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.Effect of Yigan Fupi Prescription (抑肝扶脾方) on the AKT/mTOR Pathway in the Colon Tissue of Diarrhea-Type Irritable Bowel Syndrome Model Rats with Liver Stagnation and Spleen Deficiency Pattern
Suting JIU ; Huiying LI ; Yueting SUN ; Songxiang CUI ; Xintian XU ; Hao ZHENG ; Weimin LU
Journal of Traditional Chinese Medicine 2025;66(3):290-299
ObjectiveTo explore the possible mechanism of Yigan Fupi Prescription (抑肝扶脾方, YFP) in treating diarrhea-type irritable bowel syndrome (IBS-D) by investigating the AKT/mTOR signaling pathway. MethodsSixty SD rats were randomly divided into control group, model group, YFP low-, medium-, and high-dose group, and pinaverium bromide group, with 10 rats in each group. All groups but the control group, were subjected to 21 days of tail-clamping stimulation and 14 days of senna leaf gavage to establish a liver stagnation and spleen deficiency-type IBS-D rat model. After successful modeling, the YFP low-, medium-, and high-dose group were administered 0.96, 1.93, and 3.87 g/(kg·d) of the prescription, respectively. The pinaverium bromide group was given 13.5 mg/(kg·d), while the control and model groups were given 10 ml/(kg·d) distilled water. All groups were administered once daily for 14 consecutive days. General conditions of the rats were recorded during the experiment, and after modeling and drug administration, body weight, Bristol stool score, abdominal withdrawal reflex (AWR) score, and histo pathology of colon tissue were observed under HE staining. ELISA was used to detect serum levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Immunofluorescence was employed to detect the levels of AKT/mTOR pathway-related proteins including phosphorylated AKT (p-AKT)/AKT and phosphorylated mTOR (p-mTOR)/mTOR in the colon tissue. Western Blotting was used to detect the levels of autophagy-related proteins, including UNC-51-like kinase 1 (ULK1), Beclin1 and LC3, and tight junction proteins including Occludin and ZO-1 in the colon tissue. ResultsAfter modeling, compared to the control group, the body weight of rats in the other groups decreased, and Bristol stool scores, as well as AWR scores under 20, 40, 60, and 80 mmHg increased (P<0.05 or P<0.01). After drug administration, compared to the control group, the model group showed reduced body weight, decreased ULK1, Beclin1, LC3Ⅱ/LC3Ⅰ, Occludin, and ZO-1 protein levels in the colon tissue (P<0.05 or P<0.01), and increased Bristol stool scores, AWR scores, serum TNF-α, IL-1β, and IL-6 levels, as well as p-AKT/AKT and p-mTOR/mTOR protein relative expression levels (P<0.05 or P<0.01). Pathological results showed a significant reduction in goblet cells in the upper part of the glandular layer of the colon, with mild inflammatory cell infiltration. The submucosal collagen fibers were dissolved, with unclear boundaries, pale staining, and microvascular congestion and dilation. Compared with the model group, the YFP low-, medium-, and high-dose group and the pinaverium bromide group showed increased body weight, Beclin1, Occludin, and LC3Ⅱ/LC3Ⅰ protein levels (P<0.05 or P<0.01), and decreased Bristol stool scores, AWR scores under 40, 60, and 80 mmHg, serum IL-1β, IL-6, TNF-α levels, and p-AKT/AKT, p-mTOR/mTOR protein relative expression levels (P<0.05 or P<0.01). The pathological morphology of the rats in the YFP groups and pinaverium bromide group showed varying degrees of improvement. Compared with the pinaverium bromide group, the YFP low- and medium-dose group showed increased AWR scores under 20, 40, and 60 mmHg (P<0.05). The YFP low-dose group had reduced TNF-α, IL-1β, and IL-6 levels, and increased p-mTOR/mTOR protein relative expression levels occured in all YFP groups (P<0.05). Compared with the YFP low-dose group, the YFP high-dose group and pinaverium bromide group showed decreased AWR scores under different pressure levels and reduced p-AKT/AKT protein relative expression levels, while the YFP medium- and high-dose group had elevated serum TNF-α, IL-1β levels and reduced p-mTOR/mTOR protein relative expression levels (P<0.05). ConclusionYFP can effectively improve the pathological injury of colon tissue in IBS-D model rats with liver stagnation and spleen deficiency, reduce Bristol stool and AWR scores, and its mechanism may be related to reducing level of inflammatory factors and inhibiting AKT/mTOR pathway-related proteins in colon tissue, thereby enhancing the expression of autophagy-related proteins in the colon tissue.
