1.Research progress of nano drug delivery system based on metal-polyphenol network for the diagnosis and treatment of inflammatory diseases
Meng-jie ZHAO ; Xia-li ZHU ; Yi-jing LI ; Zi-ang WANG ; Yun-long ZHAO ; Gao-jian WEI ; Yu CHEN ; Sheng-nan HUANG
Acta Pharmaceutica Sinica 2025;60(2):323-336
Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.
2.Advances in oral distant targeted nanodelivery systems
Min SUN ; Chuan-sheng HUANG ; Li-ping WANG ; Xu-li RUAN ; Yun-li ZHAO ; Xin-chun WANG
Acta Pharmaceutica Sinica 2025;60(1):72-81
Due to patient compliance and convenience, oral medication is likely the most common and acceptable method of drug administration. However, traditional dosage forms such as tablets or capsules may lead to low drug bioavailability and poor therapeutic efficiency. Therefore, with advancements in material science and micro/nano manufacturing technology, various carriers have been developed to enhance drug absorption in the gastrointestinal tract. In this context, we initially discuss the key biological factors that hinder drug transport and absorption (including anatomical, physical, and biological factors). Building on this foundation, recent progress in both conventional and innovative oral drug delivery routes aimed at improving drug bioavailability and targeting is reviewed. Finally, we explore future prospects for oral drug delivery systems as well as potential challenges in clinical translation.
3.Analysis of epidemiological and clinical characteristics of 1247 cases of infectious diseases of the central nervous system
Jia-Hua ZHAO ; Yu-Ying CEN ; Xiao-Jiao XU ; Fei YANG ; Xing-Wen ZHANG ; Zhao DONG ; Ruo-Zhuo LIU ; De-Hui HUANG ; Rong-Tai CUI ; Xiang-Qing WANG ; Cheng-Lin TIAN ; Xu-Sheng HUANG ; Sheng-Yuan YU ; Jia-Tang ZHANG
Medical Journal of Chinese People's Liberation Army 2024;49(1):43-49
Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6%),Mycobacterium tuberculosis 249(20.0%),other bacteria 150(12.0%),fungi 68(5.5%),parasites 18(1.4%),Treponema pallidum 18(1.4%)and rickettsia 1(0.1%).The number of cases increased by 177 cases(33.1%)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ¥29,500(¥16,000,¥59,200).The mortality rate from CNS infectious diseases is 1.6%.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.
4.Ku70 Functions as an RNA Helicase to Regulate miR-124 Maturation and Neuronal Cell Differentiation
Ai-Xue HUANG ; Rui-Ting LI ; Yue-Chao ZHAO ; Jie LI ; Hui LI ; Xue-Feng DING ; Lin WANG ; Can XIAO ; Xue-Mei LIU ; Cheng-Feng QIN ; Ning-Sheng SHAO
Progress in Biochemistry and Biophysics 2024;51(6):1418-1433
ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.
5.Effects of curcumol on iron death and epithelial-mesenchymal transition in hepatic stellate cells
Lei WANG ; Jin-Biao HUANG ; Yan-Qing HUANG ; Ze-Yu WANG ; Jia-Hui WANG ; Yang ZHENG ; Wei-Sheng LUO ; Tie-Jian ZHAO
The Chinese Journal of Clinical Pharmacology 2024;40(4):539-543
Objective To elucidate the effect of curcumol on hepatic stellate cell iron death and epithelial-mesenchymal transition(EMT),and to investigate the molecular mechanism of its anti-liver fibrosis effect.Methods A model of hepatic stellate cell activation was constructed using normal cultured hepatic stellate cells in vitro,and the cells were divided into blank group and experimental-L,-M,-H groups.The blank group was given DMEM complete culture solution for normal culture;the experimental-L,-M,-H groups were given DMEM complete culture solution containing 12.5,25.0 and 50.0 mg·L-1 curcumol for 48 h of intervention.The effects of curcumol on the proliferation of hepatic stellate cells was observed by CCK-8.The expression levels of glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were detected by Western blot.The expression levels of E-cadherin and N-cadherin were detected by immunofluorescence.Results The cell proliferation rates of the experimental-M,-H groups and blank group were(68.97±5.61)%,(61.91±4.40)%and(118.07±10.01)%;the relative expression levels of GPX4 were 0.37±0.04,0.28±0.03 and 0.58±0.05;the relative expression levels of SLC7A11 were 0.38±0.04,0.28±0.03 and 0.60±0.05;E-cadherin levels were 6.76±1.09,9.57±1.73 and 2.05±0.72;N-cadherin levels were 5.66±0.66,3.44±0.78 and 10.37±0.66.The differences of above indicators were statistically significant between the blank group and the experimental-M,-H groups(P<0.05,P<0.01).Conclusion Curcumol promotes iron death in hepatic stellate cells,thereby inhibiting hepatic stellate cell EMT,which may be its molecular mechanism to prevent and treat liver fibrosis.
