BACKGROUNDEstrogen deficiency causes atrophic changes within the urogenital tract, and is associated with urinary symptoms. The purpose of this study was to investigate the effects of estrogen and tibolone on bladder histology, and the changes of estrogen receptor alpha and beta (ERalpha and beta) protein expression in the detrusor muscle.

METHODSForty female rats were separated into four groups of ten each. They received a sham operation (Sham), ovariectomy (Ovx), ovariectomy plus estrogen replacement (Ovx + E), or ovariectomy plus tibolone treatment (Ovx + T). After 12 weeks each rat was anesthetized and the bladders were removed. The bladders' ultra structure, collagen fiber (CF) to smooth muscle (SM) ratio and ER subtypes were studied. Statistical analyses were performed using the one-way analysis of variance test.

RESULTSOvx resulted in significant degeneration in bladder ultra structure; however, estrogen and tibolone reversed those changes. Ovx increased the CF/SM ratio, estrogen and tibolone resulted in an increase. Two estrogen receptors (ERs) were expressed in the bladder detrusor, with ERbeta the main subtype. Ovx resulted in up-regulation of ERalpha and down-regulation of ERbeta. With estrogen and tibolone treatment, ERbeta showed a significant increase but ERalpha showed no significant difference compared with Ovx.

CONCLUSIONSEstrogen deficiency deteriorates bladder ultra structure and histology. Supplementary estrogen can improve bladder function which may be due to inhibition of collagen hyperplasia and increased SM density. ERbeta has an important role in mediating estrogen function in the bladder. Tibolone has a mild estrogenic action and has an effect on bladder function and structure to some degree.

Animals ; Estrogen Receptor Modulators ; pharmacology ; Estrogens ; pharmacology ; Female ; Immunohistochemistry ; Microscopy, Electron, Transmission ; Norpregnenes ; pharmacology ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Receptors, Estrogen ; metabolism ; Urinary Bladder ; drug effects ; metabolism ; ultrastructure

OBJECTIVETo study the impact of the chloride channel dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) on the cytoskeleton of Sertoli cells in the mouse.

METHODSTM4 Sertoli cells were cultured and treated with CFTR(inh)-172 at the concentrations of 1, 5, 10 and 20 μmol/L for 48 hours. Then the cytotoxicity of CFT(inh)-172 was assessed by CCK-8 assay, the expressions of F-actin and Ac-tub in the TM4 Sertoli cells detected by immunofluorescence assay, and those of N-cadherin, vimentin and vinculin determined by qPCR.

RESULTSCFTR(inh)-172 produced cytotoxicity to the TM4 Sertoli cells at the concentration of 20 μmol/L. The expressions of F-actin and Ac-tub were decreased gradually in the TM4 Sertoli cells with the prolonging of treatment time and increasing concentration of CFTR(inh)-172 (P < 0.05). The results of qPCR showed that different concentrations of CFTR(inh)-172 worked no significant influence on the mRNA expressions of N-cadherin, vimentin and vinculin in the Sertoli cells.

CONCLUSIONThe CFTR chloride channel plays an important role in maintaining the normal cytoskeleton of Sertoli cells. The reduced function and expression of the CFTR chloride channel may affect the function of Sertoli cells and consequently spermatogenesis of the testis.

Actins ; metabolism ; Animals ; Benzoates ; pharmacology ; Chloride Channels ; physiology ; Cystic Fibrosis Transmembrane Conductance Regulator ; antagonists & inhibitors ; Cytoskeleton ; drug effects ; Male ; Mice ; Sertoli Cells ; drug effects ; metabolism ; Spermatogenesis ; Thiazolidines ; pharmacology ; Time Factors

