Effectiveness of TruScreen for detecting CIN2+ in women with ThinPrep cytologic test results indicating atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions.

Objective: To evaluate the effectiveness of TruScreen (TS) for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with abnormal ThinPrep cytologic test (TCT) results. Methods: 466 women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) were enrolled and underwent TS, colposcopy and biopsy examination. Results: Compared with the high-risk human papillomavirus (hrHPV) test for CIN2+, significantly higher specificity of TS, combined TS and hrHPV (69.6 and 75.0 vs 36.8% in ASCUS; 59.0 and 69.9 vs 30.1% in LSIL), significantly higher positive predictive value of combined TS and hrHPV were observed (32.7 vs 24.6% in ASCUS; 47.9 vs 35.6% in LSIL). Conclusion: TS combined with hrHPV showed better performance in diagnosing CIN2+ in ASCUS/LSIL.

Fance deficiency inhibits primordial germ cell proliferation associated with transcription-replication conflicts accumulate and DNA repair defects.

Fanconi anemia (FA) gene mutations are critical components in the genetic etiology of premature ovarian insufficiency (POI). Fance-/- mice detected meiotic arrest of primordial germ cells (PGCs) as early as embryonic day (E) 13.5 and exhibited decreased ovarian reserve after birth. However, the mechanism of Fance defect leading to dysgenesis of PGCs is unclear. We aimed to explore the effect of Fance defects on mitotic proliferation of PGCs. Combined with transcriptomic sequencing and validation, we examined the effect of Fance defects on cell cycle, transcription-replication conflicts (TRCs), and multiple DNA repair pathways in PGCs during active DNA replication at E11.5 and E12.5. Results showed Fance defects cause decreased numbers of PGCs during rapid mitosis at E11.5 and E12.5. Mitotic cell cycle progression of Fance-/- PGCs was blocked at E11.5 and E12.5, shown by decreased cell proportions in S and G2 phases and increased cell proportions in M phase. RNA-seq suggested the mechanisms involved in DNA replication and repair. We found Fance-/- PGCs accumulate TRCs during active DNA replication at E11.5 and E12.5. Fance-/- PGCs down-regulate multiple DNA repair pathways at E11.5 and E12.5 including the FA pathway, homologous recombination (HR) pathway, and base excision repair (BER) pathway. In conclusion, Fance defect impaired the mitotic proliferation of PGCs leading to rapidly decreased numbers and abnormal cell cycle distribution. Proliferation inhibition of Fance-/- PGCs was associated with accumulated TRCs and down-regulation of FA, HR, BER pathways. These provided a theoretical basis for identifying the inherited etiology and guiding potential fertility management for POI.

Efficacy and Safety of Ultrasound-Guided High-Intensity Focused Ultrasound Ablation in Women With Multiple Uterine Fibroids: An Exploratory Study.

OBJECTIVE: The aim of the work described here was to explore the clinical efficacy and safety of ultrasound-guided high-intensity focused ultrasound (USg-HIFU) treatment in women with multiple fibroids and identify the characteristic parameters predicting USg-HIFU efficacy in multiple fibroids. METHODS: From February 2021 to August 2022, 138 patients with multiple fibroids (group A comprising 125 patients with two to four fibroids and 13 patients with five or more fibroids) and 149 patients with solitary fibroids (group B) were included. HIFU treatment information, efficacy comparisons and adverse events were recorded. A nomogram model of the characteristic parameters used to predict the efficacy of USg-HIFU in multiple fibroids was established. RESULTS: After USg-HIFU treatment, the statistical comparison of pre-operative versus post-operative symptom scores and fibroid volume in the two groups indicated obvious symptom relief and substantial shrinkage of fibroid volume (all p values <0.001). Nevertheless, group A required more energy and longer treatment and sonication times to achieve a 70% non-perfused volume (NPV) ratio, and had a lower energy efficiency factor than group B (all p values <0.05). No severe complications were observed in either group. The nomogram model included fibroid volume, fibroid location and signal intensity on T2-weighted imaging (T2WI). The area under the receiver operating characteristic curve and the accuracy of the model were 0.698 and 0.686, respectively. CONCLUSION: USg-HIFU appears to be an effective and safe treatment option for multiple fibroids. Knowledge of the fibroid volume, location and signal intensity on T2WI may help determine the efficacy of USg-HIFU in multiple fibroids.

