Objective:To investigate the effect of metformin(MET)on endoplasmic reticulum stress-induced apoptosis and its role and molecular mechanisms in preeclamptic(PE)rats.Methods:Thirty SD rats were ran-domly assigned into control,PE and MET groups,10 in each group.From days 14 to 18 of gestation,rats in the PE and MET groups were subcutaneously injected with L-nitro-arginine methyl ester(L-NAME)at a dose of 200 mg/(kg·d),while the control group was administered subcutaneous injections containing a 0.9％solution of sodium chloride at the same dose.Additionally,the MET group was administered MET by gavage at a dose of 200 mg/(kg·d)from days 13 to 18 of gestation.On days0,6,12,15,17,and 19 of pregnancy,blood pressure of rats was measured.On days 12 and 19 of pregnancy,24-hour urinary protein content was assessed.On day 20 of pregnan-cy,rats were anesthetized and underwent cesarean section to measure pup weight,crown-rump length,placental weight,and diameter.We used reverse transcription quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry(IHC)to detected mRNA and protein expression of apoptosis-related genes in rat placental tissue,and enzyme-linked immunosorbent assay(ELISA)to assess the expression of apopto-sis-related genes in rat serum.Results:Compared with the control group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuria level on day 19 of gestation were significantly higher,and body mass and top rump length of littermates were lower in the PE group,and the differences were statistically significant(P＜0.05);Compared with the PE group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuri-a level on day 19 of gestation were significantly decreased,and body mass and top rump length of littermates were increased in the MET group,and the differences were all statistically significant(P＜0.05).Pairwise com-parisons of placental weight,placental diameter,and the number of pups born among the three groups showed no statistically significant differences(P＞0.05).Compared to the control group,the PE group exhibited significantly increased expression of B-cell lymphoma-2(Bcl-2)associated X protein(Bax),bcl-2 antagonist/killer 1(Bak),and apoptosis-inducing factor(AIF)mRNA and protein in placental tissues,decreased expression of Bcl-2 mRNA and protein,as well as elevated levels of Bax,Bak,and AIF in serum,while Bcl-2 expression levels were de-creased.These differences were statistically significant(P＜0.05).Compared to the PE group,the MET group exhibited decreased expression of Bax,Bak,and AIF mRNA and protein in placental tissue,along with increased expression of Bcl-2 mRNA and protein.Serum levels of Bax,Bak,and AIF were decreased,while Bcl-2 expression levels were increased.All differences were statistically significant(P＜0.05).Conclusions:L-NAME significantly induced elevated levels of apoptosis in rat placental tissues,whereas MET was able to effectively inhibit L-NAME-induced apoptosis induced by endoplasmic reticulum stress,which has the potential to be a new therapeu-tic intervention point for PE.

Objective:To investigate the effect of metformin(MET)on endoplasmic reticulum stress-induced apoptosis and its role and molecular mechanisms in preeclamptic(PE)rats.Methods:Thirty SD rats were ran-domly assigned into control,PE and MET groups,10 in each group.From days 14 to 18 of gestation,rats in the PE and MET groups were subcutaneously injected with L-nitro-arginine methyl ester(L-NAME)at a dose of 200 mg/(kg·d),while the control group was administered subcutaneous injections containing a 0.9％solution of sodium chloride at the same dose.Additionally,the MET group was administered MET by gavage at a dose of 200 mg/(kg·d)from days 13 to 18 of gestation.On days0,6,12,15,17,and 19 of pregnancy,blood pressure of rats was measured.On days 12 and 19 of pregnancy,24-hour urinary protein content was assessed.On day 20 of pregnan-cy,rats were anesthetized and underwent cesarean section to measure pup weight,crown-rump length,placental weight,and diameter.We used reverse transcription quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry(IHC)to detected mRNA and protein expression of apoptosis-related genes in rat placental tissue,and enzyme-linked immunosorbent assay(ELISA)to assess the expression of apopto-sis-related genes in rat serum.Results:Compared with the control group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuria level on day 19 of gestation were significantly higher,and body mass and top rump length of littermates were lower in the PE group,and the differences were statistically significant(P＜0.05);Compared with the PE group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuri-a level on day 19 of gestation were significantly decreased,and body mass and top rump length of littermates were increased in the MET group,and the differences were all statistically significant(P＜0.05).Pairwise com-parisons of placental weight,placental diameter,and the number of pups born among the three groups showed no statistically significant differences(P＞0.05).Compared to the control group,the PE group exhibited significantly increased expression of B-cell lymphoma-2(Bcl-2)associated X protein(Bax),bcl-2 antagonist/killer 1(Bak),and apoptosis-inducing factor(AIF)mRNA and protein in placental tissues,decreased expression of Bcl-2 mRNA and protein,as well as elevated levels of Bax,Bak,and AIF in serum,while Bcl-2 expression levels were de-creased.These differences were statistically significant(P＜0.05).Compared to the PE group,the MET group exhibited decreased expression of Bax,Bak,and AIF mRNA and protein in placental tissue,along with increased expression of Bcl-2 mRNA and protein.Serum levels of Bax,Bak,and AIF were decreased,while Bcl-2 expression levels were increased.All differences were statistically significant(P＜0.05).Conclusions:L-NAME significantly induced elevated levels of apoptosis in rat placental tissues,whereas MET was able to effectively inhibit L-NAME-induced apoptosis induced by endoplasmic reticulum stress,which has the potential to be a new therapeu-tic intervention point for PE.

