This study investigated the effect of epigenetic modification of maspin on extravillous trophoblastic function. The mRNA expression of maspin in placentae from normotensive and preeclamptic pregnant women was detected by RT-PCR. TEV-1 cells, a human first-trimester extravillous trophoblast cell line, were cultured and treated with CoCl(2) (300 μmol/L) to induce chemical hypoxia and with 5-aza (500 nmol/L) to induce demethylation. The mRNA expression of maspin in TEV-1 cells subjected to different treatments was determined by RT-PCR, and the proliferative and migratory abilities of TEV-1 cells were assessed by cell counting kit-8 (CCK-8) and Transwell assays. Our results showed that the maspin mRNA expression level in placentae from preeclamptic women was much higher than that from normotensive women. CoCl(2) or 5-aza could up-regulate the mRNA expression of maspin and significantly suppress the proliferation and migration of TEV-1 cells. It was concluded that the epigenetic modification in promoter region of maspin contributes to incomplete trophoblast invasion, which offers a novel approach for predicting and treating placental dysfunction.

This study investigated the effect of epigenetic modification of maspin on extravillous trophoblastic function. The mRNA expression of maspin in placentae from normotensive and preeclamptic pregnant women was detected by RT-PCR. TEV-1 cells, a human first-trimester extravillous trophoblast cell line, were cultured and treated with CoCl(2) (300 μmol/L) to induce chemical hypoxia and with 5-aza (500 nmol/L) to induce demethylation. The mRNA expression of maspin in TEV-1 cells subjected to different treatments was determined by RT-PCR, and the proliferative and migratory abilities of TEV-1 cells were assessed by cell counting kit-8 (CCK-8) and Transwell assays. Our results showed that the maspin mRNA expression level in placentae from preeclamptic women was much higher than that from normotensive women. CoCl(2) or 5-aza could up-regulate the mRNA expression of maspin and significantly suppress the proliferation and migration of TEV-1 cells. It was concluded that the epigenetic modification in promoter region of maspin contributes to incomplete trophoblast invasion, which offers a novel approach for predicting and treating placental dysfunction.
Adult ; Chorionic Villi ; physiology ; Epigenesis, Genetic ; genetics ; Female ; Humans ; Pregnancy ; Serpins ; genetics ; Trophoblasts ; physiology

OBJECTIVE：To systematically evaluate the efficacy an d s afety of apatinib combined with transcatheter arterial chemoembolization（TACE）in the treatment of moderate and advanced liver cancer ，and to provide evidence-based reference for rational drug use in the clinic. METHODS ：Retrieved from Cochrane Library ，Embase，PubMed，Web of Science ，SinoMed， CNKI，Wanfang，VIP database ，RCTs about apatinib combined with TACE （trial group ）versus TACE （control group ）in the treatment of moderate and advanced liver cancer were collected from inception to Sep. 2019. After screening the literature and extracting the data ，the quality of included literatures was evaluated by using bias risk assessment tool recommended by the Cochrane system evaluator manual 5.1.0 and the modified Jadad scale. Meta-analysis was carried out by using Stata 12.0 software. RESULTS：Totally 16 RCTs were included ，involving 1 043 patients. Results of Meta-analysis showed that objective response rate [OR ＝3.10，95％CI（2.38，4.03），P＜0.001]，disease control rate [OR ＝3.56，95％CI（2.62，4.83），P＜0.001] and survival rate [OR ＝2.40，95％ CI（1.86，3.10），P＜0.001]，the incidence of diarrhea [OR ＝2.27，95％ CI（1.21，4.24），P＝0.011]， hypertension [OR ＝6.97，95％ CI（1.21，40.15），P＝0.030]， proteinuria [OR ＝12.44，95％CI（2.51，61.71），P＝0.002] and com hand foot syndrome [OR ＝32.50，95％CI（12.03，87.77），P＝ 0.001] of trial group were significantly higher than those of control group. The serum level of VEGF [SMD ＝－ 3.64， 95％CI（－5.06，－2.22），P＜0.001]，MMP-9 [SMD＝－3.21，95％CI（－4.31，－2.10），P＜0.001]，AFP [SMD ＝－3.54， 95％CI（－7.03，－0.06），P＝0.046] after treatment ，the incidence of myelosuppression [OR ＝0.61，95％CI（0.39，0.97），P＝ 0.035]，fever [OR ＝0.63，95％CI（0.42，0.95），P＝0.027]，nausea and vomiting [OR ＝0.70，95％CI（0.51，0.97），P＝0.030] in trial group were significantly lower than those of control group. There was no statistical significance in the incidence of abdominal pain [OR ＝0.87，95％CI（0.54，1.39），P＝0.547] and skin itching [OR ＝1.63，95％CI（0.36，7.50），P＝0.530] between 2 groups. CONCLUSIONS：Apatinib combined with TACE can significantly improve clinical efficacy ，prolong survival time ，reduce tumor recurrence and metastasis. It can reduce the occurrence of related ADR as diarrhea after TACE ，but increase the occurrence of apatinib-related ADR as myelosuppression.

