Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

A rapid analytical method for determination of paraquat and diquat in tea samples was established by improving the QuEChERS pre-treatment method combined with ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry(UPLC-MS/MS).Four kinds of tea powder were extracted by using acetonitrile-0.1％formic acid solution(3∶7,V/V)and ultrasonic treatment,and the supernatant was purified with 400 mg C18 and 400 mg PSA and separated on hydrophilic HILIC(100 mm×2.1 mm,1.8 μm)column by using 0.1％formic acid aqueous solution(Containing 5 mmol/L ammonium formate)and acetonitrile as mobile phases.In the electrospray ion source positive ion mode(ESI+),multiple reaction monitoring scanning technology(MRM)was used for determination,and the matrix-matched standard solution external standard method was used for quantitative analysis.The results showed that paraquat obtained good linear relationship in the content range of 0.18-200 μg/kg and diquat obtained good linear relationship in the content range of 0.36-200 μg/kg,and the correlation coefficients(R2)were 0.9939-0.9976 and 0.9959-0.9987,respectively.The limits of detection(LODs)were 0.06 and 0.12 μg/kg,and the limits of quantitation(LOQs)were 0.18 and 0.36 μg/kg,respectively.The average spiked recoveries for tea samples varied from 84.4％to 128.8％,with the relative standard deviations(RSDs)from 0.6％to 13.5％.The method was simple and efficient,with accurate quantification ability and low detection limit,which could realize efficient determination of paraquat and diquat in tea samples.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

Objective: To investigate the effect of asiaticoside for fibrosis in lung tissues of rats exposed to silica and to explore its possible mechanism. Methods: 144 SD male rats were randomly divided into control group, model group, positive drug control group, asiaticoside high-dose group, medium-dose group and low-dose group, each group included 24 rats. Rats in the control group were perfused with 1.0 ml of normal saline, and the other groups were given 1.0 ml 50 mg/ml SiO(2) suspension. Gavage of herbal was given from the next day after model establishment, once a day. Rats in the positive drug control group were administration with 30 mg/kg tetrandrine and rats in the low-dose group, medium-dose group and high-dose group were given 20 mg/kg, 40 mg/kg and 60 mg/kg asiaticoside for fibrosis respectively. Rats in the control group and the model group were given 0.9% normal saline. The rats were sacrificed in on the 14th, 28th and 56th day after intragastric administration and collect the lung tissues to detect the content of hydroxyproline, TGF-β(1) and IL-18, observe the pathological changes of the lung tissues by HE and Masson staining and determine the expressions of Col-I, a-SMA, TGF-β in lung tissues by Western Blot. Results: On the 14th day, 28th day and 56th day after model establishment, the lung tissues of rats in the model group showed obvious inflammatory response and accumulation of collagen fibers, and the degree of inflammation and fibrosis increased with time. The intervention of asiaticoside could effectively inhibit the pathological changes of lung tissues. The contents of hydroxyproline, IL-18 and TGF-β1 in lung tissues of model group were higher than those in the control group (P<0.05) , while the level of hydroxyproline, IL-18 and TGF-β1 in asiaticoside groups were significantly decreased, and the difference was statistically signicant (P<0.05) . Compared with the control group, the expression levels of Col-I, TGF-β1and α-SMA in lung tissue of model group were increased (P<0.05) , while the expression level of Col-I, TGF-β1 and α-SMA were decreased after the intervention of asiaticoside, and the difference was statistically signicant (P<0.05) . Conclusion: Asiaticoside can inhibit the increase of Col-I, TGF-β1 and α-SMA content in the SiO(2)-induced lung tissues of rats, reduce the release of TGF-β1 and IL-18 inflammatory factors in lung tissue, and then inhibit the synthesis and deposition of extracellular matrix in rat lung tissue, and improve silicosis fibrosis.
Animals ; Dust ; Lung ; Male ; Pulmonary Fibrosis/metabolism* ; Rats ; Silicon Dioxide/adverse effects* ; Silicosis/metabolism* ; Transforming Growth Factor beta1/metabolism*

