In recent years， with the extensive application of traditional Chinese medicine （TCM） both domestically and internationally， safety concerns associated with TCM have been frequently reported. Notably， some TCM substances traditionally regarded as ''non-toxic'' have exhibited significant adverse reactions during clinical use， drawing substantial attention to TCM safety. This study first analyzed the risk factors contributing to the potential toxicity of TCM from perspectives such as drug properties， individual constitution， and clinical medication practices. Subsequently， it proposed research strategies and methodologies for investigating potential TCM toxicity： ① conduct studies under the guidance of TCM theory， adhering to the principle of diversity and unity. ② adopt an integrated research paradigm of ''originating from clinical practice-syndrome-based foundation-returning to clinical practice-serving supervision''. ③ implement a three-tier technical system of ''Mathematical modeling-high-throughput screening via liquid chromatography-mass spectrometry （LC-MS）-systems biology'' to systematically elucidate the causes， material basis， and mechanisms of toxicity. Finally， scientific regulatory recommendations for potential TCM toxicity are proposed： ① establish a multidimensional prevention and control system addressing drug properties， physical constitution factors， and clinical medication practices. ② address the impact of modern processing techniques on the safety of new TCM drugs. ③ strengthen the revision of standards for Chinese medicinal materials to ensure their safety. ④ account for disease-syndrome combination animal models and interspecies differences in safety assessment outcomes. This study aims to overcome critical challenges in TCM regulation by advancing evaluation through research and driving research through evaluation. By establishing a high-level scientific regulatory framework， it seeks to not only safeguard clinical medication safety but also propel the high-quality development of the TCM industry， thereby providing scientific support for the inheritance and innovative evolution of TCM.

In recent years， with the extensive application of traditional Chinese medicine （TCM） both domestically and internationally， safety concerns associated with TCM have been frequently reported. Notably， some TCM substances traditionally regarded as ''non-toxic'' have exhibited significant adverse reactions during clinical use， drawing substantial attention to TCM safety. This study first analyzed the risk factors contributing to the potential toxicity of TCM from perspectives such as drug properties， individual constitution， and clinical medication practices. Subsequently， it proposed research strategies and methodologies for investigating potential TCM toxicity： ① conduct studies under the guidance of TCM theory， adhering to the principle of diversity and unity. ② adopt an integrated research paradigm of ''originating from clinical practice-syndrome-based foundation-returning to clinical practice-serving supervision''. ③ implement a three-tier technical system of ''Mathematical modeling-high-throughput screening via liquid chromatography-mass spectrometry （LC-MS）-systems biology'' to systematically elucidate the causes， material basis， and mechanisms of toxicity. Finally， scientific regulatory recommendations for potential TCM toxicity are proposed： ① establish a multidimensional prevention and control system addressing drug properties， physical constitution factors， and clinical medication practices. ② address the impact of modern processing techniques on the safety of new TCM drugs. ③ strengthen the revision of standards for Chinese medicinal materials to ensure their safety. ④ account for disease-syndrome combination animal models and interspecies differences in safety assessment outcomes. This study aims to overcome critical challenges in TCM regulation by advancing evaluation through research and driving research through evaluation. By establishing a high-level scientific regulatory framework， it seeks to not only safeguard clinical medication safety but also propel the high-quality development of the TCM industry， thereby providing scientific support for the inheritance and innovative evolution of TCM.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

"MS/MS spectrum to structure"plays a critical role in the confirmative identification of complicated matrices and is currently regarded as an extremely challenging endeavor.MS/MS information provides vital clues to structural identification.In this study,a strategy was proposed to facilitate unambiguous identification through matching MS3 with MS2 spectra.Initially,MS3 spectra of the featured ions(c-and y-type ions)generated by the decomposition of ester functional group in esters and the MS2 spectrum of the structural unit([M-H]-)were all captured on the Qtrap-MS platform equipped with two tandem-in-space collision cells,including the second quadrupole cell(q2)and linear ion trap(LIT)chambers(actually the third quadrupole unit).Subsequently,the MS/MS spectrum matching between MS3 spectra of the ester compound and MS2 spectra of the structural unit(s)were achieved.As a result,the findings corresponding to MS3 and MS2 spectra matching were summarized.Finally,based on HR-MS/MS information of total salvianolic acid derivatives(TSA),36 kinds of compounds were preliminarily identified through matching with literature information and database retrieval.The applicability of MS3 and MS2 spectra matching strategy was further justified by the confirmative identification of phenolic acid compounds(Rosmarinic acid and salvianolic acid B)in TSA.Above all,MS3 and MS2 spectra matching strategy was quite meaningful towards advancing"MS/MS spectrum to structure"analysis through recognizing and identifying featured fragment ions,and also provided inspiration and new insights for the structural characterization.