6.Bioequivalence study of vardenafil hydrochloride tablets in Chinese healthy subjects
Yuan-Yuan XU ; Xiao-Ni WANG ; Jing XIE ; Feng ZHANG ; Wen ZHANG ; Sheng-Long ZHAO ; Huan ZHOU ; Shun-Wang HUANG
The Chinese Journal of Clinical Pharmacology 2024;40(16):2373-2377
Objective To evaluate the bioequivalence of the vardenafil hydrochloride tablets in fasting and fed conditions in healthy Chinese adult subjects with the test and reference formulations.Methods A randomized,open,single-dose,two-preparation,two-sequence,two-period,crossover design was used,and 40 healthy male subjects enrolled in the fasting state and 66 healthy male subjects enrolled in the fed state.The trial was conducted in two cycles,with 20 mg of either the subject formulation or the reference formulation,vardenafil hydrochloride tablets,being administered in each cycle.The drug concentration of vardenafil in plasma was determined by the liquid chromatography-tandem mass spectrometry(LC/MS-MS)method.Pharmacokinetic parameters were calculated using the non-compartment model,and the safety evaluation indexes were statistically analyzed using SAS 9.4 or above version program data statistical software.Results Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of vardenafil hydrochloride tablets and the reference formulation in the fasting state:Cmaxwere(34.94±18.33)and(36.69±19.45)ng·mL-1;AUC0-t were(74.38±34.11)and(74.25±33.37)ng·mL-1·h;AUC0-∞ were(76.70±34.36)and(76.46±33.84)ng·mL-1·h,respectively.Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of vardenafil hydrochloride tablets and the reference formulation in the fed state:Cmax were(22.84±12.48)and(21.68±11.12)ng·mL-1;AUC0_twere(70.82±35.88)and(72.71±34.63)ng·mL-1·h;AUC0-∞ were(73.48±36.44)and(75.29±35.12)ng·mL-1·h,respectively.The 90%confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters such as Cmax,AUC0-t and AUC0-∞ of the prototype drug vardenafil in plasma after oral administration of 20 mg of the test and reference formulations of vardenafil tablets to the subjects in fasting and postprandial states fell within the equivalence interval of 80.00%to 125.00%.Conclusion The subject formulation of vardenafil hydrochloride tablets was bioequivalent to the reference formulation in fasting and fed conditions in healthy Chinese subjects.
7.Innovation and Practice of Chinese Medicinal Materials Resource Chemistry Leading the Whole Industry Chain Recycling and Green Development of Chinese Medicinal Materials
Jin'ao DUAN ; Sheng GUO ; Shulan SU ; Lanping GUO ; Ming ZHAO ; Rui LIU ; Hui YAN ; Tuanjie WANG ; Zhenzhong WANG ; Wei XIAO ; Luqi HUANG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(10):1114-1122
The concept,connotation and extension,goals and tasks of the discipline of Chinese medicinal materials resource chem-istry have been proposed and developed for 20 years.Looking back at the 20-year construction and development process,continuous exploration and innovative practice have been carried out around the scientific production and effective utilization of traditional Chinese medicinal materials.The theoretical connotation has been further enriched,the research mode has been further improved,and the tech-nical system has been further expanded.A series of research results have been formed and promoted for application,serving the high-quality development of the traditional Chinese medicinal materials industry,and contributing to the improvement of quality,efficiency,and green development of the entire industry chain of Chinese medicinal resources.However,with the rapid growth of Chinese medici-nal materials industry and the continuous expansion and extension of the industry chain,the waste and by-products generated in the production process of Chinese medicinal agriculture and industry are increasing day by day,causing resource waste and environmental pollution,which has become a new major problem facing the development of the industry.This article focuses on the establishment and case analysis of a model for the full industry chain recycling and low-carbon green development of Chinese medicinal materials,as well as the creation of an ecological industry demonstration park for the recycling of Chinese medicinal materials.It showcases the phased a-chievements made in recent years,aiming to provide demonstration and reference for the low-carbon and green transformation of the Chinese medicinal materials industry from a linear economy model to a circular economy model.It provides reference for improving the efficiency of Chinese medicinal materials utilization and creating new quality productivity,and helps promote low-carbon and green de-velopment in the field of Chinese medicinal materials industry.
