1.Therapeutic efficacy and mechanism of artesunate for mouse model of polycystic ovary syndrome
Xueling WANG ; Peiling ZHONG ; Zhipeng ZHAO ; Fei CHEN ; Xin LIU ; Sijia LIU ; Lie YUAN ; Lu FANG ; Qianyi YAO ; Xiong YANG ; Chao LIU ; Jiakun CHENG ; Yongqing CAI ; Xiaoli LI ; Weihong LI
Journal of Army Medical University 2025;47(3):193-204
Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P<0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P<0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P<0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P<0.05),and reduced HOMA-IR,TC and TG levels(P<0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P<0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.
2.p300 promotes hepatic lipid accumulation in dyslipidemia by regulating SREBP-1c acetylation
Nyewneh Abdul-Rauf NUHU ; Xiaoli LI ; Lu FANG ; Yongqing CAI ; Fei CHEN ; Lie YUAN ; Xiong YANG ; Qingsong JIANG ; Yinbo LIU ; Chao LIU ; Peiling ZHONG ; Menghua ZENG
Journal of Army Medical University 2025;47(22):2735-2748
Objective To investigate the role of p300 in lipid metabolism disorders.Methods Bioinformatics analysis was performed to analyze the expression patterns of p300 in lipid metabolism disorder-related diseases and its correlation with SREBP-1c and downstream lipid metabolic enzymes.Immunofluorescence assay was used to detect the expression of p300 in the liver tissues of the patients with varying disease severity of non-alcoholic fatty liver disease(NAFLD).A mouse model of lipid metabolism disorder was established in male C57BL/6J mice by feeding high-fat diet(HFD)for 12 weeks.Western blotting was employed to assess p300 expression level in the liver tissues of HFD-fed mice.A cell model of lipid metabolism disorder was established in HepG2/AML-12 cells induced with free fatty acid(FFA).The effects of siRNA-mediated knockdown of p300 was observed to measure the levels of intracellular total cholesterol(TC)and triglyceride(TG),lipid deposition,and production of reactive oxygen species(ROS).Results Clinically,p300 was highly expressed in lipid metabolism disorders,and its level was positively correlated with NAFLD severity(P<0.05).Gene Set Enrichment Analysis(GSEA)revealed that p300 expression was significantly associated with fatty acid metabolism,cholesterol homeostasis,lipogenesis,PPAR signaling pathway,and peroxisome pathway.In vivo,p300 was significantly up-regulated in the livers of HFD-fed mice(P<0.01).In vitro,FFA stimulation markedly increased p300 expression in both HepG2 and AML-12 cells(P<0.01),whereas p300 knockdown significantly reduced intracellular TG and TC levels(P<0.01),attenuated lipid droplet accumulation,and reversed FFA-induced ROS elevation(P<0.01).Furthermore,p300 expression was positively correlated with the expression of SREBP-1c and its downstream key lipid synthesis enzymes.Conclusion p300 may promote hepatic lipid accumulation by acetylating and activating SREBP-1c and regulating downstream lipid metabolic enzymes,thereby affecting lipid synthesis and oxidative stress.These findings suggest that p300 may be a potential therapeutic target for lipid metabolism disorder-related diseases.
3.Study of KCNJ11 rs5219 Gene Polymorphism on the Efficacy of Metformin Combined with Gliclazide in Newly Diagnosed Diabetes Mellitus Type 2 Patients
Lie XIONG ; Fang YAO ; Limin JIN ; Fan NING ; Hanqiang SHI ; Shuqin DU ; Yanbo SHI
Chinese Journal of Modern Applied Pharmacy 2023;40(24):3431-3438
Abstract
OBJECTIVE To explore the effect of the polymorphisms of ATM(rs11212617), KCNJ11(rs5219), CYP2C9(rs1799853, rs1057910), TCF7L2(rs12255372, rs290487) and IRS1(rs1801278) on efficacy of metformin and gliclazide combined treatment for diabetes mellitus type 2. METHODS Eighty-one patients with newly diagnosed diabetes mellitus type 2 in Standardized Metabolic Disease Management Center of the Endocrinology Department of of Zhejiang Chinese Medical University Affiliated Jiaxing TCM Hospital were enrolled in this study, and they were treated with metformin hydrochloride tablets and gliclazide modified release tablets. MassARRAY was used to type the above single nucleotide polymorphism(SNP), and followed up for 3 months. Fasting plasma glucose(FPG), glycosylated hemoglobin type Alc(HbA1c) and fasting insulin(FINS) were compared before and after treatment. RESULTS The gene frequencies of all SNPs were compliant to Hardy-Weinberg equilibrium, the samples were well represented. The rs1799853, rs1057910, rs12255372 and rs1801278 had low mutation frequencies with poor clinical significance. The benefits of FPG compliance rate, increase of FINS, decrease of HbAlc after treatment were stronger in patients with homozygous rs5219 C allele than those with T-allele carriers (P<0.05). However, there were no significant differences in treatment effects among the genotypes of rs11212617 and rs290487. CONCLUSION The rs5219 polymorphism of KCNJ11 gene is associated with the efficacy of metformin hydrochloride tablets and gliclazide modified release tablets in treating diabetes mellitus type 2, with a more significant effect observed in individuals homozygous for the C allele. This finding can serve as a reference for personalized medication in clinical treatment of diabetes mellitus type 2.
