Objective To assess the effect of clomiphene citrate(CC)on the proliferative stage of endometrium by the addition of low-doge estrogen(progynova,PGV)and aspirin.Methods Sixty women with unexplained infertility were divided into 4 groups randomly.Untreated group,CC treated group(C group),CC+PGV treated group(CE group)and CC+PGV+aspirin treated group(CEA group),each group Was 15 cases.Endometrium thickness,pattern of endometrium and resistant index(RI)of uterine artery were detected by ultrasound,all at end proliferative stage of endometrium.Results The endometrium thickness,the rate of the endometrium thickness≥8 mm and the rate of A-endometrium in C group were significantly less than those in other 3 groups(P<0.05).The rate of A-endometrium in CE group was significantly less than that in untreated group and CEA group(P<0.05).The number of follicle diameter≥15 mm in untreated group(1.01±0.25)was signifieantly less than that in other 3 groups(1.56±0.64,1.52±0.70,1.61±0.67)(P<0.os).RI of uterine artery in C group(0.93±0.07)and CE group(0.95±0.04)were significantly higher than that in untreated group(0.81±0.05)and CEA group(0.83±0.03)(P<0.05).Conclusion Low-dese estrogen can reverse the deleterious effect of CC on.endometrial development,and low-dose estrogen and aspirin can promote uterine perfusion and improve uterine compatibility.

Objective To use tetraploid embryo complementation combined with gene transfer to produce genetically modified embryonic stem cells (EsCs) clones. Methods In this study, EGFP was introduced into ESCs by electroporation, and transfected positive cells were selected by G418 resistance. The tetraploid embryos were obtained from diploid blastomere electrofusion which preformed at 2-cell stage. Afterwards, 19-21 EGFP-ESCs were inserted into each tetraploid blastocyst cavity by piezo drilled microinjection,then the injected blastocysts were transferred into the uterus of pseudo-pregnancy at 2.5-day or the oviduct of 0.5-day female mice. Results The transfected ESCs maintained normal karyotype even after long-term passage (2n=40). The rate of fusion was 95.07%, and the developmental rate of tetraploid blastocyst was 95%.Totally 410 injected blastocysts were obtained. Unfortunately, we have not got any vital offsprings, except 151 implantation sites (pseudo-pregnancy 2.5 days:29.41%;the oviduct of half one day:64.37%). Furthermore, scattered EGFP expressions in transgenic fetus were observed under invert fluorescent microscope. Conclusion The transfected ESCs were observed in transgenic fetus, and the implantation rate in oviduct was higher than that in uterine.

ObjectiveTo investigate the effect of macrophages (MCs) on the differentiation of mouse induced pluripotent stem cells (iPSCs) into hepatic progenitor cells (HPCs). MethodsA total of 24 C57BL/6N mice were used to obtain MCs by peritoneal irrigation, and the supernatant was collected to obtain the conditioned medium of MCs (MC-CDM). Activin A, bone morphogenetic protein 4, and fibroblast growth factor were used to induce the differentiation of mouse iPSCs into HPCs. The differentiation of HPCs were randomly divided into control group (normal medium) and experimental group (MC group; use of MC-CDM medium on day 5 of induction). Morphology, immunofluorescence assay, and Western blot were used to compare the morphology of HPCs and the expression of related proteins between the control group and the MC group. The t-test was used for comparison of continuous data between two groups. ResultsHPCs derived from iPSCs were established in vitro, and HPCs had the potential to differentiate into hepatocytes. Immunofluorescence assay showed that compared with the D12 control group, the D12 MC group had a significant increase in the protein expression of the HPC-specific protein CK19 (0.901±0.072 vs 0.686±0.097, t=-3.093, P＜0.05). Western blot showed that compared with the D12 control group, the D12 MC group had a significant increase in the protein expression of the HPC-related protein CK19 (1.922±0.103 vs 1.448±0.012, t =-7.881, P ＜005), as well as a significant increase in the protein expression of the autophagy-related protein LC3 (1.392±0.042 vs 1.101±0048, t =-5.978, P＜005). ConclusionMCs can promote the differentiation of mouse iPSCs into HPCs, possibly by increasing the autophagy level of HPCs.

OBJECTIVE：To study the effects of different penetration enhancers on in vitro transdermal permeation of Flavaspidic acid BB cream. METHODS ：Flavaspidic acid BB cream was prepared ，containing 11 kinds of different penetration enhancers as 1％ azone，2％ azone，3％ azone，4％ azone，1％ menthol，1％ propylene glycol ，1％ oleic acid ，1％ azone+1％ menthol，1％ azone+1％ propanediol，1％ azone+1％ oleic acid or 1％ menthol+1％ propanediol. Modified Franz diffusion cell was adopted using abdominal skin of isolated male rat as transdermal barrier. The content of flavaspidic acid BB was determined by UPLC. The accumulative transdermal amount （Q24 h）and percutaneous permeability （Jss）within 24 h were calculated ；and compared with Flavaspidic acid BB cream without transdermal enhancer ，the enhancement ratio （ER）was calculated. RESULTS ： Q24 h of Flavaspidic acid BB cream with above 11 kinds of transdermal enhancers were （82.96±7.15），（80.17±0.66），（78.22± 1.87），（73.53±1.24），（35.65±2.23），（34.02±1.73），（42.68±2.66），（33.94±1.37），（34.16±1.54），（46.78±1.21），（43.66±1.69） μg/cm2，respectively. Jss value were （5.26±0.10），（4.69±0.12），（4.45±0.45），（4.00±0.06），（3.74±0.33），（3.23±0.18）， （3.73±0.53），（3.14±0.47），（3.54±0.11），（3.98±0.34），（4.34±0.14）μg（/ cm2·h），respectively. ER were 2.055，1.831，1.738， 1.564，1.462，1.263，1.456，1.227，1.385，1.557，1.698，respectively. CONCLUSIONS ：All of the above transdermal absorption enhancers can enhance the percutaneous absorption of Flavaspidic acid BB cream ，among which ，1％ azone is the best.

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.