1.Human amniotic mesenchymal stem cells overexpressing neuregulin-1 promote skin wound healing in mice
Taotao HU ; Bing LIU ; Cheng CHEN ; Zongyin YIN ; Daohong KAN ; Jie NI ; Lingxiao YE ; Xiangbing ZHENG ; Min YAN ; Yong ZOU
Chinese Journal of Tissue Engineering Research 2025;29(7):1343-1349
BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.
2.Preparation and evaluation of quality,targeting and cytotoxicity of triptolide-loaded targeting nanoparticles
Moli YIN ; Wenbin LUO ; Jingzhe XU ; Zebo TANG ; Ni GUO ; Youxing LAO ; Huiyan WANG
China Pharmacy 2025;36(12):1457-1462
OBJECTIVE To prepare nanoparticle-based targeting preparation loaded with triptolide (TP), and evaluate its quality, targeting ability and cytotoxic effects. METHODS Polymer nanoparticles carrying TP-targeted folic acid (FA) receptor (TP@PLGA-PEG-FA) were fabricated using poly (lactic-co-glycolic acid)/polyethylene glycol/FA (PLGA-PEG-FA) as the carrier by emulsion and volatilization technique. The morphology and distribution were observed, and their particle size, Zeta potential, polydispersity index (PDI), drug loading capacity and encapsulation efficiency were measured. Their stability, blood compatibility, in vitro drug release, uptake by RAW264.7 cells (localization with fluorescent dye Cy3.5), and in vitro cytotoxicity were evaluated. RESULTS TP@PLGA-PEG-FA exhibited spherical shape and uniform distribution, with particle size of (122.60±0.02) nm, Zeta potential of (-17.6±0.6)mV, and PDI of 0.26±0.02; drug loading capacity and encapsulation efficiency of TP were measured to be (7.78±0.05)% and (68.62±0.03)%, respectively. The hemolysis rates of 100, 200, 300, 400 µg/mL TP@PLGA- PEG-FA were 0.77%, 0.92%, 1.34% and 1.63%, respectively. There were no significant changes in particle size, PDI and Zeta potential when TP@PLGA-PEG-FA were placed in 4 ℃ water for 14 days and in DMEM culture medium containing 10% fetal bovine serum at 37 ℃ for 12 h. The cumulative release rate of TP@PLGA-PEG-FA was (84.83±0.29)% in phosphate buffer at pH5.5 for 72 h, which was significantly higher than the cumulative release rates in phosphate buffer solutions at pH7.4 and 6.5 for 72 h ([ 42.37±0.35)% and (63.83±0.29)% , respectively] (P<0.05). Activated RAW264.7 cells took up significantly more Cy3.5@PLGA-PEG-FA than they took up Cy3.5@PLGA-PEG-FA+free FA and Cy3.5@PLGA-PEG. When the mass concentration of TP was≥15.63 ng/mL, the survival rates of activated cells in the TP@PLGA-PEG-FA groups were significantly lower than those of the same mass concentration of free TP groups (P<0.05). CONCLUSIONS The prepared TP@PLGA-PEG-FA has high stability, good blood compatibility, active targeting and cytotoxicity to inflammatory cells.
3.Application Value of 18F-FDG PET/CT Metabolic Parameters in Prognosis of Nasopharyngeal Carcinoma
Shanshan HE ; Nana LUO ; Xiaoyan HU ; Lei LI ; Yin NI ; Dasheng QIU
Cancer Research on Prevention and Treatment 2025;52(9):741-746
Objective To investigate the value of 18F-FDG PET/CT metabolic parameters in the prognostic assessment of nasopharyngeal cancer patients. Methods The clinical data and PET/CT metabolic parameters of 185 nasopharyngeal cancer patients were retrospectively analyzed. The collected parameters were SUVmax, MTV, TLG, total metabolic tumor volume (TMTV) and whole-body total lesion glycolysis (WTLG). The ROC curve was used to determine the optimal cut-off values of PET/CT metabolic parameters. Univariate and multivariate Cox regression models were used to screen the independent prognostic factors. Kaplan–Meier curves were used to analyze the survival differences. Results The results of univariate Cox regression analysis showed that age, pathologic type, WTLG, TMTV, MTV, and TLG were closely associated with OS and PFS; and SUVmax was associated with PFS (P<0.05). Multivariate Cox regression analysis results showed that age, TMTV, and WTLG were the independent prognostic factors for OS and PFS (P<0.05). The combination of WTLG with T/N staging (AUC=0.781 and 0.781) and TMTV with T/N staging (AUC=0.800 and 0.790) yielded greater predictive accuracy than that of WTLG and TMTV alone (AUC=0.724 and 0.719) or T/N staging (AUC=0.593 and 0.575). Conclusion TMTV and WTLG are important prognostic predictors of nasopharyngeal carcinoma. TLG and MTV of primary lesions are prognostic factors for patients’ PFS and OS. SUVmax has limited prognostic value. Systemic metabolic indexes (TMTV and WTLG), when combined with T/N staging, can optimize prognostic stratification.
