1.Ferroptosis and osteoporosis
Cheng YANG ; Weimin LI ; Dongcheng RAN ; Jiamu XU ; Wangxiang WU ; Jiafu XU ; Jingjing CHEN ; Guangfu JIANG ; Chunqing WANG
Chinese Journal of Tissue Engineering Research 2025;29(3):554-562
BACKGROUND:It has also been confirmed that ferroptosis is closely related to a variety of musculoskeletal diseases,such as rheumatoid arthritis,osteosarcoma,and osteoporosis.The pathophysiological mechanisms of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and osteoporosis.It will provide research ideas for the future elucidation of new mechanisms of osteoporosis and the development of new technologies and drugs for the treatment of osteoporosis. OBJECTIVE:To provide an overview of the current status of research on ferroptosis in osteoporosis,to provide a new direction for future research on the specific molecular mechanisms of osteoporosis,and to provide more effective and better options for osteoporosis treatment strategies. METHODS:The first author used the computer to search the literature published from 2000 to 2024 in CNKI,WanFang,VIP,and PubMed databases with search terms"ferroptosis,iron metabolism,osteoporosis,osteoblast,osteoclast,bone metabolism,signal pathway,musculoskeletal,review"in Chinese and English.A total of 68 articles were finally included according to the selection criteria. RESULTS AND CONCLUSION:(1)Ferroptosis is a new type of cell death discovered in recent years,which is usually accompanied by a large amount of iron accumulation and lipid peroxidation during cell death,and its occurrence is iron-dependent.This is distinctly different from several types of cell death that are currently being hotly studied(e.g.,cellular pyroptosis,necrotic apoptosis,cuproptosis,and autophagy).(2)Intracellular iron homeostasis is manifested as a balance between iron uptake,export,utilization,and storage.The body's iron regulatory system includes systemic and intracellular regulation.The main factor of systemic regulation is hepcidin produced by hepatic secretion,and cellular regulation depends on the iron regulatory protein/iron response element system.Of course,intracellular iron homeostasis can be controlled by other factors,such as hypoxia,cytokines,and hormones.(3)Lipid peroxidation causes oxidative damage to biological membranes(plasma membrane and internal organelle membranes),lipoproteins,and other lipid-containing molecules.Polyunsaturated fatty acid-containing phospholipids are important targets of lipid peroxidation.Free polyunsaturated fatty acid is an important substrate for lipid oxidation and can bind to the phospholipid bilayer,leading to over-oxidation and thus triggering lipid apoptosis.(4)Several studies have shown that osteoblasts are overloaded with iron in different ways,resulting in the accumulation of unstable ferrous iron and the generation of reactive oxygen species and lipid peroxides,causing ferroptosis of osteoblasts and ultimately a decrease in bone formation,affecting bone homeostasis and the development of osteoporosis.(5)Osteoclasts are large multinucleated cells formed by the fusion of mononuclear macrophage cell lines or bone marrow mesenchymal stem cells induced by nuclear factor-κB ligand receptor activator,and they have the function of bone resorption.Iron ions can promote osteoclast differentiation and bone resorption through the production of intracellular lipid reactive oxygen species,while iron chelators can inhibit osteoclast formation in vitro and thus affect the occurrence and development of osteoporosis.
2.Correlation between serum cystatin C and bone turnover markers in elderly patients with type 2 diabetes mellitus and osteoporosis
Mengqian WANG ; Shaohong ZHANG ; Mengyue SUN ; Min CHEN ; Weimin WANG
Journal of Public Health and Preventive Medicine 2025;36(4):89-92
Objective To analyze the correlation between serum cystatin C (Cys-C) and bone turnover markers in elderly patients with type 2 diabetes mellitus (T2DM) and osteoporosis. Methods A retrospective analysis was conducted on the data of 320 elderly patients with T2DM admitted to Huai'an First People's Hospital from August 2021 to June 2024. Patients were divided into the osteoporosis group and the non-osteoporosis group according to whether they had osteoporosis. General information, bone turnover markers, and serum Cys-C levels were collected from all patients. The data were compared between the two groups to analyze the influencing factors of osteoporosis in elderly patients with T2DM and the correlation between serum Cys-C and bone turnover markers. Results The levels of total cholesterol and LDL-C in the osteoporosis group were higher than those in the non-osteoporosis group, and the bone mineral density was lower than that in the non-osteoporosis group (P<0.05). The levels of TPINP, β-CTX, and Cys-C in the osteoporosis group were higher than those in the non-osteoporosis group, and 25-OH-D3 level was lower than that in the non-osteoporosis group (P<0.05). Serum Cys-C was positively correlated with TPINP and β-CTX, and negatively correlated with 25-OH-D3 (P<0.05). Multivariate logistic regression analysis found that total cholesterol, LDL-C, TPINP, β-CTX, 25-OH-D3, and Cys-C were factors influencing osteoporosis in elderly patients with T2DM (P<0.05). Conclusion Serum Cys-C levels in elderly patients with T2DM and osteoporosis are elevated. There is a significant correlation between Cys-C level and bone turnover markers.