Optical Coherence Tomography Can Reduce Colposcopic Referral Rates in Patients With High-Risk Human Papillomavirus.

OBJECTIVE: This study aimed to evaluate the feasibility of combined human papillomavirus (HPV) and optical coherence tomography (OCT) cervical cancer screening strategies. MATERIALS AND METHODS: The OCT and cytology results were compared with the pathological results to calculate the sensitivity, specificity, positive predictive value, negative predictive value, and immediate cervical intraepithelial neoplasia grade 3 or worse (CIN3+) risk. The authors compared the efficiency of colposcopy by using different triage strategies. They discussed differentiation in OCT screening in different age groups. RESULTS: Eight hundred thirteen participants with high-risk HPV-positive and cervical cytology results underwent OCT before colposcopy between March 1 and October 1, 2021. The HPV16/18 genotyping with OCT triage has a specificity of CIN3+ lesions (61.1%; 95% CI = 57.6%-64.6%), intraepithelial neoplasia grade 2 or worse (CIN2+) (66.0%; 95% CI = 62.4%-69.6%). The HPV16/18 genotyping with cytology triage has a specificity of CIN3+ (44.0%; 95% CI = 40.4%-47.6%), CIN2+ (47.0%; 95% CI = 43.2%-50.8%). The OCT triage has a higher positive predictive value compared with the cytology, with a significant difference in CIN2+ lesions (45.0%; 95% CI = 38.8%-51.3% vs 29.2%; 95% CI = 24.7%-33.7%). CONCLUSIONS: The combination of OCT and high-risk HPV triage (both genotyping and nongenotyping) had a similar immediate CIN3+ risk stratification and reduced the number of colposcopies compared with the cytological triage strategy.

Histological and transcriptomic analysis of Fance-deficient PGCs reveal the possible mechanisms of their depletion.

In brief: Fanconi anemia results in subfertility and germ cell deficiency in women. We present histological and RNA-seq analysis of Fance-deficient primordial germ cells to explore the possible mechanisms of their progressive depletion. Abstract: Primordial germ cells (PGCs) development is a subtle and complex regulatory process. Fance is an important substrate molecule necessary for the activation of the Fanconi anemia pathway, and its homozygous mutant causes massive oogonia loss as early as embryonic day 13.5 (E13.5). Here, we present histological and RNA-seq analysis of Fance-deficient PGCs to explore the possible mechanisms responsible for its progressive depletion of germ cells. In Fance-/- embryos, the reduction of PGCs was already evident at E9.5 and the progressive loss of PGCs led to the PGCs being almost exhausted at E12.5. An increase of apoptotic cells was detected among Fance-/- PGCs, which may intuitively explain their reduced number in embryos. Moreover, abnormal cell proliferation and accumulating DNA damage were detected in E12.5 Fance-/- PGCs. We identified 3026 differentially expressed genes in E12.5 Fance-/- PGCs compared to Fance+/+. KEGG pathway analysis revealed that the upregulated genes were highly associated with 'lysosome', and various metabolism pathways, whereas the downregulated genes were mainly enriched in 'cell cycle', 'oocyte meiosis', 'ribosome', and various DNA repair pathways. In addition, multiple genes of various cell death pathways were found to be differentially expressed in E12.5 Fance-/- PGCs, indicating that PGCs death in Fance-/- embryos might diverge from canonical apoptosis. These findings indicate that Fance is essential for PGCs survival and the potential mechanisms involve cell cycle regulation, DNA damage repair, cell death prevention, and by regulating lysosome and ribosome function. Our results provide an important reference for further studies.

Efficacy of optical coherence tomography in the triage of women with minor abnormal cervical cytology before colposcopy.