3.Comparison of efficacy and safety of oral mucosa grafts and acellular dermal matrix grafts in the treatment of long-segment urethral stricture.
Wenyuan LENG ; Duan GAO ; Xiaoyu LI ; Wei ZUO ; Weimin HU ; Zhenpeng ZHU ; Chunru XU ; Jian LIN ; Xuesong LI
Journal of Peking University(Health Sciences) 2025;57(5):975-979
OBJECTIVE:
To investigate the differential efficacy and safety profiles of oral mucosa (OM) grafts compared with acellular dermal matrix (ADM) grafts in the surgical management of long-segment urethral strictures.
METHODS:
A retrospective cohort study was conducted involving 27 patients who underwent graft urethroplasty for long-segment urethral strictures in Peking University First Hospital, spanning from May 2010 to September 2023. The patient cohort comprised 14 individuals who received OM grafts and 13 who underwent ADM grafts. The participants were stratified into two groups based on the type of grafts material utilized during surgery. The demographic and clinical baseline characteristics included an average age of (43.3±14.0) years in the OM group and (54.2±15.9) years in the ADM group. The mean body mass index (BMI) for the respective groups were (24.7±4.3) kg/m2 for OM and (25.4±4.8) kg/m2 for ADM. Etiological differences were noted, with idiopathic causes predominantly in the OM cohort and lichen sclerosus in the ADM cohort.
RESULTS:
The surgical interventions were successfully executed for all the patients. The median stricture length was 4.5 (2.5, 9.0) cm for the OM group and 5.0 (2.0, 14.0) cm for the ADM group (P=0.555). The median operative duration was 160 (71, 221) min for the OM group and 134 (112, 274) min for the ADM group (P=0.065). The catheterization durations was 1.5 (1.0, 6.0) months for the OM group and 3.0 (1.0, 3.0) months for the ADM group. The median postoperative follow-up duration was 12.5 (1.0, 170.0) months for the OM group and 59.0 (3.0, 142.0) months for the ADM group. The surgical success rates were 50.00% in the OM group and 53.85% in the ADM group. No statistically significant differences were observed in postoperative quality of life (QoL) or international prostate symptom score (IPSS) at the final follow-up. The stricture-free survival rates did not differ significantly (HR=0.875, 95%CI: 0.507-1.511, P=0.6). In terms of safety, three patients in the OM group experienced sexual dysfunction, and two had oral complications, whereas the ADM group had one case of postoperative infection.
CONCLUSION
The findings suggest that ADM grafts are comparable to OM grafts in terms of efficacy and safety for the treatment of long-segment urethral strictures, including complex cases attributed to lichen sclerosus. However, given the small sample size of this study, the above conclusions may have certain limitations. Larger cohort studies will be needed in the future to further validate these findings.
Humans
;
Urethral Stricture/surgery*
;
Acellular Dermis
;
Mouth Mucosa/transplantation*
;
Retrospective Studies
;
Middle Aged
;
Male
;
Adult
;
Treatment Outcome
;
Skin Transplantation/methods*
;
Aged
4.Impact of early antimicrobial therapy on clinical outcomes in patients with suspected sepsis in emergency and outpatient settings: a prospective cohort study.
Xianxian XU ; Hongqing SHEN ; Weimin ZHU ; Ping LI ; Peng YANG ; Renfei SHAN ; Nanjin CHEN ; Yongpo JIANG
Chinese Critical Care Medicine 2025;37(4):337-342
OBJECTIVE:
To investigate the impact of early antimicrobial therapy on the prognosis of patients with suspected sepsis in emergency and outpatient settings.
METHODS:
A prospective cohort study was conducted. Patients with suspected sepsis admitted to the emergency department of Taizhou Hospital, Zhejiang Province, from May 1, 2022, to July 31, 2023, were enrolled. Participants were divided into an early group (0-1 hour) and a delayed group (> 1 hour) according to duration from admission to antimicrobial administration. General information, initial vital signs, laboratory parameters within 24 hours after admission, disease severity scores, vasoactive drug usage, and clinical outcomes of the patient were collected. Kaplan-Meier survival curve was used to analyze 28-day survival. Multivariate Cox proportional hazards regression was performed to identify independent risk factors for prognosis of the patients with suspected sepsis in emergency and outpatient settings. Sensitivity analyses were conducted through subgroup analyses.
