OBJECTIVE: To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. METHODS: BMSCs were isolated from bone marrow of 8-week-old Spragur Dawley rats and identified [cell surface antigens CD90, CD44, and CD45 were analyzed by flow cytometry, and osteogenic and adipogenic differentiation abilities were assessed by alizarin red S (ARS) and oil red O staining, respectively]. Cells of passage 3 were used for the Erastin-induced ferroptosis model, with different concentrations of VPA for intervention. The optimal drug concentration was determined using the cell counting kit 8 assay. The experiment was divided into 4 groups: group A, cells were cultured in osteogenic induction medium for 24 hours; group B, cells were cultured in osteogenic induction medium containing optimal concentration Erastin for 24 hours; group C, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA for 24 hours; group D, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA, and 8 μmol/L EX527 for 24 hours. The mitochondrial state of the cells was evaluated, including the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Osteogenic capacity was assessed by alkaline phosphatase (ALP) activity and ARS staining. Western blot analysis was performed to detect the expressions of osteogenic-related proteins [Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN)], ferroptosis-related proteins [glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11)], and pathway-related proteins [adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1)]. RESULTS: The cultured cells were identified as BMSCs. VPA inhibited Erastin-induced ferroptosis and the decline of osteogenic ability in BMSCs, acting through the activation of the AMPK/SIRT1 pathway. VPA significantly reduced the levels of ROS and MDA in Erastin-treated BMSCs and significantly increased GSH levels. Additionally, the expression levels of ferroptosis-related proteins (GPX4, FTH1, and SLC7A11) significantly decreased. VPA also upregulated the expressions of osteogenic-related proteins (RUNX2 and OPN), enhanced mineralization and osteogenic differentiation, and increased the expressions of pathway-related proteins (AMPK and SIRT1). These effects could be reversed by the SIRT1 inhibitor EX527. CONCLUSION VPA inhibits ferroptosis in BMSCs through the AMPK/SIRT1 axis and promotes osteogenesis.
Mesenchymal Stem Cells/metabolism* ; Ferroptosis/drug effects* ; Animals ; Valproic Acid/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism* ; Cell Differentiation/drug effects* ; Cells, Cultured ; AMP-Activated Protein Kinases/metabolism* ; Osteogenesis/drug effects* ; Piperazines/pharmacology* ; Bone Marrow Cells/cytology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects*

Objective To investigate the distribution characteristics and future trends of clinical trials related to TCM prevention and treatment of constipation by analyzing the clinical trials registered in the Chinese Clinical Trial Registry(ChiCTR).Methods The clinical trials data related to TCM prevention and treatment of constipation in the ChiCTR database were retrieved from the establishment of the database to April 15,2024.Excel 2019 was utilized for de-duplication.Subsequently,SPSS 26.0 was employed to analyze the general characteristics,research types,intervention measures,etc.of the included trials,charts were drawn,and the clinical trial characteristics were summarized.Results A total of 107 clinical trials were included,with 102 being pre-registered,involving 21 provincial-level administrative regions and 75 clinical institutions.The top five regions in terms of the number of registered clinical trials were Beijing(19.63%),Shanghai(15.89%),Guangdong(14.02%),Sichuan(10.28%)and Jiangsu(9.35%).The top three sources of funding were local finance(28.97%),self-raised funds(18.69%)and hospital-funded funds(15.89%).The research types were mostly intervention studies(92.52%),of which 41 explicitly stated the use of blinding methods,and the main research design type is randomized parallel controlled trial.Conclusion The number of clinical trials related to TCM prevention and treatment of constipation registered in ChiCTR is on an upward trend.However,there is a noticeable geographical imbalance in the distribution of these trials,and there is a need for further improvement in the quality of trial design and the standardization of registration information.