OBJECTIVES: To evaluate the efficacy of Optical Coherence Tomography (OCT) for detecting cervical lesions in women with minor abnormal cytology results (atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL)). METHODS: A prospective study was conducted at gynecologic clinic from Mar 2021 to Sep 2021. The recruited women with cervical cytological findings of ASC-US or LSIL were inspected with OCT before colposcopy-directed cervical biopsy. The diagnostic performance of OCT, alone and in combination with high-risk human papillomavirus (hrHPV) testing were evaluated to detect cervical intraepithelial neoplasia of grade 2 or worse (CIN2+)/CIN3 or worse (CIN3+). The rate of colposcopy referral and the immediate risk of CIN3+ of OCT were calculated. RESULTS: A total of 349 women with minor abnormal cervical cytology results were enrolled. For detection of CIN2+/CIN3+, the sensitivity and NPV of OCT were lower than those of hrHPV testing (CIN2+: 71.3% vs. 95.4%, 89.0% vs. 91.1%, P < 0.001; CIN3+: 75% vs. 93.8%, 96.5% vs. 95.6%, P < 0.001), but the specificity, accuracy and PPV were higher than those of hrHPV testing (CIN2+: 77.5% vs. 15.6%, 75.9% vs. 35.5%, 51.2% vs. 27.3%, P < 0.001; CIN3+: 69.4% vs. 13.6%, 69.9% vs. 20.9%, 19.8% vs. 9.9%, P < 0.001). OCT combined with hrHPV testing (CIN2+: 80.9%; CIN3+: 72.6%) showed higher specificity than that of OCT alone (P < 0.001). The colposcopy referral rate base on OCT classification was lower than that based on hrHPV testing (34.7% vs. 87.1%, P < 0.001). Patients with hrHPV-positive ASC-US and hrHPV-negative LSIL cytology, the immediate CIN3+ risk in OCT negative cases was less than 4%. CONCLUSIONS: OCT alone or combination with hrHPV testing shows good performance for detecting CIN2+/CIN3+ in patients with ASC-US/LSIL cytology. OCT is an effective method for colposcopy triage in women with hrHPV-positive ASC-US and hrHPV-negative LSIL cytology.

Comparative effectiveness of transvaginal repair vs. hysteroscopic resection in patients with symptomatic uterine niche.

Objective: To compare the efficacy of transvaginal repair and hysteroscopic resection in improving niche associated postmenstrual spotting. Methods: The improvement rate of postmenstrual spotting in women who underwent transvaginal repair or hysteroscopic resection treatment was assessed retrospectively in patients accepted at the Niche Sub-Specialty Clinic in International Peace Maternity and Child Health Hospital between June 2017 and June 2019. Postoperative spotting symptom within one year after surgery, pre- and postoperative anatomical indicators, women' satisfaction with menstruation and other perioperative parameters were compared between the two groups. Results: 68 patients in the transvaginal group and 70 patients in the hysteroscopic group were included for analysis. The improvement rate of postmenstrual spotting in the transvaginal group at the 3rd, 6th, 9th, and 12th months after surgery was 87%, 88%, 84%, and 85%, significantly higher than 61%, 68%, 66%, and 68% in the hysteroscopic group, respectively (P < 0.05). The total days of spotting improved significantly at the 3rd month after surgery but did not change over time within one year in each group (P > 0.05). After surgery, the disappearance rates of the niche are 68% in transvaginal group and 38% in hysteroscopic group, however, hysteroscopic resection had shorter operative time and hospitalization duration, less complications, and lower hospitalization costs. Conclusion: Both treatments can improve the spotting symptom and anatomical structures of uterine lower segments with niches. Transvaginal repair is better in thickening the residual myometrium than hysteroscopic resection, however, hysteroscopic resection has shorter operative time and hospitalization duration, less complications, and lower hospitalization costs.

Promoter hypermethylation analysis of host genes in cervical intraepithelial neoplasia and cervical cancers on histological cervical specimens.

