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.Construction and validation of clinical prediction model of tongue base collapse under drug-induced sleep endoscopy in OSA patients
Shiming WANG ; Yinü DONG ; Yamin LIU ; Yanqing YE ; Jingmeng ZHOU ; Xiaoxing HUANG ; Huaihong CHEN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(8):837-843
Objective:To analyze the correlation between drug-induced sleep endoscopy (DISE), results, polysomnography (PSG) indicators, and clinical parameters in patients with obstructive sleep apnea (OSA), and to establish and validate a predictive model for tongue base plane obstruction.Methods:This retrospective study analyzed 117 OSA patients diagnosed via PSG and treated at the Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, between October 2014 and March 2022. The cohort comprised of 114 males and 3 females, with an age range of 20 to 54 years (mean age 38.1±8.4 years). Data on DISE results, PSG results, and clinical indicators were collected for all 117 patients. Logistic regression analysis was performed to identify relevant indicators, and a predictive model for tongue base plane obstruction was constructed and internally validated using the R programming language.Results:Univariate logistic regression analysis identified four independent risk factors for predicting tongue root plane obstruction: tonsil grading, N2, N3, and rapid eye movement sleep(REM) stage [ OR:0.412(0.260~0.652),1.045(1.012~1.079),0.943(0.903~0.984),0.961(0.925~0.998), P <0.05]. Multivariate logistic regression analysis confirmed tonsil grading and N3 sleep stage (12.48±12.22%) as significant predictors. A nomogram model incorporating these factors demonstrated good predictive performance, with an area under curve(AUC) of 0.82 (95% CI: 0.548-1.000), an optimal cutoff of 0.519, a specificity of 80.0%, and a sensitivity of 86.7%. Internal validation of the model in the validation cohort yielded an AUC of 0.751 (95% CI: 0.625-0.876). Conclusions:Tongue base plane obstruction observed during DISE in OSA patients is associated with tonsil grading and N3 sleep stage duration. The predictive model developed for tongue base plane obstruction based on DISE demonstrates good efficacy, as evidenced by its internal validation.
3.Angiomatoid fibrous histiocytoma:a clinicopathologic study of fourteen cases
Baofeng YANG ; Libing FU ; Nan ZHANG ; Xingfeng YAO ; Jiatong XU ; Xiaoxing GUAN ; Jianwen WANG ; Lejian HE
Chinese Journal of Clinical and Experimental Pathology 2024;40(8):818-823
Purpose To study the clinical and pathological features of angiomatoid fibrous histocytoma(AFH)and to ex-plore its diagnosis,differential diagnosis and prognosis.Meth-ods The clinicopathological and follow-up data were analyzed in 14 cases of AFH,and the literatures were reviewed.Results There were 11 males and 3 females.The age ranged from 11 months to 12 years and 11 months,with average 5.9 years.3 cases were located in limbs,and 5 cases in trunk,5 cases in head and neck region,and 1 of intracranial tumor.Histological-ly,14 cases were composed of fibrous capsules and lymphocyte sheaths,and cell nucleus were vacuolar,forming fascicles with focal whirling and synteny.Intralesional pseudoangiomatous spaces were noted in 9 cases.Calcification was found in 2 ca-ses.2 cases showed high mitotic acticity(11/10 HPF).Scle-rosing and/or myxoid stroma was seen in 3 cases.Tumors were immunopositive for desmin(10/14),EMA(12/14),CD99(12/14),SMA(9/12),ALK(7/8),and the average of Ki67 index was 16%.7 cases harbored EWSR1 rearrangenent(part-ner gene not identified),2 cases had EWSR1-ATF1 fusion and 2 EWSR1-CREB1 fusion.Clinical follow-up information was a-vailable for 14 cases(average 46 months).All the 14 cases were alive without recurrence and metastasis.Conclusion AFH is a borderline or low-grade malignant tumor,often demon-strates indolent behavior in children,but rarely recurs and me-tastasizes.The diagnosis and differential diagnosis require a comprehensive analysis of clinical features,histopathologic changes,immunohistochemical finding and EWSR1 or FUS gene detection results.
4.17β-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.