RESULTS:
A total of 143 patients with suspected sepsis were enrolled in the analysis, with 66 patients in the early group and 77 in the delayed group. No statistically significant differences were observed in baseline characteristics (age, gender, vital signs, laboratory parameters, disease severity scores) or clinical outcomes [vasoactive drug usage rate, mechanical ventilation duration, length of intensive care unit (ICU) stay, total hospitalization duration] between the two groups. The 28-day mortality, multidrug resistance rate and sepsis confirmation rate did not differ significantly between the early group and delay group [28-day mortality: 18.2% (12/66) vs. 20.8% (16/77), multidrug resistance rate: 3.0% (2/66) vs. 2.6% (2/77), sepsis confirmation rate: 87.9% (58/66) vs. 88.3% (68/77), all P > 0.05]. Kaplan-Meier survival curve analysis showed no difference in 28-day cumulative survival between the two groups (Log-Rank test: χ2 = 2.528, P = 0.112). Multivariate Cox proportional hazards regression identified vasoactive drug usage [hazard ration (HR) = 2.465, 95% confidence interval (95%CI) was 1.019-5.961, P = 0.045] and endotracheal intubation (HR = 5.516, 95%CI was 2.195-13.858, P < 0.001) as independent risk factors for 28-day death of the patients with suspected sepsis in emergency and outpatient settings. Further exploration of the impact of early antimicrobial therapy on 28-day death in different subgroups of the patients with suspected sepsis in emergency and outpatient settings was conducted through subgroup analysis. The results showed that in the patients with different ages (< 60 years old: HR = 1.214, 95%CI was 0.535-2.751, P = 0.643; ≥ 60 years old: HR = 2.085, 95%CI was 0.233-18.668, P = 0.511), sequential organ failure assessment (SOFA) scores (< 6: HR = 1.411, 95%CI was 0.482-4.128, P = 0.530; ≥ 6: HR = 0.869, 95%CI was 0.292-2.587, P = 0.801), shock indexes (< 1: HR = 1.095, 95%CI was 0.390-3.077, P = 0.863; ≥ 1: HR = 1.364, 95%CI was 0.458-4.059, P = 0.577) and whether diagnosed with sepsis or not (yes: HR = 0.943, 95%CI was 0.059-15.091, P = 0.967; no: HR = 1.207, 95%CI was 0.554-2.628, P = 0.636) subgroups, early usage of antibiotics had not shown any advantage in improving prognosis compared with delayed usage.
CONCLUSION
Early antimicrobial therapy does not improve the prognosis of patients with suspected sepsis in emergency and outpatient settings.
Humans
;
Sepsis/drug therapy*
;
Prospective Studies
;
Prognosis
;
Emergency Service, Hospital
;
Outpatients
;
Female
;
Male
;
Anti-Infective Agents/therapeutic use*
;
Middle Aged
;
Aged
;
Proportional Hazards Models
;
Treatment Outcome
5.Proteomics reveals biomarkers for sepsis-associated acute kidney injury: a prospective multicenter cohort study.
Weimin ZHU ; Nanjin CHEN ; Hanzhi DAI ; Cuicui DONG ; Yubin XU ; Qi CHEN ; Fangyu YU ; Cheng ZHENG ; Chao ZHANG ; Sheng ZHANG ; Yinghe XU ; Yongpo JIANG
Chinese Critical Care Medicine 2025;37(8):707-714
OBJECTIVE:
To identify and validate novel biomarkers for the early diagnosis of sepsis-associated acute kidney injury (SA-AKI) and precise continuous renal replacement therapy (CRRT) using proteomics.
METHODS:
A prospective multicenter cohort study was conducted. Patients with sepsis admitted to five hospitals in Taizhou City of Zhejiang Province from April 2019 to December 2021 were continuously enrolled, based on the occurrence of acute kidney injury (AKI). Sepsis patients were divided into SA-AKI group and non-SA-AKI group, and healthy individuals who underwent physical examinations during the same period were used as control (NC group). Peripheral blood samples from participants were collected for protein mass spectrometry analysis. Differentially expressed proteins were identified, and functional enrichment analysis was conducted on these proteins. The levels of target proteins were detected by enzyme linked immunosorbent assay (ELISA), and the predictive value of target protein for SA-AKI were evaluated by receiver operator characteristic curve (ROC curve). Additionally, sepsis patients and healthy individuals were selected from one hospital to externally verify the expression level of the target protein and its predictive value for SA-AKI, as well as the accuracy of CRRT treatment.
