1.Effect of miR-129-3p mimetic on bone loss in tail-suspended mice
Yi WU ; Zi-dong AN ; Yong-jie PANG ; Li-qiang WANG ; Xin-yang WANG ; Yu-hai GAO ; Xue-yan LI ; Ke-ming CHEN
Chinese Pharmacological Bulletin 2025;41(4):703-709
Aim To study whether intravenous injec-tion of miR-129-3p mimetic(agomir)can resist bone loss caused by hind limb disuse,and to provide new i-deas for preventing bone loss in microgravity environ-ment.Methods Forty-eight C57BL/6J male mice were randomly divided into the control group(CON),tail suspension model group(TS),tail suspension+miR-129-3p agomir administration group(miRNA)and tail suspension+miR-129-3p negative sequence agomir control group(NC).The miRNA group was given 4 mg·kg-1 miR-129-3p agomir by intravenous injection into the medial canthus twice a week.The NC agomir group were consistent with those in the miR-129-3p agomir group,and the CON and TS groups were given only equal volumes of normal saline.After four weeks,all mice were sacrificed and samples were collected.Micro-CT scan of femur,three-point femur bending test,serum bone metabolism index detection,oxidative stress index detection and osteogenesis-related protein expression analysis in bone tissue were per-formed.Results After four weeks,the number of tra-becular bone in the TS group was significantly re-duced,and Tb.BMD,Tb.Th,Tb.N,Tb.BS/TV and Tb.BV/TV were significantly lower than those in the CON group(P<0.01).While Tb.Sp TS group was significantly higher than the CON group(P<0.05),the maximum load and flexural strength of the femur significantly decreased(P<0.01),the content of ser-um bone formation index PINP was significantly lower than that of the CON group(P<0.01),and the con-tent of bone resorption index CTX-I was significantly higher than that of the CON group(P<0.01),the content of serum oxidative damage indexes 8-iso-PGF2α and 8-OHdG significantly increased(P<0.01),and the expression of osteogenesis-related pro-teins in bone tissue markedly decreased(P<0.01).However,the increase or decrease of all indexes in miRNA group was significantly lower than that in TS group.Conclusions miR-129-3p mimetic can signifi-cantly reduce bone loss caused by hind limb disuse.This experiment provides a new idea and method for preventing bone loss in microgravity environment.
2.LINC01694 regulates the malignant biological behaviors of prostate cancer cells through the miR-128-3p/TERF1 axis
Ming ZHENG ; Hongyan KE ; Zhongjun CHEN
Chinese Journal of Cancer Biotherapy 2025;32(5):484-491
Objective:To investigate the effects of long non-coding RNA 01694(LINC01694)regulating the microRNA-128-3p(miR-128-3p)/telomeric repeat binding factor 1(TERF1)axis on the malignant biological behaviors of prostate cancer(PC)cells.Methods:Cancer tissues and corresponding adjacent tissues from 20 PC patients undergoing surgery at the Department of Urology,Jingzhou Central Hospital,between January 2023 and January 2024 were collected.Human PC cell lines(PC-3,DU145,LNCaP,C4-2)and normal human prostate epithelial RWPE-1 cells were routinely cultured.LNCaP cells were transfected with sh-LINC01694,sh-NC,miR-128-3p inhibitor,inhibitor-NC,miR-128-3pmimics,pcDNA,and pcDNA-LINC01694 using Lipo6000? transfection reagent.Cells were divided into the following groups:Ctrl,sh-NC,sh-LINC01694,sh-LINC01694+NC inhibitor,sh-LINC01694+miR-128-3p inhibitor,pcDNA,and pcDNA LINC01694 groups.The mRNA expression of LINC01694,miR-128-3p,and TERF1 in PC tissues and cells,as well as LNCap cells in each group,was detected by qPCR.The protein expression of TERF1,caspase-3,cyclin D1,E-cadherin,and N-cadherin in LNCaP cells of each group was detected by WB method.Clone formation assay,flow cytometry,and Transwell chamber assay were applied to detect proliferation,apoptosis,migration,and invasion of LNCaP cells,respectively.Dual luciferase reporter gene assay,RNA pull-down assay,and RNA-binding protein immunoprecipitation(RIP)assay were applied to verify the targeting binding relationship between LINC01694 and miR-128-3p as well as between TERF1 and miR-128-3p.Nude mouse LNCaP cell xenograft experiment was conducted to assess the effect of LINC01694 knockdown on tumor growth.Results:LINC01694 was highly expressed in PC tissues and cells(all P<0.05).Knockdown of LINC01694 in LNCaP cells promoted the protein expression of miR-128-3p,caspase-3,and E-cadherin,inhibited the protein expression of LINC01694,TERF1,cyclin D1,and N-cadherin,reduced cell proliferation,migration,and invasion,and promoted apoptosis(all P<0.05).All these effects were partially reversed by the miR-128-3p inhibitor(all P<0.05).LINC01694 could directly bind to miR-128-3p(P<0.05),while miR-128-3p could directly bind to TERF1 mRNA(P<0.05),indicating that LINC01694 regulates the miR-128-3p/TERF1 axis.Knockdown of LINC01694 significantly inhibited the growth of LNCaP cell xenografts in nude mice(P<0.05).Conclusion:LINC01694 regulates the malignant biological behaviors of LNCaP cells through the miR-128-3p/TERF1 axis.
