1.Study on synergistic promotion of ferroptosis in human hypertrophic scar fibroblasts by erastin combined with shikonin
Jian-jun WANG ; Yan-hua WANG ; Yu-ting TANG ; Jing-yi ZHANG ; Fang MA ; Xi HE ; Hui-xia YANG ; Qi-peng ZHAO ; Zhi-gang BAI ; Yin-ju HAO ; Gui-zhong LI ; Yi-deng JIANG ; Jiang-yong SHEN
Chinese Pharmacological Bulletin 2025;41(2):268-276
Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50%).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P<0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P<0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P<0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P<0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.
2.Effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage via TLR4/MyD88/NF-κB signaling pathway in rats with opioid-induced constipation of Spleen-Kidney Yang Deficiency Syndrome
Lu-mei ZHANG ; Zhi-ming ZHANG ; Zhong-yang SONG ; Xin WANG ; Qian XU ; Xia YANG ; Xin-yu LI ; Yan-yun SHEN ; Hai-hong ZHAO ; Zhi-gang WANG
Chinese Traditional Patent Medicine 2025;47(7):2205-2212
AIM To investigate the effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage in rats with opioid-induced constipation(OIC)of Spleen-Kidney Yang Deficiency Syndrome.METHODS In contrast to the 10 rats of the blank group,the 50 rats of the modeling group were induced into models of OIC of Spleen-Kidney Yang Deficiency Pattern by 7 days consecutive administration of both subcutaneous loperamide injection and alternating gavage of activated carbon ice water and vinegar.Following successful modeling,rats were randomly allocated into the model group,the mosapride citrate tablet group(1.35 mg/kg),and the high-dose,medium-dose,and low-dose Yunpi Tongchang Formula groups(15.12,7.56,3.78 g/kg),with 8 mice in each group.Upon the completion of the 14 days treatment,the rats had their TCM Syndrome scores assessed;their fecal water content,initial black stool excretion time,and small intestine propulsion rate measured;their colon tissue morphology observed by HE staining;their serum levels of IL-6,TNF-α,and IL-1β detected by ELISA;their expressions of occludin and zonula occludens-1(ZO-1)in colon tissues detected by immunohistochemistry;their mRNA expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by RT-qPCR;and their protein expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by Western blot.RESULTS Compared to the blank group,the model group had higher TCM Syndrome scores(P<0.01);lower fecal water content and small intestine propulsion rate(P<0.05,P<0.01);longer initial black stool excretion time(P<0.01);more mucosal edema in colon tissue,obvious inflammatory infiltration,and glandular disorder;increased serum levels of IL-6,TNF-α and IL-1 β(P<0.05);decreased colon expressions of ZO-1 and occludin(P<0.01);and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P<0.01).Compared to the model group,both the medium-dose Yunpi Tongchang Formula group and the mosapride citrate tablet group demonstrated effectively reduced TCM syndrome scores(P<0.01);increased fecal water content and small intestine propulsion rate(P<0.05,P<0.01);and shorter initial black stool excretion time(P<0.01);improved colon mucosal edema and inflammatory infiltration;decreased serum levels of IL-6,TNF-α and IL-1β(P<0.01);upregulated protein expressions of ZO-1 and occludin(P<0.01);and downregulated mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P<0.05,P<0.01).CONCLUSION Yunpi Tongchang Formula significantly ameliorates constipation symptoms in OIC rat models of Spleen-Kidney Yang Deficiency Syndrome because of its efficacy in attenuating intestinal inflammation and preserving the integrity of intestinal epithelial barrier structure,with its mechanistic action in downregulating TLR4/MyD88/NF-κB signaling pathway activation.
3.Long-term follow-up of percutaneous pulmonary valve implantation using domestic self-expanding valve-prospective single-center experience
Qian-bei HE ; Qiao LI ; Yi-jian LI ; Rui-tao LI ; Bo-feng CHAI ; Zhi-cheng CHEN ; Zhi-xiang YU ; Zhen-gang ZHAO ; Yuan FENG
Chinese Journal of Interventional Cardiology 2025;33(5):241-248
Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation<moderate and peak trans-pulmonary pressure gradient<40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.
4.Mechanisms and research progress of tanshinone ⅡA in the prevention and treatment of radiation-induced heart disease
Yan-ling LI ; Zhi-ling GAO ; Gang WANG ; Ping XIE
Chinese Pharmacological Bulletin 2025;41(12):2236-2240
Radiation-induced heart disease(RIHD)is a common and severe complication following radiotherapy for thoracic tumors,significantly impacting patients' long-term prognosis and quality of life.Its pathogenesis is complex,primarily involving oxidative stress,inflammatory responses,endothelial dysfunction,and chronic fibrosis.Currently,there is a lack of effective clini-cal prevention and treatment methods,highlighting the urgent need to develop intervention strategies for RIHD.Tanshinone ⅡA,the main active component of Salvia miltiorrhiza,exhibits mul-tiple pharmacological effects,including antioxidant,anti-inflam-matory,anti-fibrotic,and anti-apoptotic properties.Studies have shown that Tanshinone ⅡA can significantly mitigate radiation-induced myocardial injury and fibrosis,as well as improve cardi-ac function,by scavenging reactive oxygen species,inhibiting in-flammatory pathways,and modulating fibrotic signaling path-ways.This article summarizes the pathogenesis of RIHD and the research progress on Tanshinone ⅡA in the prevention and treat-ment of RIHD,providing new theoretical insights for developing effective cardioprotective strategies.