4.Long-term trend of viral hepatitis mortality and potential years of life lost in Jing’an District of Shanghai, 1976-2015
Qui-ping WAN ; Jun-ling ZHU ; Jin HUANG ; Jian-jing XIONG ; Xiao-lie YIN ; Xiao-ming YANG ; Ling-li SHI ; Yun-hui WANG ; Xiao-ting CHU
Shanghai Journal of Preventive Medicine 2021;33(7):593-598
Objective:To analyze the long-term trend of viral hepatitis mortality in Jing’an District of Shanghai, and to provide a reference for viral hepatitis prevention and control. Methods:Mortality rate, standard mortality rate, PYLL and potential years of life lost rate (PYLL‰) of viral hepatitis in Jing’an district of Shanghai from 1976 to 2015 were calculated. The annual percent change (APC) of the mortality and PYLL‰ were analyzed by Joinpoint regression analysis. Results:From 1976 to 2015, there were 1 342 viral hepatitis death cases, including 832 males and 510 females. The average crude mortality rate was 8.31/100 000, and the average age-standardized mortality rate was 5.45/100 000. Among the deaths of viral hepatitis, men had a higher mortality rate, age-standardized mortality rate and PYLL% than women (
5.Trends in the incidence and mortality of colorectal cancer in Jing'an District of Shanghai from 1993 to 2017
Yan-min WANG ; Jian-jing XIONG ; Wen-jun GAO ; Xiao-lie YIN ; Xiao-ming YANG ; Guang-wen CAO
Shanghai Journal of Preventive Medicine 2021;33(10):905-912
Objective:To characterize the trends in the incidence and mortality of colorectal cancer in Jing'an District of Shanghai, thus optimizing the prophylactic options for this malignancy. Methods:Data from Shanghai Cancer Registration and Reporting System were used to analyze the colorectal cancer prevalence in Jing'an District from 1993 to 2017. Joinpoint software was used to analyze the trends in the standardized incidence rate and mortality rate by calculating the annual percentage of change (APC) and the average annual percentage of change (AAPC). Results:A total of 13 580 new cases of colorectal cancer were reported in Jing'an District during 1993 and 2017, with an average crude incidence rate of 52.94/105 and a standardized incidence rate of 24.77/105. The total number of deaths was 7 572, with an average crude mortality rate of 29.52/105 and a standardized mortality rate of 12.20/105. The standardized incidence rate of colorectal cancer in Jing'an District from 1993 to 2017 showed an increasing trend (AAPC=1.64%,
6.Comparison of efficacy and safety between two different methods of nephroureterectomy in two centers.
Jin Feng WU ; Rong Cheng LIN ; You Cheng LIN ; Wang Hai CAI ; Qing Guo ZHU ; Dong FANG ; Geng Yan XIONG ; Lei ZHANG ; Li Qun ZHOU ; Lie Fu YE ; Xue Song LI
Journal of Peking University(Health Sciences) 2019;51(4):646-652
OBJECTIVE:
To compare the efficacy and safety of complete transperitoneal laparoscopic nephroureterectomy (CTNU) and traditional retroperitoneoscopic nehroureterectomy (TRNU) for the management of upper urinary tract urothelial carcinoma(UTUC).
METHODS:
We retrospectively collected the clinical data of UTUC patients who underwent CTNU or TRNU surgery from January 2011 to December 2018 in Peking University First Hospital and Fujian Provincial Hospital, and compared the clinical characteristics, perioperative parameters, and follow-up results between the CTNU and TRNU surgeries.