3.Research progress on the role of MTAP in malignant mesothelioma
Xudong JIN ; Zhongjian CHEN ; Weimin MAO
Journal of International Oncology 2024;51(2):99-104
Methylthioadenosine phosphorylase (MTAP) is a rate-limiting enzyme in the methionine and purine salvage pathway, and is closely related to polyamine metabolism, adenine metabolism and methionine metabolism. MTAP is frequently deleted in malignant mesothelioma (MM) and plays an important role in the diagnosis and differential diagnosis of MM. At the same time, metabolic reprogramming caused by MTAP deletion creates new therapeutic strategies for MM. Besides, MTAP gene is also associated with the prognosis of MM, therefore MTAP is a significant biomarker for the diagnosis, treatment and prognosis of MM.
4.Comparative Study on the Topological Attributes of Deficiency and Excess Pattern of Cerebral Small Vessel Disease Mild Cognitive Impairment Based on fMRI Graph Theory Network
Jianjun WANG ; Weimin YANG ; Haotao ZHENG ; Jianxiang CHEN ; Dongbin CAI ; Hanqing LYU ; Xiude QIN ; Lanying LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):69-75
Objective This study aimed to explore the differences in global and local brain network topological properties between deficient pattern(DP)and excess pattern(EP)of mild vascular cognitive impairment caused by subcortical small vessel disease based on graph theory network.Methods Patients were recruited prospectively and were classified with DP and EP subtype.The global small-world topological attributes and local nodes were calculated for the comparison of DP,EP,and healthy controls(CN)using the GRETNA platform.Results The three groups all had small-world attributes,but only the patients in EP had a significantly lower small world attribute δ in the range of 0.05-0.26 than the control group(P<0.05).The node efficiency and node strength indicators of multiple brain region were able to significantly distinguish the DP group from the EP group.However,there was no positive brain region in the node efficiency of the DP patients(P>0.05),and only a few brain regions showed increased node strength efficiency(P<0.05).Conclusion The results indicate that the syndrome of DP and EP have significantly different neuroimaging phenotypes,providing a basis for further research of biological classification based on Chinese Medicine syndromes.
5.Effect of Jinghou Zengzhi Granules on ovarian GDF9 secretion and granulosa cells apoptosis in controlled ovarian hyperstimulation rats
Zhen YANG ; Shaoru JIANG ; Xiaoyan CHEN ; Xiaolin CHEN ; Weimin DENG ; Xinyu GUO
The Journal of Practical Medicine 2024;40(7):918-923
Objective To explore the effects of Jinghou Zengzhi Granules(JHZZG),on ovarian GDF9 secretion and granulosa cells(GCs)apoptosis in controlled ovarian hyperstimulation(COH)rats through p38MAPK/CK2/IκBα/NF-κB pathway.Methods A model of COH rats was prepared and 18 rats were randomly divided into 3 groups,including natural ovulation group(NO group),COH group,and COH+JHZZG group.The expression of p38MAPK,CK2,IκBα,NF-κB,GDF9 mRNA and protein were detected by qRT-PCR and Western blot,and the apoptosis rate of ovarian GCs by TUNEL.Results Compared with the NO group,the expression of p38MAPK and NF-κB in the ovarian tissue of rats in the COH group increased,while the expression of CK2,IκBα and GDF9 decreased,and the apoptosis rate of ovarian GCs increased(all P<0.01).Compared with the COH group,the expression of p38MAPK and NF-κB in the ovarian tissue of rats in the COH+JHZZG group decreased,while the expression of CK2,IκBα and GDF9 increased(all P<0.01),and the apoptosis rate of ovarian GCs decreased(P<0.05).Conclusion Jinghou Zengzhi Granules could promote the secretion of ovarian GDF9 and inhibit the apoptosis of ovarian GCs of COH rats through p38MAPK/CK2/IκBα/NF-κB signaling pathway,which thereby improve the quality of COH oocytes.