3.Mechanism study of miR-376b-5p derived from human adipose mesenchymal stem cell exosomes inhibiting hypertrophic scars via mediating the TGF-β1/Smad pathway
Ming ZHAO ; Tao CAO ; Shiqing ZHENG ; Bo CHEN ; Bingnan LI ; Ke TAO
Journal of Chinese Physician 2025;27(11):1612-1618
Objective:To explore the molecular mechanism by which adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) inhibit hypertrophic scars (HS), and to identify the key functional miRNA and its downstream signaling pathway.Methods:A mouse model of hypertrophic scars was established by subcutaneous injection of bleomycin. The dorsal fibrotic modeling area was intervened with human ADSC-Exos (ADSC-Exos group), while the control group was injected with the same volume of PBS. HE and Masson staining were used to evaluate the morphological changes and collagen deposition of skin scar tissue in the two groups. Immunohistochemistry was performed to detect the expression of collagen 1 (Col-1) and α-smooth muscle actin (α-SMA). Western blot was used to determine the expression levels of key proteins in the transforming growth factor-β1 (TGF-β1)/Smad pathway (p-Smad2/3, Smad2/3). RNA sequencing datasets from the public database (GEO) were downloaded to analyze and screen differentially expressed miRNAs after ADSC-Exos treatment. In vitro cultured human hypertrophic scar fibroblasts (HSF) were transfected with miR-376b-5p mimic or inhibitor on the basis of ADSC-Exos treatment, and the expression of fibrosis markers (Col-1, α-SMA) as well as p-Smad2/3 and Smad2/3 was detected.Results:In vivo experiments showed that ADSC-Exos treatment significantly improved the fibrotic phenotype of mouse scar tissue, reduced the expression of Col-1 and α-SMA, and decreased the phosphorylation of Smad2/3 protein. Bioinformatics analysis revealed that miR-376b-5p was one of the most significantly upregulated miRNAs after ADSC-Exos treatment. In vitro experiments confirmed that overexpression of miR-376b-5p could mimic the antifibrotic effect of ADSC-Exos, significantly inhibit the expression of Col-1 and α-SMA in HSF, and reduce the phosphorylation level of Smad2/3. Specific inhibition of miR-376b-5p could effectively reverse the inhibitory effect of ADSC-Exos on the fibrotic phenotype of HSF and the phosphorylation of Smad2/3.Conclusions:This study reveals that ADSC-Exos exert their antifibrotic effect by mediating miR-376b-5p to target and inhibit the activation of the TGF-β1/Smad signaling pathway. miR-376b-5p is a key functional molecule in ADSC-Exos, and this finding provides a new potential target for the treatment of HS.
4.Exploration of the Medical Quality Management Pathway Based on"Internet Plus"and"Data Element Multiplier"
Anna SHEN ; Xiaojun CHEN ; Ming JIANG ; Jia KE ; Mingyue FAN ; Fangfang KONG ; Xin SUN
Chinese Hospital Management 2025;45(11):64-68
The traditional medical quality management model has many problems,such as excessive reliance on experience,poor coordination among departments,and lagging supervision,innovating medical quality management models has become an essential issue for the high-quality development of hospitals.A tertiary Grade A general hospital built a"data element multiplier"ecological chain for medical quality management,and established a complete closed-loop management system for medical quality management under the"Internet plus"model.Finally,the mobile medical quality management platform was built.Jointly driven by"Internet plus"and"data element multiplier",the level of lean management has been significantly improved,providing practical reference for hospitals at the same level.
5.Advances in the Studies of MicroRNA-1976 in Aberrant Cell Cycle Diseases.
Hao-Yu JI ; Hao CHEN ; Liang SHI ; Meng ZHANG ; Ting CHEN ; Ying-Ming KONG ; Rong-Ke FENG
Acta Academiae Medicinae Sinicae 2025;47(4):644-650
Most tumor cells and healthy neurons are at rest during G0 phase.Once the cell cycle is abnormally re-entered under certain conditions,the proliferation of tumor cells and the degenerative necrosis of neurons can be initiated.From the perspective of the cell cycle,cancer and central nervous system diseases,two seemingly different disease types,have a common pathogenesis.This type of diseases is named aberrant cell cycle diseases.As a newly discovered microRNA(miR),miR-1976 is closely related to the regulation of the cell cycle.This review summarizes the progress in the research on miR-1976 in cancer and central nervous system diseases,aiming to provide a reference for the clinical application of miR-1976 in aberrant cell cycle diseases in the future.