4.Therapeutic role of miR-26a on cardiorenal injury in a mice model of angiotensin-II induced chronic kidney disease through inhibition of LIMS1/ILK pathway.
Weijie NI ; Yajie ZHAO ; Jinxin SHEN ; Qing YIN ; Yao WANG ; Zuolin LI ; Taotao TANG ; Yi WEN ; Yilin ZHANG ; Wei JIANG ; Liangyunzi JIANG ; Jinxuan WEI ; Weihua GAN ; Aiqing ZHANG ; Xiaoyu ZHOU ; Bin WANG ; Bi-Cheng LIU
Chinese Medical Journal 2025;138(2):193-204
BACKGROUND:
Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD.
METHODS:
We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data.
RESULTS:
Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes.
CONCLUSIONS
Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals
;
MicroRNAs/metabolism*
;
Angiotensin II/toxicity*
;
Mice
;
Renal Insufficiency, Chronic/chemically induced*
;
Mice, Knockout
;
Disease Models, Animal
;
Male
;
Signal Transduction/genetics*
;
LIM Domain Proteins/genetics*
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Mice, Inbred C57BL
;
Cell Line
;
Humans
5.Comparison and study of multiple scales results in children with cochlear reimplantation, mainly the speech, spatial, and other qualities of hearing scale for parents.
Tian NI ; Jinyuan SI ; Haotian LIU ; Xinyi YAO ; Xiangling ZHANG ; Huilin YIN ; Lin ZHANG ; Xiuyong DING ; Yu ZHAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(5):433-442
Objective:To compare the outcomes of multiple scales, primarily the speech, spatial, and other qualities of hearing scale for parents(SSQ-P), in children with ipsilateral vs. Contralateral cochleareimplantat ion(CRI). Methods: A total of 69 children who received cochlear implantation surgery from April 1999 to June 2024 were included. Patients were divided into two groups based on whether the implantation was on the same side. General information such as gender, age, age at initial implantation and reimplantation was collected. The primary caregivers of the children were followed up by telephone using the categories of auditory performance(CAP), speech intelligibility rating(SIR), and SSQ-P questionnaires. Statistical methods including stepwise regression, linear regression, and permutation tests were employed to investigate if there were any statistically significant differences in the scores of CAP, SIR, SSQ-P total, SSQ-P speech perception, SSQ-P spatial hearing, and SSQ-P auditory quality dimensions between the ipsilateral and contralateral reimplantation groups. Results:Of the 69 children included, 62 were in the ipsilateral reimplantation group with a mean age of 11.1 years, and 7 were in the contralateral reimplantation group with a mean age of 11.7 years. Statistical analysis showed that patients in the contralateral reimplantation group had significantly lower SSQ-P total scores (P<0.05) and spatial hearing dimension scores (P<0.05) than those in the ipsilateral reimplantation group after controlling for the corresponding confounders. Conclusion:The effect of ipsilateral reimplantation of cochlear implants is superior to that of contralateral reimplantation in terms of overall auditory function and spatial hearing in daily life for children, but the mechanisms require further investigation.
Humans
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Cochlear Implantation
;
Child
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Parents
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Speech Perception
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Male
;
Cochlear Implants
;
Female
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Hearing
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Surveys and Questionnaires
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Speech
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Child, Preschool
6.Construction of a Prognostic Model for Lysosome-dependent Cell Death in Gastric Cancer Based on Single-cell RNA-seq and Bulk RNA-seq Data.
Peng NI ; Kai Xin GUO ; Tian Yi LIANG ; Xin Shuang FAN ; Yan Qiao HUA ; Yang Ye GAO ; Shuai Yin CHEN ; Guang Cai DUAN ; Rong Guang ZHANG
Biomedical and Environmental Sciences 2025;38(4):416-432
OBJECTIVE:
To identify prognostic genes associated with lysosome-dependent cell death (LDCD) in patients with gastric cancer (GC).
METHODS:
Differentially expressed genes (DEGs) were identified using The Cancer Genome Atlas - Stomach Adenocarcinoma. Weighted gene co-expression network analysis was performed to identify the key module genes associated with LDCD score. Candidate genes were identified by DEGs and key module genes. Univariate Cox regression analysis, and least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were performed for the selection of prognostic genes, and risk module was established. Subsequently, key cells were identified in the single-cell dataset (GSE183904), and prognostic gene expression was analyzed. Cell proliferation and migration were assessed using the Cell Counting Kit-8 assay and the wound healing assay.