6.Applications and Challenges of Artificial Intelligence in Early Diagnosis and Precise Treatment of Lung Cancer
Shouyu ZHANG ; Bojiang CHEN ; Weimin LI
Cancer Research on Prevention and Treatment 2024;51(12):1000-1006
The incidence and mortality of lung cancer are extremely high, and the 5-year survival rate of patients after diagnosis is less than 20%; as such, early screening and intervention are important. However, doctors are overwhelmed with a large workload of CT scan review in a short period of time and should ensure that the rate of missed diagnosis and misdiagnosis is low. Artificial intelligence can assist doctors in early diagnosis and precise treatment of lung cancer, but this technology has problems. This paper reviews the application of artificial intelligence in the prediction of benign and malignant lung nodules, pathology, gene mutation, intervention scheme, treatment response, and prognosis and presents the corresponding challenges.
7.Association between Yang Deficiency Syndrome and the End-point Events of Diabetic Kidney Disease: A Retrospective Cohort Study
Jiale ZHANG ; Zhezhe XUE ; Chenhui XIA ; Qiaoru WU ; Shuwu WEI ; Weimin JIANG ; Huixi CHEN ; Huijuan ZHENG ; Yaoxian WANG ; Weiwei SUN
Journal of Traditional Chinese Medicine 2024;65(11):1146-1153
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.
8.Effect of complement C1s on biological behavior of esophageal squamous cell carcinoma
Ling REN ; Yuling CHEN ; Fengmin XU ; Chunmei MENG ; Qianqian LI ; Weimin HU
Chinese Journal of Immunology 2024;40(1):127-133
Objective:To explore the effect of complement component C1s on the proliferation,migration and adhesion of esophageal squamous cell carcinoma(ESCC)cells and on the growth of xenograft tumors in nude mice.Methods:The C1S mRNA ex-pression of ESCC tissues and adjacent normal tissues(ANTs)were analyzed using NCBI-GEO database.The C1s expression of ESCC cell lines was analyzed with RT-qPCR and Western blot.The knockdown or overexpression of C1s in ESCC cells lines was performed using C1s small interfering RNA(siRNA),C1s short hairpin RNA(shRNA)or C1s overexpression lentivirus,and the cell prolifera-tion was detected by CCK-8 assay,cell migration was detected by cell wound healing assay,cell adhesion was detected by cell-matrix adhesion assay,the expressions of matrix metalloproteinases MMP1 and MMP13 were detected by Western blot,and the effect of C1s on the growth of xenograft tumors in nude mice was detected by subcutaneous tumorigenesis assay in nude mice.The expression of CD34 in the xenograft tumors was detected by immunohistochemistry,and the formation of tumor microvessel was analyzed.Results:The expression of C1S mRNA in ESCC tissues was significantly higher than that in ANTs.Knockdown of C1s significantly suppressed proliferation,migration and cell-matrix adhesion of ESCC cells,as well as growth of xenograft tumors in nude mice,while overexpres-sion of C1s had the opposite effects.The expressions of MMP1 and MMP13 were decreased in ESCC cells TE-1 with C1s knockdown.Compared with control group,the microvessel of the xenograft tumors in the C1s overexpression group were more abundant.Conclu-sion:C1s is significantly upregulated in ESCC tissues,and promotes proliferation,migration,cell-matrix adhesion of ESCC cells,and the growth of xenograft tumors.C1s may play an important role in the occurrence and development of ESCC.
