Ulcerative colitis （UC） is a chronic intestinal autoimmune disease， with clinical manifestations including abdominal pain， diarrhea， mucus and bloody stools， and its pathogenesis is complex. The classic prescription Xianglian pills （XLP） has been widely used in the clinical treatment of UC in recent years. It has few adverse reactions， good patient tolerance， and shows significant potential for clinical application. However， there is currently no comprehensive integration of evidence on its clinical research and molecular mechanisms. Through a systematic review of the clinical research and molecular mechanisms of XLP in the treatment of UC， it is found that XLP and its modified formulas， when used in combination with chemical drugs， can significantly improve the symptoms of UC patients and reduce intestinal inflammation， with superior efficacy compared to chemical drugs alone. Its mechanism of action involves regulating pan-apoptosis， immune response， signaling pathways （hypoxia-inducible factor-1α， nuclear factor-κB， etc.）， intestinal flora， and repairing the intestinal mucosal barrier. Its medicinal materials， monomers and active components can also prevent the differentiation of helper T cells 17 and restore the balance of M1/M2 cells through regulating multiple pathways such as Wnt/β -catenin and Janus kinase/signal transducer and activator of transcription， thereby reducing intestinal damage in UC.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

Nonalcoholic steatohepatitis （NASH） is a chronic liver disease with the main pathological features of hepatic steatosis， inflammatory cell infiltration， and interstitial fibroplasia， and it is an important risk factor for liver fibrosis， liver cirrhosis， and hepatocellular carcinoma. NOD-like receptor protein 3 （NLRP3） inflammasome is the core of innate immunity， and the abnormal activation of NLRP3 inflammasome is closely associated with the development and progression of NASH， which involves multiple links such as inflammatory response and oxidative stress. A large number of studies have shown that the active ingredients of traditional Chinese medicine （TCM） and TCM compound prescriptions can improve oxidative stress， regulate lipid metabolism， and alleviate liver inflammation by regulating NLRP3 inflammasome. TCM treatment applied in clinical practice has achieved a good therapeutic effect， while inflammasome is one of the key pathways or targets for TCM in improving NASH. This article reviews the mechanism of action of NLRP3 inflammasome in NASH and the research advances in TCM intervention of NLRP3 inflammasome， in order to provide ideas for the clinical TCM treatment of NASH， as well as reference targets and research directions for the research and development of new TCM drugs.

Objective To investigate the effects of TFF3 overexpression on the proliferation, migration, and invasion ability of colorectal cancer HT29 cells and the mechanisms involved in cancer metastasis. Methods HT29 cells were transfected with pIRES2-TFF3, and the expression levels of mRNAs and proteins related to TFF3 gene, TWIST1/TRIB3 signaling pathway, and epithelial-mesenchymal transition (EMT) were detected by qRT-PCR and Western blot. The proliferation, migration, and invasion ability of HT29 cells were detected by the CCK-8, cell scratch, and Transwell assays. Changes in cell morphology after TFF3 overexpression were observed through transmission electron microscopy. Results After the HT29 cells were transfected with pIRES2-TFF3, the expression levels of TFF3 mRNA and protein significantly increased (P<0.01); cell proliferation, migration, and invasion were significantly enhanced (P<0.01); and the expression of related genes, such as TWIST1, TRIB3, Vimentin, and Snail were significantly upregulated. By contrast, the expression of E-cadherin significantly decreased (P<0.05). Various changes in cell morphology were observed after TFF3 overexpression, such as decrease in cell junctions, loss of cilia, formation of pseudopodia, and increase in fusiform cells. Conclusion TFF3 overexpression may promote EMT in colorectal cancer cells through the Twist1/TRIB3 signaling pathway, increase their metastatic potential, and accelerate the malignant progression of colorectal cancer.

