Effects of pomegranate supplement on menopausal symptoms and quality of life in menopausal women: A double-blind randomized placebo-controlled trial

BackgroundMenopausal symptoms have negative effects on the aspects of quality of life and impose a high cost on the health system. In traditional Persian medicine, pomegranate is recommended to alleviate menopausal symptoms.Material and methodsA randomized double-blind placebo-controlled trial was performed among 78 healthy women. Participants were interviewed three times: Before receiving the supplement/placebo, after completing the treatment, and after 3 weeks with no intervention. They filled out the demographic information sheet, modified-Kupperman index, and Menopause-Specific Quality of Life (MENQOL) questionnaires.ResultsThe mean scores of the modified-Kupperman index and MENQOL characteristics before and after the treatment and after the follow-up period were significantly different between pomegranate and placebo groups in both modified-Kupperman and MENQOL scores (p < 0.001).ConclusionThis study demonstrated that 4 weeks' treatment with the pomegranate supplement significantly ameliorates the irritating symptoms of menopause and improves the quality of life in menopausal women even after 4 weeks' medicine deprivation.     

Nationwide outcomes of newborns with rectosigmoid versus long-segment Hirschsprung disease

PurposeHirschsprung Disease (HD) is a common congenital intestinal disorder. While aganglionosis most commonly affects the rectosigmoid colon (rectosigmoid HD), outcomes for patients in which aganglionosis extends to more proximal segments (long-segment HD) remain understudied. This study sought to compare postoperative outcomes among newborns with rectosigmoid and long-segment HD.MethodsThe Nationwide Readmission Database was queried from 2016 to 2018 for newborns with HD. Newborns were stratified into those with rectosigmoid or long-segment HD. Those who received no rectal biopsy or pull-through procedure during their newborn hospitalization were excluded. A propensity score-matched analysis (PSMA) of newborns with either type of HD was constructed utilizing 17 covariates including demographics, comorbidities, and congenital-perinatal conditions.ResultsThere were 1280 newborns identified with HD (82% rectosigmoid HD, 18% long-segment HD). Patients with rectosigmoid HD had higher rates of laparoscopic resections (35% vs. 12%) and less frequently received a concomitant ostomy (14% vs. 84%), both p < 0.001. Patients with long-segment HD were more likely to have a delayed diagnosis (12% vs. 5%) and require multiple bowel operations (19% vs. 4%), both p < 0.001. They experienced higher rates of complications, including small bowel obstructions (10% vs. 1%), infections (45% vs. 20%), and Hirschsprung-associated enterocolitis (11% vs. 5%), all p < 0.001. After PSMA, newborns with long-segment HD were found to have a longer length of stay and higher hospitalization costs.ConclusionNewborns with long-segment HD experience significant delays in diagnosis, surgery, and complications compared to those with rectosigmoid HD. This information should be utilized to improve healthcare delivery for this patient population.Type of StudyRetrospective comparative study.Level of EvidenceIII.     

Time-varying characteristics of the induced membrane and its effects on bone defect repair

PurposeThis study intended to determine the properties of induced membranes after various periods of polymethyl methacrylate (PMMA) retention and the effect of different retention intervals on subsequent defect repair.MethodsModel of a critical bone defect in rabbits was prepared to obtain the induced membrane. For varying intervals of spacer insertion (2, 4, 6, 8, 12, 16, and 20 weeks postoperatively), angiogenesis, osteogenesis, and MSC-related properties were analyzed by immunohistochemistry and western-blot. Furthermore, 2, 4, 6, and 8 weeks after PMMA insertion, bone grafting was performed. Characteristics of defect repair were analyzed by X-ray and micro-CT analysis.ResultsThe induced membrane displayed angiogenesis, osteogenesis, and MSC-related properties from the 2- to 20-week intervals. Quantitation of protein expression (RUNX2, ALP, VEGF, TGF-beta, OCT4, and STRO1) revealed that selected proteins gradually rose to a high level at 4–8 weeks postoperatively and then decreased to a low level over a long time period. Following bone grafting, the most new bone formation was in the group when grafting was performed at 4 weeks, followed by the groups at 2 and 6 weeks, with the least in the group at 8 weeks.ConclusionThe induced membrane displays angiogenesis, osteogenesis, and MSC-related properties from the 2- to 20-week intervals. These were increased to a peak level at 4–8 weeks postoperatively and then gradually decreased. The optimal timing for bone grafting at the second stage in the presented model was 4 weeks after PMMA insertion.     

Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.     

中国非小细胞肺癌免疫检查点抑制剂治疗专家共识（2020年版）

非小细胞肺癌（non-small cell lung cancer, NSCLC）是肺癌最常见的病理类型。晚期NSCLC的系统性抗肿瘤治疗经历了化疗、靶向治疗及免疫治疗的变革，患者总体生存时间不断延长。免疫检查点抑制剂（immune checkpoint inhibitors, ICIs），尤其是程序性死亡分子-1（programmed cell death protein 1, PD-1）/程序性死亡分子配体-1（programmed death-ligand 1, PD-L1）抗体已成为表皮生长因子受体（epidermal growth factor receptor, EGFR）/间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）阴性晚期NSCLC一线及二线的标准治疗和局部晚期NSCLC同步放化疗后标准治疗，并在辅助/新辅助治疗中显示出可喜的结果，改变了NSCLC整体治疗格局。随着越来越多的ICIs在国内获批肺癌适应证，中国临床肿瘤学会（Chinese Society of Clinical Oncology, CSCO）NSCLC专家委员会牵头，组织该领域的专家，结合2019年版专家共识，参考最新国内外文献、临床研究数据及系统评价，在专家共同讨论的基础上，达成统一意见并制定、更新本共识，为国内同行更好地应用ICIs治疗NSCLC提供参考意见。     

Pediatric Wilson disease presenting as acute liver failure: Prognostic indices

BACKGROUNDAcute liver failure (ALF) can be a primary presentation of Wilson disease (WD). Mortality rates are high in WD with ALF (WDALF). Predictions of mortality in WDALF vary by model and are sometimes contradictory, perhaps because few patients are studied or WD diagnoses are questionable. AIMTo determine the outcomes among well-documented WDALF patients and assess mortality model performance in this cohort.METHODSWe reviewed the medical records of our pediatric WDALF patients (n = 41 over 6-years-old, single-center retrospective study) and compared seven prognostic models (King’s College Hospital Criteria, model for end-stage liver disease/pediatric end-stage liver disease scoring systems, Liver Injury Unit [LIU] using prothrombin time [PT] or international normalized ratio [INR], admission LIU using PT or INR, and Devarbhavi model) with one another.RESULTSAmong the 41 Han Chinese patients with ALF, WD was established by demonstrating ATP7B variants in 36. In 5 others, Kayser-Fleischer rings and Coombs-negative hemolytic anemia permitted diagnosis. Three died during hospitalization and three underwent liver transplantation (LT) within 1 mo of presentation and survived (7.3% each); 35 (85.4%) survived without LT when given enteral D-penicillamine and zinc-salt therapy with or without urgent plasmapheresis. Parameters significantly correlated with mortality included encephalopathy, coagulopathy, and gamma-glutamyl transpeptidase activity, bilirubin, ammonia, and serum sodium levels. Area under the receiver operating curves varied among seven prognostic models from 0.981 to 0.748 with positive predictive values from 0.214 to 0.429.CONCLUSIONWDALF children can survive and recover without LT when given D-penicillamine and Zn with or without plasmapheresis, even after enlisting for LT.     