The bone formation promoter recombinant human parathyroid hormone 1-34 [PTH (1-34)] has a short half-life and low bioavailability. In this study, we prepared a biodegradable and temperature-sensitive hyaluronic acid-poly-N-isopropyl acrylamide (AHA-g-PNIPAAm), and further investigated its effects of PTH (1-34) release and cell behavior as drug carrier. The structure of AHA-g-PNIPAAM was confirmed by hydrogen nuclear magnetic resonance spectroscopy and infrared spectroscopy. Next, PTH (1-34) loaded thermo-sensitive hydrogels were prepared by physical swelling method and their stability was investigated. The morphology of hydrogel was observed by scanning electron microscope. The minimum critical transition temperature and drug release behavior of hydrogels were investigated by ultraviolet spectrophotometry. The tetrazolium-based colorimetric assay (MTT assay) was used to investigate the toxicity and proliferation effects of PTH (1-34)-loaded thermo-sensitive hydrogel on mouse mononuclear macrophage RAW264.7 and mouse precranial osteoblasts MC3T3-E1. The effect of PTH (1-34)-loaded thermo-sensitive hydrogel on the differentiation of RAW264.7 was investigated by the tartrate-resistant acid phosphatase assay. The results showed that the PTH (1-34)-loaded thermo-sensitive hydrogel prepared in this study displayed regular three-dimensional honeycomb structure, and had good stability, thermo-sensitivity and sustained and controlled release properties, which could promote the proliferation of MC3T3-E1 cells more effectively and inhibit the differentiation of RAW264.7 into osteoclasts.

ObjectiveTo assess the predictive performance of four creatinine-based equations for estimated glomerular filtration rate （eGFR）： 2012 chronic kidney disease epidemiology collaboration （CKD-EPIcr） equation ， 2021CKD-EPIcr equation， Xiangya equation and European kidney function consortium （EKFC） equation. MethodsA total of 198 patients with chronic kidney disease from the Third Affiliated Hospital of Sun Yat-sen University and the Kiang Wu Hospital in Macau were enrolled. We compared the GFR measured （mGFR） by iohexol plasma clearance and the eGFR calculated by four equations. The agreement between mGFR and eGFR was analyzed by Bland-Altman plots， concordance correlation coefficient （CCC）， coverage probability （CP） and total deviation index （TDI）. The performance of eGFR equations， including their bias， precision， root square mean error （RSME）， and percentage of estimates within 30% deviation of measured GFR （P₃₀）， were evaluated. Bootstrap method （2 000 samples） was used to calculate bias， interquartile range （IQR）， RSME， and 95% confidence intervals （CI） for P_30. After selecting the optimal eGFR equation as the reference， we statisticlly tested other equations by ① Wilcoxon signed-rank test for bias； ② McNemar-Bowker test for P₃₀； ③ comparing RMSE and IQR with independent samples t test after 2 000 bootstrap samples were obtained. ResultsThe median mGFR and four eGFR equations （EKFC， 2012CKD-EPIcr， 2021CKD-EPIcr and Xiangya equation） in the overall population were 56.2 mL·min^-1·（1.73m²）^-1， 67.1 mL·min^-1·（1.73m²）^-1， 73.0 mL·min^-1·（1.73m²）^-1， 66.9 mL·min^-1·（1.73m²）^-1 and 63.8 mL·min^-1·（1.73m²）^-1， respectively. The Bland-Altman plots showed that EKFC equation had the lowest mean difference and the narrowest 95% limit of agreement. The EKFC equation had the optimal performance on CCC， TDI and CP with values of 0.90， 24.41 and 0.50， respectively. Overall， the bias， accuracy， P₃₀ and RSME from the EKFC equation was -0.99， 14.64， 0.80， and 14.68， respectively， with 95% CI ranging from -2.53 to 0.94， 11.82 to 17.35， 0.73 to 0.85， and 12.69 to 17.35， respectively， which were superior to those values from other three eGFR equations. The differences were statistically significant （all P < 0.05）. The results in the mGFR subgroups were basically consistent with the overall trend. ConclusionsOf the four eGFR equations validated in this study， the EKFC equation comprehensively surpasses 2012CKD-EPIcr equation， 2021CKD-EPIcr equation， and Xiangya equation. With P₃₀>75%， the EKFC equation can meet clinical diagnostic needs. Therefore， the EKFC equation is recommended for estimating GFR in a Chinese population， but more participants need be included to further support this conclusion.