Objective To investigate the possibility of neutrophil-to-lymphocyte ratio (NLR),platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) as biomarker for early atherosclerosis in patients with newly diagnosed type 2 diabetes.Methods 420 newly diagnosed type 2 diabetes were enrolled in the study.They were divided into three groups:patients with normal carotid artery were group A (n =152),patients with unilateral carotid plaque were group B (n =138),patients with bilateral carotid plaque were group C (n =130).Their neutrophil,lymphocyte,mean platelet volume,lipid and glucose,carotid intimal medial thickness (CIMT),ankle brachial index (ABI) were all performed in these individuals.Results Compared with group A,the age,systolic pressure,neutrophil count (NC),platelet count (PLT),NLR,PLR,low density lipoprotein-cholesterol (LDL-C),total cholesterol (TC),fasting blood glucose (FBG),hemoglobin A1c (HbA1c) and CIMT were higher while ABI were lower in group B and group C;Compared with group B,the age,systolic pressure,NC,PLT,NLR,PLR,LDL-C,TC,CIMT and were higher while ABI was lower in group C (P ＜ 0.05).CIMT was positively correlated to age,systolic pressure,NLR,PLR,LDL-C,TC,FBG and HbA1c (P ＜ 0.05) while ABI was negtively correlated to age,NLR,PLR,LDL-C,FBG and HbA1c (P ＜ 0.05).In multiple linear regression analyses,after adjustment for age,lipid,glucose and so on,NLR and PLR were also significantly correlated to CIMT and ABI.Conclusions NLR and PLR were significantly correlated with CIMT and ABI in newly diagnosed type 2 diabetes.Therefore,NLR and PLR may have the potential to serve as biomarkers for early arteriosclerosis in type 2 diabetic patients.

Objective To study the value of Lp (a) in risk assessment of patients with NSTE-ACS.Methods Eighty NSTE-ACS patients were divided into elderly NSTE-ACS group (n=58) and non elderly NSTE-ACS group (n=22) with 22 elderly patients with their coronary artery stenosis ＜ 50％ served as a control group.The relationship of serum Lp (a) level with Gensini score and GRACE risk score was analyzed.Results The incidence of hypertension and DM was significantly higher,the smoking history was significantly longer,the serum LDL-C and FBG level,Gensini score and GRACE risk score were significantly higher in elderly NSTE-ACS group than in control group (P＜0.05).The age was significantly older and the GRACE risk score was significantly higher in elderly NSTE-ACS group than in non elderly NSTE-ACS group (P＜0.05).The Gensini score and GRACE risk score were positively related wtih the serum Lp (a) level (r=0.494,P＜ 0.01;r=0.432,P＜0.01).Serum Lp (a) level was an independent risk factor for NSTE-ACS (P＜0.01).Conclusion Serum Lp (a) level is closely related with the severity and outcome of NSTE-ACS,indicating that serum Lp (a) level can be used as a predictor of risk assessment in NSTE-ACS patients.

OBJECTIVETo evaluate the efficacy of iloprost in acute vasodilatation test during cardiac catheterization and to explore a useful hemodynamic indication regarding operability in the patients with severe pulmonary hypertension (PH) related to congenital heart disease (CHD).

METHODSThe clinical data of 46 patients [mean age (12 ± 9) years] with severe PH related to CHD from June 2006 to December 2008 was retrospectively analyzed. All patients underwent standard right and left cardiac catheterization and a trial of inhaled iloprost test during cardiac catheterization. The mean pulmonary arterial pressure was (80 ± 13) mm Hg (1 mm Hg = 0.133 kPa) and pulmonary vascular resistance index was (17 ± 10) wood.m². A positive response to inhaled iloprost was defined as a decrease of at least 20% in pulmonary vascular resistance index (PVRI) without changes on systemic artery pressure. Patients with positive response to iloprost underwent cardiac surgical repair. The pulmonary artery pressure and PVRI was monitored by Swan-Ganz catheter postoperatively.