Objective To investigate early diagnosis and treatment of Paget disease of breast. Methods The clinicopathological data of 26 cases of breast Paget disease in the First Affiliated Hospital of Wenzhou Medical University from January 1995 to June 2018 was analyzed. Results The main clinical manifestation of 26 patients was eczema like papillae in 19 cases (73.1%), and associated with nipple discharge in 9 cases (34.6% ) and breast mass in 6 cases (23.1% ). The diagnosis of this disease was based on curettage cytology in 4 cases (15.4% ), biopsy in 8 cases (30.8% ), and needle aspiration cytology or post resection pathological examination in 14 cases (53.8% ). Paget disease consisted of simple papillary Paget disease in 3 cases (11.5%), ductal carcinoma in 18 cases (69.2%) and invasive ductal carcinoma in 5 cases (19.2%). Pathological TNM staging was 0 stage in 19 cases (73.1%), stageⅠin 3 cases (11.5%), stageⅡin 2 cases (7.7%), stageⅢin 2 cases (7.7%) and no stage inⅣcase. In this group, 2 cases underwent radical mastectomy, 18 cases underwent modified radical mastectomy, 4 cases underwent simple mastectomy, and 2 cases underwent mastectomy combined with low axillary lymph node dissection and intraoperative rapid frozen examination. Fourteen patients received adjuvant chemotherapy with CEF(cyclophosphamide + pharmorubicin + tegafur)/EC (pharmorubicin + cyclophosphamide) + T(docetaxel) or TP(docetaxel + cis- platinum)regiment after operation, 2 cases were treated with trastuzumab targeted therapy and 5 cases with adjuvant radiotherapy. Twenty-five of 26 patients were followed up for 8-108 months except one patient lost in follow-up. The 5-year survival rate was 96.0% (24/25), and the 10-year survival rate was 52.0% (13/25). Conclusions The diagnosis of Paget disease of the breast depends on cytology or pathology, and multidisciplinary treatment based on surgery is judged of by tumor stage and coincident other types of breast cancer and axillary lymph node involvement.

There is a high risk of myelosuppression in pelvic malignant tumors during concurrent chemoradiotherapy. The dose-volume relationship of pelvic exposed bone marrow( bone) is related to acute hematological toxicity during radiotherapy and chemotherapy,but lacks recognized parameters in this respect. The hematopoietic capacity of the bone marrow(bone)in different parts of the pelvic cavity is heterogeneous,and the pelvic bone marrow near the central axis has the strongest hematopoietic capacity,namely functional bone marrow. The relationship between dose-volume parameters of pelvic functional bone marrow and acute hematologic toxicity during chemoradiotherapy of pelvic malignant tumors may be the future direction.

