Soladulcidine is a steroidal alkaloid abundant in Solanum dulcamara L. with antitumor and other biological activities. In this study, ten soladulcidine derivatives were synthesized through esterification at C-3-hydroxy group, modification at NH group of F ring of esterification of E ring-opening products. The in vitro antiproliferative activity of these synthesized derivatives against prostate cancer (PC-3) cell line was assessed. Within this series of compounds, compound 19 exhibited the most potent inhibitory effect against the proliferation of PC-3 cell line (IC50=4.80±.9μmol/L).

Objective To investigate the safety of trial of labor after cesarean (TOLAC) and clinical factors associated with successful TOLAC and to compare TOLAC with elective repeat caesarean section (ERCS) in terms of obstetric and neonatal outcomes.Methods A prospective cohort study was conducted among gravidas who had a history of lower segment cesarean section and were hospitalized in the Department of Obstetrics and Gynecology,the Affiliated Drum Tower Hospital of Medical School of Nanjing University from January to December 2014.Exclusion criteria included indications for caesarean section (such as placenta previa,placenta accreta,twin pregnancy,breech presentation and severe preeclampsia),serious maternal complications after cesarean section,lower uterine segment thinner than 3 mm and poor healing of uterine incision.Totally,287 gravidas were enrolled.Among them,142 chose TOLAC and the other 145 requested ERCS.Clinical data of those gravidas were collected and statistically analyzed by t-test,Log-rank test,Chi-square or Fisher's exact test.Results (1) The success rate of TOLAC was 90.8％ (129/142).There was no significant difference in maternal age,gestational age,thickness of lower uterine segment,interval between the two deliveries and neonatal birth weight and asphyxia rate between the successful (n=129) and unsuccessful (n=13) groups (all P＞0.05).Although the two groups had no significant difference in postpartum hemorrhage (PPH) rate,the gravidas who failed in TOLAC lost more blood than those who succeeded [425 (195-675) vs 200 (50-1 400) ml,P＜0.05].Moreover,higher amniotic fluid contamination rate was observed in the unsuccessful group [6/13 vs 17.1％ (22/129),P＜0.05].In the TOLAC group,99.3％ (141/142) were under continuous fetal heart rate monitoring.Incomplete uterine rupture occurred in one women without serious maternal or neonatal outcomes.The reasons for 13 failed TOLAC cases were unbearable pain during labor,abnormal labor,fetal distress and threatened rupture of uterus.(2) Compared with the ERCS group,the TOLAC group showed shorter interval from last cesarean section to the indexed delivery[5 (2-18) vs 6 (2-19) years],younger maternal age [(31±4) vs (33 ±4) years old] and less blood loss [200 (50-1 400) vs 300 (100-1 500) ml] (all P＜0.05).Conclusion Our study shows that,those who preferred TOLAC were younger,or had shorter pregnancy interval from last cesarean section.The success rate of TOLAC is high for women undergoing systematic prenatal assessment and close management during labor with less blood loss and non-serious maternal and neonatal complications compared with ERCS.