5.Role and mechanism of MANF in inhibition of malignant biological behaviors of gastric cancer cells by rhynchophylline
Li-wei WANG ; Qiang ZHAO ; Da-yong LIU ; Hao ZHENG ; Zhi-gang WEI
Chinese Pharmacological Bulletin 2025;41(12):2326-2333
Aim To investigate the role of mesence-phalic astrocyte-derived neurotrophic factor(MANF)in the inhibitory effect of rhynchophylline(Rhy)on the malignant biological behaviors of gastric cancer cells and its underlying regulatory mechanisms.Meth-ods SGC-7901 gastric cancer cells were transfected using adenovirus and liposome transfection techniques.The experimental groups included:Control group,Rhy group,Rhy+NC group(Rhy+adenovirus-transfected MANF-irrelevant fragment),Rhy+si-MANF group(Rhy+adenovirus-transfected MANF siRNA),Vec-tor group(empty vector),OVE-MANF group(recom-binant plasmid overexpressing MANF).After 24 hours of intervention,cell proliferation,apoptosis,migra-tion,and invasion were assessed using the MTT assay,Hoechst staining,and Transwell assays,respectively.The expressions of MANF,Cyclin D1,and cleaved caspase-3 proteins were measured using Western blot.NF-κB transcriptional activity was evaluated via a lucif-erase reporter assay.Results Compared to the control group,Rhy treatment significantly inhibited gastric cancer cell growth in a dose-dependent manner(P<0.05),induced typical apoptotic morphological chan-ges,and increased the expression of MANF and cleaved caspase-3 proteins(P<0.05),while reduc-ing Cyclin D1 protein expression and NF-κB transcrip-tional activity(P<0.05).Additionally,Rhy treat-ment markedly decreased cell migration and invasion capabilities(P<0.05).In comparison to the Rhy group,adenovirus-mediated transfection of MANF siR-NA suppressed apoptosis,promoted gastric cancer cell proliferation,migration,and invasion,inhibited MANF and cleaved caspase-3 expression(P<0.05),and enhanced Cyclin D1 protein levels and NF-κB transcriptional activity(P<0.05).Compared to the Vector group,OVE-MANF(overexpression of MANF)induced apoptosis,suppressed proliferation,invasion,and metastasis of gastric cancer cells,upregulated MANF and cleaved caspase-3 expression(P<0.05),and inhibited Cyclin D1 protein levels and NF-κB tran-scriptional activity(P<0.05).Conclusion Rhy in-hibits the proliferation,migration,and invasion of gas-tric cancer cells and induces apoptosis,with its mecha-nism linked to the promotion of MANF expression and suppression of NF-κB transcriptional activity.
6.Applied value of physical motor function assessment system in the risk assessment of recruit training injury
Wei WEI ; Wei-Xu ZHANG ; Lv-Gang ZHU ; Liang TANG ; Huan-Le LI ; Zhi-Chao XUE ; Liang ZHANG ; Hao-Feng WANG ; Qi CHANG
Medical Journal of Chinese People's Liberation Army 2025;50(5):531-535
Objective To assess the effectiveness of the evaluation of military physical function(EMPF)system in predicting the occurrence of military training injuries among new recruits to provide scientific guidance and methodological choice for military training.Methods A total of 527 new recruits from 5 grassroots units from July 2016 to February 2018 were selected for the study.The recruits underwent EMPF testing,and their military training injuries were monitored over a 2-year follow-up period.Those who sustained injuries during training were divided into injury group(n=163),while the remaining recruits were placed in healthy group(n=364).The predictive ability of the total EMPF score for training injuries was assessed using the receiver operating characteristic curve(ROC),and the correlation between the total EMPF score,individual test scores,and military training injuries were analyzed using binary logistic regression.Results The total EMPF score of new recruits in injury group(19.52±1.97)was significantly lower than that of healthy group(24.31±1.54)(P<0.001),which also demonstrated a high diagnostic value in predicting the risk of military training injuries,with an area under the curve(AUC)of ROC of 0.971(P<0.001).A cut-off value of 22 scores was found to have the highest accuracy in predicting future training injuries,with an odds ratio(OR)of 25.63,sensitivity of 0.939,specificity of 0.879,positive likelihood ratio of 7.76,and a post-test probability of 0.67.Binary logistic regression analysis revealed that 6 EMPF tests,including holding the ball over and leaning back,bending forward and touching the ground with the ball,lunge squat and twist,swallow balance with holding the ball afterward,vertical jump,and respiratory pattern assessment,were negatively associated with the risk of military training injuries(P<0.0001).Conclusion The EMPF system can effectively predict the risk of military training injuries,with military personnel whose total EMPF score is less than 22 being at higher risk of sustaining such injuries.
