1.Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation
Tingting YANG ; Jiayu YUAN ; Yuting PENG ; Jiale PANG ; Zhen QIU ; Shangxiu CHEN ; Yuhan HUANG ; Zhenzhou JIANG ; Yilin FAN ; Junjie LIU ; Tao WANG ; Xueyan ZHOU ; Sitong QIAN ; Jinfang SONG ; Yi XU ; Qian LU ; Xiaoxing YIN
Journal of Pharmaceutical Analysis 2024;14(1):52-68
The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.
2.Intervention effect of "Internet plus" postpartum health care service on postpartum depression
Jinfang YUAN ; Jun LYU ; Jinmei QIN ; Jian YANG ; Xiaofang XU
Shanghai Journal of Preventive Medicine 2024;36(9):899-903
ObjectiveTo explore the influence of "Internet plus" postpartum health care service on postpartum depression, and to provide an evidence for reducing the incidence of postpartum depression and improving the quality of life for postnatal women. MethodsMothers who gave birth between August 1, 2021 and June 30, 2023 lived in the six streets of Xuhui District were selected as the research subjects. The puerperants were randomly divided into the intervention group and the control group according to the order of enrollment using a numerical numbering system, with 210 cases in each of the intervention group and control group. The intervention group adopted the "Internet plus" postpartum health care services, while the control group adopted the conventional postpartum health care services. The risk factors related to postpartum mental health and the incidence of postpartum depression were compared between the two groups. ResultsThere was no statistically significant difference in the scores of postpartum mental health-related risk factors between the two groups at the first 2 weeks and 1st month after delivery (t=0.736 and t=1.260, P>0.05). However, there was a statistically significant difference in the scores of postpartum mental health-related risk factors at the 3rd months after delivery and 6th months after delivery (t=2.089, P<0.05; t=2.655, P<0.05). There was no statistically significant difference in depression scores at the first 2 weeks after the birth (t=0.560, P>0.05). In the 1st month, the 3rd month and the 6th month after delivery, the intervention group adopted the "Internet plus" postpartum health care service, thus the differences in depression scores were statistically significant (t=2.616, t=2.793 and t=3.107, P<0.05). Conclusion"Internet plus" postpartum health care service is conducive to reducing postpartum depression, promoting maternal mental health, and significantly improving the well-being of postnatal women.
3.17β-Estradiol,through activating the G protein-coupled estrogen receptor,exacerbates the complication of benign prostatic hyperplasia in type 2 diabetes mellitus patients by inducing prostate proliferation
Yang TINGTING ; Qiu ZHEN ; Shen JIAMING ; He YUTIAN ; Yin LONGXIANG ; Chen LI ; Yuan JIAYU ; Liu JUNJIE ; Wang TAO ; Jiang ZHENZHOU ; Ying CHANGJIANG ; Qian SITONG ; Song JINFANG ; Yin XIAOXING ; Lu QIAN
Journal of Pharmaceutical Analysis 2024;14(9):1372-1386
Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.
4.Application of urinary luteinizing hormone in the prediction of central precocious pu-berty in girls
Jinfang YUAN ; Xinli WANG ; Yunpu CUI ; Xuemei WANG
Journal of Peking University(Health Sciences) 2024;56(5):788-793
Objective:To evaluate the level of first morning voided(FMV)urinary luteinizing hor-mone(LH)in girls with breast development,and to determine the value of FMV urine LH in the evalua-tion of central precocious puberty(CPP).Methods:From September 2018 to April 2021,among the patients who were admitted to the Department of Pediatrics of Peking University Third Hospital for"pre-cocious puberty"and underwent gonadotropin-releasing hormone(GnRH)stimulation test,a total of 108 girls were enrolled.According to CPP diagnostic criteria,they were divided into CPP group(n=45)and non-CPP group(n=63).The clinical characteristics and hormone levels of the two groups were com-pared.Receiver operating characteristic(ROC)curve was used to analyze the cut-off value of FMV uri-nary LH in the diagnosis of CPP in girls.Further analyses were done to evaluate the value of FMV urinary LH in the diagnosis of CPP using correlation analysis between urinary LH level and common clinical cha-racteristics.Results:ROC curve analysis showed that FMV urine LH level was significant for the diagno-sis of CPP.The cut-off value of FMV urine LH was 0.69 IU/L(specificity 56.9%,sensitivity 85.0%,area under curve 0.804,P<0.001).The basic clinical characteristics without GnRH stimulation test were analyzed by binary Logistic regression analysis,indicating that the level of FMV urine LH,uterine volume,ovarian volume and advanced T-bone age had predictive significance for CPP diagnosis in girls(OR values were 2.125,1.961,1.564 and 2.672,respectively).The prediction model was established and the area under the ROC curve was 0.904,P<0.001.The level of FMV urine LH was positively cor-related with the levels of serum LH,FSH and estrogen before GnRH stimulation test,the peak value of blood LH after GnRH stimulation test,T bone age and uterine volume,with r values of 0.462,0.373,0.242,0.360,0.373 and 0.263,respectively,and P values were<0.001,<0.001,0.013,<0.001,<0.001 and 0.007,respectively.Conclusion:FMV urine LH can provide a good indication for the diagnosis of CPP.Combining with bone age advanced level and pelvic ultrasound measurement,the pre-dictive value of FMV urine LH can be further improved for the diagnosis of CPP in girls.
