1.Identification of a JAK-STAT-miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions.
Songyang LI ; Yongjie LIU ; Xiaofeng YIN ; Yao YANG ; Xinjia LIU ; Jiaxing QIU ; Qinglan YANG ; Yana LI ; Zhiguo TAN ; Hongyan PENG ; Peiwen XIONG ; Shuting WU ; Lanlan HUANG ; Xiangyu WANG ; Sulai LIU ; Yuxing GONG ; Yuan GAO ; Lingling ZHANG ; Junping WANG ; Yafei DENG ; Zhaoyang ZHONG ; Youcai DENG
Acta Pharmaceutica Sinica B 2025;15(4):1922-1937
The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.
2.Study on mechanism of LncRNA NEAT1 on improving myocardial injury in rats with myocardial infarction through miR-136/ERK1/2 axis
Chinese Journal of Immunology 2025;41(1):75-84
Objective:To explore the mechanism of long non-coding RNA nuclear-enriched transcript 1(LncRNA NEAT1)on improving myocardial injury in rats with myocardial infarction(MI)mechanism through miR-136/extracellular signal-regulated kinase 1/2(ERK1/2)axis.Methods:Using the random number table method,120 male SD rats were divided into 6 groups(n=20):sham group,myocardial infarction group(MI group),control interference group(sh-NC group),NEAT1 interference group(sh-NEAT1 group),NEAT1 interference+miR-136 control inhibition group(sh-NEAT1+antagomiR-NC group)and NEAT1 interference+miR-136 suppression group(sh-NEAT1+antagomiR-136 group).Seven days before MI operation,100 μl of corresponding adenovirus vector was injected into the myocardium.Rats in each group were ligated the left anterior descending vessel to establish MI model.In sham group,only the left chest was opened and the heart was exposed without ligation.H9C2 cardiomyocyte were divided into:control group,vehicle group,sh-NC group,sh-NEAT1 group,sh-NEAT1+antagomiR-NC group and sh-NEAT1+antagomiR-136 group.Car-diomyocyte were transfected with corresponding NEAT1 interference vector and negative control,miR-136 inhibitor and negative con-trol.StarBase prediction and dual luciferase report experiment verify the targeted regulation of LncRNA NEAT1 on miR-136;myocar-dial infarct size was measured by TTC staining,and myocardial histopathological changes were observed by HE staining;Echocardiog-raphy was used to detect rat cardiac function;detection of apoptosis in rat myocardial tissue and H9C2 cells by flow cytometry.ELISA method was used to detect serum oxidative stress,corresponding indexes of myocardial enzymes and the contents of inflammatory fac-tors in myocardial tissue and H9C2 cells.CCK8 and EdU staining were used to detect the proliferation ability of H9C2 cells.RT-qPCR was used to detect the expressions of miR-136,SIRT1 mRNA in myocardial tissue and H9C2 cells.Western blot was used to detect the expressions of ERK1/2,p-ERK1/2,B-cell lymphoma-2(Bcl-2),Bcl2-related X protein(Bax)protein in rat myocardial tissue and H9C2 cells.Results:The expression of LncRNA NEAT1 was up-regulated in injured myocardial tissues and cells,and the expression of miR-136 was down-regulated(P<0.05).At the same time,NEAT1 targets and regulates the level of miR-136.Inhibition of NEAT1 expression could increase left ventricular ejection fraction(LVEF),left ventricular fraction shortening(LVFS),Bcl-2 level,and de-crease the activities of creatine kinase(CK),lactate dehydrogenase(LDH),and aspartame Acid transaminase(AST),superoxide dismutase(SOD),reduce Bax,troponin Ⅰ(cTnⅠ),malondialdehyde(MDA),TNF-α,IL-1β,IL-6,ERK1/2/p-ERK1/2 levels(P<0.05),promote the proliferation of myocardial cells,inhibit cell apoptosis,reduce the area of myocardial infarction,inhibit oxida-tive stress and inflammation,and improve myocardial damage Inhibiting miR-136 can save the above effects.Conclusion:The expres-sion of LncRNA NEAT1 is up-regulated and the expression of miR-136 is down-regulated in injured myocardial tissue and cells.Inhibi-tion of LncRNA NEAT1 expression inhibits apoptosis,oxidative stress and inflammation through miR-136/ERK1/2 axis,thus improving myocardial injury.