9.A nationwide multicenter prospective study on the perioperative impact of closure of mesen-teric fissure in laparoscopic right hemicolectomy
Gang LIU ; Weimin XU ; Da LI ; Lei QIAO ; Jieqing YUAN ; Dewei ZHANG ; Yan LIU ; Shuai GUO ; Xu ZHANG ; Wenzhi LIU ; Yingfei WANG ; Hang LU ; Xiaowei ZHANG ; Xin CHEN ; Zhaohui XU ; Xingyang LUO ; Ge LIU ; Cheng ZHANG ; Jianping ZHOU
Chinese Journal of Digestive Surgery 2024;23(6):812-818
Objective:To investigate the perioperative impact of closure of mesenteric fissure in laparoscopic right hemicolectomy.Methods:The prospective randomized controlled trial was conducted. The clinical data of 320 patients who underwent laparoscopic right hemicolectomy in 11 medical centers, including The First Affiliated Hospital of China Medical University et al, from November 2022 to August 2023 were selected. Based on block randomization, patients were alloca-ted into the mesenteric fissure non-closure group and the mesenteric fissure closure group. Observa-tion indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postopera-tive conditions. Measurement data with skewed distribution were represented as M( Q1, Q3) and com-parison between groups was conducted using the Mann-Whitney U test. Count data were represen-ted as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher's exact probability. Comparison of ordinal data was conducted using the rank sum test. Comparison of visual analog scores was analyzed using generalized estimating equations. Results:(1) Grouping of the enrolled patients. A total of 320 patients with colon cancer were screened for eligibility, including 156 males and 164 females, aged 68(59,73)years. All the 320 patients were allocated into the mesenteric fissure non-closure group with 164 cases and the mesenteric fissure closure group with 156 cases. There was no significant difference in the age, body mass index, American Society of Anesthesiologist score, maximum tumor diameter, anastomosis location, anastomosis method, surgical approach, range of lymph node dissection, tumor staging between the two groups ( P>0.05) and there was a significant difference in the sex between them ( P<0.05). (2) Intraoperative conditions. There was no significant difference between the mesenteric fissure closure group and the mesenteric fissure non-closure group in the volume of intraoperative blood loss, operation time, conversion to laparotomy, intraoperative complication ( P>0.05). Three patients in the mesenteric fissure non-closure group were converted to laparotomy. One patient in the mesenteric fissure closure group was converted to laparotomy, and 2 cases with intraoperative complication were mesenteric hematoma. (3) Postoperative conditions. There was no significant difference between the mesenteric fissure non-closure group and the mesenteric fissure closure group in the overall postoperative complications ( χ2=0.28, P>0.05). There was no significant difference in the occurrence of postoperative intestinal obstruction, abdominal distension, ascites, pleural effusion, gastric paralysis, anastomotic bleeding, anastomotic leakage, or surgical wound infection between the two groups ( P>0.05). There was no significant difference between the two groups in the reoperation, postoperative gastric tube replacement. There was no significant differ-ence in time to postoperative first flatus, time to postoperative initial liquid food intake, time to post-operative resumption of bowel movements, duration of postoperative hospital stay, total hospital expenses between the two groups ( Z=-0.01, 0.43, 1.04, -0.54, -0.36, P>0.05). One patient in the mesenteric fissure non-closure group received reoperation. No perioperative internal hernia or death occurred in either group. The visual analog score decreased with time in both groups. There was no significant difference in the visual analog score between the mesenteric fissure closure group and the mesenteric fissure non-closure group [ β=-0.20(-0.53,0.13), P>0.05]. Conclusion:Compared with closure of mesenteric fissure, non-closure of mesenteric fissure during laparoscopic right hemi-colectomy dose not increase perioperative complications or postoperative management risk.
10.Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China: A nationwide, multi-center, population-based cross-sectional study
Weiyu ZHANG ; Huixin LIU ; Ming LIU ; Shi YING ; Renbin YUAN ; Hao ZENG ; Zhenting ZHANG ; Sujun HAN ; Zhannan SI ; Bin HU ; Simeng WEN ; Pengcheng XU ; Weimin YU ; Hui CHEN ; Liang WANG ; Zhitao LIN ; Tao DAI ; Yunzhi LIN ; Tao XU
Chinese Medical Journal 2024;137(11):1324-1331
Background::Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods::Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results::A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.Conclusions::PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.


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