Topical delivery of drugs in the treatment of high-grade cervical squamous intraepithelial lesions: A meta-analysis.

OBJECTIVE: The present study aims to evaluate the efficacy and effect of localized delivery of drugs in the treatment of high-grade squamous intraepithelial lesion (HSIL) based on a meta-analysis. STUDY DESIGN: Databases including Cochrane Library, PubMed, Embase, Scopus, CNKI, and Wanfang were searched from their inception till August 2022. Randomized controlled trials (RCTs) that compared the efficacy of drugs and surgery in the treatment of HSIL were collected. A meta-analysis was performed using the software of Review Manager (version 5.4.1). RESULTS: Eight RCTs involving 523 patients were included in the meta-analysis. For HSIL, the rate of cervical lesions histological regression was 69.85 % in the surgery group and 59.88 % in the drug group, there was no significant difference between the two groups [OR = 0.45, 95 % CI (0.07, 3.03), P = 0.41]. The histological regression rate of cervical lesions in the placebo group was 37.76 %, and the difference between the drug group and the placebo group was statistically significant [OR = 4.94, 95 % CI (2.65, 9.20), P < 0.00001]. CONCLUSION: A total of four drugs were involved in the eight RCTS included in this study, which were imiquimod, 5-fluorouracil (5-FU), cidofovir and interferon. The results showed that although drug administration was effective in the histological regression of HSIL, the efficacy was less than about 10% of surgical treatment. Considering the recurrence of the disease after surgery and the problems of abortion, premature delivery and premature rupture of membranes after cervical conization in reproductive women, drug therapy can be used as a supplement to surgery or conservative treatment to promote the histological regression of cervical lesions in patients with HSIL.

Analysis of Compressive Fatigue Failure of Recycled Aggregate Concrete.

Using recycled aggregate in concrete is effective in recycling construction and demolition waste. It is of critical significance to understand the fatigue properties of recycled aggregate concrete (RAC) to implement it safely in structures subjected to repeated or fatigue load. In this study, a series of fatigue tests was performed to investigate the compressive fatigue behavior of RAC. The performance of interfacial transition zones (ITZs) was analyzed by nanoindentation. Moreover, the influence of ITZs on the fatigue life of RAC was discussed. The results showed that the fatigue life of RAC obeyed the Weibull distribution, and the S-N-p equation could be obtained based on the fitting of Weibull parameters. In the high cycle fatigue zone (N≥104), the fatigue life of RAC was lower than that of natural aggregate concrete (NAC) under the same stress level. The fatigue deformation of RAC presented a three-stage deformation regularity, and the maximum deformation at the point of fatigue failure closely matched the monotonic stress-strain envelope. The multiple ITZs matched the weak areas of RAC, and the negative effect of ITZs on the fatigue life of RAC in the high cycle fatigue zone was found to be greater than that of NAC.

Comparison of Mechanisms of Endothelial Cell Protections Between High-Density Lipoprotein and Apolipoprotein A-I Mimetic Peptide.

Apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, exhibits anti-atherogenic effects similar to high-density lipoprotein (HDL). However, it remains elusive whether D-4F and HDL share similar molecular mechanisms underlying anti-atherogenic effects and endothelial cell protections. We here compared the metabolic changes in endothelial cells induced by D-4F and HDL against oxidized low-density lipoprotein (ox-LDL), which may be of benefit to understanding the protective mechanisms of HDL and D-4F. Functional assays, including wound healing, transwell migration, and tube formation, were used to evaluate the pro-angiogenic effects of HDL and D-4F. NMR-based metabolomic analysis was employed to explore the protective mechanisms underlying HDL and D-4F. Partial least-squares discriminant analysis (PLS-DA) was performed to assess metabolic profiles, and orthogonal PLS-DA (OPLS-DA) was carried out to identify characteristic metabolites. Moreover, significantly altered metabolic pathways were also analyzed. We found that ox-LDL impaired the migration and tube formation of endothelial cells. Metabolomic analysis showed that ox-LDL triggered oxidative stress, impaired glycolysis, and enhanced glycerophospholipid metabolism. Both HDL and D-4F improved the migration and angiogenesis of endothelial cells, alleviated oxidative stress, and ameliorated disordered glycolysis impaired by ox-LDL. Strikingly, HDL partially attenuated the disturbed glycerophospholipid metabolism, whereas D-4F did not show this effect. In summary, although D-4F shared the similar protective effects with HDL on the migration and angiogenesis of endothelial cells, it could not deduce the molecular mechanisms of HDL completely. Nevertheless, D-4F possesses the potentiality to be exploited as clinically applicable agent for endothelial cell protection and cardiovascular disease treatment.

Tissue remodeling after ocular surface reconstruction with denuded amniotic membrane.

