxR was able to repress the promoter activities of scrA, scrG and vpa0198 in both V. parahaemolyticus and E. coli 100λpir. EMSA results showed that His-ToxR was able to bind to the regulatory DNA regions of scrA and scrG, but not to the regulatory DNA region of vpa0198. In conclusion, ToxR inhibited the production of c-di-GMP in V. parahaemolyticus via directly regulating the transcription of enzyme genes associated with c-di-GMP metabolism, which would be beneficial for V. parahaemolyticus to precisely control bacterial behaviors including biofilm formation.
Vibrio parahaemolyticus/metabolism* ; Escherichia coli/metabolism* ; Bacterial Proteins/metabolism* ; Transcription Factors/genetics* ; Gene Expression Regulation, Bacterial

OBJECTIVE: To establish a clinically applicable model of rapid identification of adverse drug reaction program (RiADP) for risk management and decision-making of clinical drug use. METHODS: Based on the theory of disproportion analysis, frequency method and Bayes method, a clinically applicable RiADP model in R language background was established, and the parameters of the model were interpreted by MedDRA coding. Based on the actual monitoring data of FDA, the model was validated by the assessing hepatotoxicity of lopinavir/ritonavir (LPV/r). RESULTS: The established RiADP model included four parameters: standard value of adverse drug reaction signal information, empirical Bayesian geometric mean value, ratio of reporting ratio and number of adverse drug reaction cases. Through the application of R language parameter package "phViD", the model parameters could be output quickly. After being encoded by MedDRA, it was converted into clinical terms to form a clinical interpretation report of adverse drug reactions. In addition, the evaluation results of LPV/r hepatotoxicity by the model were matched with the results reported in latest literature, which also proved the reliability of the model results. CONCLUSIONS In this study, a rapid identification method of adverse reactions based on post marketing drug monitoring data was established in R language environment, which is capable of sending rapid warning of adverse reactions of target drugs in public health emergencies, and providing intuitive evidence for risk management and decision-making of clinical drugs.
Databases, Pharmaceutical ; Decision Making, Computer-Assisted ; Drug Monitoring ; Drug-Related Side Effects and Adverse Reactions ; HIV Protease Inhibitors ; adverse effects ; pharmacology ; Humans ; Liver ; drug effects ; Lopinavir ; adverse effects ; toxicity ; Models, Statistical ; Reproducibility of Results ; Software ; standards

For lack of cognitive screening standard system and controversy over the value of imaging for cerebrovascular diseases in China, the research group of Alzheimer′s Disease Chinese (ADC) studied the knowledge of neuropsychology, neuroimaging and clinical neurology, systematically reviewed the diagnostic techniques such as memory, language, visuospatial, executive, function, and magnetic resonance imaging (MRI) of cerebrovascular diseases, and their optimal threshold and diagnostic value for vascular dementia. Via a consensus meeting, the diagnostic guidelines and practical screening process are combined to construct a framework in Chinese population, which is based on the objective evidence of medical history and clinical evaluation. The diagnosis of vascular dementia is supported by imaging evidence of cerebrovascular diseases and differentiates from other causes of dementia or comorbidities. This consensus is applicable to medical units in China, and is of great significance for early detection, early diagnosis and early treatment of vascular dementia.

Criteria for diagnosis of Alzheimer's disease (AD) is not available in China.The international criteria is not a proper choice due to issues such as translation and lead to low diagnostic rate and high rate of missed diagnosis.The research group of Alzheimer's Disease Chinese (ADC) reviewed knowledge and techniques in neuropsychology,neuroimaging,molecular biology,and clinical neurology,and systematically studied the detection techniques such as memory,language,visuospatial,executive function,and medial temporal lobe visual scores on MRI,and their optimal threshold and diagnostic value for the diagnosis of AD.Through a systematic review and consensus meeting,a diagnostic framework for screeningAD in the Chinese population was established.Among these methods,an operational standard for clinical pathology models increased the diagnostic sensitivity by 15％.The sensitivity and specificity of screening memory impairment increased by 18.1％ and 11.6％,respectively.The sensitivity of screening medialtemporal lobe atrophy increased by 24.5％ and missed diagnosis was decreased by 34.5％.An operational standard for clinical biology models,incorporating the latest molecular imaging and molecular biology techniques,has enabled the early diagnosis of AD in China.The framework combines a principled diagnostic guideline with an operational screening protocol,which is applicable to all clinical settings and of great significance for the early detection,early diagnosis and early treatment of AD.

Objective: To analyze the hand-foot-mouth disease (HFMD) enterovirus 71 (EV-A71) infection epidemic characteristics of Guangdong Province from 2011 to 2015. Methods: We colleted data on common cases of hand-foot-mouth disease infected with EV-A71 reported from eight sentinel hospitals in Guangdong Province from January 2011 to December 2015, through the "Guangdong Province Acute Infectious Disease Surveillance Information Platform System" , including the age and incidence of cases. Time and etiological data, etc.We also collected data on the number of reported cases of HFMD disease and the number of laboratory-confirmed cases, through the "China Disease Prevention and Control Information System" , including data on common cases of HFMD disease, data on epidemics of severe cases and deaths, and the age, onset time, and pathogens of cases. Learning data, etc.The data from two sources were used to estimate the incidence of HFMD in EV-A71 and describe its distribution characteristics.Chi-square test was used to compare the positive rate of HF-A71 infection in hand-foot-mouth disease and the difference in estimated incidence among different age groups and months. Results: Eight sentinel hospitals from 2011 to 2015 reported a total of 1 855 common cases of EV-A71 infection, of which the highest was in 2014 (31.6%, 605/1 916) and the lowest was in 2015 (6.8%, 134/1 971) (χ²=521.85, P<0.001).According to the Disease Surveillance Reporting Information System, 1 772 516 cases of HFMD disease were reported from 2011 to 2015 in Guangdong Province, and 1 902 cases of severe and fatal cases of EV-A71 infection.The composition ratio of EV-A71 infected was 72.6% (1 775/2 444) and 97.0% (127/131) of severe HFMD disease in Guangdong province during 2011-2015.The average annual incidence of HF-A71 infection in all age groups showed a decreasing trend with age (χ^2trend=990 273.20, P<0.001), and it was the highest in the 1-year-old group, which was 1 697.67/100 000, and the lowest in the 4-year-old group, which was 705.46/100 000. The difference of monthly average incidence of EV-A71 infection in HF-A71 in each month was statistically significant (χ²=401.23, P<0.001), the highest in May at 15.51 per 100 000, and the lowest in July at 9.42 per 100 000. Conclusion EV-A71 infection rate of ordinary HFMD varies in different years. The most severe and death cases of HFMD were EV-A71 infected. 1 year old children were the high-risk group of infected with EV-A71 HFMD. April was the epidemic months of EV-A71 HFMD infection.