Objective To investigate the prevalence of high urine albumin-to-creatinine ratio (ACR) among health check up population and evaluate the potential predictors for ACR. Methods A cross-sectional study was conducted among health check up population in the Zhongshan Hospital during 2015. Potential participants completed urine ACR test,body mass index (BMI) and blood test. ACR level was divided into two groups according to the K/DOQI recommendation:ACR Group(male:ACR≥17 mg/g;female:≥25 mg/g), Normal Group (male:ACR<17 mg/g;female:ACR<25 mg/g). Univariate and multivariate logistic regression models were performed to evaluate the associations of ACR with potential predictors (including age,sex,over-weight or obesity,hypertension,glucose metabolism disorders, hypertriglyceridemia,hypercholesterolemia,high low HDL-C and hyperuricemia). Result Totally 670 people from the health check up population were screened for ACR test, 54 cases were positive, the prevalence was 8.1％. Age, BMI, waist-to-height ratio, SBP, DBP, blood sugar and uric acid had statistical significance between Normal group and ACR group[Age 47.62 ± 11.29 vs. 53.83 ± 11.93, t=-3.858, P<0.01;BMI (24.05±3.12) kg/m2 vs. (24.94±3.49) kg/m2, t=-1.982, P<0.05;waist-to-height ratio 0.51±0.52 vs. 0.53 ± 0.06, Z=-2.146, P<0.05; SBP (mmHg, 1 mmHg=0.133 kPa) 115.31 ± 15.59 vs. 130.91 ± 23.66, t=-4.755, P<0.01;DBP(mmHg) 72.31 ± 9.16 vs. 80.02 ± 9.81, t=-5.897,P<0.01;blood sugar (mmol/L) 4.64 ± 1.20 vs. 5.57 ± 2.77, t=-2.466, P<0.01;uric acid (μmol/L) 362.99 ± 92.80 vs. 397.76 ± 95.62, t=-2.633, P<0.01]. Age, hypertension, glucose metabolism, HDL reduction were risk factors for urinary albumin/creatinine ratio. In the multivariate logistic regression model, hypertension status was found to be associated with ACR positive [odd ratio (OR): 2.843, 95％ confidence interval [CI, 1.472-5.493, P<0.01], glucose metabolism disorders (OR, 2.132, 95％CI, 1.042-4.365, P<0.05). As the number of risk factors increases, the rate of positive of ACR showed marked increase, comparing persons with no risk factors to those with four or more risk factors , the OR value rose up to 18.281. Conclusion Hypertension and glucose metabolism disorder are risk factors of chronic renal dysfunction. With the increase of risk factors, the rate of positive of ACR was higher. ACR test is recommended routine screening for people over the age of 50.

OBJECTIVEThe purposes of our study were to investigate the association between maternal urinary phthalate metabolites and the levels of inhibin B (INHB) and insulin-like factor 3 (INSL3) in the cord blood in a Chinese pregnant population.

METHODSMaternal urine samples in the third trimester of pregnancy of 69 participants were collected and stored, and the samples of cord blood (10 ml) were collected at delivery between June 2011 and September 2012 in a comprehensive hospital of gynecology and obstetrics in Tianjin, China.Four phthalate metabolites, monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), and mono-2-ethylhexyl phthalate (MEHP) were measured in the urine samples using liquid chromatography-tandem mass spectrometry. The levels of INHB, INSL3 in the cord blood were tested by ELISA. Associations of phthalate exposure with INHB and INSL3 levels were determined by spearman correlation and multiple regression model analysis.

RESULTSThe median concentrations of observed metabolites in descending order were 49.74 µg/L for MMP, 24.96 µg/L for MEHP, 19.52 µg/L for MEP and 17.73 µg/L for MBP. The median concentrations of INHB and INSL3 were 89.09 and 106.21 ng/L.Significant negative associations between INHB and MMP(β' = -0.252), MEP(β' = -0.363) or the sum value (∑PAEs) (β' = -0.346) were found by the multiple regression model analysis. For INSL3, only the sum value (β' = -0.313) was inversely significantly associated with the levels of INSL3 in the cord blood.

CONCLUSIONSMaternal urinary phthalate metabolites were associated with INHB and INSL3 in the cord blood in a Chinese population.

Adult ; Diethylhexyl Phthalate ; analogs & derivatives ; urine ; Female ; Fetal Blood ; chemistry ; Humans ; Infant, Newborn ; Inhibin-beta Subunits ; blood ; Insulin ; blood ; Male ; Maternal Exposure ; Phthalic Acids ; urine ; Pregnancy ; Proteins ; Testicular Hormones ; blood ; Young Adult

The self-renewal and multipotent potentials in neural stem cells (NSCs) maintain the normal physiological functions of central nervous system (CNS). The abnormal differentiation of NSCs would lead to CNS disorders. However, the mechanisms of how NSCs differentiate into astrocytes, oligodendrocytes (OLs) and neurons are still unclear, which is mainly due to the complexity of differentiation processes and the limitation of the cell separation method. In this study, we modeled the dynamics of neural cell interactions in a systemic approach by mining the high-throughput genomic and proteomic data, and identified 8615 genes that are involved in various biological processes and functions with significant changes during the differentiation processes. A total of 1559 genes are specifically expressed in neural cells, in which 242 genes are NSC specific, 215 are astrocyte specific, 551 are OL specific, and 563 are neuron specific. In addition, we proposed 57 transcriptional regulators specifically expressed in NSCs may play essential roles in the development courses. These findings provide more comprehensive analysis for better understanding the endogenous mechanisms of NSC fate determination.
Animals ; Astrocytes ; cytology ; metabolism ; Cell Differentiation ; genetics ; Gene Expression Profiling ; Gene Regulatory Networks ; Mice ; Neural Stem Cells ; cytology ; metabolism ; Oligodendroglia ; cytology ; metabolism ; Protein Interaction Mapping