BACKGROUND: DNA methylation is an essential factor in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer. The aim was to investigate the diagnostic value provided by methylation biomarkers of six tumor suppressor genes (ASTN1, DLX1, ITGA4, RXFP3, SOX17 and ZNF671) for cervical precancerous lesions and cervical cancer. METHODS: The histological cervical specimens of 396 cases including 93 CIN1, 99 CIN2, 93 CIN3 and 111 cervical cancers were tested for methylation-specific PCR assay (GynTect®) of score and positive rate. Among them, 66 CIN1, 93 CIN2, 87 CIN3 and 72 cervical cancers were further used for paired analysis. A chi-square test was used to analyze the difference of methylation score and positive rate in cervical specimens. The paired t-test and paired chi-square test were for analyzing the methylation score and positive rate in paired CIN and cervical cancer cases. The specificity, sensitivity, odds ratio (OR) and 95% confidence interval (95% CI) of the GynTect® assay for CIN2 or worse (CIN2 +) and CIN3 or worse (CIN3 +) were evaluated. RESULTS: According to the chi-square test trend, hypermethylation increased with severity of the lesions as defined by histological grading (P = 0.000). The methylation score above 1.1 was more common in CIN2 + than in CIN1. The DNA methylation scores in the paired groups of CIN1, CIN3 and cervical cancer were significant differences (P = 0.033, 0.000 and 0.000, respectively), except for CIN2 (P = 0.171). While the positive rate of GynTect® in each paired group had no difference (all P > 0.05). The positive rate of every methylation marker in the GynTect® assay showed differences in four cervical lesion groups (all P < 0.05). The specificity of GynTect® assay for detection of CIN2 + /CIN3 + were higher than high-risk human papillomavirus test. With CIN1 as a reference, the positive status of GynTect®/ZNF671 were significantly higher in CIN2 + : odds ratio (OR) 5.271/OR 13.909, and in CIN3 + : OR 11.022/OR 39.150, (all P < 0.001). CONCLUSION: The promoter methylation of six tumor suppressor genes is related to the severity of cervical lesions. The GynTect® assay based on cervical specimens provides diagnostic values for detecting CIN2 + and CIN3 + .

Adjunctive azithromycin prophylaxis protects women from uterine cesarean scar defect: A randomized controlled trial.

INTRODUCTION: Cesarean scar defect (CSD) is a long-term outcome of cesarean section (CS) and associated with numerous gynecological and obstetric problems. Previous studies indicate that infection may be a risk factor for CSD. Adjunctive azithromycin was shown to reduce the risk of postoperative infection in patients undergoing non-elective primary cesarean delivery in labor or after the rupture of membranes compared with standard antibiotic prophylaxis. This study investigated the protective effect of adjunctive azithromycin in combination with single-dose cephalosporin against CSD in women undergoing non-elective cesarean delivery. MATERIAL AND METHODS: A randomized, double-blind, controlled clinical trial was conducted in a University hospital in Shanghai, China. A total of 242 women who underwent their first non-elective CS were randomly assigned to receive 1500 mg cefuroxime sodium plus 500 mg intravenous azithromycin (n = 121; experimental group) or 1500 mg cefuroxime sodium plus a placebo (n = 121; placebo group). The primary outcome was CSD prevalence, as determined by transvaginal ultrasound and saline infusion sonohysterography within 6 months of delivery. Secondary outcomes were changes in infectious indicators (eg hypersensitive C-reactive protein and procalcitonin), postoperative morbidity, and use of postoperative antibiotics. We also examined the operative procedure, pathogenic microorganism cultures, and fetal outcomes. Outcomes were compared between groups with the chi-squared test, Fisher's exact test, or Student's t test. RESULTS: Between May 2018 and May 2021, 121 women were randomized to each arm. Because the sonographic follow up was disrupted by the coronavirus disease 2019 pandemic and strict management policies, we merged the follow-up time points (6 weeks and 6 months) into a single time period (6 weeks to 6 months); 104 and 108 women in the experimental and placebo groups, respectively, completed the first sonographic follow up. CSD was diagnosed by sonography in 34/104 (32.7%) and 50/108 (46.3%) patients in the experimental and placebo groups, respectively (relative risk 0.71, 95% confidence interval 0.50-0.99; p = 0.043). Characteristics of CSD and short-term infection outcomes did not differ between groups. CONCLUSIONS: A single dose of intravenous 500 mg azithromycin adjunctive to single-dose cefuroxime prophylaxis significantly reduced the incidence of CSD in women undergoing non-elective CS.

Invasive versus conservative strategy in the very elderly with non-ST-elevation acute coronary syndrome: A meta-analysis of randomized controlled trials.

