[Investigation and analysis on the detection of IgG antibodies against the rubella virus among rural childbearing-age women in preconception period in Yunnan Province from 2013 to 2019].

A study was conducted on rural women of childbearing age aged 20-49 who underwent the National Free Preconception Health Examination Project (NFPHEP)in Yunnan Province from 2013 to 2019. Descriptive analysis was conducted to determine the negative rate of IgG antibodies against the rubella virus and its differences among various socio-demographic characteristics. Among the 1 511 203 study subjects, the negative rate of IgG antibodies against the rubella virus was 24.36%. Only 2.64% of the population had received rubella virus vaccine. The negative rate of IgG antibodies among rural childbearing-age women in the preconception period in Yunnan Province decreased with age and educational level (Ptrend<0.001). The negative rate of IgG antibodies in ethnic minority women of childbearing age in the preconception period (25.19%) was higher than that of Han women (23.88%). Among the 22 ethnic groups with over 1 000 participants, the negative rates of IgG antibodies in women of childbearing age from the Blang (32.85%), Bouyei (31.03%), Zhuang (31.01%), and Miao (30.70%) ethnic groups were higher than those of women from other ethnic groups. Among the 16 states (cities) in Yunnan Province, the negative rate of IgG antibodies in pregnant women of childbearing age in Wenshan Zhuang and Miao Autonomous Prefecture (38.06%) and Lincang City (32.63%) was higher than that in other states (cities). The negative rate of serum IgG antibodies in women who reported having received rubella virus vaccine (18.60%) was lower than that in other non-vaccinated populations (24.52%). The proportion of rural women of childbearing age in Yunnan Province who were susceptible to the rubella virus before pregnancy was still high. It is necessary to promote rubella vaccination among people susceptible to rubella, especially pregnant women, to prevent rubella virus infection and reduce the incidence rate and disease burden of rubella people.

[Comparative study of next generation sequencing and immunohistochemistry on molecular classification of endometrial carcinoma].

Objective: To investigate the differences in molecular classification of endometrial carcinoma (EC) between various technical methods and to explore molecular classification schemes suitable for Chinese population. Methods: The study used a comprehensive scheme of next generation sequencing (NGS) and immunohistochemistry for molecular classification of 254 EC cases that were obtained at Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China from April 2021 to March 2022. According to the recommended threshold of Sanger sequencing which was approximate-20% variant allele fraction (VAF), NGS data were extracted to simulate the results of Sanger sequencing. Results: The 254 EC patients had a mean age of 51 years (range, 24 to 89 years). Combination of POLE (9-14 exons), TP53 total exons and microsatellite instability (MSI) detection was a better single scheme than NGS alone, while combination of MSI fragment analysis and conventional immunohistochemistry was the best solution and seemed best aligned with TCGA data and recent studies. POLE ultramuted type, mismatch repair defect type, TP53 mutant type and non-specific molecular characteristic type accounted for 11.4% (29/254), 31.5% (80/254), 22.4% (57/254) and 34.6% (88/254) of the cases, respectively. If Sanger sequencing was adopted for POLE and TP53 detection, the frequencies of these EC types were 9.1% (23/254), 31.5% (80/254), 12.9% (33/254) and 46.6% (118/254), respectively, with greatly increasing non-specific molecular characteristics cases. If POLE was detected by Sanger sequencing and others by immunohistochemistry, they were 9.1% (23/254), 42.2% (92/218), 13.8% (35/254) and 40.9% (105/254), respectively, with increasing the false positive rates of the mismatch repair defect group. Conclusions: Small and medium-sized NGS panels with MSI detection is a better solution than NGS alone. Sanger sequencing is currently available for POLE mutation detection, which is not sensitive enough for TP53 mutation detection, and seems equivalent to the efficiency of TP53 by immunohistochemistry. Further optimization of small and medium-sized NGS panels covering MSI detection and POLE and TP53 full exons may be the best choice for the future to meet national conditions.

[Value of high-risk HPV E6/E7 mRNA in situ hybridization in grading of cervical intraepithelial neoplasia].

