Persistent inflammation plays a pivotal role in the initiation and progression of renal fibrosis. Activation of the pattern recognition receptor retinoic acid-inducible gene-I (RIG-I) is implicated in the initiation of inflammation. This study aimed to investigate the upstream mechanisms that regulates the activation of RIG-I and its downstream signaling pathway. Eight-week-old male C57BL/6 mice were used to establish unilateral ureteral obstruction (UUO)-induced renal fibrosis model, and the renal tissue samples were collected 14 days later for analysis. Transforming growth factor-β (TGF-β)-treated mouse renal tubular epithelial cells were used in in vitro studies. The results demonstrated that, compared to the control group, UUO kidney exhibited significant fibrosis, which was accompanied by the increases of RIG-I, p-NF-κB p65 and inflammatory cytokines, such as TNF-α and IL-1β. Additionally, the protein level of the E3 ubiquitin ligase RNF125 was significantly downregulated and predominantly localized in the renal tubular epithelial cells. Similarly, the treatment of tubular cells with TGF-β induced the increases in RIG-I, p-NF-κB p65 and inflammatory cytokines while decreasing RNF125. Co-immunoprecipitation (Co-IP) assays confirmed that RNF125 was able to interact with RIG-I. Overexpression of RNF125 promoted the ubiquitination of RIG-I, and accelerated its degradation via the ubiquitin-proteasome pathway. Overexpression of RNF125 in UUO kidneys and in vitro tubular cells effectively mitigated the inflammatory response and renal fibrosis. In summary, our results demonstrated that the decrease in RNF125 under pathological conditions led to reduction in RIG-I ubiquitination and degradation, activation of the downstream NF-κB signaling pathway and increase in inflammatory cytokine production, which promoted the progression of renal fibrosis.
Animals ; Fibrosis ; Male ; Ubiquitination ; Mice ; Mice, Inbred C57BL ; DEAD Box Protein 58 ; Ubiquitin-Protein Ligases/physiology* ; Inflammation/metabolism* ; Ureteral Obstruction/complications* ; Kidney/pathology* ; Signal Transduction ; Transforming Growth Factor beta/pharmacology*

OBJECTIVE: To investigate the regulatory effects of two traditional mineral medicines (TMMs), Gypsum Fibrosum (Shigao, GF) and Terra Flava Usta (Zaoxintu, TFU), on gut-beneficial bacteria in mice, and preliminarily explore their mechanisms of action. METHODS: Mice were randomly divided into 3 groups (n=10 per group): the control group (standard diet), the GF group (diet supplemented with 2% GF), and the TFU group (diet supplemented with 2% TFU). After 4-week intervention, 16S rRNA gene sequencing was used to analyze the changes in the gut microbiota (GM). Scanning electron microscopy, in combination with coumarin A tetramethyl rhodamine conjugate and Hoechst stainings, was used to observe the bacteria and biofilm formation. RESULTS: Principal coordinate analysis revealed that GF and TFU significantly altered the GM composition in mice. Further analysis revealed that GF and TFU affected different types of gut bacteria, suggesting that different TMMs may selectively modulate specific bacterial populations. For certain bacteria, such as Faecalibaculum and Ileibacterium, both GF and TFU exhibited growth-promoting effects, implying that they may be sensitive to TMMs and that different TMMs can increase their abundance through their respective mechanisms. Notably, Lactobacillus reuteri, a widely recognized and used probiotic, was significantly enriched in the GF group. Random forest analysis identified Ileibacterium valens as a potential indicator bacterium for TMMs' impact on GM. Further mechanistic studies showed that gut bacteria formed biofilm structures on the TFU surface. CONCLUSIONS This study provides new insights into the interaction between TMMs and GM. As safe and effective natural clays, GF and TFU hold promise as potential candidates for prebiotic development.
Animals ; Gastrointestinal Microbiome/drug effects* ; Bacteria/growth & development* ; Mice ; Biofilms/drug effects* ; Male ; RNA, Ribosomal, 16S/genetics*