Objective:To investigate the value of enhanced MRI in evaluating the tissue permeability of pancreatic ductal adenocarcinoma (PDAC) animal model.Methods:The experimental animals were 27 female C57BL/6 mice. The mice were divided into 3 groups with 9 mice in each group by random number method. Murine pancreatic adenocarcinoma (Panc02) and embryonic fibroblasts (NIH/3T3) were implanted subcutaneously at the ratio of 2∶1 and 1∶1 to establish PDAC models with different tissue permeability, which were low fibroblast group and high fibroblast group, respectively, and simple Panc02 implantation model was control group. The positive expression rate of α-smooth muscle actin (α-SMA), the positive expression rate of fibroblast activating protein (FAP), the coverage rate of collagen fibers, number of blood vessels and the long/short diameter of tissue vessels were quantitatively evaluated by tissue staining, and the tissue permeation efficiency was quantified by the average optical density (AOD) of tissue sections stained by Evans blue (EB). Enhanced MRI was performed on mice, and the enhancement degree and the enhancement rate of 20 min were obtained. One-way ANOVA was used to compare the overall differences of tumor histological indexes and MRI enhancement parameters in each group, and the correlation between the indexes was analyzed by Pearson correlation analysis. Multiple linear stepwise regression analysis was conducted with 20 min enhancement rate as dependent variable, while α-SMA positive expression rate, collagen fiber coverage rate and vascular long/short diameter as independent variables.Results:There were significant differences in AOD value, α-SMA positive expression rate, FAP positive expression rate, collagen fiber coverage rate, vascular long/short diameter, 20 min enhancement degree and 20 min enhancement rate among the three groups ( P<0.001), but there was no significant difference in the number of blood vessels ( P=0.650). The AOD value was negatively correlated with the positive expression rate of α-SMA, the coverage rate of collagen fibers and the long/short diameter of blood vessels in PDAC model, respectively ( r=-0.888, P=0.001; r=-0.813, P=0.008; r=-0.915, P<0.001). The 20 min enhancement degree was positively correlated with AOD value ( r=0.954, P<0.001). The positive expression rate of α-SMA, collagen fiber coverage and vascular long/short diameter were negatively correlated with 20 min enhancement rate ( r=-0.901, P<0.001; r=-0.837, P=0.005; r=-0.880, P=0.002). The results of multiple linear stepwise regression analysis showed that the positive expression rate of α-SMA was an important influencing factor for the 20 min enhancement rate (R 2=0.813, P=0.001). Conclusions:The increase of fibroblast implantation ratio significantly decreased the permeation efficiency of tumor tissue. The positive expression rate of α-SMA, the coverage rate of collagen fibers and the long/short diameter of blood vessels were negatively correlated with the permeation efficiency of tumor tissue. The 20 min enhancement degree was positively correlated with tissue permeation efficiency.

OBJECTIVETo describe the distribution of plasma folate concentrations and prevalence of folate deficiency in adults aged 35 to 64 years in some areas and different seasons in China.

METHODSStudy subjects were sampled from the representative rural and urban areas in the south and north of China aged 35 to 64 years totaling 2 545, and their plasma folate concentrations were determined and analyzed.

RESULTSPlasma concentrations of folate in the southern population were significantly higher (16.9 nmol/L) than those in the north (8.3 nmol/L), and the prevalence of folate deficiency in the south (5.8%) was significantly lower than that in the north (37.1%). Plasma folate concentration varied with season either in the south or north. Plasma concentrations of folate were lower during the summer and the fall (15.0 nmol/L) than those during the winter and the spring (18.8 nmol/L) in the south, but without significant changes in the prevalence of folate deficiency in different seasons. However, the plasma folate concentrations were significantly higher during the summer and the fall (9.7 nmol/L) than those during the winter and the spring (7.1 nmol/L) in the north. And the prevalence of folate deficiency in the north was significantly higher in winter and spring (48.0%) than that in summer and fall (26.2%).

CONCLUSIONSThere existed significant difference in plasma folate concentrations in adults between varied geographic areas in China, which differed from their seasonal changes.

Adult ; China ; epidemiology ; Female ; Folic Acid ; blood ; Folic Acid Deficiency ; epidemiology ; Humans ; Male ; Middle Aged ; Rural Health ; statistics & numerical data ; Seasons ; Urban Health ; statistics & numerical data

