AIM To investigate the pharmacokinetic behaviors of total flavonoids from Epimedii Folium in osteoporotic rats in vivo.METHODS Twelve rats were divided into model group and sham group,after which the osteoporotic rat model was established by removing bilateral ovaries.After intragastric administration with total flavonoids (500 mg/kg),HPLC-DAD was applied to detecting the plasma concentrations of total flavonoids' prototype glycosides (epimedin A,epimedin B,epimedin C,icariin) and their metabolites (sagittatoside A,sagittatoside B,2-O-rhamnosylicariside Ⅱ,baohuoside Ⅰ,icaritin) at thirteen time points (0.083,0.25,0.5,0.75,1,2,3,4,6,8,12,24 and 48 h),then the plasma concentration-time curves were drawn,followed by the calculation of pharmacokinetic parameters.RESULTS Doubled peaks were observed in the plasma concentration-time curves of total flavonoids' prototype glycosides and their metabolites in both groups.Compared with the sham group,the integrated AUC and Cmax in the model group were significantly decreased (P ＜ 0.01),as well as the prolonged t1/2 (P ＜ 0.01).CONCLUSION The in vivo absorption and metabolism of total flavonoids from Epimedii Folium are much slower in the state of osteoporosis,thus affects the efficacy.

Objective:To explore the expression of mammalian target of rapamycin (mTOR)and its relationgship with the prognosis of breast cancer,and to provide evidence-based basis for the using of mTOR inhibitor in the treatment of breast cancer.Methods: A systemical literature search was conducted based on the following databases:PubMed,EMBbase,Cochrane Library,ISI Web of Science,and CNKI up to November 24,2015.The outcome measures were hazard ratio (HR)with 95% confidence interval (CI) for the association between the mTOR expression and the prognosis of patients with breast cancer.The primary end points including disease-free survival (DFS ), and overall survival (OS ). STATA 12.0 was used to conduct the statistical analysis. Results:A total of seven cohort studies,1 758 patients were included. The risk of recurrence and metastasis of the breast cancer patients with positive expression of mTOR was 2.05 times of the patients with negative expression of mTOR (HR= 2.05, 95% CI: 1.01 - 4.13,P = 0.003);the risk of death in the breast cancer patients with positive expression of mTOR was 2.63 times of the patients with negative expression of mTOR (HR = 2.63, 95%CI:1.45-4.80,P = 0.736).Conclusion:The positive expression of mTOR can significantly increase the recurrence,metastasis and death risk of the patients with breast cancer.

Objective To observe the effect of hyperbaric oxygen (HBO)on neuropathic pain and detect the expression of Wnt/β-catenin signaling pathway in the mechanism of treatment. Methods A total of 30 healthy male SD rats were randomly divided into three groups (n =10):group S(sham group),group CCI(chronic sciatic nerve constrictive injury group),group HBO(HBO treat-ment for seven days group).Rats of group HBO received HBO one time per day for 7 days since the 1st day after surgery.Rats of group S and group CCI were just placed inside the chamber for approxi-mately 100 min,no HBO treatment.The mechanical withdrawal threshold (MWT)and thermal with-drawal latency (TWL)of all rats were measured on 1 d before CCI,1 d,3 d,5 d,7 d after CCI respec-tively.The animals were sacrificed after the last measurement of pain threshold,and the lumbar spinal cord specimen were taken to detect the expression of Wnt3a,β-catenin by immuno-histochemis-try and Western blot analysis.Results Compared with group S,MWT decreased significantly and TWL shortened significantly in CCT and HBO groups at 1,3,5,7 d after operation (P <0.05).Com-pared with group CCI,MWT was elevated and TWL was prolonged in group HBO at 1,3,5,7 d after operation (P <0.05).The Wnt3a,β-catenin expression increased after CCI treatment compared with group S and group HBO (P <0.05).Compared with group CCI,the expression of Wnt3a,β-catenin decreased significantly in the group HBO and group S at 7 d after operation (P <0.05).There was no significant difference between group S and group HBO.Conclusion HBO post-conditioning may relieve the neuropathic pain of rats by inhibiting the activation of spinal path of Wnt3a,β-catenin.