RESULTS:
A total of 37 patients with sepsis (including 19 with AKI and 18 without AKI) and 31 healthy individuals were enrolled for proteomic analysis. Seven proteins were identified with significantly differential expression between the SA-AKI group and non-SA-AKI group: namely cystatin C (CST3), β 2-microglobulin (β 2M), insulin-like growth factor-binding protein 4 (IGFBP4), complement factor I (CFI), complement factor D (CFD), CD59, and glycoprotein prostaglandin D2 synthase (PTGDS). Functional enrichment analysis revealed that these proteins were involved in immune response, complement activation, coagulation cascade, and neutrophil degranulation. ELISA results demonstrated specific expression of each target protein in the SA-AKI group. Additionally, 65 patients with sepsis (38 with AKI and 27 without AKI) and 20 healthy individuals were selected for external validation of the 7 target proteins. ELISA results showed that there were statistically significant differences in the expression levels of CST3, β 2M, IGFBP4, CFD, and CD59 between the SA-AKI group and non-SA-AKI group. ROC curve analysis indicated that the area under the curve (AUC) values of CST3, β 2M, IGFBP4, CFD, and CD59 for predicting SA-AKI were 0.788, 0.723, 0.723, 0.795, and 0.836, respectively, all exceeding 0.7. Further analysis of patients who underwent CRRT or not revealed that IGFBP4 had a good predictive value, with an AUC of 0.84.
CONCLUSIONS
Based on proteomic analysis, CST3, β 2M, IGFBP4, CFD, and CD59 may serve as potential biomarkers for the diagnosis of SA-AKI, among which IGFBP4 might be a potential biomarker for predicting the need for CRRT in SA-AKI patients. However, further clinical validation is required.
Humans
;
Sepsis/complications*
;
Acute Kidney Injury/blood*
;
Proteomics
;
Prospective Studies
;
Biomarkers/blood*
;
Male
;
Female
;
beta 2-Microglobulin/blood*
;
Middle Aged
;
Cystatin C/blood*
;
Aged
6.Analysis on correlation between serum pro-inflammatory cytokines and muscle mass in elderly patients with sarcopenic obesity and diabetes
Di QIN ; Lihong HUAGN ; Qingshuang ZHENG ; Jingjing SUN ; Weimin XU
Journal of Jilin University(Medicine Edition) 2025;51(5):1293-1302
Objective:To discuss the relationship between three proinflammatory factors and muscle mass(MM)in the elderly patients with sarcopenic obesity and diabetes,and to provide theoretical basis for the development of clinical treatment protocols in the elderly patients with sarcopenic obesity and diabetes.Methods:The elderly patients with diabetes who visited our hospital from January 2021 to May 2023 were selected,including 41 patients with obesity and diabetes(OD group)and 46 patients with sarcopenic obesity and diabetes(SOD group);80 healthy subjects(control group)and 62 subjects with simple obesity(SO group)who underwent physical examination in our hospital during the same period were included.The clinical data of the subjects in four groups were compared,and the correlations between proinflammatory factors and MM and fat mass(FM)were analyzed.All the subjects were divided into sarcopenia group and normal group based on the presence of sarcopenia.Logistic regression model was used to analyze the independent influencing factors of sarcopenia;receiver operating characteristic(ROC)curve was drawn to determine the predictive value of the above factors for sarcopenia.Results:Compared with control group,the body mass index(BMI),FM and body fat percentage(BFP)of the subjects in SOD,OD and SO groups were significantly increased(P<0.05);compared with control group,OD group and SO group,the appendicular skeletal muscle mass(ASM),appendicular skeletal muscle mass index(ASMI)and grip strength(GS)of the subjects in SOD group were significantly decreased(P<0.05),and the levels of serum interleukin-6(IL-6),C-reactive protein(CRP)and tumor necrosis factor-α(TNF-α)were significantly increased(P<0.05).In all the subjects,the IL-6,CRP and TNF-α were negatively correlated with ASMI(r=-0.589,r=-0.621,r=-0.620;P<0.05),and positively correlated with BFP(r=0.252,r=0.221,r=0.147;P<0.05).Compared with normal group,the ASM,ASMI and GS of the subjects in sarcopenia group were significantly decreased(P<0.05),and the levels of serum proinflammatory factors IL-6,CRP and TNF-α were significantly increased(P<0.05).The univariate Logistic regression analysis results showed that IL-6,CRP and TNF-α were the influencing factors of sarcopenia(P<0.05).The multivariate Logistic regression analysis results showed that the increased levels of IL-6 and TNF-α were the independent risk factors for sarcopenia(OR>1,P<0.05).The ROC curve results showed that the area under the curve(AUC)values of IL-6,CRP and TNF-α were all>0.700,indicating that the above indicators had good predictive value for sarcopenia.Conclusion:The increased levels of proinflammatory factors IL-6,CRP and TNF-α are associated with the decrease of MM in the elderly patients with sarcopenic obesity and diabetes,and IL-6 and TNF-α are the independent risk factors for the sarcopenia.
