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.

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.

Stimulator of interferon genes (STING) is an important factor in the auto-immune response of our bodies.Considering the mechanism of activating CD8+ T cells after the activation of STING protein, the combination of STING agonists and immune checkpoint inhibitors for the treatment of tumor immunotherapy has good clinical application prospect.In this paper, the research progress of molecular types, mechanism of action and structural modifications of STING agonists were reviewed.The developing tendency were outlined to provide some references for further investigation.

OBJECTIVES: Intrauterine adhesions (IUA) is the damage of the basal layer of the endometrium caused by various reasons, resulting in adhesion of the uterine muscle walls to each other, which is manifested as clinical symptoms such as spanomenorrhea, amenorrhea, and infertility. Hysteroscopic adhesiolysis (HA) is the main treatment, for patients with moderate or severe adhesion or angular adhesion, the incidence of postoperative adhesion is high. Traditional Chinese medicine "Yangmo decoction" can promote endometrial growth. Three-dimensional transvaginal ultrasonography (3D-TVUS) can judge IUA and evaluate uterine receptivity through three-dimensional imaging. This study aims to investigate the value of 3D-TVUS in judging the efficacy of Yangmo decoction in the treatment of intrauterine adhesions. METHODS: The clinical data of patients who underwent HA at two different centers in department of Gynecology of Third Xiangya Hospital of Central South University and Changsha Jiangwan Hospital from January 2021 to August 2021 were retrospectively collected. A total of 275 eligible patients were included. According to the postoperative management measures, the selected patients were divided into two groups. Yangmo decoction group (n=138): the use of Yangmo decoction and uterine-shaped silicon stent post HA; Hormone group (n=137): the use of estrogen, progesterone and uterine-shaped silicon stent post HA. The preoperative general data, preoperative and postoperative 3D-TVUS parameters of the two groups were analyzed. RESULTS: The endometrial thickness of Yangmo decoction group was thicker than that of hormone group (P<0.001), the intercornual distance was wider (P=0.016), the endometrial echo was more homogeneous (P=0.018), the percentage of bilaterally visible tubal opening was higher (P<0.001), the endometrial morphology was better (P=0.012), and endometrial blood flow, endometrial motility and uterine motion were better in Yangmo decoction group than that in the hormone group (all P<0.001). CONCLUSIONS The endometrial thickness, echo, blood flow, and peristalsis, the number of visible tubal opening, uterine motion, and the intercornual distance obtained by 3D-TVUS examination are important factors to evaluate the prognosis of postoperative drug treatment for IUA. 3D-TVUS is of great significance in evaluating the efficacy of Yangmo decoction in the treatment of IUA.
Humans ; Retrospective Studies ; Hormones

The proteolysis targeting chimeras (PROTACs) technology has been rapidly developed since its birth in 2001, attracting rapidly growing attention of scientific institutes and pharmaceutical companies. At present, a variety of small molecule PROTACs have entered the clinical trial. However, as small molecule PROTACs flourish, non-small molecule PROTACs (NSM-PROTACs) such as peptide PROTACs, nucleic acid PROTACs and antibody PROTACs have also advanced considerably over recent years, exhibiting the unique characters beyond the small molecule PROTACs. Here, we briefly introduce the types of NSM-PROTACs, describe the advantages of NSM-PROTACs, and summarize the development of NSM-PROTACs so far in detail. We hope this article could not only provide useful insights into NSM-PROTACs, but also expand the research interest of NSM-PROTACs.

Post-intensive care syndrome (PICS) is the most common complication in patients discharged from intensive care unit (ICU), which seriously affects the life quality of the patients. At present, there is still lack of standardevaluation methods for PICS. Continuous and dynamic assessment can earlyidentify PICS, moreover, early identification and intervention of PICS can improve the life quality of patients those patients, which is critical to improve the long-term outcome of the patients. In this paper, we reviewed the current research states of evaluation timing, contents, tools and modalities of PICS domestic and abroad, analyzed the problems and prospects of the existing evaluation methods, aiming to provide a reference for clinical staff to effectively and comprehensively evaluate PICS.

Glucose-regulated protein 94(Grp94), an endoplasmic reticulum resident Hsp90 paralog, has a limited set of client proteins. Selective inhibition of Grp94 has emerged as a new direction for the development of drugs targeting the Hsp90 chaperone system. Now Grp94-Probe, an affinity-based probe of Grp94, was designed and synthesized based on DDO-5813, a most potent Grp94-selective inhibitor we found previously. Using fluorescence polarization(FP)assay and double staining assay with ER-Red in cells, we confirmed the binding of Grp94-Probe with ER Grp94. The FR results showed that the probe exhibited high affinity for Grp94N(EC50=117. 9 nmol/L)without exhibiting obvious Hsp90α inhibition, Moreover, as a fluorescence probe molecule, Grp94-Probe could better distinguish the inhibitory activity of compounds for Grp94N. The results of fluorescence analysis in cells showed that Grp94-Probe could co-stain with ER-Red in the endoplasmic reticulum, and the fluorescence did not decay rapidly with time after 4 h of staining, which further indicated the binding of Grp94-Probe with Grp94 in cells. This Grp94 selective probe can be further used for biology evaluation of Grp94 inhibitor and exploration of Grp94 biological functions.