Safety, tolerability, and immunogenicity of a CpG/Alum adjuvanted SARS-CoV-2 recombinant protein vaccine (ZR202-CoV) in healthy adults: Preliminary report of a phase 1, randomized, double-blind, placebo-controlled, dose-escalation trial.

This was a phase 1 dose-escalation study of ZR202-CoV, a recombinant protein vaccine candidate containing a pre-fusion format of the spike (S)-protein (S-trimer) combined with the dual-adjuvant system of Alum/CpG. A total of 230 participants were screened and 72 healthy adults aged 18-59 years were enrolled and randomized to receive two doses at a 28-day interval of three different ZR202-CoV formulations or normal saline. We assessed the safety for 28 days after each vaccination and collected blood samples for immunogenicity evaluation. All formulations of ZR202-CoV were well-tolerated, with no observed solicited adverse events ≥ Grade 3 within 7 days after vaccination. No unsolicited adverse events ≥ Grade 3, or serious adverse events related to vaccination occurred as determined by the investigator. After the first dose, detectable immune responses were observed in all subjects. All subjects that received ZR202-CoV seroconverted at 14 days after the second dose by S-binding IgG antibody, pseudovirus and live-virus based neutralizing antibody assays. S-binding response (GMCs: 2708.7 ~ 4050.0 BAU/mL) and neutralizing activity by pseudovirus (GMCs: 363.1 ~ 627.0 IU/mL) and live virus SARS-CoV-2 (GMT: 101.7 ~ 175.0) peaked at 14 days after the second dose of ZR202-CoV. The magnitudes of immune responses compared favorably with COVID-19 vaccines with reported protective efficacy.

Neuron-Derived Exosomes Promote the Recovery of Spinal Cord Injury by Modulating Nerve Cells in the Cellular Microenvironment of the Lesion Area.

During spinal cord injury (SCI), the homeostasis of the cellular microenvironment in the injured area is seriously disrupted, which makes it extremely difficult for injured neurons with regenerative ability to repair, emphasizing the importance of restoring the cellular microenvironment at the injury site. Neurons interact closely with other nerve cells in the central nervous system (CNS) and regulate these cells. However, the specific mechanisms by which neurons modulate the cellular microenvironment remain unclear. Exosomes were isolated from the primary neurons, and their effects on astrocytes, microglia, oligodendrocyte progenitor cells (OPCs), neurons, and neural stem cells were investigated by quantifying the expression of related proteins and mRNA. A mouse SCI model was established, and neuron-derived exosomes were injected into the mice by the caudal vein to observe the recovery of motor function in mice and the changes in the nerve cells in the lesion area. Neuron-derived exosomes could reverse the activation of microglia and astrocytes and promote the maturation of OPCs in vivo and in vitro. In addition, neuron-derived exosomes promoted neurite outgrowth of neurons and the differentiation of neural stem cells into neurons. Moreover, our experiments showed that neuron-derived exosomes enhanced motor function recovery and nerve regeneration in mice with SCI. Our findings highlight that neuron-derived exosomes could promote the repair of the injured spinal cord by regulating the cellular microenvironment of neurons and could be a promising treatment for spinal cord injury.

Role of Oxidative Stress in Ulcerative Colitis and Traditional Chinese Medicine Prevention and Treatment： A Review / 中国实验方剂学杂志

Ulcerative colitis （UC） is a commonly seen digestive system disease with unclear pathogenesis. The condition is complex and variable， often chronic， and has a long treatment period with no specific cure. Currently， the treatment of UC often involves the use of corticosteroids， aminosalicylates， and biologics in western medicine， which provide fast-acting and definite efficacy in the short term. However， with prolonged medication， some patients may develop drug resistance and worsening of the disease， leading to the occurrence of colon cancer. Research has found that oxidative stress is one of the important pathogenic factors in UC and influences its onset and development. Oxidative stress is a state of imbalance between oxidative products and the antioxidant system in the body， characterized by overexpression of oxidative products such as malondialdehyde （MDA）， reactive oxygen species （ROS）， nitric oxide （NO）， or deficiency of antioxidant enzymes such as superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH）. It is worth noting that traditional Chinese medicine （TCM）， as a unique characteristic medicine of China， has achieved significant efficacy in the treatment of UC. Studies have shown that TCM effectively inhibits the occurrence of UC by suppressing the accumulation of metabolites and antagonizes the development of UC by enhancing the antioxidant system. Therefore， using TCM to regulate the oxidative balance as a diagnostic and therapeutic approach may be a new method and direction for the treatment of UC in the future. Based on the above research， this article summarized the mechanisms of key pathogenic proteins in oxidative stress and the occurrence and development of UC， and compiled the effective ingredients of Chinese medicine， single drugs， prescriptions， and acupuncture and moxibustion in regulating upstream and downstream target proteins of oxidative stress. These interventions can reduce pathological damage to the intestinal mucosa， lower the colon injury index， enrich the intestinal microbiota， increase colon length， and improve clinical symptoms of UC. The article is expected to expand the application of TCM in the treatment of UC and provide a reliable scientific theoretical basis.