RESULTS:
Finally, a total of 266 cases were included, with 94 cases in the CTNU group and 172 cases in the TRNU group. The proportion of left side lesions was bigger in TRNU group when compared with CTNU group (P<0.05). No significant differences were observed in clinical characteristics, such as age, gender, body mass index (BMI), American society of anesthesiologists score (ASA score) and tumor laterality. All surgery procedures were completed. The vascular resparing was performed by reason that left arteria renalis was injured accidently during surgical operation in one case of TRNU group. No serious complications were observed in both CTNU and TRNU groups. In CTNU group, operating time was (202.9±76.7) min, estimated blood loss was (68.4±73.3) mL, drainage duration was (3.9±1.5) d, drainage volume was (181.7±251.5) mL, and postoperative hospital stay was (7.8±4.1) d. In TRNU group, operating time was (203.5±68.7) min, estimated blood loss was (130.2±252.1) mL, drainage duration was (4.3 ±1.6) d, drainage volume was (179.1±167.5) mL, and postoperative hospital stay was (8.2±3.7) d. The estimated blood loss in CTNU group was significantly less than that in TRNU group (P=0.005).The median follow-up time was 39 months (range: 1-88 months). The 5-year overall survival rate (OS), cancer specific survival rate (CSS), intra-vesical recurrence free survival rate (IvRFS), disease free survival rate (DFS) of CTNU group was 75.6%, 86.9%, 73.8%, 57.5%, respectively. The OS, CSS, IvRFS and DFS of TRNU group was 66.3%, 83.5%, 75.9%, 58.6%, respectively.No significant differences were observed in the OS, CSS, IvRFS and DFS between the CTNU and TRNU groups.
CONCLUSION
CTNU technique is a safe and effective surgical option, and further prospective randomized controlled trial is needed for further evaluation.
Carcinoma, Transitional Cell
;
Humans
;
Nephrectomy
;
Nephroureterectomy
;
Retrospective Studies
;
Treatment Outcome
;
Urologic Neoplasms
7.Effect of Shouwu Shudi Yin on dopaminegic neurons in MPTP induced Parkinson's disease mouse model.
Reginachizi TUNJE ; Yang-Lie YE ; Ahmed SONAUDDIN ; Bhugun HANSRAJ ; Sangye NGAWANG ; Sharma SHIVANI ; Xiong ZHANG ; Jian-Hong ZHU ; Rong-Pei LIU
China Journal of Chinese Materia Medica 2016;41(18):3439-3442
In order to investigate the effect of Shouwu Shudi Yin on dopaminegic neurons in MPTP induced Parkinson's disease mouse model and the possible mechamism, the experimental mice were randomly divided into 4 groups: control, Shouwu Shudi Yin, MPTP and the treatment (MPTP+Shouwu Shudi Yin) groups. The number of tyrosine hydroxylase (TH) positive cells in the substantia nigra was measured by immunohistochemistry, and mRNA expression of TH and glutathione peroxidase (GPX) were detected by PCR. The results showed that the number of TH positive cells and mRNA expression of TH were significantly reduced in MPTP group compared with the control (P<0.05), and pretreated with Shouwu Shudi Yin didn't show protective effect. Compared to MPTP group, the mRNA expression of four subtypes of GPX were increased in various degrees in the treatment group pretreated with Shouwu Shudi Yin, although the difference was not statistically significant. These indicated that the preventive medication of Shouwu Shudi Yin don't have protective effect on the mice with Parkinson' s disease induced by MPTP, but it may enhance the antioxidant capacity through increasing the expression of GPX.
8.Differentiation of mild from moderate liver fibrosis with 256-slice CT perfusion imaging
Yuefu ZHAN ; Xiong WANG ; Guang YANG ; Yueqiong CHENG ; Lie CHEN ; Shun TAN ; Jianqiang CHEN
Journal of Practical Radiology 2016;32(5):721-724
Objective To assess the value of CT perfusion imaging in differentiation of mild from moderate liver fibrosis .Methods 18 patients with mild liver fibrosis (F1 phase) and 21 ones with moderate fibrosis (F2 and F3 phase) confirmed by liver biopsy were analyzed ,and all patients underwent the liver 256‐slice CT perfusion imaging .The differences in the CT parameters including hepatic arterial perfusion (HAP) ,portal venous perfusion (PVP) ,total liver perfusion (TLP) and time to peak (TTP) between dif‐ferent fibrosis were analyzed .ROC curve was used to evaluate the ability of perfusion indexes to distinguish mild from moderate liver fibrosis ,then the maximum Youden index was selected as a cutoff point to calculate the sensitivity and specificity .Results Compared with the mild fibrosis ,the TTP [(43 .86 ± 13 .41)s vs (37 .84 ± 9 .97)s ,P=0 .034)] in liver with moderate fibrosis was significantly increased .However ,no differences in the HAP ,PVP and TLP were found .The ROC curve analysis showed that a TTP threshold of 41 .7 s allowed discrimination of mild from moderate fibrosis with a sensitivity of 72 .7% and a specificity of 75% .Conclusion 256‐slice CT perfusion imaging can reflect the hemodynamic changes of liver fibrosis ,and the TTP may help to discriminate mild from moderate fibrosis .