RESULTSOf the 46 patients, 29 (63.1%) showed a positive response after iloprost inhalation, defined by a significant reduction in PVRI from (15 ± 6) wood.m(2) at baseline to (9 ± 4) wood.m² in response to iloprost inhalation therapy (P < 0.05). The ratio of pulmonary to systemic resistance (Rp/Rs) decreased from 0.7 ± 0.2 to 0.4 ± 0.2 (P < 0.05). Seventeen patients (36.9%) didn't respond to iloprost displayed only little changes in PVRI [from (21 ± 10) wood.m(2) to (19 ± 9) wood.m²] and Rp/Rs (from 1.0 ± 0.5 to 0.9 ± 0.5). Out of 29 positive patients, 21 (72%) underwent successful cardiac surgical repair with a reduction of mean pulmonary arterial pressure (mPAP) to an average of (27 ± 10) mm Hg after the operation. Only 2 patients out of the 17 patients from the negative group were referred to surgery. Their mPAP was greater than 45 mm Hg.

CONCLUSIONSA significant reduction in pulmonary artery pressure after cardiac surgery was observed in patients with positive response to inhaled iloprost. Inhaled iloprost may be a valuable tool in the preoperative evaluation of patients with severe PH related to CHD.

Administration, Inhalation ; Adolescent ; Child ; Child, Preschool ; Female ; Heart Defects, Congenital ; physiopathology ; surgery ; Hemodynamics ; drug effects ; Humans ; Hypertension, Pulmonary ; physiopathology ; surgery ; Iloprost ; pharmacology ; Infant ; Lung ; blood supply ; Male ; Preoperative Care ; Retrospective Studies ; Vasodilator Agents ; pharmacology ; Young Adult

OBJECTIVETo evaluate the clinical effects of Chinese medicine (CM) on acute myocardial infarction (AMI) with a prospective cohort study.

METHODSA total of 334 AMI patients from January 2007 to March 2009 were consecutively enrolled, and were assigned to a treatment group (169 cases) treated with combined therapy (CM for at least one month and Western medicine) and a control group (165 cases) with Western medicine alone. Clinical data including age, gender, smoking, medical history, infarction area, heart functional classification, CM syndrome scores, blood-stasis syndrome score, primary end-point (death, nonfatal myocardial infarction, and revascularization) and secondary end-point (ischemic stroke, rehospitalization due to angina, heart failure and shock), were collected. CM syndrome scores, blood-stasis syndrome score, primary end-point and secondary end-point were collected during the 6-month follow-up. Kaplan-Meier method was used for the survival analysis. The multifactor analysis was analyzed by Cox proportional hazards regression.

RESULTSAt the end of 6-month the CM syndrome score and bloodstasis syndrome score in the treatment group were lower than those in the control group (P<0.01), especially the symptoms of chest pain, spontaneous perspiration and insomnia. Rehospitalization rate due to angina during the 6-month follow-up in the treatment group (2.96%) was lower than that in the control group (7.88%, P<0.05). Kaplan- Meier survival curve showed that event-free cumulated survival of rehospitalization due to angina during the 6-month follow-up in the treatment group was higher than that in the control group (Log rank 4.700, P=0.03). Cox regression analysis showed that heart dysfunction [hazard ratio (HR)=1.601, 95% CI=1.084-2.364, P=0.018] and diabetes mellitus (HR=1.755, 95% CI=1.031-2.989, P=0.038) were hazard factors to end-point, whereas CM (HR 0.405, 95% CI=0.231-0.712, P=0.002), percutaneous coronary intervention (PCI, HR=0.352, 95% CI=0.204-0.607, P<0.001) and angiotensin converting enzyme (ACE) inhibitors (HR=0.541, 95% CI=0.313-0.936, P=0.028) were protective factors.

CONCLUSIONSCM therapy could decrease CM syndrome scores and blood-stasis syndrome score, reduce the rehospitalization rate during 6-month follow-up due to angina. Heart dysfunction and diabetes mellitus were hazard factors to end-point, whereas CM, PCI and ACE inhibitors were protective factors.