Objective Through the safety evaluation of Chinese patent medicines containing cinnabar,the correlation between the evaluation score and the content of drug instructions was analyzed.And the methods and suggestions for improving the label quality of Chinese patent medicines were proposed.Methods Establish a database of Chinese patent medicines and sim-ple preparations containing cinnabar that meet the screening criteria in the 2020 edition of the Chinese Pharmacopoeia,and quan-titatively score such Chinese patent medicines and simple preparations from the two first level dimensions of safety and toxicity characteristics of Chinese patent medicines and simple preparations,and at the same time,grade the level of safety evidence.Results From the perspective of safety evaluation dimension,Chinese patent medicines and simple preparations with relatively high safety score(safety score ≥ 5 points)has a certain correlation with the content of adverse drug reactions clearly reported in the instructions of this kind of medicine,and 54.55％of the evidence risk of this kind of Chinese patent medicines and simple preparations is controllable,with good safety.From the perspective of the evaluation dimension of toxicity characteristics of Chi-nese patent medicines and simple preparations,the types of toxic ingredients in the compatibility of prescriptions and the scores of daily maximum dosage have certain guiding significance for clinical medication precautions.Conclusion For improving the ad-verse reaction information in the instructions of Chinese patent medicines and simple preparations containing cinnabar,and remin-ding the special population of drug use restrictions,it not only has an important impact on drug safety evaluation and grading,but also provides warning and reference for clinical and patient safety in drug use.

The European Society of Cardiology (ESC) released the "2024 ESC guidelines for the management of elevated blood pressure and hypertension" on August 30, 2024. This guideline updates the 2018 "Guidelines for the management of arterial hypertension." One notable update is the introduction of the concept of "elevated blood pressure" (120-139/70-89 mm Hg). Additionally, a new systolic blood pressure target range of 120-129 mm Hg has been proposed for most patients receiving antihypertensive treatment. The guideline also includes numerous additions or revisions in areas such as non-pharmacological interventions and device-based treatments for hypertension. This article interprets the guideline's recommendations on definition and classification of elevated blood pressure and hypertension, and cardiovascular disease risk assessment, diagnosing hypertension and investigating underlying causes, preventing and treating elevated blood pressure and hypertension. We provide a comparison interpretation with the 2018 "Guidelines for the management of arterial hypertension" and the "2017 ACC/AHA guideline on the prevention, detection, evaluation, and management of high blood pressure in adults."

OBJECTIVE To investigate the pharmaceutical affairs management in healthcare institutions from Haidian district of Beijing， and propose countermeasures and suggestions for improving the related work. METHODS The current status of pharmaceutical affairs management in 66 healthcare institutions from Haidian district of Beijing was surveyed through on-site inspections， and the results were statistically analyzed. The inspection items included six special projects： pharmaceutical affairs management and organizational structure of pharmacy departments； drug quality management and control， prescription review， clinical application management of antimicrobial drugs， management of adverse drug events， and management of special drugs. These areas were further divided into a total of 27 specific inspection sub-items. RESULTS & CONCLUSIONS The total proportion of healthcare institutions that fully complied or basically complied with each special project was 90.9%， 97.0%， 86.3%， 90.9%， 90.9%， and 96.9%， respectively. The overall comparison among healthcare institutions that fully or substantially met the standards across medical institutions at different levels showed that the performance of tertiary healthcare institutions was better than that of secondary and primary healthcare institutions. The pharmaceutical affairs management in healthcare institutions within the jurisdiction was proceeding in an orderly manner. There is still room for improvement in further establishing and perfecting the functions of the pharmaceutical affairs management committee， implementing the 2021 Edition of Management Regulations for β -lactam Antimicrobial Skin Tests， enforcing the adverse drug reaction management system， and strengthening the refined management of narcotics and psychotropic drugs.