Partial trisomy 16q and partial monosomy 7p of a fetus derivated from paternal balanced translocation: A case report

Introduction:Subchromosomal deletions and duplications could currently be detected by noninvasive preliminary screening (NIPS). However, NIPS is a screening test that requires further diagnosis. Here we report a fetus with an autosomal abnormality revealed by NIPS and conventional karyotype combined with copy number variations sequencing (CNV-seq) confirmed the fetus with an unbalanced translocation.Patient concern:This was the fourth pregnancy of a 30-year-old woman who underwent 2 spontaneous abortions and gave birth to a child with a normal phenotype. The woman and her husband were healthy and nonconsanguineous. NIPS indicated a repeat of about 19-Mb fragment at the region of 16q22.1-q22.4 at 17-week gestation.Diagnoses:The combination of traditional karyotype and CNV-seq could better locate the abnormal chromosomal region and further identify the source of fetal chromosomal abnormalities. Simultaneously, we evaluated the fetal morphology by ultrasound examination. The karyotype of the fetus was 46,XX,der(7)t(7;16)(p22;q23) and CNV-seq results showed an approximately 20.96-Mb duplication in 16q22.1-q24.3 (69200001-90160000) and an approximately 3.86-Mb deletion in 7p22.3-p22.2 (40001-3900000). Prenatal ultrasound revealed the fetal micrognathia. The paternal karyotype was 46,XY, t (7;16) (p22;q23), while the maternal was normal. The fetus inherited an abnormal chromosome 7 from its father.Interventions:No treatment for the fetus.Outcomes:Pregnancy was terminated.Conclusions:To our knowledge, the occurrence of de novo partial trisomy 16q (16q22.1-qter) and partial monosomy 7p (7p22.2-pter) has not previously been reported up to now. Here, we present the perinatal findings of such a case and a review of the literatures. CNV-seq combined with karyotype is a useful tool for chromosomal abnormalities indicated by NIPS.     

Lack of effectiveness of 13-valent pneumococcal conjugate vaccination against pneumococcal carriage density in Papua New Guinean infants

BackgroundPapua New Guinea (PNG) introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in 2014, with administration at 1, 2, and 3 months of age. PCV13 has reduced or eliminated carriage of vaccine types in populations with low pneumococcal carriage prevalence, carriage density and serotype diversity. This study investigated PCV13 impact on serotype-specific pneumococcal carriage prevalence, density, and serotype diversity in PNG infants, who have some of the highest reported rates of pneumococcal carriage and disease in the world.MethodsNasopharyngeal swabs were collected at 1, 4 and 9 months of age from PCV13-vaccinated infants (n = 57) and age-/season-matched, unvaccinated infants (at approximately 1 month, n = 53; 4 months, n = 57; 9 months, n = 52). Serotype-specific pneumococcal carriage density and antimicrobial resistance genes were identified by qPCR and microarray.ResultsPneumococci were present in 89% of swabs, with 60 different serotypes and four non-encapsulated variants detected. Multiple serotype carriage was common (47% of swabs). Vaccine type carriage prevalence was similar between PCV13-vaccinated and unvaccinated infants at 4 and 9 months of age. The prevalence of non-vaccine type carriage was also similar between cohorts, with non-vaccine types present in three-quarters of samples (from both vaccinated and unvaccinated infants) by 4 months of age. The median pneumococcal carriage density was high and similar at each age group (~7.0 log₁₀ genome equivalents/mL). PCV13 had no effect on overall pneumococcal carriage density, vaccine type density, non-vaccine type density, or the prevalence of antimicrobial resistance genes.ConclusionPNG infants experience dense and diverse pneumococcal colonisation with concurrent serotypes from 1 month of age. PCV13 had no impact on pneumococcal carriage density, even for vaccine serotypes. The low prevalence of vaccine serotypes, high pneumococcal carriage density and abundance of non-vaccine serotypes likely contribute to the lack of PCV13 impact on carriage in PNG infants. Indirect effects of the infant PCV programs are likely to be limited in PNG. Alternative vaccines with broader coverage should be considered.