8.Iodine nutritional status and influencing factors of pregnant women in Hangzhou City
Tingting ZHAO ; Liangliang HUO ; Xuhui ZHANG ; Bing ZHU ; Liming HUANG ; Xingyi JIN ; Sujuan ZHU ; Qilin SHENG
Chinese Journal of Endemiology 2024;43(1):49-55
Objective:To investigate the iodine nutritional status of pregnant women in Hangzhou City and analyze its influencing factors, in order to provide a basis for guiding pregnant women in Hangzhou City to supplement iodine scientifically.Methods:A stratified random sampling method was used to conduct a questionnaire survey on 1 400 pregnant women in Hangzhou City from March to October 2018. Random urine samples and household salt samples from pregnant women were collected, and the levels of urine iodine and salt iodine were measured using arsenic cerium catalytic spectrophotometry and direct titration, respectively. The iodine nutritional status of pregnant women with different basic characteristics and dietary levels were analyzed and compared (Kruskal-Wallis test), and the main influencing factors affecting the urinary iodine concentration level of pregnant women were identified (the ordinal multiple classification logistic regression analysis).Results:The median urinary iodine of pregnant women was 135.00 μg/L, and the qualified iodized salt consumption rate of pregnant women was 83.36% (1 167/1 400). In terms of basic characteristics, there were statistically significant differences in the distribution level of urine iodine among pregnant women with different pregnancy frequency, delivery frequency, and natural abortion frequency ( P < 0.05). In terms of diet, the frequency of consuming milk, yogurt, meat, and whether pregnant women consumed cabbage and cauliflower showed statistically significant differences in urinary iodine distribution levels ( P < 0.05). Ordinal multiple classification logistic regression analysis showed that the urine iodine levels of pregnant women who were pregnant twice were higher than those who were pregnant ≥3 times ( OR = 1.64, P = 0.003). Pregnant women who never or occasionally consumed yogurt had lower urine iodine levels than or equal to those who consumed 2 bottles of yogurt per day ( OR = 0.53, P = 0.044). Pregnant women who never or occasionally consumed meat and those who consumed meat once a week had higher urinary iodine levels than that who consumed meat ≥2 times per week ( OR = 1.40, 1.47, P < 0.05). Conclusions:The overall iodine nutrition of pregnant women in Hangzhou City is at an deficiency level. Pregnancy experience and dietary level are influencing factors on iodine nutrition of pregnant women. It is necessary to carry out in-depth health education for pregnant women, improve the dietary structure during pregnancy, and improve the abnormal iodine nutrition of pregnant women.
9.Association of copy number variation in X chromosome-linked PNPLA4 with heterotaxy and congenital heart disease
Han GAO ; Xianghui HUANG ; Weicheng CHEN ; Zhiyu FENG ; Zhengshan ZHAO ; Ping LI ; Chaozhong TAN ; Jinxin WANG ; Quannan ZHUANG ; Yuan GAO ; Shaojie MIN ; Qinyu YAO ; Maoxiang QIAN ; Xiaojing MA ; Feizhen WU ; Weili YAN ; Wei SHENG ; Guoying HUANG
Chinese Medical Journal 2024;137(15):1823-1834
Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.
10.Sentinel surveillance data of influenza in Hunan Province from 2014 to 2023
Xiao-Lei WANG ; Chao-Yang HUANG ; Qian-Lai SUN ; Zhi-Hong DENG ; Yi-Wei HUANG ; Shan-Lu ZHAO ; Kai-Wei LUO ; Xiang REN ; Sheng-Bao CHEN ; Zhi-Hui DAI
Chinese Journal of Infection Control 2024;23(11):1413-1420
Objective To understand the prevalence characteristics of influenza and changes of influenza virus strains,and provide reference for the prevention and control of influenza in the province.Methods Surveillance da-ta about influenza in Hunan Province from 2014 to 2023 were exported from China Influenza Surveillance Informa-tion System.Differences in the percentage of influenza-like illness(ILI)cases(percentage of influenza-like cases[ILI%]in outpatient and emergency department visits)among different years and different populations,as well as the positive rate of influenza virus in ILI specimens were compared.Results From 2014 to 2023,over 2.65 million cases of ILI were reported,with an ILI%of 4.70%.ILI%among different years presented statistically significant differences(P<0.001).People aged 0-14 years old were the main population with ILI,accounting for 82.90%.The positive rate of influenza virus in ILI specimens was 14.14%,the positive rate of influenza virus among diffe-rent years and age groups were both significantly different(both P<0.001).The main prevalent influenza strains from 2014 to 2023 included types A(H1N1),A(H3N2),B(Victoria),and B(Yamagata),alternating among di-fferent years.However,type B(Yamagata)strains were not detected from 2020 to 2023.There were basically two influenza prevalence seasons every year,namely winter-spring and summer.Conclusion People<15 years old are the main population of influenza,and the prevalence peaks are in winter-spring and summer.From 2021 to 2023,the prevalence alternates mainly among 3 types:A(H1N1),A(H3N2),and B(Victoria).

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