Objective To investigate the influence of hyperactivity, Stereotyped behaviors , self-injury and irritabili?ty on parenting stress and emotions of the caregivers for patients with pervasive developmental disorders (PDDs). Methods Abnormal behaviors during last month were assessed in 138 PDDs patients by using Aberrant Behavior Checklist (ABC) and Conners Index of Hyperactivity (CIH). The parenting stress and the emotional state of the patients’parents were evalu?ated by the Caregiver Strain Questionnaire (CGSQ) and Hospital Anxiety and Depression Scale (HAD), respectively. Re?sults Anxiety, depression and combination of anxiety and depression were present in 6.2%, 17.8%and 29.5%of PDDs caregivers, respectively. The partial correlation analysis showed that CGSQ score of patients’parents positively correlated with CIH score (r=0.201, P=0.023) and stereotyped act (r=0.189, P=0.033) of the patients, and negatively correlated with stereotyped speech (r=-0.219, P=0.013). The anxious mood of parents positively correlated with stereotyped act (r=0.206, P=0.021). Conclusions Anxiety and depression are common in caregivers of PDDs. Except for stereotyped speech, aber?rant behaviors of the PDDs increase parenting stress and worsen anxious mood of caregivers.

Aim To investigate the effects of dopamine(DA)on insulin secretion from rat islets and the possible mechanism.Methods Pancreatic islets were obtained from the pancreatic of male SD rats by collagenase P digestion and histopaque-1077 density gradient separation.Insulin secretion experiment was used to observe the change of insulin release after DA treatments.As to study the potential mechanisms of the effects of DA,patch-clamp experiment and calcuim image technique were applied to test the depolarization-evoked Ca2+ currents,action potential duration and intracellular Ca2+ concentration.Results In 2.8 mmol·L-1 glucose,DA had no effect on insulin secretion;in 16.7 mmol·L-1 glucose,dopamine inhibited insulin secretion in a dose-dependent manner.DA inhibited the inward calcium current,shorten the action potential duration,and reduced the intracellular Ca2+ concentration.Conclusion DA inhibits insulin secretion maybe by decreasing the inward calcium current leading to shorten the action potential duration and reduce the intracellular Ca2+ concentration.

Objective:To establish the model of rats with UC by 2,4,6 trinitrobenzene sulfonic acid ( TNBS)/ethanol to understand the changes of IL-17,IL-23,TGF-β1,IFN-γin pathogenesis of ulcerative colitis (UC) and the impacts of mesalazine,mont-morillonite powder and clostridium on that.Methods:85 rats were divided randomly into 6 groups including the model ,mesalazine, montmorillonite,clostridium,mesalazine combined with montmorillonite powder group (15 rats per group ) and an additional control group of 10 normal rats.TNBS/ethanol was used to establish the model of rats with UC.The dosage of model, mesalazine, montmorillonite powder ,clostridium and mesalazine combined with montmorillonite powder were converted by surface area of rat and given to the rats by gastric-tube daily.All rats were executed at the 12th day of the molding and treatment ,and the blood and colon samples were collected.The content of IL-17,IL-23,TGF-β1,IFN-γwas measured in the blood by the ELISA method.The different changes of the four cytokines were compared separately.Results: ( 1 ) TNBS/ethanol was used to establish the model of rats with UC.The obvious inflammation can be observed on distal colon of rats by pathologic sections of HE stained .(2) The levels of plasma IL-17,IL-23 and IFN-γin the model,mesalazine,montmorillonite,clostridium and mesalazine combined with montmorillonite powder group were higher than ones in the control gruop (P<0.05),meanwhile,the levels of plasma TGF-β1 are lower (P<0.05).3.Comparing with the model group,the levels of plasma IL-17,IL-23 and IFN-γin the mesalazine,montmorillonite,clostridium and mesalazine combined with montmorillonite powder group were lower , and the levels of TGF-β1 were higer.The differences have statistic significative ( P<0.05).(4)Comparing the efficacy of treatment among mesalazine ,montmorillonite powder,clostridium and mesalazine combined with montmorillonite powder ,mesalazine and mesalazine combined with montmorillonite powder gets the best results ( P<0.05 ).The efficacy between montmorillonite powder and clostridium is similar.Conclusion:(1) TNBS/ethanol can be used to establish the model of rats with UC and can be successfully approved by the measurement of symptoms and pathologic investigation .(2)The IL-17,IL-23 and IFN-γare very active higher in the blood of rats with experimental ulcerative colitis induced by TNBS /ethanol, and have a positive correlation with inflammation.The TGF-β1 is in decrease in the blood of rats with colitis , and has a Negative Correlation with inflammation.(3)Mesalazine,montmorillonite powder,clostridium and mesalazine combined with montmorillonite powder may renovate the damage of inflammatory tissues of rats with experimental ulcerative colitis , and relieve the symptom of inflammation by reducing exudation of proinflammatory cytokines IL-17, IL-23 and immune regulatory cytokines IFN-γby producing the exudation of proinflammatory cytokines TGF-β1 to be good for recovery of UC.