Association of folic acid with the development and progression of liver cancer / 临床肝胆病杂志

So far, liver cancer is still a highly malignant tumor with a high incidence rate in China, and it seriously affects the life and health of Chinese people. Previous studies have shown that the development of liver cancer is associated with various factors such as virus, smoking, drinking, and nonalcoholic fatty liver disease. With continuous exploration, more and more studies have pointed out that nutritional factors and living environment are associated with the development and progression of liver cancer. Folic acid is a necessary nutrient for cell growth and reproduction, and its level in human body has an impact on the growth of tumor cells and is closely associated with liver cancer. This article reviews the research advances in the association between folic acid and liver cancer in recent years, so as to provide new reference and basis for the prevention and treatment of liver cancer.

Effect of potassium-competitive acid blockers on human gut microbiota: a systematic review and meta-analysis.

Background: Vonoprazan has been reported to exert more potent and long-lasting gastric acid inhibition than proton pump inhibitors, potentially leading to a greater impact on the gut microbiota. This study aimed to clarify changes in microbial diversity and bacterial composition after VPZ treatments. Methods: We searched from PubMed, Embase, WOS, Scopus, Cochrane Library, and ClinicalTrials.gov (all years up to May 2023). The primary outcomes were alpha and beta diversity, as well as differences in gut microbiota composition between before and after VPZ treatments. We performed a meta-analysis to uncover the potential changes in human gut microbiota among VPZ users by pooled mean difference (MD) with a 95% confidence interval (CI). The risk of bias was assessed using the ROBINS-I tool. Results: A total of 12 studies were included to compare differences before and after VPZ treatments. Compared with baseline, alpha diversity was significantly reduced after VPZ treatments and gradually returned to baseline with longer follow-up. At the phylum level, there was a decrease in the relative abundance of Firmicutes and Actinobacteria, while Bacteroidetes increased compared with baseline. At the genus level, we found a significant decrease in the relative abundance of Coprococcus and Bifidobacterium and a significant increase in the relative abundance of Bacteroides compared with those before treatment. In subgroup analyses according to country and participants, we found differences in microbial changes after VPZ treatments. Conclusion: Vonoprazan can affect the changes of gut microbiota, which may be potentially associated with its strong ability of acid inhibition. However, due to the large heterogeneity, further studies are required to validate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023412265.

Impact of Antimicrobial Stewardship Programs on Antibiotic Use and Drug Resistance: Analysis of Data from Maternal and Child Health Care Hospitals in Hubei Province, China.

OBJECTIVE: To evaluate the impact of Antimicrobial Stewardship Programs (ASPs) on antibiotic use and drug resistance. METHODS: This was a retrospective, multicenter, management intervention study. The data from 85 maternity hospitals (maternal and child health care hospitals) in Hubei province from 2012 to 2019 were collected. The indicators related to antimicrobial drug use included the utilization rate of different grades of antimicrobial drugs, the intensity of antimicrobial agent use, the rational use of prophylactic antimicrobial agents before class I surgical incision, and pathogenic detection and consultation rates before antimicrobial drug use. RESULTS: Since the implementation, the purchase of antimicrobial agents in hospitals has been maintained within the prescribed range, and the defined daily dose system (DDDs) of antimicrobial agents has been reduced, prophylactic use and accurate treatment of antimicrobial agents related to class I surgical incision have been more reasonable. With the implementation of ASPs, the detection rate of imipenem-resistant Acinetobacter baumannii, cefotaxime-resistant Escherichia coli, and methicillin-resistant Staphylococcus aureus has been decreased in China from national bacterial resistance surveillance data. CONCLUSION: ASPs have positive effects on antibiotic use and drug resistance in 85 maternity hospitals (maternal and child health care hospitals).