AIM: To investigate the optimal treatment strategy in patients older than 80 years with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS: All published randomized, placebo-controlled trials (RCTs) reporting on comparisons between invasive and conservative strategies for patients aged 80 years or older with NSTE-ACS were identified. The literature search was performed using PubMed, EMBASE, Cochrane Library, and the ISI Web of Science, from their establishment to July 2021 with no language restriction. The pooled risk ratios (RRs) with 95% confidence intervals (CI) for dichotomous outcomes were calculated. RESULTS: Three RCTs involving a total of 893 cases met the inclusion criteria. Compared with the conservative group, the invasive strategy could significantly improve the incidence rate of composite endpoint (I2  = 21.9%; RR 0.727, 95% CI 0.619 to 0.855, P < 0.001), recurrent myocardial infarction (MI) (I2  = 0.0%; RR 0.585, 95% CI 0.441 to 0.776, P < 0.001) and revascularization (I2  = 0.0%; RR 0.239, 95% CI 0.126 to 0.455, P < 0.001). However, no benefits were observed on outcomes of all-cause death (I2  = 0.0%; RR 0.888, 95% CI 0.681 to 1.160, P = 0.384), cardiac death (I2  = 0.0%; RR 0.769, 95% CI 0.412 to 1.433, P = 0.408) and stroke (I2  = 0.0%; RR 0.778, 95% CI 0.392 to 1.543, P = 0.473). The major bleeding events were comparable between the two groups (I2  = 0.0%; RR 1.582, 95% CI 0.622 to 4.025, P = 0.336). CONCLUSIONS: Compared with a conservative strategy, the invasive treatment could reduce the incidence of composite endpoint, recurrent MI, and revascularization in the very elderly with NSTE-ACS. However, no benefits were observed on mortality. Geriatr Gerontol Int 2022; 22: 36-41.

Mitochondria-Rich Extracellular Vesicles Rescue Patient-Specific Cardiomyocytes From Doxorubicin Injury: Insights Into the SENECA Trial.

BACKGROUND: Anthracycline-induced cardiomyopathy (AIC) is a significant source of morbidity and mortality in cancer survivors. The role of mesenchymal stem cells (MSCs) in treating AIC was evaluated in the SENECA trial, a Phase 1 National Heart, Lung, and Blood Institute-sponsored study, but the mechanisms underpinning efficacy in human tissue need clarification. OBJECTIVES: The purpose of this study was to perform an in vitro clinical trial evaluating the efficacy and putative mechanisms of SENECA trial-specific MSCs in treating doxorubicin (DOX) injury, using patient-specific induced pluripotent stem cell-derived cardiomyocytes (iCMs) generated from SENECA patients. METHODS: Patient-specific iCMs were injured with 1 µmol/L DOX for 24 hours, treated with extracellular vesicles (EVs) from MSCs by either coculture or direct incubation and then assessed for viability and markers of improved cellular physiology. MSC-derived EVs were separated into large extracellular vesicles (L-EVs) (>200 nm) and small EVs (<220nm) using a novel filtration system. RESULTS: iCMs cocultured with MSCs in a transwell system demonstrated improved iCM viability and attenuated apoptosis. L-EVs but not small EVs recapitulated this therapeutic effect. L-EVs were found to be enriched in mitochondria, which were shown to be taken up by iCMs. iCMs treated with L-EVs demonstrated improved contractility, reactive oxygen species production, ATP production, and mitochondrial biogenesis. Inhibiting L-EV mitochondrial function with 1-methyl-4-phenylpyridinium attenuated efficacy. CONCLUSIONS: L-EV-mediated mitochondrial transfer mitigates DOX injury in patient-specific iCMs. Although SENECA was not designed to test MSC efficacy, consistent tendencies toward a positive effect were observed across endpoints. Our results suggest a mechanism by which MSCs may improve cardiovascular performance in AIC independent of regeneration, which could inform future trial design evaluating the therapeutic potential of MSCs.

[Compound heterozygous NDUFS1 variants identified in a Chinese pedigree affected with mitochondrial respiratory chain complex I deficiency].

OBJECTIVE: To explore the genetic basis for a Chinese pedigree with suspected mitochondrial functional defects through combined next-generation sequencing (NGS), copy number variation sequencing (CNV-seq), and mitochondrial DNA (mtDNA) sequencing. METHODS: Clinical data of the proband and his family members were collected. The patient and his parents were subjected to family-trio whole-exome sequencing (WES), CNV-seq and mtDNA variant detection. Candidate variant was verified by Sanger sequencing. RESULTS: Trio-WES revealed that the proband has carried compound heterozygous variants of the NDUFS1 gene, including a paternally derived c.64C>T (p.R22X) nonsense variant and a maternally derived c.845A>G (p.N282S) missense variant. Both variants may cause loss of protein function. No variant that may cause the phenotype was identified by CNV-seq and mtDNA variant analysis. CONCLUSION: Children with suspected mitochondrial disorders may have no specific syndromes or laboratory findings. A comprehensive strategy including mtDNA testing may facilitate the diagnosis and early clinical interventions.