Adult ; Aged ; Case-Control Studies ; Cohort Studies ; Female ; Hematologic Diseases ; complications ; epidemiology ; Hospitalization ; statistics & numerical data ; Humans ; Male ; Medicine, Chinese Traditional ; adverse effects ; methods ; Middle Aged ; Myocardial Infarction ; complications ; epidemiology ; therapy ; Prospective Studies ; Research Design ; Syndrome ; Treatment Outcome

Objective:To verify the clinical efficacy and safety of Qufeng Tongxuan method in treating low- and moderate-volume intracerebral hemorrhage at acute stage.Methods:A prospective, multicenter, randomized, double-blind, placebo-controlled study was performed; patients with low- and moderate-volume intracerebral hemorrhage at the basal ganglia and/or thalamus accepted treatment in 16 hospitals from September 2019 to April 2022 were enrolled. These patients were divided into experimental and control groups with a block randomized method by SAS software. Patients in control group were given conventional western medicine treatment; those in experimental group accepted Qufeng Tongxuan method (sequential therapy of Shexiang Huayu Xingnao granules and Zhilong Huoxue Tongyu granules) besides conventional western medicine treatment. NIHSS was used to assess neurological function before treatment and on 7 th, 14 th, 30 th, and 90 th d of treatment. Prognoses of these patients were assessed by modified Rankin scale (mRS) before treatment and on 180 th d of treatment. Brain CT was performed before treatment and on 7 th and 14 th d of treatment to calculate the hematoma volume. Before treatment and on 14 th d of treatment, changes of coagulation function, liver and kidney functions of the 2 groups were compared. Adverse reactions during treatment in the 2 groups were recorded. Results:No significant differences in NIHSS scores were noted between the 2 groups before treatment, on 7 th, 14 th, and 30 th d of treatment ( P>0.05); NIHSS scores in experimental group on 90 th d of treatment were signficantly lower than those in control group ( P<0.05); NIHSS scores in experimental group decreased gradually before treatment and on 7 th, 14 th, 30 th and 90 th d of treatment, with statistical significances ( P<0.05). No significant differences in mRS scores were noted between the 2 groups before treatment ( P>0.05); mRS scores in experimental group on 180 th d of treatment were signfciantly lower than those in control group ( P<0.05). No significant difference in hematoma volume was noted between the 2 groups before treatment and on 7 th and 14 th d of treatment ( P>0.05); both groups had gradually decreased hematoma volumes before treatment and on 7 th and 14 th d of treatment, respectively, with significant differences ( P<0.05); the volume difference of hematoma between 14 th d of treatment and before treatment in experimental group (6.42[4.10, 11.73]) was significantly higher than that in control group (4.00[1.25, 10.58], P<0.05). No significant differences in liver and kidney function indexes or coagulation function indexes were noted between the 2 groups before treatment and on 14 th d of treatment ( P>0.05). Adverse reaction incidence was 9.52% ( n=12) in experimental group and 10.34% ( n=12) in control group, without statistical difference ( P>0.05). Conclusion:Under premise of conventional western medicine treatment, Qufeng Tongxuan method can promote hematoma absorption and improve neurological deficit symptoms in low- and moderate-volume intracerebral hemorrhage at acute stage, without obvious adverse reactions.

OBJECTIVETo analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC).

METHODSThis is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death.

RESULTSThe objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P > 0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P > 0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P > 0.05).