Optimization of Heat Treatment for 38Si7 Spring Steel with Excellent Mechanical Properties and Controlled Decarburization.

Optimizing the heat treatment procedure with 13 mm diameter 38Si7 spring steel is critical for developing high-performance, low-cost, large spring steel for railway clips. The effects of quenching temperature, holding time, tempering temperature, and tempering time on the microstructure and mechanical properties were investigated using an orthogonal experiment, designed with four factors and three levels. The best heat treatment settings were explored, as well as the variation laws of mechanical properties, decarburization behavior, and fracture morphology. The results demonstrated that quenching temperature and tempering temperature had the most impact on plasticity and tempering temperature, while time had the most effect on strength. The optimized heat treatment schemes made the elongation increase by up to 106% and the reduction in area increase by up to 67%, compared with the standard BS EN 10089-2002, and there were mixed fractures caused by ductility and brittleness. The fracture tests showed a good performance of 20.2 GPa·%, and the heat treatment processes' minimum decarburization depth of 93.4 µm was determined. The optimized process would obtain stronger plastic deposition and better decarburization performance. The microstructure was simply lightly tempered martensite, and the matrix still retained the acicular martensite. The optimal heat treatment process is quenching at 900 °C for 30 min (water cooling), followed by tempering at 430 °C for 60 min (air cooling). The research led to a solution for increasing the overall mechanical characteristics and decreasing the surface decarburization of 38Si7 spring steel with a diameter of 13 mm, and it set the foundation for increasing the mass production of railway clips of this size.

Role of platelets in the development and progression of hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma is one of the common causes of tumor-related death, and it has high morbidity and mortality rates in China. Recent studies have shown that platelets are closely associated with the development of hepatocellular carcinoma. Literature review shows that platelets not only participate in hemostasis, but also act on liver cells and tumor microenvironment, promote the formation of new blood vessels, and participate in the development and progression of hepatocellular carcinoma as a cell mediator through immune response and other pathways. In addition, platelets and their derivatives can be used as potential therapeutic targets for hepatocellular carcinoma. Therefore, antiplatelet therapy is expected to become a new adjuvant strategy for the treatment of hepatocellular carcinoma, which has important clinical significance.

Research progress of miRNA involvement in plant polyphenols in regulating lipid metabolism / 中国药理学通报

Lipid metabolism disorder is an important risk factor for obesity,type 2 diabetes mellitus,non-alcoholic fatty liver disease and other chronic metabolic diseases.Micro RNAs(miRNAs)are short stranded RNA molecules with the size of 19 to 25 nucleotides that regulate lipid metabolism,within a number of physiological functions.Studies have shown that miRNAs can participate in the regulation of lipid metabolism by polyphenolic phytochemicals.In this paper,the mechanism of plant polyphenols improving lipid metabolism disorders and maintaining lipid balance through miRNA is summarized from the synthesis of triglyceride,fatty acid β oxidation,cholesterol efflux and cholesterol esterification,aiming to provide a new thought for the application and development of plant polyphenols to improve the diseases related to lipid metabolism disorders,and offer theoretical basis for the research and development of miRNA as a potential target for the prevention and treatment of diseases related to lipid metabolism disorders.

Advances in the treatment of potassium-competitive acid blockers in reflux esophagitis / 中国临床药理学与治疗学

Reflux Esophagitis (RE) is a gastroesophageal motility disorder mainly caused by lower esophageal sphincter disorder caused by a variety of injury factors, acid-suppressing drugs such as Proton Pump Inhibitors (PPIs) are often used clinically. With the increase of PPIs-resistant reflux esophagitis cases, the demand for the pharmacokinetics and pharmacodynamics of acid-suppressing drugs is higher. In recent years, the emergence of a new class of acid-suppressing drugs, potassium-competitive acid blockers (P-CABs), has solved some clinical deficiencies of traditional proton pump inhibitors. It has the characteristics of effective, longer-lasting acid suppression, the inhibitory effect on gastric acid secretion is not affected by the state of gastric acid secretion, the individual differences in drug metabolism and efficacy are smaller, and the drug efficacy is not affected by food intake or not. It has obvious advantages in the efficacy of severe erosive esophagitis and PPIs-resistant severe erosive esophagitis, and is more cost-effective, and is expected to replace PPI as the first-line treatment for reflux esophagitis.