3.Correlation analysis of urinary sodium excretion and early renal functional impairment in patients with primary hypertension
Jiaqi BAI ; Nana YIN ; Lijun LI ; Chi WANG ; Xiangyu WANG ; Siyu YAO ; Kaiwei ZHANG ; Qian XIN ; Hao XUE
Chinese Journal of General Practitioners 2025;24(6):679-685
Objective:To analyze the correlation between 24-hour urinary sodium excretion and early renal function impairment in patients with primary hypertension.Methods:This cross-sectional study included patients with primary hypertension who were admitted to the Department of Cardiology of the Chinese People′s Liberation Army General Hospital between January 2021 and October 2024. Patients were divided into low-sodium, medium-sodium, and high-sodium groups based on their 24-hour urinary sodium excretion. General clinical data were collected using the electronic medical record system. Urinary sodium, protein, and microalbumin excretion were analyzed from 24-hour urine samples. Spearman correlation analysis was used to explore the relationship between 24-hour urinary sodium excretion and urinary microalbumin excretion. A multiple linear regression model was used to further assess the independent association between these variables. Subgroup analyses were conducted based on age were performed to determine whether age influenced the relationship between urinary sodium excretion and renal function impairment.Results:A total of 1 065 patients with primary hypertension were included, with a mean age of (55.26±14.06) years, including 568(53.33%) males. The low-sodium, medium-sodium, and high-sodium groups included 223, 579, and 263 patients, respectively. The 24-hour urinary microalbumin excretion in the high-sodium group was significantly higher than in the medium-sodium and low-sodium groups, and this trend remained consistent across different age groups (all P<0.05). Spearman correlation analysis showed a positive correlation between 24-hour urinary sodium excretion and urinary microalbumin excretion ( r=0.220, P<0.001), and this relationship was observed in all age groups (all P<0.05). Multiple linear regression analysis confirmed an independent association between 24-hour urinary sodium excretion and urinary microalbumin excretion (all P<0.001), which persisted across different age groups (all P<0.05). Conclusion:In patients with primary hypertension, 24-hour urinary sodium excretion is closely associated with microalbumin excretion, suggesting a potential link to early renal function impairment.
4.Study on mechanism of LncRNA NEAT1 on improving myocardial injury in rats with myocardial infarction through miR-136/ERK1/2 axis
Chinese Journal of Immunology 2025;41(1):75-84
Objective:To explore the mechanism of long non-coding RNA nuclear-enriched transcript 1(LncRNA NEAT1)on improving myocardial injury in rats with myocardial infarction(MI)mechanism through miR-136/extracellular signal-regulated kinase 1/2(ERK1/2)axis.Methods:Using the random number table method,120 male SD rats were divided into 6 groups(n=20):sham group,myocardial infarction group(MI group),control interference group(sh-NC group),NEAT1 interference group(sh-NEAT1 group),NEAT1 interference+miR-136 control inhibition group(sh-NEAT1+antagomiR-NC group)and NEAT1 interference+miR-136 suppression group(sh-NEAT1+antagomiR-136 group).Seven days before MI operation,100 μl of corresponding adenovirus vector was injected into the myocardium.Rats in each group were ligated the left anterior descending vessel to establish MI model.In sham group,only the left chest was opened and the heart was exposed without ligation.H9C2 cardiomyocyte were divided into:control group,vehicle group,sh-NC group,sh-NEAT1 group,sh-NEAT1+antagomiR-NC group and sh-NEAT1+antagomiR-136 group.Car-diomyocyte were transfected with corresponding NEAT1 interference vector and negative control,miR-136 inhibitor and negative con-trol.StarBase prediction and dual luciferase report experiment verify the targeted regulation of LncRNA NEAT1 on miR-136;myocar-dial infarct size was measured by TTC staining,and myocardial histopathological changes were observed by HE staining;Echocardiog-raphy was used to detect rat cardiac function;detection of apoptosis in