7.The effect of oxycodone or oliceridine for sedation during endoscopic retrograde cholangiopancreatography in elderly patients
Ke LIU ; Shasha MEI ; Zhuang GUO ; Weimin XU ; Wenxue YE
Journal of Interventional Radiology 2025;34(10):1089-1093
Objective To discuss the application effect of intravenous anesthesia with oxycodone plus propofol or oliceridine plus propofol for sedating elderly patients during endoscopic retrograde cholangiopancreatography(ERCP).Methods Sixty elderly patients,who were planned to receive ERCP in Shengli Oilfield Central Hospital from March to Sepcember 2024,were randomly divided into oxycodone group and oliceridine group,with 30 patients in each group.Intravenous anesthesia with oxycodone plus propofol or oliceridine plus propofol was adopted for the patients of the corresponding group.The patient's postoperative comfort score,the dosage of propofol used during surgery,the number of additional analgesics administered,the time of patient entering the operation room(T0),3 minutes after analgesia(T1),after anesthesia induction(T2),immediately upon examination(T3),time on arrival at the duodenal papilla(T4),and time on consciousness waking-up(T5)were recorded.The surgical time,consciousness waking-up time,endoscopist satisfaction degree,patient's satisfaction rate,and incidence of anesthesia-related adverse events were documented.Results The comparison of postoperative comfort scores showed that the score in the oliceridine group was(7.6±1.9)points,which was significantly higher than(6.6±1.3)points in the oxycodone group(t=2.23,P=0.03).The dosage of propofol used during surgery in the oliceridine group was significantly lower than that in the oxycodone group(P<0.05).The mean arterial pressure(MAP),heart rate(HR),and respiratory rate(RR)at T1-T4 time points were significantly decreased in both groups when compared with their values at T0 time point(all P<0.05).The reduction degrees of the above indexes at T1-T3 time points in the oxycodone group were more pronounced than those in the oliceridine group(all P<0.05).At T4,MAP and HR were increased in both groups,which in the oxycodone group were remarkably higher than those in the oliceridine group(both P<0.05).No statistically significantly difference in oxygen saturation(SpO2)existed between T1 time point and T0 time point(P>0.05);but at the other time points,SpO2 was decreased to varying degrees in both groups,and the within-group comparison and between-group comparison showed that the differences in SpO2 were statistically significant(all P<0.05).In oliceridine group,the time of patient's consciousness waking-up was obviously shorter than that in the oxycodone group(P<0.05),and the endoscopist satisfaction degree and patient satisfaction rate were strikingly higher than those in the oxycodone group(both P<0.05).The incidence of intraoperative adverse events in the oliceridine group was prominently lower than that in the oxycodone group(P<0.05).No statistically significant difference in the incidence of adverse events during consciousness waking-up time existed between the two groups(P>0.05),but the incidences of postoperative nausea,vomiting and respiratory depression in the oliceridine group was obviously lower than those in the oxycodone group(all P<0.05).Conclusion In performing ERCP for elderly patients,oliceridine plus propofol is clinically safe and feasible with less adverse events,high satisfaction rate and higher patient's comfort level when compared with oxycodone plus propofol.