RESULTS:
A total of 4,465 DEGs, 95 candidate genes, and 4 prognostic genes, including C19orf59, BATF2, TNFAIP2, and TNFSF18, were identified in the analysis. Receiver operating characteristic curves indicated the excellent predictive power of the risk model. Three key cell types (B cells, chief cells, and endothelial/pericyte cells) were identified in the GSE183904 dataset. C19orf59 and TNFAIP2 exhibited predominant expression in macrophage species, whereas TNFAIP2 evolved over time in endothelial/pericyte cells and chief cells. Functional experiments confirmed that interfering with C19orf59 inhibited proliferation and migration in GC cells.
CONCLUSION
C19orf59, BATF2, TNFAIP2, and TNFSF18 are prognostic genes associated with LDCD in GC. Furthermore, the risk model established in this study showed robust predictive power.
Stomach Neoplasms/pathology*
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Humans
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Prognosis
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Lysosomes/physiology*
;
RNA-Seq
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Cell Death
;
Single-Cell Analysis
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Gene Expression Regulation, Neoplastic
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Cell Proliferation
;
Single-Cell Gene Expression Analysis
7.Near Peer Learning in Neurology Residency Training on Electromyography
Ying TAN ; Yuehui HONG ; Jia LI ; Dongchao SHEN ; Jiayu SHI ; Hexiang YIN ; Lixin ZHOU ; Jun NI ; Yicheng ZHU
Medical Journal of Peking Union Medical College Hospital 2024;16(1):263-268
To explore the effectiveness of "near peer learning" (NPL) in the electromyography(EMG)teaching module for neurology residents. The Department of Neurology, Peking Union Medical College Hospital implemented an NPL instructional design for a course on EMG for residents from November 2020 to March 2024. This teaching session was held annually, in which senior residents instructed juniors who were 1 or 2 years earlier in their training. The residents participated in the pre-course/post-course tests and completed a feedback survey at the end of the session. This evaluation method was used to understand the effectiveness of the NPL intervention in EMG teaching. Over four years, a total of 83 residents participated. Among them, there were 24 postdoctoral students, 52 postgraduates and 7 junior residents. The results showed that the post-course test scores were significantly improved compared with pre-course test scores (74.33±2.43 The NPL intervention is suitable for the teaching of EMG, because of its contribution to knowledge acquisition and basic clinical skills improvement. The NPL is worth replicating in other teaching and learning programs.
8.Analysis of causes of bleeding after endoscopic duodenal papillary adenoma resection and establishment of prediction model
Chun-Yan JIN ; Hua YANG ; Lei WANG ; Qin YIN ; Meng-Yun HU ; Xu FANG ; Mu-Han NI
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(4):398-402,406
Objective The causes of bleeding after endoscopic duodenal papilloma resection were analyzed and discussed,and the prediction model of nomogram was established.Methods A total of 233 patients who underwent endoscopic duodenal papilloma resection in our hospital from January 2018 to December 2023 were retrospectively analyzed,and they were divided into bleeding group(n=31 cases)and non-bleeding group(n=202 cases)according to whether postoperative bleeding occurred.The clinical data of the two groups were compared,the independent risk factors for postoperative bleeding were analyzed by multi-factor logistic regression,the risk nomogram prediction model was constructed,and the Bootstrap method was used for 1000 repeated samples to carry out internal verification.Results Anticoagulant drugs(OR=9.063,95%CI:2.132-38.525),lesion diameter ≥2 cm(OR=2.802,95%CI:1.073-7.321),intraoperative fragment resection(OR=27.653,95%CI:3.055~619.174)and pancreatic complications(OR=6.859,95%CI:1.930~24.377)were independent risk factors for postoperative bleeding after endoscopic duodenal papilloma resection(P<0.05).A risk prediction nomogram model was constructed according to the Logistic regression analysis results.The samples were repeatedly sampled 1000 times through Bootstrap method for internal verification.The area under the ROC curve was 0.850,and the 95%CI was 0.780-0.913,indicating good differentiation ability of the model.Calibration curve analysis indicated that the prediction probability of postoperative bleeding predicted by the nomogram prediction model was in good agreement with the actual probability of postoperative bleeding,and Hosmer-Lemeshow showed good goodness of fit(x2=3.304 9,P=0.913 8).Conclusion Taking anticoagulant drugs,lesion diameter ≥2 cm,intraoperative segmentary resection,and postoperative combination of pancreas were independent risk factors for bleeding after endoscopic duodenal papilloma resection.A nomogram prediction model was established to help clinical assessment of postoperative bleeding risk in patients and improve decision-making basis for early prevention.
