The intersection of big data and epidemiology for epidemiologic research: The impact of the COVID-19 pandemic.

Big data epidemiology facilitates pandemic response by providing data-driven insights by utilizing big data tools that differ from traditional methods. Aspects regarding 'garbage in, garbage out', such as insufficient data, inaccessibility of data, missing data, uncertainty in handling data and bias in analysis or common findings are addressable by combining techniques across disciplines.

[Situation analysis and standard formulation of pesticide residues in traditional Chinese medicines].

Chinese Pharmacopoeia provides nine pesticide Maximum Residual Limits(MRLs) of traditional Chinese medicines(TCMs), The number of pesticides used in production are far more than those listed in pharmacopoeia. The lack of the standards make it's hard to reflect the real situation of pesticide residues in TCMs correctly. The paper is aimed to analyze the data of pesticide residues in TCMs from 7 089 items in 140 reports, and judging the exceedance rate of pesticides in TCMs using the MRLs of European pharmacopoeia，which is widely accepted in many countries. The results show that：①Pesticide residues in 18 kinds of TCMs are higher than MRLs，while in 137 kinds are below MRLs, such as Atractylodis Macrocephalae Rhizoma, Menthae Haplocalycis Herba and Fritillariae Thunbergii Bulbus. The average exceedance rate of all TCMs is 1.72%. The average exceedance rates of organochlorine, organophosphorus and pyrethroid are 2.26%, 1.51%, 0.37%，respectively. ②The average exceedance rate of pesticides is 2.00%, and the exceedance rate is more than 5%, accounting for 8.33%, the exceedance rate is between 1%-5%, accounting for 18.75%. the exceedance rate is between 0%-1%, accounting for 18.75%. The remaining 29 kinds of pesticides were not exceeded, accounting for 60.42%.Some reports like Greenpeace's organization exaggerated the pesticide residues in TCMs.But the pesticide residue question is still worthy of attention, so we proposed to amend the Chinese Pharmacopoeia pesticide residues standards, to increase the pesticide species of traditional Chinese medicine in production on the basis of retaining the existing types of pesticide residues, to strengthen the system research of pesticide residues in TCMs, providing a basis for making standard and promoting import and export trade in TCMs.

Lamivudine-resistant rtL180M and rtM204I/V are persistently dominant during combination rescue therapy with entecavir and adefovir for hepatitis B.

Adefovir (ADV) sequential monotherapy was included in the 2005 Asia-Pacific guidelines for the management of patients with lamivudine (LAM) resistance. However, following the development of ADV resistance, the proportion of resistant variants during combined rescue therapy with ADV and entecavir (ETV) were unknown. The present study characterized the dynamics of resistant variants in patients with chronic hepatitis B (CHB) and LAM-resistant variants during antiviral therapy consisting of ADV monotherapy followed by ADV-ETV combination therapy. A total of 3 patients were selected from a cohort of 55 patients with CHB due to developing ADV resistance. The patients had been previously treated with LAM (100 mg daily) for 21-24 months. At the initiation of sequential monotherapy with ADV, LAM-resistant variants (rtM204V/I and rtL180M) were detected in the three patients. These patients developed ADV resistance during 19-30 months of ADV sequential monotherapy, and then switched their antiviral regimen to ADV-ETV combination therapy. During ADV monotherapy and ADV-ETV combination therapy, the patients were monitored every 3 months for the first year of therapy, and then every 6 months thereafter. A total of 30 serum samples were collected from the patients throughout the monitoring period. In total, 10 mutants that were associated with commonly-used antiviral drugs were detected by pyrosequencing. During ADV sequential monotherapy, LAM-resistant variants were gradually decreased, whereas ADV-resistant rtA181V/T and rtN236T variants gradually increased in the viral population. During 30-41 months of ADV-ETV combination therapy, viral load reduction was 2.59-3.28 log10 copies/ml; ADV-resistant variants rtA181T/V and rtN236T were undetectable following 11-24 months of combination therapy; and rtL180M and rtM204I/V remained dominant in the viral population. In conclusion, the results of the present study suggested that, in patients with LAM and ADV-resistant variants that developed during LAM-ADV sequential monotherapy, ETV-ADV combination therapy may partially inhibit the replication of HBV DNA; however, LAM-resistant rtL180M and rtM204I/V variants remained predominant following 30-41 months combination therapy.

Evolution of entecavir-resistant hepatitis B virus during entecavir and adefovir dipivoxil combination therapy.

The emergence of entecavir (ETV) resistance is rare, particularly in a longitudinal study. The aim of the present study was to characterize the evolution of ETV-resistant variants during antiviral therapy using entecavir monotherapy followed by ETV-adefovir dipivoxil (ADV) combination therapy. The study included a prospective cohort of 53 consecutive chronic hepatitis B (CHB) patients. During the 60-month period of ETV therapy, 2 patients exhibited ETV resistance and their medical records were comprehensively reviewed. A total of 25 consecutive serum samples were regularly collected from the 2 patients. All the samples were used to characterize the evolution of the polymerase gene mutations using pyrosequencing. The linkage of the variants was analyzed from 87 reverse transcriptase sequences of 3 selective samples using clone sequencing. The 2 patients presented with viral breakthrough during ETV monotherapy. In patient A, the rtL180M, rtS202G and rtM204V mutant variants were detected using pyrosequencing prior to virological breakthrough. Although the viral load declined following the administration of ADV, the ETV-resistant variants were persistently dominant in the viral populations. In patient B, the rtL180M, rtM204I and rtM204V mutants were present in ~70, 30 and 10% of the viral populations, respectively, at the time of study entry. In addition, rtT184F was present in ~20% of the viral population during virological breakthrough, at month 24. The rtL180M, rtT184F and rtM204V were predominant during the combination treatment. Clonal analysis further revealed that the rtS202G or rtT184F was in all cases co-localized with rtL180M and rtM204V in any single virus isolate clone. The results of the present study indicate that the addition of ADV therapy with ETV for treating ETV-resistant mutation may not inhibit the replication of ETV-resistant variants that developed previously in lamivudine-treated CHB patients.

Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues.

There are two forms of brain-derived neurotrophic factor (BDNF), precursor of BDNF (proBDNF) and mature BDNF, which each exert opposing effects through two different transmembrane receptor signaling systems, consisting of p75 neurotrophin receptor (p75NTR) and tyrosine receptor kinase B (TrkB). Previous studies have demonstrated that proBDNF promotes cell death and inhibits the growth and migration of C6 glioma cells through p75NTR in vitro, while mature BDNF has opposite effects on C6 glioma cells. It is hypothesized that mature BDNF is essential in the development of malignancy in gliomas. However, histological data obtained in previous studies were unable distinguish mature BDNF from proBDNF due to the lack of specific antibodies. The present study investigated the expression of mature BDNF using a specific sheep monoclonal anti-mature BDNF antibody in 42 human glioma tissues of different grades and 10 control tissues. The correlation between mature BDNF and TrkB was analyzed. Mature BDNF expression was significantly increased in high-grade gliomas, and was positively correlated with the malignancy of the tumor and TrkB receptor expression. The present data have demonstrated that increased levels of mature BDNF contribute markedly to the development of malignancy of human gliomas through the primary BDNF receptor TrkB.