OBJECTIVE: To investigate cisplatin-induced cardiovascular toxicity and explore the protective effects and potential mechanism of curcumin co-treatment. METHODS: Forty adult male Sprague-Dawley rats were numbered and randomly divided into control group, cisplatin group (7.5 mg/kg, once a week, for 2 weeks), curcumin group (200 mg/kg per day, for 2 weeks) and cisplatin+curcumin group (cisplatin 7.5 mg/kg, once a week, and curcumin 200 mg/kg per day for 2 weeks) by a random number table method, with 10 rats in each group. Cardiac and vascular morphology and functions were assessed using hematoxylin-eosin and Masson's trichrome staining, serum indexes detection, echocardiography, electrocardiogram (ECG), blood pressure monitoring, vascular ring isometric tension measurement, and left ventricular pressure evaluation. The expressions of extracellular signal-regulated kinases (ERK) and phosphorylated-ERK (p-ERK) were analyzed by immunohistochemical staining. RESULTS: Cisplatin treatment induced notable cardiac alteration, as evidenced by changes in cardiac morphology, elevated serum enzymes (P<0.05), ECG abnormalities, and increased left ventricular end-diastolic pressure (P<0.05). Meanwhile, cisplatin significantly increased arterial pulse pressure (P<0.01), primarily due to a decrease in diastolic blood pressure. Severe fibrosis was also observed in the thoracic aorta wall. In vascular ring experiments, cisplatin treatment led to a significant reduction in phenylephrine-induced contraction (P<0.05) and acetylcholine-induced relaxation (P<0.01). Notably, Curcumin co-administration significantly alleviated cisplatin-induced cardiovascular damages, as demonstrated by improvement in these parameters. Furthermore, ERK expression in the myocardium and p-ERK expression in vascular smooth muscle cells were significantly upregulated following curcumin co-treatment. CONCLUSIONS Curcumin protects the heart and vasculature from cisplatin-induced damages, likely by upregulating ERK/p-ERK expression. These findings suggest that curcumin may serve as a promising therapeutic strategy for mitigating cisplatin-associated cardiovascular toxicity during tumor chemotherapy. In vitro cell culture experiments are needed to clarify the underlying mechanism.
Animals ; Curcumin/therapeutic use* ; Cisplatin/adverse effects* ; Rats, Sprague-Dawley ; Male ; Up-Regulation/drug effects* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Phosphorylation/drug effects* ; Electrocardiography ; Blood Pressure/drug effects* ; Rats ; MAP Kinase Signaling System/drug effects*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Objective To systematically evaluate the value of optical coherence tomography angiogra-phy (OCTA) for detecting the vessel density (VD) changes after open-angle glaucoma (OAG) surgery.Meth-ods The studies on OCTA for detecting the VD changes after OAG surgery were searched in the CNKI,WanFang,VIP,SinoMed,PubMed,Embase and Web of Science databases from the database establishment to May 2024.Literature screening,data extraction and risk of bias assessment of included studies were conducted independently by two reviewers.Descriptive analysis was adopoted for the systematic evaluation,the meta a-nalysis was conducted by using the R software and mean difference (MD) and its 95％CI were calculated.Re-sults A total of 13 studies were included,involving 472 patients with 500 tested eyes.The results of meta-a-nalysis showed that compared with pre-surgery,VD around the optic nerve head (ONH) and in nasal superi-or,temporal inferior,temporal superior,superior temporal and superior nasal regions at postoperative 6 months were significantly decreased.VD in the perimacular,perimacular superior hemisphere,permacular su-perior hemisphere,perimacular superior and permacular superior regions at postoperative 6 months were sig-nificantly increased.Conclusion OCTA could effectively detect the postoperative VD changes in the patients with OAG and predict postoperative visual function changes in glaucoma,and could serve as an effective test means for assessing the clinical treatment effect of the patients with OAG.