Objective To investigate the correlation between subclinical peripheral neuropathy(sDPN)and time in range(TIR)in type 2 diabetes mellitus(T2DM),and to explore the risk factors of sDPN.Methods A total of 485 T2DM patients without DPN symptoms and underwent EMG examination during hospitalization were divided into the sDPN group(n=209)and the non-sDPN group(n=276)according to nerve function conduction examination.The differences of age,course of the disease,blood pressure,complications,biochemical index and continuous glucose monitoring index were compared between the two groups of patients.The correlation between sDPN and TIR was analyzed.Logistic regression analysis was used to analyze influence factors of sDPN.Results Compared with the non-sDPN group,patients in the sDPN group were older and had longer diabetes course,higher systolic blood pressure(SBP),urinary albumin/urinary creatinine(UACR),blood glucose 1 h postprandial(1 h-PG),2 h-PG,TBR,mean blood glucose fluctuation range(MAGE),standard deviation of blood glucose level(SD)and glycemic coefficient of variation(CV)levels,higher proportion of hypertension(HT),diabetic nephropathy(DN),diabetic retinopathy(DR)and diabetic peripheral vascular disease(PAD),and lower levels of total cholesterol(TC),right limb ankle brachial index(R-ABI),L-ABI,hemoglobin A1c(HbA1c)and TIR.The differences in the above indexes were statistically significant(P＜0.05).The occurrence of sDPN was positively correlated with TBR(rs=0.104,P＜0.05),and negatively correlated with TIR(rs=-0.093,P＜0.05).Logistic regression analysis showed that increased TBR(OR=1.093,95%CI:1.009-1.183),combined with DN(OR=3.004,95%CI:1.020-8.849)and DR(OR=9.736,95%CI:3.499-27.087)were independent risk factors for sDPN,and increased R-ABI(OR=0.005,95%CI:0.000-0.424)was protective factor for sDPN.Conclusion sDPN was negatively correlated with TIR.For patients with T2DM complicated with DN,DR and decreased ABI,it is necessary to timely improve neuroelectrophysiological examination to identify sDPN as soon as possible and give early intervention.

Risk perception in patients with cardiovascular disease (CVD) can predict their adoption of health behaviors. A significant discrepancy between perceived risk and objective risk estimates can adversely affect individuals' risk response behaviors. This paper introduces the status quo of risk perception bias among CVD patients and analyzes the influencing factors from demographic factors, disease risk factors, individual psychological factors, socio-cultural factors, risk communication, and risk characteristics. It summarizes intervention strategies to reduce risk perception bias, aiming to enhance healthcare professionals' understanding of this issue in CVD patients and provide a reference for developing reasonable intervention measures in the future.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of hyperoside,kaempferol-3-O-rutinoside,esculin,chlorogenic acid,berberine,quercetin,rehmannioside D,palmatine,leonurin A,paeoniflorin,timosaponin BⅡand rutin in Guanhuangmu Granules.METHODS The analysis was performed on a 40℃ thermostatic Acquity UPLC HSS T3 column(100 mm×2.1 mm,1.8 μm),with the mobile phase comprising of 0.05%formic acid(containing 2 mmol/L ammonium acetate)-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning.RESULTS Twelve constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 93.46%-102.01%with the RSDs of 2.13%-3.65%.CONCLUSION This rapid,accurate,stable and sensitive method can be used for the quality control of Guanhuangmu Granules.

AIM To investigate the clinical effects of Lingxian Tongluo Capsules combined with Wentong Acupuncture Method on patients with lumbar disc herniation.METHODS One hundred and four patients were randomly assigned into control group(52 cases)for 30-day intervention of both Wentong Acupuncture Method and conventional treatment,and observation group(52 cases)for 30-day intervention of Lingxian Tongluo Capsules,Wentong Acupuncture Method and conventional treatment.The changes in clinical effects,TCM syndrome scores,lumbar function indices(ODI index score,JOA score),VAS score,inflammatory factors(TNF-α,IL-1β,IL-6),hemorheological indices(plasma viscosity,whole blood high-shear viscosity,whole blood low-shear viscosity)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,ODI index score,VAS score,inflammatory factors and hemorheological indices(P＜0.05),and increased JOA score(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with lumbar disc herniation,Lingxian Tongluo Capsules combined with Wentong Acupuncture Method can safely and effectively relieve clinical symptoms,promote lumbar function recovery,reduce pain degree,alleviate inflammatory responses,and improve hemorheology.

Objective:To retrieve, evaluate, and integrate the best practice evidence for targeted temperature management in neurocritically ill patients.Methods:PIPOST tool was used to identify evidence-based issues; the Chinese and English terms were chosen as "Traumatic brain injuries", "Craniocerebral trauma/Cerebral hemorrhage/Stroke/Subarachnoid hemorrhage/Cerebral vascular disease", and "Mild hypothermia therapy/Target body temperature/Cyotherapy". According to top-down design of the "6S" evidence model, databases such as French guideline network, US guideline network, UpToDate, Chinese Biomedical Literature Database, China Yimaitong Guide network, CNKI, and Wanfang Medical Network were searched. Two researchers independently evaluated the quality of the included literature, and extracted and summarized the evidences of the literature that met the quality standards.Results:A total of 10 articles were included, including 1 clinical decision, 4 guidelines, 1 evidence summary, and 4 expert consensuses. Finally, 27 pieces of best evidences were summarized, including 6 aspects as evaluation, preparation before implementation, targeted body temperature selection, intervention duration, chill management, and other complication prevention.Conclusion:Best evidence for temperature management in neurocritically ill patients can provide evidence-based evidence for healthcare professionals.