Objective To investigate the role and possible mechanism of celastrol(Cel)in sodium oxalate(NaOx)-induced acute kidney injury(AKI)and crystal deposition in the kidney tissues in mice.Methods Male C57BL/6 mice(aged 8～12 weeks,weighing 22～24 g)were randomly divided into 3 groups.Saline group(control group,intraperitoneal injection with normal saline and drinking water freely),NaOx group(injured group,intraperitoneal injection of 75 mg/kg NaOx,and drinking water containing 50 μmol/L NaOx),and NaOx+Cel group(treatment group,intraperitoneal injection of 1 mg/kg Cel firstly and then 75 mg/kg NaOx in 24 h later,drinking water containing 50 μmol/L NaOx).All specimens were collected in 24 h after NaOx injection.HK-2 cells were randomly divided into 4 groups:Medium group(no treatment),NaOx group(500 μmol/L NaOx),NaOx+Cel group(400 nmol/L Cel pre-treatment for 2 h followed by 500 μmol/L NaOx treatment),and NaOx+Cel+BA group[8 μmol/L betulinic acid(BA,NF-κB agonist)after the interventions as the NaOx+Cel group].Cells of each group were collected in 24 h after corresponding treatments.Von Koosa and cell adhesion assays were used to observe crystal deposition.HE staining was employed to observe renal histopathology and score the damage.CCK-8 assay was utilized to detect cell viability to obtain the optimal concentrations of NaOx and Cel.Serum urea and creatinine levels were detected.Immunohisotochemical assay was conducted to detect the expression of OPN,CD44,KIM-1,NGAL,p65,IL-1β,BAX,and Caspase-3,and Western blotting was performed for protein levels of OPN,CD44,KIM-1,p65,P-p65 and IL-1β.Results The mice in the NaOx+Cel group showed reduced crystal deposition(P<0.0001),attenuated renal tubular damage(P<0.01),decreased serum urea and creatinine levels(P<0.05),and declined expression levels of the renal adhesion molecules OPN and CD44,the kidney injury molecules KIM-1 and NGAL,the inflammation-associated molecules p65 and IL-1β,and the apoptosis related molecules BAX and Caspase-3 when compared with the NaOx group(P<0.05).In in vitro study,the NaOx+Cel group showed reduced crystal adhesion(P<0.0001),decreased expression of the adhesion molecules OPN and CD44(P<0.05),down-regulation of the inflammatory molecule IL-1β and P-p65/p65 ratio(P<0.05),and down-regulation of the renal injury molecule KIM-1(P<0.05)when compared with the NaOx group.In the NaOx+Cel+BA group,crystal adhesion was significantly increased(P<0.0001),the inflammatory molecule IL-1β and the ratio of P-p65/p65 were increased(P<0.05),and the kidney injury molecule KIM-1 was increased when compared with the NaOx+Cel group(P<0.05).Conclusion Cel may reduce NaOx-induced crystal deposition and AKI by inhibiting NF-κB activation.

Objective:To explore the effects of parathyroid hormone(PTH)on the osteogenic differentiation of osteoblasts by reg-ulating macrophage polarization in inflammatory microenvironment.Methods:Macrophages were pretreated with lipopolysaccharide(LPS)for 2 h to establish an inflammatory microenvironment model,and then treated with PTH for 24 h.Macrophages and osteo-blasts were co-cultured in Transwell cells.Alkaline phosphatase staining,alizarin red staining,RT-qPCR and Western blot were applied to detect osteogenic differentiation.The expression of SOCS1/JAK2/STAT3 protein in macrophages was detected by West-ern blot.The change of STAT3 expression was detected after adding AG490.The expression of miR-155-5p,SOCS1,IL-1β,IL-6 and i-NOS was detected by ELISA and RT-qPCR.Results:LPS induced M1-type polarization of macrophages and inhibited the osteogenic differentiation of osteoblasts.PTH inhibited the polarization of M1-type macrophages and promoted the osteogenic differ-entiation of osteoblasts in inflammatory microenvironment(P＜0.05).PTH down-regulated the expression of miR-155-5p,IL-1β,IL-6,i-NOS,p-JAK2/JAK2 and p-STAT3/STAT3 in macrophages under inflammatory microenvironment(P＜0.05),and up-reg-ulated SOCS1(P＜0.05).AG490 further inhibited p-STAT3/STAT3 expression.Conclusion:PTH inhibits the polarization of M1-type macrophages and promotes osteogenic differentiation of osteoblasts by down-regulating miR-155-5p and then targeting SOCS1/JAK2/STAT3 signaling pathway in inflammatory microenvironment.

