OBJECTIVE:To obverse the efficacy and safety of tolynicate and napthylacetic acid and atorvastation combined with Danshen injection in the treatment of alcoholic hyperlipemia syndrome. METHODS:21 patients with alcoholic hyperlipemia syndrome were enrolled. All patients were given maintaining acid-base balance,oxygen inhalation and other conventional treatment. Based on it,they were orally given 75 mg Tolynicate and napthylacetic acid tablet,3 times a day+20 mg Atorvastatin calcium tab-let,once a day+4 ml Compound danshen injection,adding into 150 ml 5% Glucose injection by intravenous infusion,once a day. The treatment course for both groups was 30 d. Clinical efficacy,ALT,AST,TBIL,TC,TG,RBC and Hb before and after 6, 12,18,24 and 30 d,and incidence of adverse reactions were observed. RESULTS:After treatment,the total effective rate was 95.3%and incidence of adverse reactions was 28.5%. The ALT,AST and TBIL after 6,12,18,24 and 30 h and TC and TG after 18,24 and 30 h were significantly lower than before and gradually decreased by time;RBC and Hb after 12,18,24 and 30 h were significantly higher than before and gradually increased by time,the differences were statistically significant(P<0.05). CON-CLUSIONS:tolynicate and napthylacetic acid and atorvastation combined with Danshen injection is effective in the treatment of al-coholic hyperlipemia syndrome,with good safety.

OBJECTIVE:To observe therapeutic efficacy and safety of amlodipine besylate combined with valsartan in the treatment of hypertension. METHODS:158 patients with hypertension were randomly divided into control group (n=78) and treatment group (n=80). Control group was treated with amlodipine besylate,2.5 mg/time,3 times/d;treatment group was addi-tionally treated with valsartan,80 mg/time,once a day. A treatment course lasted for 4 weeks,and both received 5 courses. Clini-cal efficacy,blood pressure,plasma concentrations of ET-1,NT-proBNP and Ang Ⅱ were compared between 2 groups. RE-SULTS:The compliance rates of treatment group after 4,8,12,16,20 weeks were higher than that of the control group(P<0.05). Compared with control group,SBP and DBP of treatment group were decreased significantly after 4,8,12 and 20 weeks,with sta-tistical significance(P<0.05). After 20 weeks,the serum levels of ET-1,NT-proBNP and Ang Ⅱwere decreased significantly,es-pecially treatment group,with statistical significance (P<0.05). There was no statistical significance in the incidence of ADR be-tween 2 groups (P>0.05). CONCLUSIONS:Amlodipine besylate combined with valsartan can effectively control the blood pres-sure in patients with hypertension,which may be related to the inhibition of ET-1,NT-proBNP and AngⅡ.

Objective To investigate the efficacy and safety of progressive dose-adding of alprazolam midazolam in the treatment of chronic tinnitus.Methods A total of 80 chronic tinnitus patients were divided into observation group and control group,with 40 cases in each group.The control group was treated with conventional nutritional nerve and improved circulation treatment,while the observation group was additionally treated with alprazolam progressive incremental treatment.The therapeutic effects of the two groups were observed.The THI score,VAS score,tinnitus loudness and adverse reactions after treatment were observed.Results The total effective rate of the observation group was significantly higher than that of the control group (80％ vs.57.5％,P ＜ 0.05).There were no significant differences in the THI score,VAS score and tinnitus loudness between the two groups before treatment (P ＞ 0.05).After treatment,the THI score,VAS score and tinnitus loudness of the two groups were lower than treatment before (P ＜ 0.05),and the observation group was lower than the control group (P ＜ 0.05).There was no significant difference in the incidence of adverse reactions between the two groups (P ＞ 0.05).Conclusion Application of progressive incremental alprazolam therapy for patients with chronic tinnitus has prominent efficacy and higher safety.

Objective To investigate the efficacy and safety of progressive dose-adding of alprazolam midazolam in the treatment of chronic tinnitus.Methods A total of 80 chronic tinnitus patients were divided into observation group and control group,with 40 cases in each group.The control group was treated with conventional nutritional nerve and improved circulation treatment,while the observation group was additionally treated with alprazolam progressive incremental treatment.The therapeutic effects of the two groups were observed.The THI score,VAS score,tinnitus loudness and adverse reactions after treatment were observed.Results The total effective rate of the observation group was significantly higher than that of the control group (80％ vs.57.5％,P ＜ 0.05).There were no significant differences in the THI score,VAS score and tinnitus loudness between the two groups before treatment (P ＞ 0.05).After treatment,the THI score,VAS score and tinnitus loudness of the two groups were lower than treatment before (P ＜ 0.05),and the observation group was lower than the control group (P ＜ 0.05).There was no significant difference in the incidence of adverse reactions between the two groups (P ＞ 0.05).Conclusion Application of progressive incremental alprazolam therapy for patients with chronic tinnitus has prominent efficacy and higher safety.

As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.

Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming (CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR co-cultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase (ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years' development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.