ObjectiveTo investigate the impact of yang deficiency syndrome on the progression to end-point events of diabetic kidney disease （DKD）. MethodsA retrospective study among patients with stage Ⅳ DKD admitted to Dongzhimen Hospital of Beijing University of Chinese Medicine from September 1st， 2016 to September 30th， 2021 was conducted. Data on the patients' general information， clinical indicators including duration of diabetes， duration of proteinuria， history of smoking and drinking， hemoglobin （HGB）， fasting blood glucose （FBG）， albumin （ALB）， serum creatinine （Scr）， urea nitrogen （BUN）， uric acid （UA）， cholesterol （TC） ， triglycerides （TG）， low-density lipoprotein （LDL）， 24-hour urine protein quantification （24h-UTP） and estimated glomerular filtration rate （eGFR）， and TCM syndromes including symptoms， tongue and pulse， and syndrome scores were collected. The patients were divided into exposure group （yang-deficiency group） and non-exposure group （non-yang-deficiency group）. The general information， clinical indicators and incidence rates of end-point events were compared， and the impact of yang deficiency syndrome on the end-point events of stage Ⅳ DKD was analyzed. Survival analysis was performed using Kaplan-Meier method， and multivariate Cox proportional risk models were used to identify independent predictors of end-point events. ResultsA total of 160 patients with stage Ⅳ DKD were included in the study， including 43 cases of yang deficiency syndrome and 117 cases of non-yang deficiency syndrome. Compared to those in the non-yang deficiency group， the waist circumference， BUN and the incidence of end-point events in the yang deficiency group were significantly higher （P＜0.05 or P＜0.01）. Spearman correlation analysis showed that yang deficiency syndrome was positively correlated with incidence of end-point events of stage Ⅳ DKD （r = 0.167， P = 0.035）. Furthermore， 24h-UTP and BUN levels were also positively correlated with end-point events in stage Ⅳ DKD patients （P＜0.01）， while ALB and HGB levels were negatively correlated （P＜0.01）. Kaplan-Meier survival curves showed that yang deficiency syndrome was associated with an increased risk of end-point events （Log Rank P = 0.011）. Moreover， 24h-UTP levels ≥3500 mg， BUN level ≥8 mmol/L， ALB level ＜30 g and HGB level ＜11 g were all associated with the increase of the risk of end-point events （P＜0.05 or P＜0.01）. Multivariate Cox regression analysis showed that yang deficiency syndrome was an independent risk factor for patients with stage Ⅳ DKD to progress into end-point events （HR = 2.36， 1.32 to 4.21； P = 0.004）， as well as 24h-UTP ≥ 3500 mg， BUN ≥ 8 mmol/L， HGB＜11 g and ALB＜30 g （P＜0.05 or P＜0.01）. ConclusionsFor stage Ⅳ DKD， patients with yang deficiency syndrome are more likely to have end-point events， which is an independent risk factor for the progression into end-point events.