Intracoronary Thrombolysis in Patients With ST-Segment Elevation Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The effects of intracoronary (IC) thrombolysis therapy in patients with ST-segment elevation myocardial infarction (STEMI) receiving primary percutaneous coronary intervention (PPCI) remain unclear. METHODS: The meta-analysis was conducted according to the PRISMA statement. All relevant studies were identified by searching the PubMed, EMBASE, Cochrane Library, and Web of Science, with no time or language limitation. The pooled risk ratio (RR) and weighted mean difference (WMD) with a 95% CI were calculated. RESULTS: Nine randomized controlled trials involving a total of 1341 patients were included. Compared with the control group, IC thrombolysis in patients with STEMI could reduce the incidence of major adverse cardiac events (MACE; RR 0.632, 95% CI, 0.474-0.843, P = .002) and improve left ventricular ejection fraction (RR 0.343, 95% CI, 0.178-0.509, P < .001) and myocardial microcirculation. However, there was no difference noted in the mortality (RR 0.759, 95% CI, 0.347-1.661, P = .490). The incidence rate of major bleeding and minor bleeding was comparable between the 2 groups. CONCLUSIONS: Intracoronary thrombolysis was associated with improved MACE and myocardial microcirculation in patients with STEMI having PPCI, though it failed to improve mortality.

Diagnostic value of four neuroendocrine markers in small cell neuroendocrine carcinomas of the cervix: a meta-analysis.

Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a highly invasive cervical cancer. The immunohistochemical criteria is an important aspect for assistant diagnosis of SCNECC. However, which markers can be appropriate selection for diagnosing SCNECC were not determined. The aim was to systematically evaluate expression levels of four neuroendocrine markers (containing synaptophysin (Syn), neural cell adhesion molecules (CD56), neuron-specific enolase (NSE) and chromograninA (CgA)) and to find out the appropriate selection for diagnosing SCNECC. Four English and three Chinese libraries were retrieved between 1984 and 2020. 23 studies about NSE, 36 studies about Syn, 23 studies about CD56 and 36 studies about CgA (all studies containing 581 patients) were eligible for meta-analyses. The pooled positive expression percentages (95% CI; I2) were as follows: 84.84% (79.41-90.27%; 76.7%) for Syn, 84.53% (79.43-89.96%; 37.5%) for CD56, 77.94% (69.13-86.76%; 83.5%) for NSE, and 72.90% (67.40-78.86%; 59.7%) for CgA. The positive proportions (95% CI; I2) ranked top three of simultaneous expressions of two markers were 87.75% (82.03-93.87%, 33.3%) for Syn and CD56, 70.92% (50.50-87.68%, 82.7%) for Syn and NSE, 65.65% (53.33-76.98%, 73.5%) for Syn and CgA. This confirms that Syn and CD56 are reliable indicators for diagnosing SCNECC.

Effects of nanoparticle-mediated delivery of pitavastatin on atherosclerotic plaques in ApoE-knockout mice and THP-1-derived macrophages.

The treatment of atherosclerosis remains complex. Pitavastatin serves an important role in the prevention and treatment of atherosclerosis. The present study aimed to investigate the effects of nanoparticle (NP)-mediated delivery of pitavastatin into atherosclerotic plaques as a novel treatment method for atherosclerosis. The results of the present study demonstrated that pitavastatin-NP was more effective in attenuating the size of atherosclerotic plaques and enhancing the stability of plaques in vitro compared with pitavastatin alone. In an apolipoprotein E (ApoE)-knockout mouse model of atherosclerosis, a single intravenous injection of fluorescein isothiocyanate-NP resulted in the delivery of NP into atherosclerotic plaques for up to 7 days post-injection. In ApoE-knockout mice and THP-1-derived macrophages, pitavastatin-NP attenuated the development of atherosclerosis, which was associated with regulating lipid metabolism, and inhibited the secretion of inflammatory markers compared with pitavastatin alone. Additionally, the treatment advantages of pitavastatin-NP were independent of lipid lowering. The results demonstrated that pitavastatin-NP administration was more effective in attenuating the development of atherosclerotic plaques compared with systemic administration of pitavastatin.