According to the association between liver injury and pregnancy, liver diseases during pregnancy can be classified as pregnancy-specific liver diseases and liver diseases with pregnancy. Pregnancy-specific liver diseases refer to the liver diseases that only occur during pregnancy, while liver diseases with pregnancy refer to pregnancy with previous liver diseases. Due to the particularity of maternal and fetal health during pregnancy, the diagnosis and treatment of liver diseases during pregnancy is challenging for both obstetricians and hepatologists. Rapid identification, diagnosis, and treatment of related diseases during pregnancy are very important for the prognosis of the mother and the fetus. This article summarizes and reviews the research advances in the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of liver diseases during pregnancy, in order to provide a reference for more clinicians.

Objective:To investigate the clinical efficacy of Omalizumab in the treatment of moderate-to-severe allergic asthma with allergic comorbidities in children.Methods:The clinical data of 50 children with moderate-to-severe allergic asthma and allergic comorbidities, who were treated with Omalizumab and completed 12-month follow-up in the Department of Pediatrics of Peking University First Hospital from July 2018 to March 2022, were retrospectively analyzed.A comparison was performed on the scale scores of childhood allergic asthma and allergic comorbidities including allergic rhinitis (AR) and chronic spontaneous urticaria (CSU), pulmonary function test indices and fractional exhaled nitric oxide (FeNO) concentration before and after treating with Omalizumab.The data were compared by ANOVA, paired t-test, chi- square test and rank sum test. Results:(1)Improvement of clinical symptoms: after 12 months of Omalizumab treatment, the childhood asthma control test score of 42 children aged ≤11 years increased from (20.98±5.03) points to (26.95±0.22) points ( F=18.189, P<0.001). The asthma control questionnaire 7 score of 50 children decreased from (0.89±0.11) points to (0.10±0.02) points ( F=5.662, P=0.006). The score of visual analogue scale of 47 children with AR decreased from (11.00±1.65) points to (0.2±0.14) points ( F=14.901, P<0.001), and the urticaria control test score of 13 children with CSU decreased from (4.82±0.88) points to (1.87±0.61) points ( F=4.329, P=0.018). (2)Improvement of quality of life: compared with those before treatment, the pediatric asthma quality of life questionnaire score in 50 children increased from (124.50±32.13) points to (159.40±6.21) points ( F=12.052, P<0.001), and global evaluation of asthma treatment effectiveness decreased from (2.23±0.70) points to (1.07±0.26) points ( F=68.865, P<0.001) after Omalizumab treatment for 12 months.(3)Improvement of pulmonary function results: after 12 months of Omalizumab treatment, the number of children with forced expiratory volume in one second/forced vital capacity< 80% decreased from 13 cases (26%) to 1 case (2%), and the values increased from (91.39±12.88)% to (96.96±8.54)%( χ2=11.960; t=2.486, all P<0.05). The peak expiratory flow of predicted value increased from (86.73±16.05)% to (94.01±13.11)% ( t=2.445, P<0.05). The number of children with two indicators among the forced expiratory flow at 50% of forced vital capacity exhaled, forced expiratory flow at 75% of forced vital capacity exhaled and maximal mid-expiratory flow lower than 65% decreased from 31 cases (62%) to 7 cases (14%) ( χ2=24.450, P<0.001). There was no significant difference in FeNO concentration before and after treatment ( P>0.05). Safety of Omalizumab: no obvious adverse reactions were found during treatment and follow-up. Conclusions:Omalizumab can significantly improve the clinical symptoms, small airway function and quality of life of children with allergic asthma and concomitant AR or CSU.It is a potential targeted drug for treating a variety of allergic diseases in children.