Objective: To investigate the value of high-risk HPV E6/E7 mRNA in situ hybridization in the grading of cervical squamous intraepithelial neoplasia (CIN). Methods: A total of 261 cases with diagnosis of CIN and cervical squamous cell carcinoma (SCC) at west China University Second Hospital, Sichuan University from July 2019 to June 2020 were collected, including 60 cases of CIN1, 41 cases of CIN2, 51 cases of CIN3, 72 cases of SCC, and 37 cases of normal cervical control tissue (10 HPV negative and 27 HPV positive). All pathologic tissues were made into tissue microarrays, and HE staining, HPV E6/E7 mRNA in situ hybridization (ISH) and p16 immunohistochemical (IHC) staining were performed respectively. The staining was assessed by light microscopy, and the positive rate and positive pattern were analyzed statistically. Results: HPV mRNA ISH in CIN1 mainly showed spot staining in predominantly basal to mid-epithelial layers (≤BME) with a diffuse nuclear signals in the superficial layer (supD), that is, the pattern of ≤BME+supD; in CIN2, it mainly showed spot staining in predominantly basal to above mid-epithelial but not the full layer (>BME) and some cases with supD staining, that is, the pattern of>BME+supD; In CIN3, the mainly pattern was >BME, and the spot staining was distributed throughout the epithelium. In CIN1, CIN2 and CIN3, there were significantly statistical differences among the above three staining patterns (P<0.05). Conclusions: HPV mRNA ISH contributes to the accurate diagnosis and grading of CIN, and has better specificity than p16 IHC staining.

[Idiopathic pleuroparenehymal fibroelastosis: five case reports and review of literature].

Objective: To raise the awareness of idiopathic pleuroparenehymal fibroelastosis (iPPFE) through investigating the clinical, radiographic and pathological features. Methods: Five cases of iPPFE proved by pathology. The clinical data were studied respectively, and the relevant literature was reviewed. Results: All the cases of iPPFE were manifested by cough and dyspnea. The patients including 3 males and 2 females, aged from 30 to 70 years Chest CT scan showed pleural thickening, subpleural consolidation in both upper lungs complicated with tractive bronchiectasis.Computed tomography-guided percutaneous lung biopsy or surgical lung were performed and the same pathological showed pleura and subpleural dense elastic and collagen fibers. The elastic fibers stain was also positive,which was consistent with PPFE. One patient received low-dose corticosteroid, two received pirfenidone therapy, the others received no treatment. Three patients were stable during the follow-up. Conclusions: iPPFE has characteristic pathological features. However, the number of clinically reported cases is low due to missed diagnosis or misdiagnosed. Improving the understanding of features of iPPFE is helpful for the dianosis, therapy, and prognosis of this disease.

[Fetal cardiac intervention and perioperative management of fetus with hypoplastic right heart syndrome].

Objective: To summarize the experience of perioperative management strategy of fetal pulmonary valvuloplasty (FPV) for hypoplastic right heart syndrome (HRHS). Methods: In the retrospective study of perioperative data, 13 fetuses of HRHS were treated with FPV in Qingdao Women and Children's Hospital from July 2018 to June 2019. Results: (1) The evaluation indexes of the right ventricle in 13 fetuses before FPV: the mean ratio of tricuspid/mitral annulus, right/left ventricular length, pulmonary/aortic annulus, and tricuspid inflow time/cardiac cycle were 0.81±0.04, 0.56±0.14, 0.69±0.06, and 0.35±0.03, respectively. (2) All pregnant mothers underwent general anesthesia. The basic fetal heart rate was (156±12) beats per minutes before FPV, and 9 fetuses showed bradycardia during the operation, and recovered to normal after drug resuscitation. On the first day after FPV, two cases had bradycardia and pregnancy was terminated. The fluctuation of systolic blood pressure of pregnant mother was less than 20%, and there was no significant difference between preoperative and intraoperative pulse pressure [(36.0±5.6) vs (35.8±6.9) mmHg (1 mmHg=0.133 kPa); t=8.102, P=0.951]. (3) All cases of HRHS fetus successfully underwent FPV. The average gestational age was (27.3±0.8) weeks. The average operation time was (23.2±1.0) minutes. The ratio of tricuspid to mitral annulus (t=-2.513, P=0.022) and the ratio of right to left ventricular length (t=-3.373, P=0.003) were significantly improved at 6 weeks postoperatively. Ten fetuses were delivered, and there was no death after early intervention. (4) Of 13 pregnant women, 3 cases were nausea and vomiting on the day of FPV operation, the treatment of the symptoms was improved by tropisetron; one case had tolerable abdominal pain and improved without special treatment. Pregnant women had no major complications such as cardiac failure, abortion and death. (5) Chromosome karyotype analysis and microarray analysis of amniotic fluid was retained during the operation. No typical chromosome abnormality or other abnormal genetic diagnosis was found. Conclusions: FPV colud be used as an effective intervention measure to promote the development of right ventricle in HRHS fetuses. The scientific management of multidisciplinary professional technical team in perioperative period is particularly important to ensure the success of FPV and the safety of pregnant women and fetuses.