rat myocardial tissue and H9C2 cells by flow cytometry.ELISA method was used to detect serum oxidative stress,corresponding indexes of myocardial enzymes and the contents of inflammatory fac-tors in myocardial tissue and H9C2 cells.CCK8 and EdU staining were used to detect the proliferation ability of H9C2 cells.RT-qPCR was used to detect the expressions of miR-136,SIRT1 mRNA in myocardial tissue and H9C2 cells.Western blot was used to detect the expressions of ERK1/2,p-ERK1/2,B-cell lymphoma-2(Bcl-2),Bcl2-related X protein(Bax)protein in rat myocardial tissue and H9C2 cells.Results:The expression of LncRNA NEAT1 was up-regulated in injured myocardial tissues and cells,and the expression of miR-136 was down-regulated(P<0.05).At the same time,NEAT1 targets and regulates the level of miR-136.Inhibition of NEAT1 expression could increase left ventricular ejection fraction(LVEF),left ventricular fraction shortening(LVFS),Bcl-2 level,and de-crease the activities of creatine kinase(CK),lactate dehydrogenase(LDH),and aspartame Acid transaminase(AST),superoxide dismutase(SOD),reduce Bax,troponin Ⅰ(cTnⅠ),malondialdehyde(MDA),TNF-α,IL-1β,IL-6,ERK1/2/p-ERK1/2 levels(P<0.05),promote the proliferation of myocardial cells,inhibit cell apoptosis,reduce the area of myocardial infarction,inhibit oxida-tive stress and inflammation,and improve myocardial damage Inhibiting miR-136 can save the above effects.Conclusion:The expres-sion of LncRNA NEAT1 is up-regulated and the expression of miR-136 is down-regulated in injured myocardial tissue and cells.Inhibi-tion of LncRNA NEAT1 expression inhibits apoptosis,oxidative stress and inflammation through miR-136/ERK1/2 axis,thus improving myocardial injury.
5.Correlation analysis of urinary sodium excretion and early renal functional impairment in patients with primary hypertension
Jiaqi BAI ; Nana YIN ; Lijun LI ; Chi WANG ; Xiangyu WANG ; Siyu YAO ; Kaiwei ZHANG ; Qian XIN ; Hao XUE
Chinese Journal of General Practitioners 2025;24(6):679-685
Objective:To analyze the correlation between 24-hour urinary sodium excretion and early renal function impairment in patients with primary hypertension.Methods:This cross-sectional study included patients with primary hypertension who were admitted to the Department of Cardiology of the Chinese People′s Liberation Army General Hospital between January 2021 and October 2024. Patients were divided into low-sodium, medium-sodium, and high-sodium groups based on their 24-hour urinary sodium excretion. General clinical data were collected using the electronic medical record system. Urinary sodium, protein, and microalbumin excretion were analyzed from 24-hour urine samples. Spearman correlation analysis was used to explore the relationship between 24-hour urinary sodium excretion and urinary microalbumin excretion. A multiple linear regression model was used to further assess the independent association between these variables. Subgroup analyses were conducted based on age were performed to determine whether age influenced the relationship between urinary sodium excretion and renal function impairment.Results:A total of 1 065 patients with primary hypertension were included, with a mean age of (55.26±14.06) years, including 568(53.33%) males. The low-sodium, medium-sodium, and high-sodium groups included 223, 579, and 263 patients, respectively. The 24-hour urinary microalbumin excretion in the high-sodium group was significantly higher than in the medium-sodium and low-sodium groups, and this trend remained consistent across different age groups (all P<0.05). Spearman correlation analysis showed a positive correlation between 24-hour urinary sodium excretion and urinary microalbumin excretion ( r=0.220, P<0.001), and this relationship was observed in all age groups (all P<0.05). Multiple linear regression analysis confirmed an independent association between 24-hour urinary sodium excretion and urinary microalbumin excretion (all P<0.001), which persisted across different age groups (all P<0.05). Conclusion:In patients with primary hypertension, 24-hour urinary sodium excretion is closely associated with microalbumin excretion, suggesting a potential link to early renal function impairment.