Efficacy of adjunctive azithromycin versus single-dose cephalosporin prophylaxis for caesarean scar defect: study protocol for a randomised controlled trial.

INTRODUCTION: Perioperative infections may be considered predictors of caesarean scar defect (CSD), and multidose antibiotics have a protective effect against CSD. However, the ability of adjunctive azithromycin combined with cephalosporin to reduce the prevalence of CSD remains unclear. The planned study aims to clarify the protective effect of antibiotics against CSD and to assess the effectiveness of adjunctive azithromycin prophylaxis for CSD. METHODS AND ANALYSIS: This study is a double-blind, parallel-control randomised clinical trial that will be carried out at the International Peace Maternity and Child Health Hospital. A total of 220 eligible patients will be randomised (1:1) to receive either adjunctive azithromycin or single-dose cephalosporin 30 min before the incision. The evaluation criteria are the prevalence and characteristics of CSD as assessed by transvaginal ultrasound (TVU) and saline infusion sonohysterography (SIS) at 42 days, 6 months and 12 months after delivery. The primary outcome will be the prevalence of CSD, and the characteristics of CSD will be assessed by TVU and SIS 42 days after delivery; all other outcomes are secondary. ETHICS AND DISSEMINATION: This protocol received authorisation from the Medical Research Ethics Committee of International Peace Maternity and Child Health Hospital on 25 April 2018 (approval no. GKLW2017-84). The findings will be reported in peer-reviewed publications and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: ChiCTR-INR-17013272.

Effects of Intracoronary Nicorandil on Myocardial Microcirculation and Clinical Outcomes in Patients with Acute Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The amelioration of myocardial reperfusion in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PPCI) remains a significant issue. OBJECTIVE: We conducted a meta-analysis of randomized controlled trials (RCTs) to better assess the effects of intracoronary nicorandil administration on myocardial microcirculation and clinical outcomes in these patients. METHODS: The meta-analysis was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. A literature search was performed in the PubMed, Embase, Cochrane Library, and Web of Science databases up to April 2019, with no time or language limitations. Pooled risk ratios (RRs) were calculated to evaluate the treatment effects. RESULTS: Seven RCTs involving a total of 562 patients were included. Compared with control, intracoronary nicorandil significantly reduced the incidence of thrombolysis in myocardial infarction (TIMI) grade ≤ 2 (RR 0.349; 95% confidence interval [CI] 0.199-0.611; P < 0.001) and TIMI myocardial perfusion grade ≤ 2 (RR 0.611; 95% CI 0.438-0.852; P = 0.004) and was associated with higher complete ST-segment resolution rates (RR 1.326; 95% CI 1.090-1.614; P = 0.005). However, no significant benefits were observed on clinical outcomes, including death (RR 0.370; 95% CI 0.085-1.618; P = 0.187), recurrent myocardial infarction (RR 0.507; 95% CI 0.156-1.655; P = 0.261), heart failure (RR 0.528; 95% CI 0.224-1.247; P = 0.145), and target lesion/vessel revascularization (RR 1.109; 95% CI 0.553-2.224; P = 0.770). CONCLUSIONS: Intracoronary nicorandil can significantly improve myocardial microcirculation in patients with AMI undergoing PPCI, but it failed to offer clinically significant benefits.

Association between serum uric acid levels and coronary artery disease in different age and gender: a cross-sectional study.

BACKGROUND: The association between uric acid (UA) and coronary artery disease (CAD) was controversial. It was still unclear how the UA level changes with age and gender. AIMS: To confirm the relationship between the change of UA with age and gender and CAD, especially in elderly people. METHODS: 8285 individuals were investigated. The changes of UA and hyperuricemia in female and male with age were analyzed. The associations of UA, and hyperuricemia with CAD in different age and sex were assessed. RESULTS: Individuals were stratified into four groups according to their age: ≤ 39 years; 40-59 years; 60-79 years, and ≥ 80 years. The level of UA and the proportion of hyperuricemia increased significantly with age in female (P < 0.001), but showed a downward trend in male (P < 0.001). After adjusting for confounding factors, hyperuricemia remained an independent risk factor for the incident of CAD in all women (P = 0.029). In ≥ 80 year groups of female, UA and hyperuricemia became independent risk factors for the incident of CAD in the univariate and multivariate logistic regression analyses (all P ≤ 0.001). DISCUSSION: The level of UA showed significantly different changes with age in different gender. The relationship between UA and CAD showed differences in different age and sex. CONCLUSIONS: There were significant correlations between UA, hyperuricemia, and CAD only in female, particularly in the ≥ 80 year elderly women, but not in men.