Amniotic membrane (AM) has been widely used as a temporary or permanent graft in the treatment of various ocular surface diseases. In this study, we compared the epithelial wound healing and tissue remodeling after ocular surface reconstruction with intact amniotic membrane (iAM) or denuded amniotic membrane (dAM). Partial limbal and bulbar conjunctival removal was performed on New Zealand rabbits followed by transplantation of cryo-preserved human iAM or dAM. In vivo observation showed that the epithelial ingrowth was faster on dAM compared to iAM after AM transplantation. Histological observation showed prominent epithelial stratification and increased goblet cell number on dAM after 2 weeks of follow up. Collagen VII degraded in dAM within 2 weeks, while remained in iAM even after 3 weeks. The number of macrophages and α-SMA positive cells in the stroma of remodelized conjunctiva in the dAM transplantation group was considerably less. In conclusion, dAM facilitates epithelial repopulation and goblet cell differentiation, further reduces inflammation and scar formation during conjunctival and corneal limbal reconstruction.

The apolipoprotein A-I mimetic peptide, D-4F, alleviates ox-LDL-induced oxidative stress and promotes endothelial repair through the eNOS/HO-1 pathway.

Apolipoprotein A-I (apoA-I) mimetic peptide exerts many anti-atherogenic properties. However, the underlying mechanisms related to the endothelial protective effects remain elusive. In this study, the apoA-I mimetic peptide, D-4F, was used. Proliferation assay, wound healing, and transwell migration experiments showed that D-4F improved the impaired endothelial proliferation and migration resulting from ox-LDL. Endothelial adhesion molecules expression and monocyte adhesion assay demonstrated that D-4F inhibited endothelial inflammation. Caspase-3 activation and TUNEL stain indicated that D-4F reduced endothelial cell apoptosis. A pivotal anti-oxidant enzyme, heme oxygenase-1 (HO-1) was upregulated by D-4F. The Akt/AMPK/eNOS pathways were involved in the expression of HO-1 induced by D-4F. Moreover, the anti-oxidation, pro-proliferation, and pro-migration capacities of D-4F were diminished by the inhibitors of both eNOS (L-NAME) and HO-1 (Znpp). Additionally, downregulation of ATP-binding cassette transporter A1 (ABCA1) by siRNA abolished the activation of Akt, AMPK and eNOS, and reduced the upregulation of HO-1 triggered by D-4F. Furthermore, D-4F promoted the reendothelialization of injured intima in carotid artery injury model of C57BL/6J mice in vivo. In summary, these findings suggested that D-4F might be a powerful candidate in the protection of endothelial cells and the prevention of cardiovascular disease (CVD).

Efficacy and safety of misoprostol compared with the dinoprostone for labor induction at term: a meta-analysis.

OBJECTIVE: The purpose of this study was to compare the efficacy and safety of intravaginal misoprostol and the dinoprostone vaginal insert for labor induction at term. METHOD: PubMed, EMBASE, MEDLINE, CNKI, EBSCO and the Cochrane Library were searched for articles published in English language from 2000 to 2014, Using the keywords misoprostol, dinoprostone, labor induction. RESULTS: Eight of 436 studies (1669 women) identified met the criteria for meta-analysis. We assigned a quality rating to each included article. The use of misoprostol showed less oxytocin augmentation when compared with dinoprostone (RR = 0.78, 95% CI = 0.67-0.90). There was no difference in the risk of tachysystole (RR = 1.18, 95% CI = 0.78-1.79), uterine hyperstimulation (RR = 1.24, 95% CI = 0.75-2.06), vaginal delivery within 24 h (RR = 1.10, 95% CI = 1.00-1.20), cesarean delivery (RR = 0.84, 95% CI = 0.56-1.24), Neonatal Intensive Care Unit admission (RR = 0.86, 95% CI = 0.58-1.28), Apgar scores <7 in 5 min (RR = 1.18, 95% CI = 0.39-3.63) between misoprostol and dinoprostone. CONCLUSION: Misoprostol compared with dinoprostone appears to show less oxytocin augmentation for labor induction at term. The other outcomes of both drugs were similar. However, these findings were based on small-scale trials. Further studies assessing the effectiveness and safety of misoprostol and dinoprostone in selected groups of patients are warranted.

Which is the safer method of labor induction for oligohydramnios women? Transcervical double balloon catheter or dinoprostone vaginal insert.

OBJECTIVE: To compare the effectiveness and safety of two cervical ripening methods in term primiparous women with unfavorable cervices and oligohydramnios. METHODS: Women (126 cases) with oligohydramnios [amniotic fluid index (AFI) ≤5 cm] and a low Bishop Score (≤6) were assigned randomly to use double balloon catheter (mechanical method group, 67 cases) or dinoprostone 10 mg controlled-release vaginal insert (pharmacological method group, 59 cases) for induction of labor. The study's primary outcome was caesarean section rate (CSR). The secondary outcome measures included maternal and neonatal morbidity, an incremental changes in Bishop Score, and intrapartum interventions. RESULTS: There was no significant difference between the mechanical method group and the pharmacological method group in CSR and change in Bishop Score. Tacysystole, non-reassuring fetal heart patterns, and cases of newborn umbilical-cord arterial blood pH<7.1 were significantly lower with the mechanical method compared with the pharmacological method (p < 0.05). More patients needed additional intervention in the mechanical method group. CONCLUSIONS: Both methods resulted in a similar CSR. Double balloon catheter resulted in fewer labor complications, but more frequent use of oxytocin and amniotomy. Compared with dinoprostone vaginal insert, double balloon catheter use may be less problematic in women with oligohydramnios.