BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Astragaloside Ⅳ （AS-Ⅳ） is a natural triterpenoid saponin compound derived from Astragalus membranaceus and has shown significant potential in the regulation of liver diseases. This article reviews the latest research advances in AS-Ⅳ in the field of liver diseases in China and globally， and it is found that AS-Ⅳ exerts a liver-protecting effect by regulating lipid metabolism， exerting an anti-tumor/anti-inflammatory/anti-fibrotic effect， and modulating gut microbiota. Its mechanism of action involves multiple signaling pathways， such as AMPK， NLRP3， NF-κB， JAK2/STAT3， and Nrf2. These research findings provide a scientific basis for the development of liver-protecting drugs or functional foods based on the natural product AS-Ⅳ.

The innate immune system employs diverse pattern recognition receptors (PRRs) to monitor pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), thereby initiating innate immune responses against pathogenic invasions. This review focuses on RNA, double-stranded DNA (dsDNA), and non-canonical conformational nucleic acid as structural triggers, comprehensively analyzing the immune recognition mechanisms of nucleic acid-sensing PRRs, their disease relevance, and therapeutic advancements. Key receptors highlighted include Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), cyclic GMP-AMP synthase (cGAS), and Z-DNA-binding protein 1 (ZBP1). We elucidate their pivotal roles in antiviral defense, antitumor immunity, and immune homeostasis maintenance, aiming to provide insights for the development of novel PRR-targeted drugs.

Objective:To investigate the epidemiological and genetic characteristics of hand, foot and mouth disease (HFMD) caused by coxsackievirus A6 (CVA6) in Xi′an city from 2021 to 2023.Methods:Collected clinical cases of HFMD, epidemiological information and samples were obtained. The specimens were tested by the real-time RT-PCR for enterovirus A71(EVA71), CVA16, CVA6 and CVA10, respectively. The VP1 regions of CVA6 were amplified and sequenced, MEGA X was used for phylogenetic analysis.Results:From 2021 to 2023, a total of 1 393 HFMD samples were collected, 1 106 (79.40%, 1 106/1 393) of which were positive for enteroviruses. The proportions of EVA71, CVA16, CVA6 and CVA10 were 0.45% (5/1 106), 16.64% (184/1 106), 72.42% (801/1 106) and 2.17% (24/1 106). A total of 801 HFMD cases tested positive for CAV6, including 783 mild cases and 18 severe cases, mainly in children aged ≤5 years (86.02%, 689/801), with a male/female ratio of 1.49∶1. The composition ratio of CVA6 infection differed with year(χ 2=332.62, P<0.01), and the highest composition ratio of CVA6 was in 2023 (91.01%, 638/701). The nucleotide and amino acid similarities in the VP1 region of Xi′an strains of CVA6 were 92.4%-99.8% and 98.3%-100.0%, respectively. Compared with the CVA6 prototype strain(Gdula), the nucleotide and amino acid similarities in the VP1 region of Xi′an strains were 82.2%-84.0% and 95.4%-96.0%, respectively, and there were 18 amino acid mutations in different degrees. Based on the phylogenetic analysis of VP1 region sequences, the CVA6 strains in Xi′an city from 2021 to 2023 belonged to D3a subtype, and could be divided into two clusters with 18 strains in cluster 1 while two strain in cluster 2. Conclusions:The sub-genotype D3a of CVA6 is the predominant virus causing HFMD in Xi′an city from 2021 to 2023, and there are two transmission chains. The monitoring and prevention of CVA6 should be strengthened.