Effects of Cilostazol-Based Triple Antiplatelet Therapy Versus Dual Antiplatelet Therapy After Coronary Drug-Eluting Stent Implantation: An Updated Meta-Analysis of the Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: The results of studies on cilostazol-based triple antiplatelet therapy (TAT) after drug-eluting stent (DES) implantation were inconsistent. To assess the effects of TAT compared with dual antiplatelet therapy (DAT) after DES/second-generation DES implantation, we performed a meta-analysis of randomized controlled trials (RCTs). METHODS: All relevant studies evaluated were identified by searching the PubMed, EMBASE, Cochrane Library, and ISI Web of Science databases without time and language limitation. Subgroup analyses were performed to evaluate the efficacy and safety of TAT after second-generation DES implantation. RESULTS: Eleven RCTs involving a total of 4684 patients were included. The meta-analysis showed TAT was associated with significant beneficial effects on angiographic findings of in-stent restenosis [risk ratio (RR) 0.645, 95% confidence interval (CI) 0.470-0.885; P = 0.007], in-segment restenosis (RR 0.606, 95% CI 0.450-0.817; P = 0.001), in-stent late loss (RR - 0.095, 95% CI - 0.136 to - 0.054; P < 0.0001), in-segment late loss (RR - 0.100, 95% CI - 0.139 to - 0.061; P < 0.0001), target lesion revascularization (TLR) (RR 0.570, 95% CI 0.430-0.755; P < 0.0001), and target vessel revascularization (TVR) (RR 0.523, 95% CI 0.380-0.719; P < 0.0001). No significant difference was found in outcomes of all-cause death, cardiac death, definite/probable stent thrombosis (ST), non-fatal myocardial infarction (MI), overall bleeding, and major bleeding between the two groups, as well as some minor adverse effects including palpitations, thrombocytopenia, neutropenia, and hepatic dysfunction. However, the incidence rate of rash, gastrointestinal disorders, and headache was significantly higher in TAT. The second-generation DES subgroup showed similar results, except for the indicators of all-cause death (RR 2.161, 95% CI 1.007-4.635; P = 0.048) and hepatic dysfunction (RR 0.176, 95% CI 0.031-0.995; P = 0.049). CONCLUSIONS: Compared with DAT, cilostazol-based TAT can significantly improve the angiographic findings of in-stent and in-segment late loss, in-stent and in-segment restenosis, TLR, and TVR after DES/second-generation DES implantation. However, no benefits were observed in outcomes of all-cause death, cardiac death, ST, and MI.

Clinic-pathologic Features and Prognostic Analysis of Thyroid Cancer in the Older Adult: A SEER Based Study.

Purpose: Age at diagnosis has been identified as a major determinant of thyroid cancer-specific survival. But the cut-off value for age was controversial. The interaction among gender, age and histologic subtypes needed to be answered. Methods: We identified 59,892 thyroid cancer (TC) patients from the Surveillance, Epidemiology, and End Results (SEER) database. We divided the patients into the following three groups according to age: 20-44 years (young), 45-64 years (middle-aged), and ≥ 65 years (elderly). Logistic regression model was used to identify factors relating to prognosis in elderly patients. Multivariable Cox regression model identified potential prognostic factors. All statistical tests were two-sided. Results: Elderly patients had significantly worse prognosis than the other two groups, P=0.001. Elderly patients had higher proportion of male gender, advanced tumor grade, follicular subtype and advanced tumor stage. There was no survival difference for elderly patients to receive lobectomy and total thyroidectomy, P=0.852. Cox proportional hazards regression model showed that gender, marital status, histology, tumor grade, tumor size, TNM stage, surgery and radiotherapy were all independent prognostic factors in the multivariable analysis. Male patients with TC had worse prognosis than their female counterparts in differentiated tumor but not in undifferentiated tumor. There were more patients of larger tumor, advanced TNM stage and histologic subtypes in male patients. Conclusions: In conclusion, there were a series of factors contributing to the poor prognosis in elderly patients including clinic-pathologic factors and therapy selection. There was no survival difference for elderly patients to receive lobectomy and total thyroidectomy.