5.Correlation of 1p/16q loss of heterozygosity and 1p gain with clinicopathological characteristics and prognosis in Wilms tumor
Chao JIA ; Xingfeng YAO ; Meng ZHANG ; Xiaoxing GUAN ; Jianwen WANG ; Hongcheng SONG ; Lejian HE
Chinese Journal of Pathology 2024;53(3):257-263
Objective:To investigate the relationship between 1p/16q loss of heterozygosity (LOH) and 1p gain in Wilms tumor and their clinicopathologic characteristics and prognosis.Methods:A total of 175 Wilms tumor samples received from the Department of Pathology, Beijing Children′s Hospital from September 2019 to August 2022 were retrospectively analyzed. The histopathologic type and presence of lymph node involvement were evaluated by two pathologists. The clinical data including patients′gender, age, tumor location, preoperative chemotherapy, and tumor stage were summarized. Fluorescence in situ hybridization (FISH) was done to detect 1p/16q LOH and 1p gain and their correlation with the clinicopathological features and prognosis were analyzed.Results:Among the 175 samples, 86 cases (49.1%) were male and 89 (50.9%) were female. The mean age was (3.5±2.9) years, and the median age was 2.6 years. There were 26 (14.9%) cases with 1p LOH, 28 (16.0%) cases with 16q LOH, 10 (5.7%) cases of LOH at both 1p and 16q, and 53 (30.3%) cases with 1q gain. 1q gain was significantly associated with 1p LOH ( P<0.01) and 16q LOH ( P<0.01). There were significant differences ( P<0.01) between 1q gain, 1p LOH and 16q LOH among different age groups. The rate of 16q LOH in the high-risk histopathological subtype (50.0%) was significantly higher than that in the intermediate-risk subtype (13.6%, P<0.05). The frequency of 1q gain, 1p LOH, and 16q LOH in children with advanced clinical stages (Ⅲ and Ⅳ) was significantly higher than that in children with early clinical stages (Ⅰ and Ⅱ). 1q gain, 1p LOH, and 16q LOH showed no significant correlation with gender, unilateral or bilateral disease, chemotherapy, or lymph node metastasis. The progression-free survival (PFS) time for patients with 1q gain and 1p LOH was significantly shorter than those without these aberrations ( P<0.05). Additionally, the PFS time of patients with 16q LOH was slightly shorter than those with normal 16q, although the difference was not statistically significant. Patients with stage Ⅲ to Ⅳ disease exhibiting 1q gain or 1p LOH had a significantly higher relative risk of recurrence, metastasis, and mortality. Conclusions:1p/16q LOH and 1q gain are associated with age, high-risk histological type, and clinical stage in Wilms tumor. 1q gain and 1p LOH are significantly correlated with the prognosis of Wilms tumor.
6.Effect of ritodrine hydrochloride combined with magnesium sulfate on immune regulation function,sex hormone levels,and maternal-fetal outcomes in older second-child patients with threatened abortion
Lihong GUO ; Caifen WEI ; Fang WANG ; Xiaoxing SHA ; Hui DONG
Journal of China Medical University 2024;53(10):893-899
Objective To explore the effect of ritodrine hydrochloride combined with magnesium sulfate in the treatment of threatened abortion in older patients with a second child and to analyze its possible mechanism of action.Methods From March 2020 to December 2021,100 older second-child patients with threatened abortion at Handan Maternal and Child Health Hospital were selected and divided into control and observation groups using a random number table method,with 50 cases in each group.The control group was treated with magnesium sulfate based on general intervention measures(bed rest,intermittent oxygen inhalation,nutrition intake,and psychological nursing),while the observation group was treated with ritodrine hydrochloride combined with magnesium sulfate based on general inter-vention measures.The treatment effects,immunoregulatory function indicators[serum blocking antibody(BA)and anticardiolipin antibody(ACA)],sex hormone levels[progesterone(P),estradiol(E2),β-human chorionic gonadotropin(β-hCG)]and related cytokines[pregnan-cy-associated plasma protein A(PAPP-A),human leukocyte antigen G(HLA-G),and interleukin-10(IL-10)]before and after treatment,as well as maternal and infant outcomes and adverse reactions were compared.Results The total efficacy rate was higher in the observa-tion group than in the control group(96%vs.80%,P<0.05).Compared with before treatment,the serum BA-positivity rate significantly increased and the ACA-positivity rate significantly decreased in both groups after treatment(both P<0.05).However,after treatment the serum BA-positivity rate was higher in the observation group than in the control group,and the ACA-positivity rate was lower than that in the control group(both P<0.05).Compared with before treatment,the serum P,E2,β-hCG,PAPP-A,HLA-G,and IL-10 levels signifi-cantly increased at the end of treatment and 2 weeks after treatment in both groups.The levels of sex hormones and related cytokines in the observation group were higher than those in the control group at the end of treatment and two weeks after treatment(both P<0.05).The success rates of pregnancy maintenance,full-term delivery,and natural labor were higher in the observation group than in the control group;however,the incidences of abortion,premature delivery,cesarean section,and adverse neonatal outcomes were lower than those in the control group(all P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P<0.05).Conclusion The combination of ritodrine hydrochloride and magnesium sulfate has significant therapeutic effects in the treatment of threatened abortion in older women with a second pregnancy.It can improve maternal immune regulation,regulate sex hormone levels and PAPP-A,HLA-G,and IL-10 levels,reduce adverse maternal and fetal outcomes,and does not increase adverse reactions.
7.A Case of Senile Langerhans Cell Histiocytosis with Soft Tissue Mass as the Main Manifestation
Mingquan XING ; Weixia WU ; Xiaoxing SUN ; Qikai WANG ; Hao HAN ; Hongfeng GE
JOURNAL OF RARE DISEASES 2023;2(3):432-435
Langerhans cell histiocytosis (LCH) is a rare disease characterized by the proliferation of Langerhans cells and the destruction of local tissue. LCH large occurs in children, whilst incidence of the elderly population is extremely low, and there are few related studies. LCH lesions can involve multiple organs and systems, including bone tissue, lymph nodes, skin, liver, and spleen. However, it is rare that multiple soft tissues are implicated for eldly patients with LCH and present with soft tissue mass as the main manifestation. Here is a report on the clinical features, treatment and prognosis of an elderly LCH with multiple soft tissue masses as the main manifestation, in order to provide clinical reference.