ObjectiveTo investigate the predictive effect of high density lipoprotein （HDL） to C-reactive protein （CRP） ratio （HDL/CRP） on the progression of chronic kidney disease （CKD） in non-dialysis patients. MethodsNon-dialysis chronic kidney disease patients with at least two sets of follow-up data from the Third Affiliated Hospital of Sun Yat-sen University （Tian-he and Ling-nan districts）from 2015 to 2019 were enrolled. The baseline demographic characteristics and biochemical examination results were collected from the electronic medical record system. The patients were grouped according to the quantile of Ln（HDL/CRP）. The demographic and biochemical data were compared among groups by one-way ANOVA for normal distribution continuous variables， Kruskal-Wallis rank-sum test for non-normal distribution continuous variables， and Chi-square analysis for categorical variables. The relationship between HDL/CRP and baseline eGFR was investigated by correlation analysis， univariate and multivariate linear regression analysis. The Cox survival analysis were used to investigate the predictive effect of Ln（HDL/CRP） on renal deterioration events. ResultsTotally 9 142 patients with CKD were enrolled， and 439 patients were included in the end. There were 100 patients （22.8%） with chronic glomerulonephritis， 145 patients （33%） with diabetic nephropathy， 40 patients （9.1%） with hypertensive nephropathy， and 154 patients （35.1%） with other causes. According to Ln（HDL/CRP） quartile， group Quartile4 had a lower incidence of renal deterioration than the other three groups （11% vs. 21.1% to 21.8%） and had the highest baseline eGFR level. From Quartile1 to quartile 4 groups， age， Hba1c and APOA1 levels decreased gradually. The prevalence of chronic heart failure， BMI， hemoglobin， albumin， TC， LDL， TG， APOB100 levels were different among groups. Through correlation analysis， Ln （HDL/CRP） were positively correlated with baseline eGFR（r=0.162， P=0.001）. After adjusting for a variety of factors by Cox regression analysis， Ln （HDL/CRP） could be included in the final equation when defined deterioration of renal function as end point ［HR=0.79， 95%CI （0.69， 0.91）， P=0.001］. ConclusionHDL/CRP can reflect the severity of chronic kidney disease， and the ratio of HDL and CRP can predict the progression of chronic kidney disease in non-dialysis patient.

Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota.However,the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations.A well-controlled envi-ronment is thus necessary to reduce undesirable confounding effects,and recapitulate age-dependent changes in the gut microbiota of healthy primates.Herein we performed 16S rRNA gene sequenc-ing,characterized the age-associated gut microbial profiles from infant to elderly crab-eating maca-ques reared in captivity,and systemically revealed the lifelong dynamic changes of the primate gut microbiota.While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium,the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants,underlining their potential role in host development.Importantly,topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity,and its tremendous decline with age could probably be linked to healthy aging.Moreover,we identified key driver microbes responsible for such age-dependent network changes,which were further linked to altered metabolic functions of lipids,carbohydrates,and amino acids,as well as phenotypes in the microbial community.The current study thus demon-strates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota,and provides new insights into their roles in the development and healthy aging of their hosts.

When this paper was first published the following ethical statement was omitted in error: This study was approved by the Ethics Committee of AAALAC (NO. 001488) and carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of Tianjin Institute of Pharmaceutical Research. The authors would like to apologise for any inconvenience caused. DOI of original article: https://doi.org/10.1016/j.chmed.2018.12.002