Objective:To analyze the incidence of complications of central venous catheterization and risk factors in the Pediatric Intensive Care Unit of Xi'an Children 's Hospital.Methods:The clinical data of 310 children who underwent central venous catheterization in the Pediatric Intensive Care Unit of Xi 'an Children's Hospital from June 2020 to February 2021 were retrospectively analyzed. The incidence of complications of central venous catheterization and risk factors were analyzed.Results:A total of 334 central venous catheters were used in 310 chidren. Among the 310 children who underwent central venous catheterization, 102 children (30.54%) had complications related to central venous catheterization. The complications related to central venous catheterization included catheter infection (13.17%), catheter malposition (8.38%), exudation at the puncture site (4.79%), catheter occlusion (2.99%), accidental removal (0.60%), and central venous thrombosis (0.60%). Central venous catheters were removed in 82 children (24.55%) because of complications. There was a significant difference in the incidence of central venous thrombosis among three surgical approaches: femoral vein, internal jugular vein, and subclavian vein ( χ2 = 7.06, P = 0.029). Longer time for catheterization resulted in a higher incidence of complications, including catheter-related infection ( χ2 = 7.17, P = 0.028), puncture point exudation and obstruction ( χ2 = 8.59, P = 0.014), central venous thrombosis ( χ2 = 6.78, P = 0.034). Regression analysis showed that suture shedding and bleeding at the insertion sites were the main risk factors for catheter-related complications (suture shedding OR = 4.85, P = 0.001; bleeding at the insertion sites OR = 1.83, P = 0.008). Conclusion:The most common complications of central venous catheterization in the Pediatric Intensive Care Unit of Xi'an Children's Hospital include catheter-related infection, catheter malposition, and puncture site exudation. Risk factors for complications during catheter retention include suture shedding and bleeding at the insertion sites.

Objective To analyze the clinical significance of endometrial abnormalities in patients with breast cancer after oral administration of tamoxifen, and to determine the risk factors for endometrial malignancy. Methods We collected data from 135 patients with breast cancer who underwent surgery for endometrial abnormalities after oral administration of tamoxifen at the Department of Gynecology from September 2011 to December 2017. According to the pathological results obtained, the patients were divided into groups A (benign endometrial lesion) and B (precancerous and malignant endometrial lesion). The relationships between endometrial malignancy and factors including age, menopausal status, body mass index, endometrial thickness, abnormal uterine bleeding, oral dose of tamoxifen, duration of oral medication, and complications (hypertension and diabetes) were compared between the groups. Results There were 124 patients in group A and 11 patients in group B. The difference in the incidence of abnormal uterine bleeding, which was a risk factor for endometrial malignancy, was significant different between the groups (P ＜ 0.05). Conclusion Physicians should pay close attention to abnormal uterine bleeding in patients taking tamoxifen after surgery for breast cancer. Hysteroscopy should be used to confirm the nature of lesions, and patients without symptoms should be followed up.