Objective To analyze the current status of clinical trial registration of common anorectal diseases in Chinese Clinical Trial Registry(ChiCTR)and the research of TCM.Methods The ChiCTR database was retrieved to collect and organize clinical trials related to hemorrhoids,anal fissures,anal fistulas,perianal abscesses,and perianal eczema.The retrieval time was from the establishment of the database to December 10,2023.Characterization of included registration trials was analyzed.Results A total of 148 registered projects were included,75 of which were TCM-related clinical trials.Among them,134 clinical trials were pre-registered and 121 passed the ethical review.Shanghai,Jiangsu,Guangdong,Beijing and Sichuan accounted for 76.35％of the total number of registrations,and the largest number of registered projects was in Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine.The top 3 funding sources were local finance,self-funding and hospital funding.The registered projects were mainly intervention studies.114 studies used randomized methods and 34 studies were blinded.Conclusion At present,the number of ChiCTR-registered clinical trials on anorectal diseases is on an increasing trend,and the treatment of anorectal diseases with TCM has obvious characteristics.However,there are cases of irregular filling of registration content and uneven regional distribution.

Objective To explore the distribution characteristics and development trend of TCM prevention and treatment for irritable bowel syndrome(IBS)by analyzing the clinical trials of TCM prevention and treatment for IBS registered in China Clinical Trial Registry(ChiCTR).Methods The ChiCTR database was retrieved to collect and organize clinical trials related to the TCM prevention and treatment of IBS from the establishment of the database to May 1,2024.Characteristics of the included trials were analyzed and summarized using SPSS 25.0 and Excel 2021.Results A total of 73 clinical trials were included,of which 65 were pre-registered.The registered research projects involved 14 provincial-level administrative regions,including Beijing,Jiangsu,Guangdong,Shanghai,and Sichuan,and 46 clinical trial institutions,among which Beijing University of Chinese Medicine(6 items,7.89%)registered a higher number.The top three sources of research funding were,in order,local finance(26 items,35.62%),state finance(20 items,27.40%),and hospital funding(10 items,13.70%).The types of studies were predominantly interventional(68 items,93.15%),and the study designs were predominantly randomized parallel controlled studies(64 items,87.67%),but only 27 studies(36.99%)used a blinded approach.The main interventions included acupuncture and moxibustion,Chinese patent medicines,classic prescriptions/hospital-prepared remedies,etc.Conclusion The number of clinical research registrations in this field has been gradually increasing in recent years,but there are problems such as uneven regional distribution,low use of blinding,and lack of standardization of registration information.

Objective To analyze the clinical trial projects of TCM treatment for psoriasis registered at the China Clinical Trial Registry(ChiCTR);To provide references for clinical research in this field.Methods Clinical trial studies on the TCM treatment for psoriasis were retrieved from the ChiCTR database from the establishment of the database to June 17,2024.Excel 2019 and GraphPad Prism 9.0 were used to organize and analyze the general characteristics included in registered clinical trials.Results Totally 65 TCM-related trials were included,of which 58(89.23%)were prospectively registered,and 55(84.62%)had undergone ethical review.The majority of trials were registered in Guangdong,Beijing and Shanghai,collectively accounting for 78.46%(n=51)of the total.The leading institution,Guangdong Provincial Hospital of Chinese Medicine,contributed 19 trials.Funding was predominantly sourced from governmental bodies,with 72.31%(n=47)supported by national or regional grants.Among the registered studies,interventional trials predominated(n=56),including 46 randomised parallel-controlled designs.Blinding was implemented in 23 trials,and biospecimen collection was reported in 48 studies.40 trials were single-centre studies,and a cumulative sample size was 17 695 participants.Common interventions included oral administration of classical TCM formulations or hospital-prepared remedies,alongside topical applications such as medicated baths and ointments.The primary outcome measure in most trials was the Psoriasis Area and Severity Index.Conclusion While the number of registered clinical trials on TCM for psoriasis in China demonstrates a fluctuating yet upward trend,the overall volume remains modest.Disparities in regional distribution,methodological variability,and incomplete trial registration details highlight areas for improvement.