8.Erratum: Author correction to "Coordinated regulation of BACH1 and mitochondrial metabolism through tumor targeted self-assembled nanoparticles for effective triple negative breast cancer combination therapy" Acta Pharmaceutica Sinica B 12 (2022) 3934-3951.
Xuan YANG ; Yalong WANG ; Junke ZHAO ; Hehui RONG ; Yujun CHEN ; Mengting XIONG ; Xiaoxing YE ; Shihui YU ; Haiyan HU
Acta Pharmaceutica Sinica B 2023;13(11):4661-4663
[This corrects the article DOI: 10.1016/j.apsb.2022.06.009.].
9.Revision and reliability and validity testing of the Arteriovenous Fistula Assessment Scale
Jinhong MIAO ; Ruoyu CAI ; Yutian LEI ; Xiaoxing WANG ; Kankan WANG ; Xiaoya ZHANG
Chinese Journal of Practical Nursing 2023;39(27):2127-2132
Objective:To translate and revise the Arteriovenous Fistula Assessment Scale (AVF-AS), test the reliability and validity of the Chinese version of AVF-AS.Methods:The modified Brislin translation model was used to translate, back translate and cross culture adjust AVF-AS, forming the Chinese version of AVF-AS. Using the convenient sampling method, 220 hemodialysis patients from the First Affiliated Hospital of Zhengzhou University were selected for investigation from July to September 2022. Two weeks later, 30 patients were randomly selected for retesting. The valid data were used for project analysis and reliability and validity evaluation.Results:The Chinese version of AVF-AS consisted of 3 factors and 18 items. Consistency level between evaluators was 0.94, the item level content validity index was 0.83-1.00, average scale level content validity index was 0.94, and the calibration validity was 0.68.Three common factors(autogenous arteriovenous fistula blood flow, stenosis and ischemia, puncture location) were extracted from exploratory factors, and the cumulative variance contribution rate was 75.255%. The total scale's Cronbach α was 0.946, the half reliability of each dimension was 0.826 - 0.898, and the test-retest reliability was 0.907.Conclusions:The Chinese version of AVF-AS has good reliability and validity, and can be used as an effective tool to evaluate the autogenous arteriovenous fistula functional status of hemodialysis patients in China.
10.The impact of " staging" hybrid coronary artery revascularization on the short-and long-term efficacy of patients with multiple coronary artery lesions
Mei JIN ; Qingbo QIAO ; Shuang GAO ; Jingwen ZHAO ; Xiaoxing ZHANG ; Xiaofeng CHEN ; Youyu WANG
Journal of Chinese Physician 2023;25(10):1511-1515
Objective:To investigate the impact of " staging" hybrid coronary artery revascularization (HCR) on the short-and long-term efficacy of patients with multiple coronary artery lesions.Methods:A retrospective case-control study was conducted. Eighty patients with multiple coronary artery lesions admitted to the Baoding Second Central Hospital from January 2017 to October 2018 were selected and divided into two groups according to different surgical methods. Forty patients were treated with " staging" HCR and were designated as the HCR group, and 40 patients were treated with off-pump coronary artery bypass grafting (OPCAB) and were designated as the OPCAB group. The perioperative related indicators and perioperative serious complications were compared between the two groups. The serum myocardial injury marker levels were detected preoperatively and 48 hours postoperatively, including heart-type fatty acid binding protein (H-FABP) and troponin I (cTnI). All subjects were followed up for at least 3 years to calculate the incidence of major adverse cardiovascular and cerebrovascular events (MACCE).Results:The bypass surgery time, mechanical ventilation time, ICU stay time, and total hospital stay time in the HCR group were all less than those in the OPCAB group (all P<0.05), and the incision length in the HCR group was shorter than that in the OPCAB group ( P<0.05). The intraoperative bleeding volume, postoperative 24-hour drainage volume, red blood cell transfusion volume, and plasma transfusion volume in the HCR group were all less than those in the OPCAB group (all P<0.05). Forty-eight hours after surgery, the serum H-FABP and cTnI levels in both groups were significantly higher than those preoperatively (all P<0.05), but the increase was more significant in the OPCAB group (all P<0.05). The perioperative serious complication rate in the HCR group was 2.50%(1/40), which was significantly lower than that in the OPCAB group [20.00%(8/40)] ( P<0.05). During the 3-year follow-up after surgery, the MACCE incidence in the HCR group was 12.50%(5/40), and that in the OPCAB group was 22.50%(9/40). There was no significant difference in the long-term MACCE incidence between the two groups ( P>0.05). Conclusions:" Staging" HCR treatment for multiple coronary artery lesions can achieve ideal surgical results. Compared with OPCAB, its short-term efficacy is more significant, and long-term efficacy is equivalent.

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