6.Arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint athrosis
Zhe ZHAO ; Hongli GENG ; Jianquan LIU ; Yongsheng LI ; Jianwen YIN ; Xiaoqiang CHEN ; Guanghui WANG ; Xiangyu CHENG ; Jiabei LI ; Zhiqin DENG ; Aozhengzheng DONG ; Manyi WANG ; Xiaofei ZHENG ; Wencui LI
Chinese Journal of Orthopaedics 2024;44(1):25-32
Objective:To analyze the clinic effects of arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint (CMCJ) Eaton stage II/III arthrosis.Methods:A retrospective study was conducted on a total of 15 cases (16 hands) of patients including 5 males (1 bilateral) and 10 females with CMCJ stage II/III arthrosis who underwent surgical treatment at the first affiliated hospital of Shenzhen university from January 2020 to June 2022, with mean age of 56.7±6.4 years (range, 46-75 years). The duration from pain to treatment was 7.8±3.2 months (range, 4-14 months). X-ray showed narrowing of CMCJ with osteophytes and distal radial subluxation. All the patients were treated with arthroscopic partial trapeziectomy and suture button suspensionplasty. The preoperative and last postoperative follow-up radiographs, visual analogue scale (VAS), thumb's Kapandji scores, disabilies of the arm, shoulder, and hand (DASH) scores, grip and pinch strength and time to return to work were compared.Results:All cases were followed up for 19.6±6.3 months (range, 11-36 months). The postoperative X-ray showed all the CMCJs were reduced with a normal height of first metacarpal. The mean time for patients to return to their daily activities was 18.69±3.70 d and the mean time to return to work was 24.63±4.91 d. The average VAS score decreased from 6.56±1.15 preoperatively to 1.00 (0.75, 1.25). The preoperative Kapandji's score was 8.00±0.82 and the postoperative Kapandji's score was 8.00 (7.25, 9.00). The average DASH values improved from 24.06±3.19 to 4.00 (3.00, 5.00). The were significant differences except for Kapandji score ( Z=-4.905, P<0.001; Z=-0.121, P=0.905; Z=-4.846, P<0.001). The mean grip and pinch strength showed improvement from an average of 16.4 (14.13, 18.68) kg and 1.70±0.35 kg to 26.14±3.27 kg and 3.58±0.91 kg with significant difference ( Z=-4.617, P<0.001; t=-7.669, P<0.001). Conclusion:Arthroscopic partial trapeziectomy and suture button suspensionplasty is a minimally invasive surgery for the treatment of first CMCJ Eaton stage II/III arthrosis. By this technique, the patients' existing instability and pain problems can be solved.
7.Clinical efficacy of semaglutide in the treatment of type 2 diabetes mellitus combined with non-alco-holic fatty liver disease and its effect on oxidative stress and inflammatory factors
Xiangyu MENG ; Liwei BAI ; Qingfeng YIN ; Beiyan LIU ; Xuehui CHEN ; Yun XU ; Di WANG ; Xu WANG ; Ruina GENG ; Qiujun LIU
Journal of Xinxiang Medical College 2024;41(5):443-448
Objective To explore the efficacy of semaglutide in the treatment of type 2 diabetes mellitus(T2DM)com-bined with non-alcoholic fatty liver disease(NAFLD)and its effect on oxidative stress and inflammatory factors.Methods Totally 80 patients with T2DM accompanied by NAFLD admitted to the First Affiliated Hospital of Xinxiang Medical University from July 2021 to December 2022 were selected and randomly assigned to the observation group and the control group,with 40 patients in each group.Patients in the control group were treated with pioglitazone metformin and dapagliflozin,while patients in the observation group were treated with pioglitazone metformin,dapagliflozin,and semaglutide.The levels of glycated hemoglobin(HbA1c),fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),body mass,body mass index(BMI),waist circumference,alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT),controlled attenuation parameter(CAP),liver stiffness measurement(LSM),malondialdehyde(MDA),glutathione peroxidase(GSH-PX),lipid peroxide(LPO),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)before and after the treatment were compared.Results After 24 weeks of treatment,the overall response rate(ORR)in the observation group and control group was 92.5%(37/40)and 72.5%(29/40),respectively;and the ORR in the observation group was significantly higher than that in the control group(x2=5.541,P<0.05).Before treatment,there was no statistically significant difference in the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,GSH-PX,LPO,TNF-α,IL-6,and IL-10 of patients between the 2 groups(P>0.05);after 24 weeks of treatment,the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,LPO,TNF-α,IL-6,and IL-10 were significantly lower than before treatment,while GSH-PX was significantly higher than before treatment(P<0.05);after 24 weeks of treatment,the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,LPO,TNF-α,IL-6,and IL-10 of patients in the observation group were significantly lower than those in the control group,and GSH-PX was significantly higher than that in the control group(P<0.05).The incidence of adverse reactions in the observation group and the control group during the treatment period was 17.5%(7/40)and 12.5%(5/40),respectively;and the difference in the incidence of adverse reactions between the two groups was not statistically significant(P>0.05).Conclusion Semaglutide significantly downregulates the levels of FBG,2hPG and HbA1c in patients with T2DM combined with NAFLD and reduces the body mass,waist circumference,liver enzyme level,hepatic fat content,hepatic fibrosis,oxidative stress,and inflammatory indicators.