Objective To analyze and explore the operative effect of coraccid process basilar part fractures combined injury of ligamental structure. Methods Use ilium-fascia lata complex tissue to reconstruct coronoid process of ulna and medial collateral ligament, recoverd anterior and wall horn anatomic structure of elbow joint. Total 9 cases of ulna coracoid process fractures concomitancy with elbow posterior dislocation . Among these one with olec-ranon fracture,five patients with head of radius fracture. Anterior trance joint approach was used,removal bone chips, restore defect with ilium-fascia lata complex tissue after cuting and trimming. Once reduction was achieved,fixed with screw. Repaird the collateral ligament and anterior joint capsule use the fascia lata, If there were combined fracture of the radius head or olecranon fracture,fixed through lateral approach,All injured extremities were treated with a posterior plaster splint with functional position for 3 weeks followed by elbow rehabilitation training. Results According to Moneys evaluation method,2 patients were classified as excellent ,5 as good,l as fair and 1 as poor. The excellent and good rate was 77. 8%. Two patients with gently ossifying myositis but no patients with wound infection,internal fixation loosening or break,elbow joint destabilizing orcorpus libemm. Conclusions Coracoid process basilar part fractures was simultaneous with the instability of osteal frame and soft tissue. To attain the favourable anatomical foundation for elbow joint functional recovery, it should rebuild the height and shape of coronoid process first and think highly of repair or rebuild medial collateral ligament and joint capsule. It reconstructed the coronoid process osteal frame and soft tissue instability at the same time to use ilium-fascia lata complex tissue. The operative procedure is simplify with reliability effect and fine functional rehabilitation.

Objective To improve the operation method of rupture of Achilles tendon for decreasing complication. Methods Total 39cases with closed rupture of Achilles tendon were selected in this study. Short incision was made at achilles tendon wall, reveal and anneal the broken ends, using Kirschner wire and steel-wire to make rectangle frame ,intradermic fixation of fracture away from the broken ends, then sutured ends with rarities and smoothing,functional exercise after 6weeks ankle rest position fixation. Results According to the Arner Lindholm evaluation system,the treatment outcome were excellent in 34 cases ,and good in 5cases. No complication including re-rupture skin ,tendon necrosis and infection were found after operation. Conclusion Repaired closed rupture of Achilles tendon with short incision and rectangle frame, assisted with ankle rest position fixation after operation wasa worthy way for treating closed rupture of a chilles tendon.

Objective To observe the application and efficacy of dynamic condylar screw (DCS) in treating intertrochanteric fractures of the femur and discuss the fixation principle, feasibility, advanta-ges and related issues. Methods A retrospective analysis was done on 23 patients with intertrochanter-ic fractures of the femur treated with DCS from January 2000 to December 2006. Of all, there were 10 elderly patients with different levels of various kinds of internal diseases and 13 young patients injuried by high-energy such as traffic accidents. According to Boyd' s classfication, there was one patient with type Ⅰ fracture, five with type Ⅱ , nine with type Ⅲ and eight with type Ⅳ. After a detailed pre-operative physical examination and targeted treatment, DCS fixation was employed for intertrochanteric fractures of the femur. Results A follow-up for average 18 months showed no death. Early complications occurred in three patients including two with pulmonary infection and one with urinary tract infection, who got cured after proper treatment. There was one patient with long-term complication, post-traumatic arthritis. All 23 patients got bone healing, with excellenee rate of 96% according to Harris criteria. There were no complications like breakage of nails, nonunion, eoxa yarn deformity, shortening or external rotation of the lower limb. Conclusions DCS has advantages of simple operation, reliable fixation and coincidence with biomechanical characteristics and hence is one of ideal methods for treatment of intertrochanteric frac-ture of the femur, especially for subtrochanteric fracture, contrary chanteric fractur, fracture involving large pyriform troehanteric and comminuted fractures of sub-trochanteric lateral os integumentale.