OBJECTIVE To systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization （TACE） combined with local ablation in the treatment of unresectable primary liver cancer （PLC）， and to provide evidence-based reference for rational clinical treatment. METHODS Retrieved from CNKI， Wanfang Data， VIP， PubMed， Embase， Cochrane Library， ClinicalTrials， Web of Science， Ovid and SinoMed， randomized controlled trial （RCT） about TACE combined with local ablation （trial group） versus TACE （control group） were collected. After screening the literature and extracting the data， the bias risk assessment tool recommended by the Cochrane System Evaluator Manual 5.1.0 was used to evaluate the quality of the included literature； Stata14.0 software was used for meta-analysis. RESULTS A total of 39 RCTs were included， including 2 294 patients， involving 6 interventions， i.e. TACE， TACE + radiofrequency ablation （RFA）， TACE + microwave ablation （MWA）， TACE + absolute ethanol injection （PEI）， TACE + cryoablation （CRA）， TACE + high-intensity ultrasound focused ablation （HIFU）， and 4 chemotherapeutic drugs， i.e. platinum， anthracycline， pyrimidine analogues， and polypeptides. The results of meta-analysis showed that in terms of objective remission rate， TACE+RFA， TACE+HIFU and TACE+MWA were higher； in terms of 1-year survival rate， TACE+PEI， TACE+HIFU and TACE+MWA were higher； in terms of 2-year survival rate， TACE+HIFU， TACE+MWA and TACE+PEI were higher； in terms of 3-year survival rate， TACE+HIFU， TACE+PEI and TACE+RFA were higher； in terms of security， TACE+MWA， TACE+RFA and TACE were 643295494@qq.com higher； there was no significant difference in the efficacy of 4 chemotherapeutic drugs in TACE+MWA （P＞0.05）. CONCLUSIONS For patients with unresectable PLC， TACE+ MWA has good efficacy and safety， which is the best combination； the 4 chemotherapeutic drugs in TACE+MWA are all effective， and suitable chemotherapeutic drugs can be selected individually.

OBJECTIVE：To improve the level of pharmaceutical care，enhance the professional value and social status of pharmacists by clarifying the development process of pharmaceutical care and summarizing the value of pharmacists in pharmaceutical care. METHODS：The development process of pharmaceutical care at home and abroad（service objects，service contents and service methods）was summarized；the current situation of pharmaceutical care in China was analyzed；the value of pharmaceutical care were defined in respects of rational drug use，humanistic value and medical resources. The development of pharmaceutical care in the future was prospected. RESULTS & CONCLUSIONS：The development of pharmaceutical care can be divided into three stages：“drug supply as the center”“promoting rational drug use as the center”and“patients as the center”，and the service objects，service contents and service methods in different stages are expanding and diversifying. Compared with developed countries，the overall level of pharmaceutical care in China lags behind，and there are differences in level of pharmaceutical care modes in hospitals at different levels. Pharmacists ensure the safety，effectiveness and economy of drug use through pharmaceutical care，and promote rational drug use；the compliance，quality of life and satisfaction of patients have been improved through pharmaceutical care；pharmacists participate in medical quality management to save medical and health resources through pharmaceutical care. Pharmaceutical care，as an important part of the medical and health system，plays an important and irreplaceable role in the medical process，which is suggested that the relevant government departments should fully understand the value of pharmaceutical care and further strengthen their support for pharmaceutical care；pharmaceutical staff should improve their self-cultivation and cooperate with other disciplines to achieve the sustainable development of hospital pharmacy in different regions and medical institutions.

BACKGROUNDAn zidovudine (AZT)-substitution regimen containing 24-week stavudine (d4T) followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associated with d4T in resource-limited settings. However, evidence is scarce. This study aims to assess the efficacy and safety of AZT-substitution regimen, aiming to find a regimen with better efficacy, less adverse events, and more affordability in resource-limited settings.

METHODSThis prospective, multicenter study enrolled 499 (190 on d4T regimen, 172 on AZT regimen, and 137 on AZT-substitution regimen) HIV-1-infected subjects who initiated combined antiretroviral therapy and attended follow-up visits over 96 weeks from 2009 to 2011. Lamivudine (3TC) and either nevirapine (NVP) or efavirenz (EFV) were the other two drugs in the antiretroviral regimens. Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96.

RESULTSIn terms of hematological adverse effects, AZT-substitution group had similar safety profiles to d4T group and was superior to AZT group. In comparison with AZT-substitution group, AZT group was associated with higher risk of developing anemia (adjusted hazard ratio (aHR) for anemia ≥ grade II, 8.44, 95% CI 1.81-39.46) and neutropenia (aHR for neutropenia ≥ grade II, 1.86, 95% CI 1.19-2.93). The prevalence of lipodystrophy in d4T group was 19.5%, while that in AZT-substitution group was zero. As to antiretroviral efficacy, these three groups showed no differences.

CONCLUSIONAZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.

Adult ; Anti-HIV Agents ; administration & dosage ; adverse effects ; therapeutic use ; Female ; HIV Infections ; drug therapy ; Humans ; Male ; Middle Aged ; Prospective Studies ; Stavudine ; administration & dosage ; adverse effects ; therapeutic use ; Zidovudine ; administration & dosage ; adverse effects ; therapeutic use