Objective:To observe whether hair follicle cells from mice of different species can integrate to generate new pigmented hair follicles, and to explore the role of different melanocyte populations in pigmented hair follicle reconstruction in mice.Methods:The epidermal cell population, hair follicle epithelial cell population and dermal cell population were isolated from the skin of fetal or neonatal C57BL/6J and BALB/C mice, and epidermal melanocytes were obtained by culture and purification of the epidermal cell population. The experiments were divided into 3 parts: (1) hair follicle reconstruction experiment in neonatal C57BL/6J mice, which included 2 groups: epidermal cells + hair follicle epithelial cells group and dermal cells group; (2) chimeric hair follicle reconstruction experiment, which included 4 groups: dermal cells of neonatal C57BL/6J mice group, dermal cells of neonatal BALB/C mice group, dermal cells of neonatal BALB/C mice + dermal cells of neonatal C57BL/6J mice group, and dermal cells of fetal BALB/C mice + dermal cells of fetal C57BL/6J mice group; (3) pigmented hair follicle reconstruction experiment, which included 3 groups: dermal cells of neonatal BALB/C mice + epidermal cells of neonatal C57BL/6J mice group, dermal cells of neonatal BALB/C mice + hair follicle epithelial cells of neonatal C57BL/6J mice group, and dermal cells of neonatal BALB/C mice + cultured C57BL/6J epidermal melanocytes group. Different cells were implanted into dorsal skin fold chambers of the nude mice, and there were 4 mice in each group. At weeks 4 and 8 after inoculation, hair follicle reconstruction was assessed by gross observation, histological examination and immunofluorescence assay.Results:Among the 8 BALB/C nude mice in the 2 groups in the hair follicle reconstruction experiment, 7 survived and 1 died of wound infections on week 4 after inoculation; at weeks 4 and 8 after inoculation, no hair growth was observed in the epidermal cells + hair follicle epithelial cells group (3 mice) , while normal hair grew out in the dermal cells group (4 mice) mixed with epithelial components. Among the 16 BALB/C nude mice in the 4 groups in the chimeric hair follicle reconstruction experiment, 14 survived and 2 died of wound infections on week 4 after inoculation; at weeks 4 and 8 after inoculation, brown-grey hair grew well in the dermal cells of neonatal BALB/C mice + dermal cells of neonatal C57BL/6J mice group (4 mice) , and dermal cells of fetal BALB/C mice + dermal cells of fetal C57BL/6J mice group (3 mice) . Among the 12 BALB/C nude mice in the 3 groups in the pigmented hair follicle reconstruction experiment, 10 survived and 2 died of wound infections on week 4 after inoculation; at weeks 4 and 8 after inoculation, only white hair grew out in the dermal cells of neonatal BALB/C mice + cultured C57BL/6J epidermal melanocytes group (3 mice) , and no hair follicle melanocytes were observed by immunofluorescence assay, while brown-grey hair grew well in the dermal cells of neonatal BALB/C mice + epidermal cells of neonatal C57BL/6J mice group (4 mice) , and dermal cells of neonatal BALB/C mice + hair follicle epithelial cells of neonatal C57BL/6J mice group (3 mice) .Conclusions:The interaction between mesenchymal cells and hair follicle epithelial cells is a necessary condition for hair follicle reconstruction. The hair follicle cells from different species of mice can integrate to generate new pigmented hair follicles. Both hair follicle melanocytes and epidermal melanocytes can participate in the formation of pigmented hair follicles, but differentiated melanocytes have no such ability.

OBJECTIVE：To study the effects of chrysophanol on the activa tion of microglia and the expression of inflammatory factors in cerebral ischemia model rats. METHODS ：SD rats were randomly divided into sham operation group ， model group and chrysophanol high ，medium，low dose groups [7.88，3.94，1.97 mg/（kg·d）]，with 20 rats in each group （the number was complemented in cases of death or unsuccessful modeling during modeling process ）. Except for sham operation group ， middle cerebral artery occlusion model was established in other groups by improved thread method. After 2 hours of ischemia ， sham operation group and model group were intraperitoneally injected with 1 mL normal saline ，and each administration group was intraperitoneally injected with 1 mL corresponding drug ，once a day ，for 7 consecutive days. After last medication ，the score of neurological impairment was recorded ；cerebral infarction of rats was observed by TTC staining ，and the percentage of cerebral infarction area was calculated. The expression of Iba- 1 positive cells in ischemic penumbra of rats was observed by immunofluorescence staining. The expression of Notch- 1，TNF-α and ICAM-1 in the ischemic penumbra of rats were detected by Western blotting assay. RESULTS ：In sham operation group ，there was no infarction area in the brain tissue ，and the Iba- 1 positive cells in the ischemic penumbra were few and branched. Compared with sham operation group ，the infarction area of cerebral tissue in rats was obvious in model group ； the 052）number of Iba- 1 positive cells in ischemic penumbra were 〔ZQ2017003〕） increased significantly ，and they were in amoeba or round shape；the neurological impairment score ，the percentage of cerebral infarction area ， relative expression of Notch- 1， TNF-α and ICAM-1 protein in ischemic penumbra were increased significantly （P＜0.05）. Compared with m odel rats ，the infarction area of cerebral tissue in each dose group of chrysophanol was reduced to different extent ；the number of Iba- 1 positive cells in ischemic penumbra was decreased ；neurological impairment score ，the percentage of cerebral infarction area ，relative expression of Notch- 1，TNF-α and ICAM-1 protein were significantly decreased （P＜0.05 or P＜0.01）. CONCLUSIONS ：Chrysophanol has a certain protective effect on the brain tissue of cerebral ischemia model rats ，and can relieve the nerve injury. Its mechanism may be associated with inhibiting the activation of microglia and expression of inflammatory factors mediated by Notch pathway.