MicroRNAs/genetics*
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Humans
;
Cell Cycle/genetics*
;
Neoplasms/genetics*
;
Central Nervous System Diseases/genetics*
6.Creation and Exploration of the"Organized Fill-in-the-Blank Format"Disci-pline Construction Model for Forensic Medicine in the New Era
Zhi-Wen WEI ; Hong-Xing WANG ; Jun-Hong SUN ; Hao-Liang FAN ; Hong-Liang SU ; Le-Le WANG ; Wen-Ting HE ; Zhe CHEN ; Jie ZHANG ; Xiang-Jie GUO ; Ji LI ; Geng-Qian ZHANG ; Xin-Hua LIANG ; Jiang-Wei YAN ; Qiang-Qiang ZHANG ; Cai-Rong GAO ; Ying-Yuan WANG ; Hong-Wei WANG ; Jun XIE ; Bo-Feng ZHU ; Ke-Ming YUN
Journal of Forensic Medicine 2025;41(1):25-29
Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.
7.Detection of Ketamine and Norketamine Using an Aptamer-Functionalized Gra-phene Oxide Fluorescent Sensor
Li-Xia WEI ; Bo LIU ; Xiao-Yuan YANG ; Xi ZHANG ; Yi-Feng LAN ; Chao ZHANG ; Juan JIA ; Dan ZHANG ; Zhi-Wen WEI ; Ke-Ming YUN ; Zhe CHEN
Journal of Forensic Medicine 2025;41(4):326-339
Objective To construct an aptamer-functionalized carboxylated graphene oxide(CGO)fluo-rescent sensor to achieve highly sensitive and specific detection of ketamine(KET)and its metabolite norketamine(NK)using an aptamer capable of simultaneously recognizing KET and NK.Methods A specific aptamer for simultaneous recognition of KET and NK was screened using graphene oxide-sys-tematic evolution of ligand by exponential enrichment(GO-SELEX)and molecular docking tech-niques.The aptamer,labeled with Cy5 fluorescence,was chemically conjugated to CGO to construct an aptamer-functionalized CGO fluorescent sensor.By optimizing detection conditions,including the mass concentration of CGO,aptamer concentration,reaction temperature,and incubation time,quantita-tive analysis of the target analytes was achieved using the ratio of fluorescence intensity changes be-fore and after target addition.The stability of the sensor in biological matrices was evaluated by moni-toring fluorescence intensity changes over incubation time in blank blood and urine,in comparison with the traditional physical adsorption-based CGO fluorescent sensor.Spiked recovery experiments in blank blood and urine were conducted to compare performance with that of HPLC-MS/MS.Results A specific aptamer A5 was selected and chemically conjugated with CGO to construct the aptamer-functionalized CGO fluorescent sensor.Under optimized conditions,the proposed fluorescent sensor ex-hibited a linear detection range of 1.0-5.0 ng/mL for KET,with a limit of detection(LOD)of 0.86 ng/mL;while for NK,the linear detection range was 1.0-5.0 ng/mL,with an LOD of 0.70 ng/mL.Com-pared with the CGO fluorescent sensor constructed via physical adsorption,this sensor demonstrated greater stability in blood and urine.The spiked recovery rates of KET and NK in blank blood and urine ranged from 81.50%to 110.03%,exhibiting detection performance comparable to that of HPLC-MS/MS.Conclusion The aptamer screening method offers a novel approach for selecting aptamers tar-geting drugs and their metabolites.The constructed aptamer-functionalized CGO fluorescent sensor pro-vides an efficient and reliable strategy for the high-performance detection of KET and NK.