Objective To investigate the the levels of magnesium,lead,iron,zinc,copper,manganese,calci-um in whole blood in children aged 0-12 years in Henan province,understand the health status of children and provide a basis for their nutrition and health management.Methods Data were collected from totally 135 385 children aged 0-12 years who underwent trace element testing at Zhengzhou Kingmed Clinical Labo-ratory Inc.from 2019 to 2023 were selected,and agilent inductively coupled plasma mass spectrometer was used to detect seven elements(magnesium,lead,iron,zinc,copper,manganese,and calcium).The elemental detection method in the laboratory has been strictly methodologically verified,and has participated in the ex-ternal quality assessment organized by National Center for Clinical Laboratories.Grouping was conducted based on gender,age,season,region,and year to compare the deficiencies and lead exceedances of six elements(magnesium,iron,zinc,copper,manganese,calcium)under different conditions.Results In this study,the mean P-values of seven elements in different age groups,gender groups,year groups,and regional groups were all＜0.001.Except for lead with a P-value of 0.002,all other elements in different season groups were＜0.001.The P-values were all less than 0.05,indicating statistically significant differences.Among them,Mag-nesium,iron,and zinc in children's whole blood showed an increasing trend with age,while copper,manga-nese,and calcium showed a decreasing trend with age.The proportions of children aged 0-1 years with iron,zinc,and manganese deficiencies were the highest,at 24.70％,48.20％,and 0.65％,respectively.The highest proportion of copper and calcium deficiency was in the age range of 11-12 years old,accounting for 20.43％and 0.17％respectively.The highest proportion of lead exceeding the standard was 0.87％among children aged 0-1.Except for manganese and calcium levels,the levels of the other five elements were higher in boys than in girls.Magnesium and copper levels were highest in spring,iron,zinc,and calcium levels were highest in winter,and manganese and lead levels were highest in summer.Magnesium deficiency,calcium deficiency,and lead excess were showing a decreasing trend year by year.Among them,the lead levels of children in Sanme-nxia and Jiyuan were relatively high compared to other areas.Conclusion 0-2 years children are mainly char-acterized by calcium and zinc deficiency in Henan province.Attention should be paid to iron and zinc supple-mentation in infants and young children.At the same time,it should also be noted that the deficiency rate of copper increases with age,and attention should be paid to the supplementation of copper in children.

Objective:To investigate the epidemiological and genetic characteristics of hand, foot and mouth disease (HFMD) caused by coxsackievirus A6 (CVA6) in Xi′an city from 2021 to 2023.Methods:Collected clinical cases of HFMD, epidemiological information and samples were obtained. The specimens were tested by the real-time RT-PCR for enterovirus A71(EVA71), CVA16, CVA6 and CVA10, respectively. The VP1 regions of CVA6 were amplified and sequenced, MEGA X was used for phylogenetic analysis.Results:From 2021 to 2023, a total of 1 393 HFMD samples were collected, 1 106 (79.40%, 1 106/1 393) of which were positive for enteroviruses. The proportions of EVA71, CVA16, CVA6 and CVA10 were 0.45% (5/1 106), 16.64% (184/1 106), 72.42% (801/1 106) and 2.17% (24/1 106). A total of 801 HFMD cases tested positive for CAV6, including 783 mild cases and 18 severe cases, mainly in children aged ≤5 years (86.02%, 689/801), with a male/female ratio of 1.49∶1. The composition ratio of CVA6 infection differed with year(χ 2=332.62, P<0.01), and the highest composition ratio of CVA6 was in 2023 (91.01%, 638/701). The nucleotide and amino acid similarities in the VP1 region of Xi′an strains of CVA6 were 92.4%-99.8% and 98.3%-100.0%, respectively. Compared with the CVA6 prototype strain(Gdula), the nucleotide and amino acid similarities in the VP1 region of Xi′an strains were 82.2%-84.0% and 95.4%-96.0%, respectively, and there were 18 amino acid mutations in different degrees. Based on the phylogenetic analysis of VP1 region sequences, the CVA6 strains in Xi′an city from 2021 to 2023 belonged to D3a subtype, and could be divided into two clusters with 18 strains in cluster 1 while two strain in cluster 2. Conclusions:The sub-genotype D3a of CVA6 is the predominant virus causing HFMD in Xi′an city from 2021 to 2023, and there are two transmission chains. The monitoring and prevention of CVA6 should be strengthened.