Objective To investigate the risk factors which can lead to chronic kidney disease (CKD) after radical nephroureterectomy and guide adjuvant chemotherapy for the patients with upper tract urothelial carcinoma (UTUC).Methods 239 patients with UTUC,who were treated at our hospital from October 2010 to February 2015 was analyzed retrospectively.Serum creatinine levels were measured preoperatively and 1 month (range:21days to 35 days) after radical nephroureterectomy.129 males and 110 females patients were enrolled.Ages were from 41 to 94,and mean age was 66 years.All patients underwent radical surgery.The pathological stages included Ta/T1/T2/T3/T4,and grades included G1/G2/G3.We calculated GFR using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in consideration of age,sex,and serum creatinine level.The new-onset CKD after RNU was defined as when the calculated CKD-EPI GFR decreased to less than 60 ml/(min · 1.73 m2).These patients were divided into 2 groups which depended on whether they got CKD after RNU.Cohorts were stratified by gender,age,smoking,BMI,hypertension,diabetes mellitus (DM),tumor location,tumor size,multifocality,pathologic stage,grade,hydronephrosis and preoperative CKD-EPI GFR.The chi-square test was used to examine the relationship among the various cohorts and the CKD after RNU.The Kaplan-Meier method was adopted to identify the relationship between Overall survival (OS).Cancer-specific survival (CSS) and CKD.Univariate and multivariate analyses were performed to study the relationship between clinical factors and CKD after RNU using the Cox proportional hazards regression model and chi-square test.Results In our study,the median follow-up time was 41.3 (range from 2-82) months for 239 patients.Median CKD-EPI GFR for all patients before and after surgery was 71.4 (65.2-108.7) ml/(min · 1.73 m2) and 54.7 (37.6-93.8) ml/(min · 1.73 m2),meanwhile 105 cases became new-onset CKD.There was no significant difference in overall or cancer specific survival between CKD + and CKD-(P =0.137,P =0.190).However age (HR =1.825,95％ CI 1.203-2.768,P =0.017),hydronephrosis (HR =0.243,95 ％ CI 0.106-0.613,P =0.034) and preoperative CKD-EPI GFR (HR =0.237,95 ％ CI 0.109-0.524,P =0.021) were significantly correlative with postoperative new-onset CKD.Conclusion Age,absence of hydronephrosis and preoperative CKD-EPI GFR were independent risk factors predicting new-onset CKD.They can be the predictor of new-onset CKD.

OBJECTIVE To accurately identify the rare adverse drug reactions （ADR） of vancomycin-pancytopenia in order to promote its safe use. METHODS Through a case report of a child with suppurative hip arthritis who developed pancytopenia combined with delayed drug fever caused by intravenous infusion of vancomycin，Naranjo score method and related literature were used to summarize the association between the ADR and vancomycin and its possible mechanism， and suggestions for rational use of vancomycin in pediatric patients were put forward. RESULTS & CONCLUSIONS The association of pancytopenia combined with delayed drug fever and vancomycin in this child is “very likely”. In clinical practice， it is difficult to distinguish between pancytopenia combined with delayed drug fever from fever and hematopenia caused by aggravation of infection. Medical staff should increase their awareness of vancomycin rare ADR such as pancytopenia， and pharmacists should assist medical staff in timely screening for ADR. The initial dose of vancomycin infusion for children should start from 60 mg/（kg·d），and the blood concentration should be monitored 48 h after the first infusion and the dose should be adjusted in time to maintain the valley concentration of vancomycin at 5-15 mg/L to prevent the occurrence of ADR caused by excessive blood concentration. For children who have been using vancomycin for more than one week，the blood routine should be rechecked regularly. Once pancytopenia occurs，the drug should be stopped immediately，and symptomatic treatment should be given according to the situation.