8.Toxicokinetics of Chlorfenapyr and Its Metabolites in Rats
Wen-Yan LI ; Jin-Feng ZHAO ; Wei-Chen LIU ; Shi-Jing LÜ ; Jia-Xin ZHANG ; Xu-Dong ZHANG ; Zhi-Wen WEI ; Ke-Ming YUN ; Chao ZHANG
Journal of Forensic Medicine 2025;41(4):380-386
Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood,and to investigate the toxicokinetics in rats.Methods Chlorfenapyr(8 mg/kg)was administered orally to rats,and blood samples were collected from rats'canthus vein at 5 min,15 min,30 min,1 h,3 h,6 h,12 h,24 h and 48 h after administration.The blood samples were extracted using 100 μL of 5%formic acid solution and 400 μL of acetonitrile.Chlorfena-pyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry(GC-MS/MS)and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry(LC-MS/MS).The DAS 3.0 software was used to fit the toxicokinetic equa-tions and calculate the toxicokinetic parameters.Results Chlorfenapyr was detectable from 5 min to 24 h with a peak time of 1 h.Tralopyril was detectable from 15 min to 48 h with a peak time of 3 h.The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model,with the toxicokinetic equation described as C=e-0.265t-e-0.175t.Tralopyril con-formed to the first-order absorption three-compartment model,and the toxicokinetic equation was C=47 361.069e-2.209t-35 404.962e-1.486t+11 956.363e-0.512t.In the equations,C stands for the concentration of the target substance in the blood,e is the natural constant(≈2.718 28),and t stands for time.Conclu-sion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood.The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.
9.Observation on the therapeutic effect of a modified Devine procedure with subcutaneous sliding fixation method for concealed penis.
Mohammed Abdulkarem AL-QAISI ; Hai-Fu TIAN ; Jia-Jin FENG ; Ke-Ming CHEN ; Jin ZHANG ; Yun-Shang TUO ; Xue-Hao WANG ; Bin-Cheng HUANG ; Muhammad Arslan Ul HASSAN ; Rui HE ; Guang-Yong LI
Asian Journal of Andrology 2025;27(4):470-474
To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis, we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University (Yinchuan, China) between September 2020 and November 2023. In all cases, the penis was observed to be short, and retracting the skin at the base revealed a normal penile body, which immediately returned to its original position upon release. All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up. A statistically significant increase in penile length was observed postoperatively, with the median length increasing from 4.0 (interquartile range [IQR]: 3.5-4.8; 95% confidence interval [CI]: 3.9-4.4) cm to 8.0 (IQR: 7.8-8.0; 95% CI: 7.7-7.9) cm, with P < 0.001. The parents were satisfied with the outcomes, including increased penile length, improved hygiene, and enhanced esthetics. Except for mild foreskin edema in all cases, no complications (such as infections, skin necrosis, or penile retraction) were observed. The edema was resolved within 4 weeks after the operation. This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications, reduced penile retraction, and high satisfaction rates among patients and their families.
Humans
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Male
;
Penis/abnormalities*
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Retrospective Studies
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Urologic Surgical Procedures, Male/methods*
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Treatment Outcome
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Child
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Plastic Surgery Procedures/methods*
10.Clinical and genetic analysis of a patient with FSIP2 compound heterozygous variants causing multiple morphological abnormalities of sperm flagella.
Yao-Qi CHEN ; Li-Qi XU ; Yi-Bo DAI ; Liang-Yu YAO ; Shen-Ming YANG ; Lu-Yu HUANG ; Xi YANG ; Yi YU ; Jing-Ming YANG ; Ke-Rong WU
National Journal of Andrology 2025;31(5):395-402
OBJECTIVE:
The aim of this study is to analyze the clinical features and genetic etiology of a patient with multiple morphological abnormalities of the sperm flagella (MMAF) retrospectively.
METHODS:
A severely oligospermic patient from the Reproductive Center of the First Affiliated Hospital of Ningbo University was selected as the study subject. Clinical data and examination results were collected. High-throughput sequencing and bioinformatics were used to analyze the genetic etiology. And Sanger sequencing was employed to validate findings in the family. Transmission electron microscopy (TEM) was used to observe the sperm ultrastructure, and immunofluorescence analysis was performed to examine the localization of FSIP2 protein in the sperm.
RESULTS:
The patient presented with severe oligospermia, and sperm morphology displayed MMAF. TEM revealed fibrous sheath and 9+2 microtubule structural disruptions in the sperm. Sequencing identified compound heterozygous variants in the FSIP2 gene (c.17798C > T, c.5927T > G), inherited from the father and mother, respectively. According to the guidelines of the American College of Medical Genetics and Genomics, the variants were classified as pathogenic. The patient's spouse underwent intracytoplasmic single sperm injection, resulting in one embryo, but no clinical pregnancy occurred after embryo transfer.
CONCLUSION
This study reported the mutation of FSIP2 gene c.17798C > T, c.5927T > G in a patient with MMAF. These findings expand the mutational spectrum of the FSIP2 gene and provide insights for genetic and assisted reproductive counseling for patients with MMAF.
Humans
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Male
;
Sperm Tail/pathology*
;
Heterozygote
;
Oligospermia/genetics*
;
Spermatozoa
;
Mutation
;
Infertility, Male/genetics*
;
Adult
;
Pedigree
;
Retrospective Studies
;
Sperm Injections, Intracytoplasmic

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