5.Effect of timing of immune checkpoint inhibitor monotherapy and application of hormone on the efficacy and safety of brain metastasis in advanced non-small cell lung cancer: a Meta-analysis
Binbin SHAN ; Jinfang ZHAI ; Hongwei LI ; Xiaoqin AN ; Chang ZHAO ; Qiao HAN ; Yuan LI ; Weihua YANG
Cancer Research and Clinic 2022;34(7):529-536
Objective:To evaluate the efficacy and safety of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1) immune checkpoint inhibitor (ICI) monotherapy for brain metastasis in advanced non-small cell lung cancer (NSCLC), and to explore the timing of immunomonotherapy and the application of hormone on the efficacy of ICI.Methods:By searching literature in CNKI, Wanfang, VIP, PubMed, CBM, Embase, Cochrane Library and Web of Science databases, the advanced NSCLC patients with brain metastasis who received ICI treatment were identified, including patients with symptomatic brain metastasis who had received hormone therapy or brain surgery or radiotherapy. Meta-analysis was performed on the collected data to evaluate the systemic objective response rate (sORR) and intracerebral tumor objective response rate (iORR), the iORR of whether ICI monotherapy was first-line therapy, and the iORR of whether hormone was used were evaluated, and the incidence of adverse reactions was evaluated.Results:Fifteen studies were finally included, with a total of 4 033 patients, including 917 patients with brain metastasis. The iORR of immunomonotherapy was 26% (95% CI 19%-34%) and the sORR was 28% (95% CI 18%-40%). The iORR of first-line immunomonotherapy was 49% (95% CI 39%-58%). The iORR of symptomatic patients with hormone therapy and asymptomatic patients without hormone therapy was 26% (95% CI 20%-33%) and 19% (95% CI 16%-22%), respectively. The overall incidence of grade 3-4 adverse reactions was 14% (95% CI 11%-17%). Conclusions:The efficacy of ICI monotherapy in the first-line treatment of PD-L1-positive NSCLC patients with brain metastasis is better than that in the subsequent line therapy, and the application of hormone does not affect the efficacy of ICI. ICI monotherapy in the treatment of advanced NSCLC patients with brain metastasis is safe.
6.Incidence and related influencing factors of parturients with postpartum depression in Xuhui District, Shanghai
Jinfang YUAN ; Jun LYU ; Jinmei QIN ; Jian YANG ; Bo YANG ; Xiaofang XU
Shanghai Journal of Preventive Medicine 2022;34(10):965-972
ObjectiveTo understand the occurrence of postpartum depression among puerperae in six communities in Xuhui District, Shanghai, and to analyze the related influencing factors of postpartum depression, so as to provide evidence for corresponding intervention measures. MethodsA total of 476 puerperae who gave birth from August 1, 2021 to February 28, 2022 in 6 communities in Xuhui District were selected as the survey subjects. They filled out a general situation questionnaire, Edinburgh Postpartum Depression Scale (EPDS) and a questionnaire on related influencing factors. Univariate and multivariate unconditional logistic regression analysis was conducted on the related influencing factors of postpartum depression. ResultsAccording to the EPDS score, 72 of the 476 puerperae in Xuhui District developed postpartum depression, and the incidence of postpartum depression was 15.13%. Multivariate unconditional logistic regression analysis showed that maternal introversion (OR=2.845, 95%CI:1.033‒7.842), artificial feeding (OR=11.448,95%CI:2.438‒53.767), postpartum insomnia (OR=2.559, 95%CI:1.244‒5.262), lack of postpartum parenting experience (OR=2.324,95%CI:1.121‒4.820), and family members caring about the gender of the child (OR=4.415, 95%CI:1.500‒12.994) were independent risk factors of postpartum depression, while the spouse being an only child(OR=0.434, 95%CI:0.224‒0.840) was a protective factor for postpartum depression. ConclusionPostpartum depression in Xuhui District is affected by many factors. Screening and intervention of high-risk groups should be strengthened to reduce the incidence of postpartum depression.