9.Combination of transrectal 125I seeds implantation brachytherapy and intermittent hormonal therapy for locally advanced prostate cancer.
Hao-Ming WU ; Jun LÜ ; Wei-Lie HU ; Jin-He ZHANG ; Wei WANG ; Yuan-Song XIAO ; Nan-Xiong WANG ; Jun-Wu RAN ; Xiao-Dong HUANG
National Journal of Andrology 2013;19(7):617-621
OBJECTIVETo evaluate the clinical efficacy of transrectal 125 I seeds implantation brachytherapy (BT) combined with intermittent hormonal therapy (IHT) in the treatment of locally advanced prostate cancer.
METHODSWe treated 27 patients with locally advanced prostate cancer by transrectal 125I seeds implantation BT combined with IHT, and dynamically observed the changes in the PSA level, prostate volume, maximum urinary flow rate (Qmax) and International Prostate Symptoms Score (IPSS).
RESULTSAll the implantation procedures were completed smoothly, lasting 20 to 35 minutes, with 40 to 58 seeds implanted. At 6 months after implantation, the PSA level was < 0.2 microg/L in all the patients (< 0.1 microg/L in 19 cases), the prostate volume was significantly reduced (P < 0.05), and Qmax and IPSS remarkably improved (P < 0.05). At 3 years after implantation, 19 cases were in the first cycle and the other 8 in the third cycle of IHT, of which 2 progressed to androgen-independent prostate cancer, and another 2 developed early bone metastasis. The rates of 3-year biochemically and clinically progression-free survival were 70.3% and 85.2%, respectively, and the rate of therapeutic effectiveness was 92.6%. No severe complications occurred in any of the cases.
CONCLUSIONTransrectal 125I seeds implantation BT combined with IHT is a safe and minimally invasive procedure for locally advanced prostate cancer, which can effectively retard its clinical progression with no such complications as severe urethral, rectal or erectile dysfunction.
Aged ; Brachytherapy ; Combined Modality Therapy ; Hormones ; therapeutic use ; Humans ; Iodine Radioisotopes ; administration & dosage ; therapeutic use ; Male ; Prostatic Neoplasms ; radiotherapy ; therapy ; Treatment Outcome
10.Comparation between modified coblation assisted uvulopalatopharyngoplasty and conventional uvulopalatopharyngoplasty in operative complication
Xiong CHEN ; Ying XIAO ; Lie-Chun HE ; Jia-Qi DONG ; Wei-Jia KONG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2012;47(2):101-106
Objective To compare the operative effectivity and incidence of postoperative complication between conventional uvulopalatopharyngoplasty (UPPP) and modified coblation assisted UPPP (M-CAUP) in treating patients with obstructive sleep apnea-hypopnea syndrome (OSAHS).And to explore the more effective,safer and minimally invasive operative method in surgical therapy of OSAHS.Methods It was a controlled trial.A retrospective analysis was made on surgical complications of conventional UPPP and of M-CAUP performed on OSAHS patients from 1995 to 2010.There were 451 patients in UPPP group and 323 patients in M-CAUP group.x2 test and Fisher's Exact test were used in statistical analysis.Results The incidence of serious surgical complications was higher in conventional UPPP group (3.77%,17/451) than that in M-CAUP group (0.62%,2/323),x2 =7.800,P < 0.01,while the incidence of short-term complications was higher in M-CAUP group (90.40%,292/323 ) than that in conventional UPPP group (60.98%,275/451),x2 =83.186,P < 0.01.The difference of long-term complications was not statistically significant between M-CAUP group and conventional UPPP group (P =0.1331,Fisher Exact test).There was no significant difference in incidence of asphyxia between M-CAUP group and conventional UPPP group (P < 0.01,Fisher Exact test).However,the incidence of post-operative primary hemorrhage was obviously lower in M-CAUP group than that in conventional UPPP group ( 3.99%,18/451 ),x2 =12.133,P < 0.01.While the incidence of delayed hemorrhage,temporal velopharyngeal insufficiency,and foreign body sensation at pharynx were higher in M-CAUP group (8.05%, 12.69%, 68.42%,respectively) than that in conventional UPPP group (3.77%,3.33%,51.00%,respectively) P <0.01,respectively.There was no significant difference in incidence of permanent velopharyngeal insufficiency,stenosis of nasopharynx and nasopharyngeal atresia,alteration of taste,throat itch and coughing.Conclusion Compared to the conventional UPPP,M-CAUP was more effective and safer in treating OSAHS with less severe complications during and after the operation.


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