CONCLUSIONSCompared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Disease Progression ; Disease-Free Survival ; Double-Blind Method ; Endostatins ; adverse effects ; therapeutic use ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Nausea ; chemically induced ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Prospective Studies ; Quality of Life ; Remission Induction

Objective To analyze the echocardiographic findings , associated anomalies and chromosomal characteristics in fetuses with pulmonary atresia with ventricular septal defect ( PA/VSD ) . Methods T he echocardiographic data and follow‐up materials were retrospectively reviewed in 30 256 fetuses from December 2012 to M arch 2018 in the consultation center of fetal heart disease in maternal‐fetal medicine in Anzhen hospital . Of all the fetuses ,59 cases ( 0 .19% ) had PA/VSD . T he echocardiographic findings ,associated anomalies and chromosomal characteristics were retrospectively analyzed in all the 59 fetuses with PA/VSD . Based on w hether the presence of the native pulmonary arteries and the major aortopulmonary collateral arteries ( M APCAs) or not ,the PA‐VSD was classified into type A ,type B ,and type C . Results A large ventricular defect was demonstrated in five‐chamber view with 61 .7% of the mean ratio of the aortic overriding . O ther fetal echocardiographic features of all the 59 fetuses with PA/VSD included :the right aortic arch ( n ＝19 ) ,reversal flow in the ductus arteriosus ( n ＝40 ) ,M APCAs ( n ＝24) . T he classification of the PA/VSD included :type A ( n ＝35) ,type B ( n ＝5) and type C ( n ＝19) . Associated anomalies :persistent left superior vena cava ( n ＝ 13 ) ,anomalous pulmonary vein connection ( n＝5 ) ,complete atrioventricular septal defect ( n ＝ 5 ) ; single umbilical artery ( n ＝ 3 ) ,right atrial isomerism ( n ＝3) . Of all the 30 cases performed chromosomal test ,3 cases had aneuploidy and 7 cases had microdeletion of chromosome . Conclusions The fetal echocardiographic findings of the PA/VSD are characteristic . For prenatal diagnosis of PA/VSD ,the type of PA/VSD should be defined and chromosomal test should be performed ,w hich can be helpful for prenatal consulting .

Objective :To analyze correlation among fasting (FBL) and postprandial blood lipids (PBL) ,blood lipid fluctuation (absolute value of PBL‐FBL) and severity of coronary artery disease .Methods :Cross‐sectional study was performed among 264 patients undergoing coronary angiography (CAG) in our hospital .According to percutaneous coronary intervention (PCI) or not based on CAG results ,patients were divided into plaque group (n＝128) and PCI group (n＝136).Gensini score was used to assess severity of coronary artery disease .Blood lipid levels and its fluctu‐ation were compared between two groups .Correlation among blood lipid levels ,blood lipid fluctuation and severity of coronary artery disease were analyzed .Results :Compared with plaque group ,there were significant rise in per‐centages of men and smokers ,waist circumference ,levels of postprandial‐fasting (P‐F ) serum LDL‐C (ΔLDL‐C ) and P‐F plasma apolipoprotein B (ΔApoB ) , and significant reduction in plasma level of P‐F apolipoprotein A1 (ΔApoA1) in PCI group , P＜0. 05 or ＜ 0. 01. Pearson correlation analysis indicated that serum fasting and post‐prandial HDL‐C levels ,plasma fasting and postprandial levels of ApoA1 and ΔApoA1 were significant inversely cor‐related with Gensini score ( r＝ －0. 130～ －0.218 , P＜0. 05 or ＜0. 01) ,and levels of plasma fasting lipoprotein a (Lp (a)) ,serum fasting and postprandial levels of free fatty acid (FFA) ,serum P‐F FFA (Δ FFA) were significant positively correlated with Gensini score ( r＝0. 139－0. 176 , P＜0.05 or ＜0.01).Multifactor linear regression anal‐ysis indicated that postprandial serum HDL‐C was protective factor for Gensini score (B＝ －22.274 , P＝0.002 ) , while postprandial serum FFA ,Δ FFA ,waist circumference and hyperlipidemia history were its influencing factors (B＝0. 388～24. 135 , P＜0. 05 or ＜0.01).Conclusion :Measurements of fasting and postprandial blood lipid levels and their fluctuation contribute to more comprehensively and objectively assessing blood lipid levels and severity of coronary disease in patients with coronary artery disease .