7.Neonatal and long-term outcomes of selective fetal growth restricted fetuses
Ruiyan SHANG ; Yuan WEI ; Jing YANG ; Yangyu ZHAO ; Jinfang YUAN ; Tianchen WU ; Xiaoyan YOU ; Pengbo YUAN ; Li LI
Chinese Journal of Perinatal Medicine 2022;25(12):933-941
Objective:To investigate the short- and long-term outcomes of fetuses with selective fetal growth restriction (sFGR).Methods:A retrospective study was conducted on monochorionic diamniotic (MCDA) twins with sFGR admitted to the Neonatal Intensive Care Unit of Peking University Third Hospital from September 2017 to December 2019. MCDA neonates delivered during the same period without significant complications were selected as the control group. MCDA twins with sFGR were divided into type Ⅰ, Ⅱ, and Ⅲ groups and then further divided into the larger and the smaller fetus subgroups according to the birth weight. These children were followed up by telephone at 2-3 years old. Height-for-age and weight-for-age Z-scores were calculated. Ages and Stages Questionnaire-Third Edition (ASQ-3) was used to determine comprehensive development. Independent sample t-test, one-way analysis of variance, non-parameter test, and Chi-square test (or rank-sum test) were used for statistical analysis. Results:(1) A total of 116 pregnant women with sFGR (232 neonates) were enrolled in this study. There were 43, 40, and 33 mothers and 86, 80, and 66 newborns in type Ⅰ, Ⅱ, and Ⅲ groups, respectively. The control group included 31 pregnant women and 62 neonates. The gestational age at onset of sFGR was younger in the type Ⅱ and Ⅲ groups than in type Ⅰ group [(23.8±4.8) and (24.1±3.1) vs (27.0±6.1) weeks, F=5.19, P<0.05; all P<0.017 during pairwise comparisons]. (2) The incidence of sepsis and treatment abandonment/death in neonates in type Ⅱ and Ⅲ groups were higher than those in type Ⅰ and control groups [neonatal sepsis: 11.3% (9/80) and 6.1% (4/66) vs 2.3% (2/86) and 0.0% (0/62), χ2=6.30, P=0.001; death or treatment abandonment rate:13.8% (11/80) and 10.6% (7/66) vs 3.5% (3/86) and 0.0% (0/62), χ2=4.68, P=0.003; all P<0.017 during pairwise comparisons]. In cases with type Ⅱ or type Ⅲ sFGR, the risk of digestive system diseases was significantly higher in the smaller fetus group than in the larger fetus group [type Ⅱ: 46.2% (37/80) vs 38.7% (31/80), χ2=16.72; type Ⅲ: 47.0% (31/66) vs 34.8% (23/66), χ2=39.69; both P<0.001], while the rate of respiratory system diseases was lower in the smaller fetus group [type Ⅱ: 35.0% (28/80) vs 45.0% (36/80), χ2=36.85; type Ⅲ: 37.9% (25/66) vs 45.4% (30/66), χ2=12.55; both P<0.001]. The incidence of neonatal sepsis in smaller fetuses was higher than that in larger ones in type Ⅱ sFGR [7.5% (6/80) vs 3.7% (3/80), χ2=4.68, P=0.034]. The incidence of neurological complications in larger fetuses was higher than that in smaller ones in type Ⅲ sFGR [15.1% (10/66) vs 4.5% (3/66), χ2=5.72, P<0.001]. (3) In type Ⅱ group, seven neonates died (one case of cerebral hemorrhage, two cases of gastrointestinal perforation, two cases of septic shock, and two cases of necrotizing enterocolitis), and four cases withdrew the treatment. In type Ⅲ group, four neonates died (two cases of necrotizing enterocolitis, one case of gastrointestinal perforation, and one case of cerebral hemorrhage), and three cases withdrew from the treatment. (4) Totally, 71 children in type Ⅰ, 61 in type Ⅱ, and 58 in type Ⅲ group were followed up at the age of 2-3. Children with type Ⅱ or type Ⅲ sFGR lagged behind those in type Ⅰ group and control group in physical growth [ M ( P25- P75), Z-scores:-0.46 (-0.87-0.42),-0.35 (-0.62-0.71), 0.05 (-0.61-0.51), and 0.14 (-0.57-0.75); H=6.20, P=0.001]. In type Ⅱ and Ⅲ groups, the smaller fetuses lagged the larger fetuses in physical growth at 2-3 years of