OBJECTIVETo examine the main effect of 10 Peroxisome proliferators-activated receptor (PPAR) SNP in contribution to non-HDL-C and study whether there is an interaction in the 10 SNPs.

METHODSParticipants were recruited within the framework of the PMMJS (Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu province) cohort-population-survey, which was initiated from April 1999 to June 2004, and 5-year follow-up data from total 4 582 subjects were obtained between March 2006 and October 2007. A total of 4 083 participants received follow-up examination. After excluding subjects who had experienced stroke or exhibited cardiovascular disease, type 2 diabetes or a BMI <18.5 kg/m(2), a total of 820 unrelated individual subjects were selected from 3 731 subjects on October of 2009. Blood samples which were collected at the baseline were subjected to PPARα, PPARδ and PPARγ 10 SNPs genotype analysis. Logistic regression model was used to examine the association between 10 SNPs in the PPARs and non-HDL-C. Interactions within the 10 SNP were explored by using the Generalized Multifactor Dimensionality Reduction (GMDR).

RESULTSA total of 820 participants (mean age was 50.05±9.41) were included in the study and 270 were males and 550 were females. Single-locus analysis showed that after adjusting gender, age, smoking, alcohol consumption, physical activity, high-fat diet and low-fiber diet factors, rs1800206-V and rs3856806-T were significantly associated with higher non-HDL-C levels. V allele (LV + VV genotype) carriers of rs1800206 have a average non-HDL-C levels on (3.15 ± 0.89)mg/L (F = 15.01, P = 0.002); T allele (CT+TT genotype) carriers of rs3856806 have a average non-HDL-C levels on (3.03±1.01) mg/L (F = 9.87, P = 0.005). GMDR model analysis showed that after adjusting the same factors, two-locus model, five-locus model, six-locus model and seven-order interaction models were all statistically significant (P<0.05), and the seven-locus model (rs1800206, rs3856806, rs135539, rs4253778, rs2016520, rs1805192, rs709158) was the best model (P = 0.001), the cross-validation consistency was 10/10 and testing accuracy was 0.656.

CONCLUSIONRs1800206 and rs3856806 were significantly associated with non-HDL-C. And there was an gene-gene interaction among rs1800206, rs3856806, rs1800206, rs135539, rs4253778, rs2016520, rs1805192, rs3856806 and rs709158 which could influence the non-HDL-C levels.

Alleles ; Cardiovascular Diseases ; Cholesterol ; Diabetes Mellitus, Type 2 ; Female ; Genetic Phenomena ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Overweight ; PPAR alpha ; PPAR delta ; PPAR gamma ; Peroxisome Proliferator-Activated Receptors ; Polymorphism, Single Nucleotide ; Stroke

This study reports the diagnosis and treatment of 2 children with isolated testicular recurrence (ITR) of acute B lymphoblastic leukemia (B-ALL) treated with CD 19 targeted chimeric antigen receptor T (CD 19 CAR-T) cells in May and December 2019 in the Department of Hematology and Oncology, Children′s Hospital of Soochow University, and explores the efficacy of CD 19 CAR-T cells therapy versus conventional radiotherapy and chemotherapy through literature review.Both cases were diagnosed as B-ALL by the morphologic, immunologic, cytogenetic and molecular biology methods.ITR was diagnosed by testicular biopsy at 60 months and 38 months after initial diagnosis in 2 cases, respectively.After infusion of CD 19 CAR-T cells at 7.0×10 6/kg and 1.5×10 7/kg, respectively for 7-10 days, testicular leukemia cell infiltration disappeared and complete remission was obtained.Among them, case 2 developed cytokine release syndrome and immune effector cell-related neurotoxicity syndrome after treatment, which was improved after drug intervention.It is suggested that CD 19 CAR-T cells are effective in the treatment of ITR in children, which may be an alternative to orchiectomy or local radiotherapy for ITR in children with B-ALL.