The intestine is the main site of oral drug absorption, and the epithelial cells of the intestine contain villi and microvilli, which promote secretion, cell adhesion, and absorption by increasing surface area and other factors. Traditional two-dimensional/three-dimensional (2D/3D) cell culture models and animal models have played an important role in studying drug absorption, but their application is limited due to the lack of sufficient predictability of human pharmacokinetics or ethical issues, etc. Therefore, mimicking the core structure and key functions of the human intestine based on in vitro live cells has been the focus of research on constructing a microfluidic chip-based intestinal model. The model is a microfluidic chip bionic system that simulates the complex microstructure, microenvironment, and physiological functions of the human intestine using microfabrication technology. Compared with 2D cell culture and animal experiments, the intestinal microarray model can effectively simulate the human in vivo environment and is more specific in drug screening. The research progress and applications in disease modeling, drug absorption and transport of intestinal microarray models and intestine-related multi-organ coupled microarray models at home and abroad were reviewed in this paper. The current challenges of intestinal chip simulating intestinal homeostasis and diseases were summarized，in order to provide reference for the further establishment of a more reliable in vitro intestinal chip model.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology has the characteristics of high specificity and high throughput, making it rapidly applied and developed in the field of clinical testing. Its application in the monitoring of therapeutic drugs can effectively improve the quantitative accuracy and sensitivity, and formulate a personalized and optimal dosing plan for patients. However, this technology still faces some challenges, and automation, quality control, and quantitative traceability will be the future development direction.

Objective::To build a reference fetal growth chart for the Chinese population based on fetal ultrasound measurements.Methods::This was a multicenter, population-based retrospective cohort study. Longitudinal ultrasound measurement data were collected from 24 hospitals in 18 provinces of China from 1 st September through 31 st October of 2019. The estimated fetal weight (EFW) was calculated based on head circumference, abdominal circumference, and femur length using Hadlock formula 3. Fetal growth curves were estimated using a two-level linear regression model with cubic splines. All participants were divided into two groups: the northern group ( n = 5829) and the southern group ( n = 3246) based on the geographical division of China and male fetus group ( n = 4775) and female fetus group ( n = 4300) based on fetal gender. The EFW was compared by fetal gender and geographical group. All statistical models were adjusted for maternal sociodemographic characteristics. Results::A total of 9075 participants with 31,700 ultrasound measurement records were included in this study. Male fetuses demonstrated significantly larger EFW compared to female ones starting at 16 weeks of gestation and extending to delivery (global test P < 0.01). The overall geographic difference in EFW was significant (global test P = 0.03), and week-specific comparisons showed that the northern group had a greater EFW starting at 15 weeks of gestation and extending to 29 weeks of gestation, although this difference did not extend to the time of delivery. The Z-score of EFW confirmed that our Chinese fetal growth charts differed from previously published standards. Conclusion::This study provides EFW and ultrasound biometric reference measurements for Chinese fetuses and reveals differences from other fetal growth charts. The chart is worth promoting in more regions of China but should be tested prudently before use.

Objective::To build a reference fetal growth chart for the Chinese population based on fetal ultrasound measurements.Methods::This was a multicenter, population-based retrospective cohort study. Longitudinal ultrasound measurement data were collected from 24 hospitals in 18 provinces of China from 1 st September through 31 st October of 2019. The estimated fetal weight (EFW) was calculated based on head circumference, abdominal circumference, and femur length using Hadlock formula 3. Fetal growth curves were estimated using a two-level linear regression model with cubic splines. All participants were divided into two groups: the northern group ( n = 5829) and the southern group ( n = 3246) based on the geographical division of China and male fetus group ( n = 4775) and female fetus group ( n = 4300) based on fetal gender. The EFW was compared by fetal gender and geographical group. All statistical models were adjusted for maternal sociodemographic characteristics. Results::A total of 9075 participants with 31,700 ultrasound measurement records were included in this study. Male fetuses demonstrated significantly larger EFW compared to female ones starting at 16 weeks of gestation and extending to delivery (global test P < 0.01). The overall geographic difference in EFW was significant (global test P = 0.03), and week-specific comparisons showed that the northern group had a greater EFW starting at 15 weeks of gestation and extending to 29 weeks of gestation, although this difference did not extend to the time of delivery. The Z-score of EFW confirmed that our Chinese fetal growth charts differed from previously published standards. Conclusion::This study provides EFW and ultrasound biometric reference measurements for Chinese fetuses and reveals differences from other fetal growth charts. The chart is worth promoting in more regions of China but should be tested prudently before use.