9.A nomogram prediction model for individualized prediction of the risk of covert (minimal) hepatic encephalopathy occurrence in patients with liver cirrhosis
Xiaoqin LI ; Yang LI ; Yueqin NI ; Wen CAO ; Tiantian YIN ; Rui LU
Chinese Journal of Hepatology 2024;32(9):828-834
Objective:To construct an individualized nomogram prediction model for predicting the risk of the occurrence of covert hepatic encephalopathy (CHE) in patients with liver cirrhosis.Methods:325 cases of liver cirrhosis admitted from January 2020 to December 2022 were selected as the study subjects. Patients were divided into training ( n=213) and validation ( n=112) sets using a cluster randomization method. The risk factors for CHE occurrence in patients with cirrhosis in the training set were analyzed by univariate and multivariate logistic regression. A prediction model related to the nomogram was established. Results:Independent risk factors for the occurrence of CHE in patients with cirrhosis were a history of hepatic encephalopathy, co-infection, gastrointestinal bleeding, severe ascites, prothrombin time ≥16 seconds, high total bilirubin, and high blood ammonia levels ( P<0.05). Nomogram model validation results: The model had a net benefit for the training and validation sets, with C-indices of 0.830 (95% CI: 0.802-0.858) and 0.807 (95% CI: 0.877-0.837), respectively, within the range of 0-96%. The calibration curves of both sets were evenly close to the ideal curves. The AUCs for the ROC curves in both sets were 0.827 (95% CI: 0.796-0.858) and 0.811 (95% CI: 0.787-0.836), respectively. Conclusion:Patients with cirrhosis have many risk factors for CHE occurrence. The nomogram model constructed based on these risk factors possesses a good predictive value for assessing CHE occurrence in cirrhotic patients.
10.Study of the relationship between the ultrasound parameters of reproductive system and the expression of endocrine hormone in female pediatric patients with precocious puberty,and the assessment of treatment effect
Yiyong ZHAO ; Peng YIN ; Pengfei ZHU ; Baoli SONG ; Xuemei CHEN ; Weidong NI
China Medical Equipment 2024;21(5):92-97
Objective:To explore the relationship between the ultrasound parameters of reproductive system and the expression of endocrine hormone in female pediatric patients with precocious puberty(PP),and to assess the treatment effect.Methods:A total of 160 female pediatric patients with PP who admitted to Beijing Jingmei Group General Hospital from January 2021 to December 2021 were selected,and they were divided into a positive group and a normal group based on the diagnostic criteria for precocious puberty,with 80 cases in each group.Ultrasound examination was performed on the uterus,ovaries and breasts of 160 female pediatric patients with PP,and the relevant parameters of them were measured,and the levels of endocrine hormone in the serums of them were detected.The pediatric patients of positive group underwent again the ultrasound examination and the detection of endocrine hormone after they completed treatment.The differences of ultrasound parameters and endocrine hormone between two groups were compared,and the correlation of ultrasound parameters and endocrine hormone between two groups were analyzed,as well as the influence factors of treatment effect.Results:The length and thickness of the uterus,the ratio of the length of the uterus to the length of cervix,the thickness of the endometrium,the size of the ovaries,the number of follicles,and the width and thickness of the hypoechoic area of the breast in the positive group were significantly larger than them in the normal group,and the differences of them were statistical significance(t=16.8,12.6,12.4,14.7,11.5,15.8,10.9,10.2,P<0.05),respectively.The resistance index(RI)of uterine artery of positive group was significantly smaller than that of normal group,and the difference was statistically significant(t=-7.9,P<0.05).The serum estradiol(E2),gonadotropin(GnRH),follicle-stimulating hormone(FSH),luteinizing hormone(LH),progesterone(P)and growth hormone(GH)levels of positive group were significantly higher than those of normal group,and the differences of them were significant(t=20.6,19.8,15.4,17.6,15.2,8.9,P<0.05),respectively.After treatment,the above-mentioned ultrasound parameters and endocrine hormone levels of the pediatric patients in the positive group were significantly improved.The relevant analysis showed that ultrasound parameters were positively correlated with levels of endocrine hormone,and they were important influence factor on the levels of endocrine hormone.In addition,the treatment effect was related to ultrasound parameters(OR=0.78-1.28,P<0.05),the levels of endocrine hormone(OR=0.73-0.77,P<0.05),age,height,weight and BMI(OR=0.70-0.72,P<0.05).Conclusion:The ultrasound parameters of the reproductive system of female pediatric patients with PP are closely related to the expression of endocrine hormones.The levels of endocrine hormones can be used as important indicators of the disease condition and prognosis of female pediatric patients with PP.

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