8.Short-term effect of arthroscopy repair for hiprotator-cufftear
Xiangyu YIN ; Yi LIU ; Quanhe JIN ; Wenguang LIU ; Qingfeng YIN
Chinese Journal of Orthopaedics 2023;43(23):1593-1600
Objective:To investigate the clinical characteristics of hip rotator-cuff tear, arthroscopic repair techniques, and short-term clinical efficacy.Methods:A retrospective analysis was performed on the patient cohort from our department who underwent arthroscopic repair for hip rotator-cuff tears from September 2019 to May 2021, with a minimum follow-up duration of two years. The sample included 17 subjects, composed of 6 males and 11 females, with a median age of 56 years (interquartile range 49.5-62.5). Notably, 9 patients (53%) reported nocturnal pain, and 10 patients (59%) exhibited a positive hip flexion resistance test. Patients' demographic details, clinical manifestations, radiographic findings, and intraoperative observations were analyzed. Pain amelioration was gauged by the visual analogue scale (VAS) at preoperative, 1 month, 3 months, and 6 months postoperative intervals. Enhancement in hip functionality was assessed by comparing the modified Harris hip score (mHHS), and the International hip outcome tool-12 (iHOT-12) at preoperative, 6 months, 12 months, and 24 months postoperative junctures.Results:All interventions were successfully completed, with an average surgical duration of 91.2±18.3 minutes. The follow-up period averaged 29 months. Every patient presented with a hip rotator-cuff tear, which was corrected using anchor suturing. 10 patients also had concomitant labrum injuries, with 5 cases undergoing labrum repair. The VAS score decreased from preoperative 5.24±1.15 to postoperative 2.29±0.69 at 1 month, 1.77±0.56 at 3 months, and 1.59±0.62 at 6 months ( F=79.31, P<0.001); The mHSS score increased from preoperative 49.59±6.11 to postoperative 81.00±3.89 at 6 months, 81.71±3.41 at 12 months, and 81.94±3.29 at 24 months ( F=232.00, P<0.001); The iHOT-12 score increased from preoperative 42.65±6.04 to postoperative 6 months 66.53±3.43, 12 months 68.12±3.48, and 24 months 69.06±3.53 ( F=150.00, P<0.001). Conclusion:Diagnosing hip rotator-cuff tears necessitates specific physical examinations complemented by high-definition magnetic resonance imaging. Arthroscopic surgery represents a potent treatment modality for hip rotator-cuff injuries, demonstrating substantial short-term clinical efficacy.
9.Research progress of urethral sling in the treatment of male urinary incontinence after prostatectomy
Mengli ZHU ; Jinze LI ; Xiangyu YANG ; Yin HUANG ; Liangren LIU ; Qiang WEI ; Dehong CAO
Journal of Modern Urology 2023;28(6):546-550
Stress urinary incontinence (SUI) following prostatectomy is an important and common problem in male, which can significantly reduce the quality of life. Urethral sling is a promising treatment for male SUI. It is easy to operate and can avoid the insertion of prosthesis, making it highly acceptable to patients. In recent years, with the advancement of technology, several kinds of slings have been put into clinical application and have achieved great outcomes. This article reviews the application of urethral sling in the treatment of SUI after prostatectomy.
10.Strategy of laparoscopic treatment of right posterior bile duct hepatolithiasis
Yunfeng LI ; Xiangyu HE ; Zicheng WANG ; Xinmin YIN
Chinese Journal of Digestive Surgery 2023;22(7):853-857
Hepatolithiasis is a common biliary disease in China. Surgical treatment principles of hepatolithiasis include "removing lesions, cleaning stones, correcting strictures, recovering the drainage and preventing the recurrence". Laparoscopic techniques have been increasingly applied in surgical treatment of hepatolithiasis recently. Right posterior bile duct is a predilection site of hepatolithiasis. Due to its unique anatomy, right posterior lobectomy, right posterior bile duct lithotomy and plasty remain challenging under laparoscopy. Based on relevant literatures and clinical experiences, the authors explore the strategy of laparoscopic treatment right posterior bile duct hepatolithiasis, aiming to provide reference for surgical colleagues.

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