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.Research progress of microRNA-mediated immune function of CD4+T cells subsets in immune thrombocytopenia
Hui SONG ; Yihui GUO ; Jiawei XU ; Qing ZENG ; Weimin CHENG
Chinese Journal of Immunology 2024;40(3):663-667
MicroRNA(miRNA)is a kind of small non-coding single stranded RNA that can participate in multiple biological processes.It also plays an important role in regulating the immune function of the body.Immune thrombocytopenia(ITP)is an autoim-mune disease,whose cause and deterioration are closely related to miRNA regulates immune function of CD4+T cells subsets.In ITP patients,different expression of miRNA can affect the immune function of CD4+T cells subsets,which causes not only unbalanced ex-pression of Th1/Th2,Th17/Treg and excessive differentiation of TFH,but also abnormal cytokine secretion furthermore.This paper summarizes the unbalanced mechanism of miRNA regulating immune function of CD4+T cells subsets in ITP,so as to provide inspira-tion for exploring the immunology and immunotherapy of ITP.
10.Effect of acupuncture on corneal morphology and nuclear factor κB signaling pathway of dry eye rabbits
Ning DING ; Qingbo WEI ; Chengyong LIU ; Weimin DENG ; Qing XU ; Weiping GAO
Recent Advances in Ophthalmology 2024;44(3):173-177
Objective To investigate the effect of acupuncture on the morphology of the dry eye rabbit's cornea and the nuclear factor κB(NF-κB)signaling pathway of the corneal tissue to analyze the mechanism of acupuncture on dry eyes.Methods Twenty-four healthy New Zealand rabbits,without restriction on sex,were randomly divided into four groups,including a blank group,a model group,an acupuncture group,and a sham acupuncture group,with 6 in each group.Rabbits in the blank group were not treated;rabbits in the other three groups were treated with scopolamine hydro-bromide 2.0 mg·kg-1 by subcutaneous injection at 8:00,11:00,14:00 and 18:00 each day for 35 consecutive days un-til the end of the experiment.Rabbits in the sham acupuncture group were treated with sham acupuncture on the 22nd day after successful modeling by quickly pricking acupoints(Jingming BL1,Cuanzhu BL2,Sizhukong SJ23,Taiyang EX-HN5 and Tongziliao GB1)with a blunt acupuncture needle,once a day,for a total of 14 days.Rabbits in the acupuncture group were treated with acupuncture at the same acupoints as the sham acupuncture group after successful modeling.The corneal fluorescence staining was conducted on Days 0,21,28 and 35 after modeling.On Day 35,corneal confocal microscope ex-aminations were conducted.Then,the rabbits were sacrificed,the corneal morphological changes were observed by light microscope and transmission electron microscope,and the expression of corneal NF-κB protein was detected by Western blot.Results Compared with the model group,the score of rabbit corneal fluorescein staining in the acupuncture group and blank group decreased on the 28th and 35th days after modeling,and the differences were statistically significant(all P<0.05).The results of the confocal microscope examination on Day 35 after modeling showed that,compared with other groups,there were a large number of globular immune cells and activated stromal cells with unclear boundaries and irregu-lar sizes in the stromal layer and inflammation in the area with irregular intercellular space in the model group and the sham acupuncture group.In the acupuncture group,the morphology of stromal layer cells improved,the cells were slightly acti-vated,and there were no obvious abnormalities in the corneal nerve morphology.On the 35th day after modeling,the re-sults of the light microscope showed that,the surface of the corneal tissue in the model group and the sham acupuncture group showed hyperkeratinized flat epithelial cells,lymphocyte infiltration,increased number of focal epithelial cell layers,and epithelial cell detachment.In the acupuncture group,there were 4-6 layers of epithelial cells in the corneal epitheli-um,and epithelial shedding decreased.In addition,the lymphocyte infiltration decreased compared with the model group.On the 35th day after modeling,the results of the transmission electron microscope showed that abnormal microvilli oc-curred and epithelial cells were absent in the corneal epithelial cells of rabbits in the model group and the sham acupuncture group,the cell space was widened,the rough endoplasmic reticulum was severely expanded,and desmosomes were dis-banded with mitochondrial swelling.In the acupuncture group,the microvilli structure of epithelial cells was sparse and short,local deletion was still observed,the rough endoplasmic reticulum was slightly expanded,and no obvious swelling of mitochondria was observed.On the 35th day after modeling,the Western blot examination results showed that,compared with the blank group,the expression of p-NF-κB p65 was up-regulated in both the model group and sham acupuncture group(both P<0.05);compared with the model group and sham acupuncture group,the expression of p-NF-κB p65 in the acupuncture group was down-regulated(both P<0.05).Conclusion Acupuncture can inhibit the NF-κB signaling path-way to play an anti-inflammatory role and relieve corneal inflammation and injury of dry eye rabbit models.

Result Analysis
Print
Save
E-mail