7.Establishment and evaluation of a lipopolysaccharide-induced acute respiratory distress syndrome model in minipigs
Chuang-Ye WANG ; Ran WANG ; Jian ZHANG ; Ling-Xiao QIU ; Bin QING ; Heng YOU ; Jin-Cheng LIU ; Bin WANG ; Nan-Bo WANG ; Jia-Yu LI ; Xing LIU ; Shuang WANG ; Jin HU ; Jian WEN ; Quan LI ; Xiao-Ou HUANG ; Kun ZHAO ; Shuang-Lin LIU ; Gang LIU ; Mei-Ju WANG ; Qing XIANG ; Hong-Mei WU ; Xiao-Rong SUN ; Tao GU ; Dong ZHANG ; Qi LI ; Zhi XU
Medical Journal of Chinese People's Liberation Army 2025;50(9):1154-1161
Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.
8.Review of potential applications of graphene nanomaterials in logistics service support
Yin WU ; Li HE ; Bang-fu ZHOU ; Zhi-gang ZHANG
Chinese Medical Equipment Journal 2025;46(8):96-103
The advantages of graphene nanomaterials were introduced when applied in the field of logistics service support,and its potential applications were reviewed in armored protective gear,uniform warmth,military portable energy equipment,nano antibacterial coating for medical devices and anti-corrosion coating.The deficiencies of graphene nanomaterials applied in logistics service support were analyzed,and its future development directions were envisioned.[Chinese Medical Equipment Journal,2025,46(8):96-103]
9.Research status of traditional Chinese medicine regulating oxidative stress to prevent and treat diabetic kidney disease
Xiao-long MEI ; Kun ZHANG ; LI-hui FAN ; Lu-mei ZHANG ; Xia YANG ; Zhi-gang WANG
The Chinese Journal of Clinical Pharmacology 2025;41(1):127-131
Diabetic kidney disease(DKD)is one of the common microvascular complications of diabetes mellitus,and it has become the main cause of chronic kidney disease and end stage renal disease.Traditional Chinese medicine can delay the progress of DKD by inhibiting oxidative stress,improving renal tissue damage,restoring renal function.This paper will summarize the relationship between oxidative stress and DKD and the prevention and treatment of DKD by traditional Chinese medicine,so as to provide reference for clinical drug application,basic research and new drug research and development of DKD.
10.Mammographic imaging features of breast cancer and its correlation with microvascular density
Li-qin MA ; Li LIU ; Heng-li HU ; Yu-lei CHEN ; Long-zhou CHEN ; Zhi-gang HAN
Journal of Regional Anatomy and Operative Surgery 2025;34(3):258-262
Objective To investigate the mammographic imaging features of breast cancer and its correlation with microvascular density(MVD).Methods A total of 86 patients with breast cancer confirmed by surgical pathology in Xinjiang Production and Construction Corps 7th Division Hospital from January 2019 to December 2022 were selected as the research objects.According to the modified Bloom Richard-son scoring system,the breast cancer patients were classified into histological grade Ⅰ(n=22),grade Ⅱ(n=25)and grade Ⅲ(n=39).All patients underwent preoperative mammographic imaging examination.Immunohistochemistry staining was performed and MVD count was conducted after operation.Spearman rank correlation was used to analyze the correlation between MVD of breast cancer with different histo-logical grades and mammographic imaging features.Results The microvascular positive expression rate of breast cancer lesions was 100%,the MVD counts per visual field were 14~276 vessels,with an average of(72.58±16.37)vessels,of which the MVD counts of patients with histological grade Ⅰ to Ⅱ were 14 to 175 vessels,with an average of(42.10±13.51)vessels;the MVD counts of patients with histological grade Ⅲ was 22~276 vessels,with an average of(93.82±22.17)vessels.The MVD counts of patients with histological grade Ⅲ was signifi-cantly higher than that of patients with histological grade Ⅰ to Ⅱ,with statistically significant difference(t=19.627,P<0.001).The incidences of irregular margin,spicular sign,axillary lymph node metastasis and fine particle calcification in patients with histological gradeⅢ were higher than those in patients with histological grade Ⅰ to Ⅱ,with statistically significant difference(P<0.05).The MVD counts of breast cancer patients with irregular margin,spicular sign,axillary lymph node metastasis and fine particle calcification were higher than those of patients with smooth margin and without spicular sign,axillary lymph node metastasis or fine particle calcification,which was positively correlated with histological grades(P<0.05).Conclusion Some mammographic imaging features of breast cancer can reflect tumor angiogenesis to a certain extent,which can provide important reference for the treatment and prognosis of the disease,with certain clinical value.

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