age. ASQ-3 scores in communication, gross motor, fine motor, problem-solving and personal-social areas were all lower in type Ⅱ and Ⅲ groups than in type Ⅰ and control groups. ASQ-3 scores in the five dimensions of the smaller fetuses in the type Ⅱ group were lower than those of the larger fetuses. In the type Ⅲ group, the smaller fetuses had lower ASQ-3 scores in communication and gross motor than the larger ones [communication ability: (42.6±18.8) vs (56.4±9.4) scores, t=19.63, P<0.001; gross motor: (45.5±19.7) vs (54.5±9.7) scores, t=12.64, P=0.003]. Conclusion:The neonatal morbidity is significantly increased in type Ⅱ and Ⅲ sFGR, and babies lagged others in height, weight, and ASQ-3 score at 2-3, which is worthy of early attention.
8. Pathophysiologic mechanism of CMTM5 low expression in multiple myeloma progression
Yuan MA ; Jinfang SHI ; Huiying QIU ; Jing YUAN ; Yang ZHANG ; Peng ZHOU ; Jingjing XU ; Qingzhen HAN
Chinese Journal of Hematology 2019;40(1):58-62
Objective:
To investigate the mechanism of chemokine-like factor superfamily member (CMTM) 5 on the proliferation of multiple myeloma cells.
Methods:
RT-qPCR method was used to detect the expression and correlation of CMTM5, caspase3 and caspase9 in U266 after decitabine demethylation treatment; U266 transfected with pcDNA3.1 plasmid overexpressed CMTM5, then cell proliferation activity was detected by CCK-8 assay.
Results:
Compared with the control group, the low-dose demethylation treatment increased mRNA expression of CMTM5, caspase3, and caspase9 in U266, and showed a time-dependent (
9. Study progress of chorioamnionitis and lung disease in preterm infants
Chinese Journal of Applied Clinical Pediatrics 2019;34(10):794-796
Preterm birth is a major cause of perinatal mortality and long-term morbidity, chorioamnionitis (CAM) is a common cause of preterm birth and characterized by inflammation.CAM produces variety of inflammatory factors in fetal, results in structural and functional impairment, and affects the contractile function of pulmonary blood vessels, so, CAM can have impact on the morbidity of lung disease in premature, and it may even affect the long-term pulmonary function.
10.Bilateral mandibular second molar impaction with paradental cyst:A case report and literature review
Jing LI ; Yuan LI ; Jinfang XIE ; Wentao GENG ; Xuebin GAO ; Na WANG ; Yingli ZHANG
Journal of Jilin University(Medicine Edition) 2017;43(2):422-424
Objective:To explore the etiology and treatment of one case of bilateral mandibular second molar impaction with paradental cyst, and to provide a reference for its diagnosis and treatment. Methods:Root canal treatment of the left mandibular first molar of the patient was performed before operation.The left mandibular second molar of the patient was removed;the residual dental follicle, the granulation tissue and the cyst wall were stroken off under local anesthesia.The diamond ball was used to polish the wound cavity and sharp bone edge, and to mill the distal apical part of left mandibular first molar.The tissue removed during the procedure was used for the pathological examination.Results:The X-ray image showed that the bilateral mandibular second molar was impacted with the left mandibular first molar root's absorption, and there was a clear round-like density reduction zone around the second molar crown.The pathologic result was paradental cyst.Conclusion:Dental impaction complicated with paradental cyst could occur in other tooth position except for the third molar.Its diagnosis should be combined with the clinical manifestations, the pathologic manifestations and the medical imaging.Multidisciplinary consultation is in favor of its diagnosis and treatment.

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