OBJECTIVE To study the protective effect of saikosaponin b2(SSb2)on corticosterone(CORT)induced PC12 cell injury and its mechanism.METHODS ① PC12 cells were divided into the cell control group(24 h of culture with RPMI-1640 medium),CORT group(24 h of culture with CORT 100-800 μmol·L-1)and SSb2 group(24 h of culture with SSb2 1.5625,3.125,6.25,12.5,25,50 and 100 μmol·L-1).MTT assay was used to detect the cell survival rate.②PC12 cells were divided into the cell control group(24 h of culture with RPMI 1640 medium),model group(24 h of culture with CORT 400 μmol·L-1),and model+SSb2 group(3 h pretreatment with SSb2 1.5625,3.125,6.25,12.5 and 25 μmol·L-1,removal of the supernatant before cells were co-incubated with CORT 400 μmol·L-1 and corresponding concentrations of SSb2 for 24 h).MTT assay was used to detect the cell survival rate while micro-plate assay was used to detect the lactate dehydrogenase(LDH)leakage rate of PC12 cells.③PC12 cells were divided into the cell control group,model group and model+SSb2 12.5 μmol·L-1 group.AnnexinV-FITC/PI flow cytometry assay was used to detect PC12 cell apoptosis,ultra-perfor-mance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)cell metabonomics was used to detect metabolic profile changes and colorimetric assay was employed to detect the glutamic acid content and glutaminase activity in PC12 cells.RESULTS Compared with the cell control group,the cell viability decreased to(55±6)%(P<0.01)when the concentration of CORT was 400 μmol·L-1.When the concentration of SSb2 was higher than 50 μmol·L-1,there was significant toxicity to PC12 cells(P<0.01).②Compared with the cell control group,the cell survival rate was signif-icantly decreased(P<0.01),while the release rate of LDH was significantly increased(P<0.01)in the model group.Compared with the model group,the cell survival rate significantly increased(P<0.05,P<0.01),while the LDH release rate significantly decreased(P<0.01)in the model+SSb2 group.③ Com-pared with the cell control group,cell apoptosis was significantly increased in the model group(P<0.05).Compared with the model group,cell apoptosis was significantly decreased(P<0.05)in the model+ SSb2 group.Metabolomics results show that SSb2 significantly back-regulated nine differential metabo-lites of glutamate,creatine,N-acetylaspartate,L-tyrosine,citric acid,L-isoleucine,lactic acid,glutamine and choline.Further network analysis of the key metabolites regulated by SSb2 yielded five major metabolic pathways:D-glutamine and D-glutamate metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,alanine,aspartate and glutamate metabolism,tyrosine metabolism and arginine biosynthesis.Compared with the cell control group,the content of glutamate and activity of glutaminase were significantly decreased in the model group(P<0.01).Compared with the model group,the content of glutamate(P<0.01)and activity of glutaminase(P<0.05)were significantly increased in the model+SSb2 group.CONCLUSION SSb2 has a neuroprotective effect on CORT-injured PC12 cells,and the mechanism of which is related to inhibition of apoptosis and regulation of metabolic disorders.

Retinal vein occlusion(RVO), the second most prevalent retinal vascular disease, has complex pathophysiological mechanism. Except for mechanical pressure on blood vessel, inflammation and endothelin have been confirmed to be involved in the pathogenesis of RVO. However, its specific mechanism remains unclear. Hypertension, diabetes and dyslipidemia have been previously shown to be the most common risk factors in elder population, while recent studies found that coagulation and hemorheological abnormalities are more common in people under 50 years old. Ocular risk factors including glaucoma, high corrected intraocular pressure and retinal vessels abnormality, have gained more and more attention. These factors probably exert a synergistic effect when present simultaneously in the same patient. Therefore, early identification and intervention of those factors could lower the incidence of RVO. This article aims to review recent research and summarize existing mechanism and theories, giving some new research ideas for potential therapy targets and providing references for identification and management of risk factors.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Objective To investigate the knowledge,demand,and use of clinical practice guide-lines(CPGs)among anesthesia professionals in Gansu province,and to explore the strategies and barriers during the implementation process.Methods A questionnaire survey was conducted to investigated the knowledge,demand,and use of CPGs,as well as the strategies and barriers during the process of guideline implementation.Statistical analysis was applied to the collected data.Results A total of 339 valid question-naires were collected,96.8%of the respondents were aware of the guidelines,and the majority of the re-spondents(86.4%)consulted the guidelines when they encountered problems in clinical practice.The main barriers for guideline utilization were identified as lack of convenience(70.2%),limited availability chan-nels(64.3%)or restricted access rights(56.9%)to obtain the guidelines,inadequate training(31.3%),and language barriers(21.5%).Multiple forms of assisting guideline use and opening up guideline access were considered by most respondents as important ways to promote guideline implementation.Conclusion Anesthesia professionals in Gansu province demonstrated good levels of awareness and compliance with guidelines.However,the primary barriers to utilization were attributed to the guidelines themselves or diffi-culties in accessing them.It is recommended to establish a national guideline clearinghouse,provide imple-mentation tools,and enhance healthcare professional training to facilitate the promotion and application of guidelines in the future.