Objective To explore the metastasis rate and related risk factors of T1 stage colonic neuroendocrine tumor(C-NET),and to compare the long-term survival outcomes of patients with non-metastatic(T1N0M0 stage)C-NET after local excision(LE)or radical surgery(RS).Methods Clinical information of 433 patients diagnosed with C-NET in the SEER database from January 1,2004 to December 31,2015 were analyzed.Cox regression was used to analyze the influencing factors of metastasis of C-NET.The patients without metastasis were divided into LE group and RS group,and assigned in a 1∶1 ratio using propensity score matching(PSM)according to gender,age,tumor largest diameter,and infiltration depth,with a caliper value set to 0.02.Kaplan-Meier survival curve was used to analyze 5-year cancer-specific survival(CSS)and overall survival(OS)of patients.Cox regression analysis was used to evaluate the influence of metastasis on survival.Results Among 419 C-NET patients,19(4.52%)had distant metastases.Cox regression analysis showed that 11-20 mm of tumor large diameter(HR=9.264,95%CI 3.322-25.835,P＜0.001),right colon location(HR=0.116,95%CI 0.042-0.321,P＜0.001),and submucosal invasion(HR=5.842,95%CI 1.858-18.371,P=0.003)were independent risk factors for distant metastasis of T1 stage C-NET.The 5-year OS rates of non-metastatic and metastatic patients were 94.5%and 47.4%,respectively(χ2=79.762,P＜0.001),and their 5-year CSS rates were 99.5%and 55.7%,respectively(χ2=164.604,P＜0.001).Before PSM,the 5-year OS rates of non-metastatic C-NET patients after LE and RS were 95.8%and 90.1%(χ2=2.679,P=0.063),and the 5-year CSS rates were 100.0%and 97.2%(χ2=0.579,P=0.038);after PSM,the 5-year OS rates of non-metastatic patients after LE and RS were 96.8%and 92.1%(χ2=3.606,P=0.058),and the 5-year CSS rates were 100.0%and 98.5%(χ2=1.015,P=0.314).After PSM,there was no significant difference in the 5-year OS and CSS of patients with defferent tumor location,tumor large diameter,or submucosal invasion between the LE and RS groups.Conclusions 11-20 mm of tumor diameter,right colon location,and submucosal invasion might be independent risk factors for distant metastasis of T1 stage C-NET,and LE could be an appropriate treatment option for non-metastatic C-NET.

The"common medicines for various diseases"in the preface of Collective Commentaries on the Classic of Materia Medica has been highly praised by medical practitioners for its unique"disease-medicine"outline and clinical practicality,and has continued to be included and developed in later works on materia medica and prescriptions,laying the foundation for the research and develop-ment of"specialized prescriptions for specialized diseases"and"specialized medicines for specialized diseases".Tao Hongjing used"the root of major diseases"in Shen Nong's Classic of the Materia Medica as the basic framework,referred to the prescriptions and med-icines in Treatise on Cold Damage and Miscellaneous Diseases,and expanded his own and other medical experience to create the"com-mon medicines for various diseases"system,relating and summarizing the representative diseases and main therapeutic effects of medi-cines,and creating a"disease-medicine"outline system.The construction of the"common medicines for various diseases"system has opened up the precedent of"specialized prescriptions for specialized diseases"and"specialized medicines for specialized diseases",providing new prescription ideas for clinical differentiation and treatment.

Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".
Humans ; Retrospective Studies ; Antineoplastic Agents/therapeutic use* ; Neoplasms/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Sesquiterpenes/therapeutic use*

Cerebral organoids are three-dimensional nerve cultures induced by embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)that mimic the structure and function of human brain.With the continuous optimization of cerebral organoid culture technology and the combination with emerging technologies such as organ transplantation,gene editing and organoids-on-chip,complex brain tissue structures such as functional vascular structures and neural circuits have been produced,which provides new methods and ideas for studying human brain development and diseases.This article reviews the latest advances in brain organoid technology,describes its application in neurological diseases and advances in stroke modeling and transplantation treatment.