Specific genes related to nucleopolyhedrovirus in Bombyx mori susceptible and near-isogenic resistant strains through comparative transcriptome analysis.

Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the primary pathogens that causes severe economic losses to sericulture. Comparative transcriptomics analysis has been widely applied to explore the antiviral mechanism in resistant strains. Here, to identify genes involved in BmNPV infection, we identified differentially expressed genes (DEGs) and performed weighted gene co-expression network analysis (WGCNA) between two Bombyx mori strains: strain 871 (susceptible to BmNPV infection) and the near-isogenic strain 871C (resistant to BmNPV). Our results showed that 400 genes were associated with resistance in strain 871C, and 76 genes were related to susceptibility in strain 871. In addition, the correlation analysis of DEGs and WGCNA showed that 40 genes related to resistance were highly expressed in the resistant strain. Among them, gene BGIBMGA004291 was the most noticeable. We further identified the effect of gene BGIBMGA004291, which encoded a multiprotein bridge factor 2 (MBF2) family member (MBF2-10), on viral infection in cells. Our data suggested that MBF2-10 inhibited viral infection. Taken together, this study showed specific module trait correlations related to viral infection in strains 871 and 871C, and we identified a resistance-related gene. These findings suggested promising candidate genes with antiviral activity, aiding in the analysis of the antiviral molecular mechanisms in resistant strains.

Activation of the NLRP3 and AIM2 inflammasomes in a mouse model of Schistosoma mansoni infection.

Schistosomiasis is an inflammatory disease that occurs when schistosome species eggs are deposited in the liver, resulting in fibrosis and portal hypertension. Schistosomes can interact with host inflammasomes to elicit host immune responses, leading to mitochondrial damage, generation of high levels of reactive oxygen species (ROS) and activation of apoptosis during inflammation. This study aims to examine whether ROS and NF-κB (p65) expression elicited other types of inflammasome activation in Schistosoma mansoni-infected mouse livers. We examine the relationship between inflammasome activation, mitochondrial damage and ROS production in mouse livers infected with S. mansoni. We demonstrate a significant release of ROS and superoxides and increased NF-κB (p65) in S. mansoni-infected mouse livers. Moreover, activation of the NLRP3 and AIM2 inflammasomes was triggered by S. mansoni infection. Stimulation of HuH-7 hepatocellular carcinoma cells with soluble egg antigen induced activation of the AIM2 inflammasome pathway. In this study, we demonstrate that S. mansoni infection promotes both NLRP3 and AIM2 inflammasome activation.

'Switch' catalysis: from monomer mixtures to sequence-controlled block copolymers.

A 'Switch' catalysis method is reviewed whereby a single catalyst is switched between ring-opening polymerization and ring-opening copolymerization cycles. It allows the efficient synthesis of block copolymers from mixtures of lactones, epoxides, anhydrides and carbon dioxide. In order to use and further develop such 'Switch' catalysis, it is important to understand how to monitor the catalysis and characterize the product block copolymers. Here, a step-by-step guide to both the catalysis and the identification of block copolymers is presented.This article is part of a discussion meeting issue 'Providing sustainable catalytic solutions for a rapidly changing world'.

The Effects of Antidepressants and Quetiapine on Heart Rate Variability.

Introduction: The autonomic effects of antidepressants and quetiapine on heart rate variability (HRV) are inconsistent based on past studies. The aim of this study was to explore their influence on the HRV of psychiatric patients without psychotic symptoms. Methods: A total of 94 patients with depression, anxiety, or somatic symptoms, were recruited into this study. Based on their medication, 4 groups were identified: the no antidepressant group (n=19), the SSRI group (using sertraline or escitalopram, n=53), the other antidepressants group (using venlafaxine or mirtazapine, n=9), and the augmentation group (AG, using an antidepressant+quetiapine, n=13). The HRV of the 4 groups were compared. The correlations between HRV and the medication(s) used were clarified. Results: Among the 4 groups, the AG had the lowest HRV with its total power (TP), very low frequency power (VLF) and low frequency power (LF) of HRV being significantly different from those of the other groups. Age and using quetiapine were found to be negatively correlated with TP, VLF and LF. With this study group, the autonomic effects of antidepressants were found not to be significant. Discussion: Among psychiatric patients without psychotic symptoms, quetiapine causes an overt decrease in HRV.

Effects of angiotensin II intervention on MMP-2, MMP-9, TIMP-1, and collagen expression in rats with pulmonary hypertension.

This study investigated the effects of angiotensin II (AngII) intervention, using captopril and losartan, on the expression of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and collagen in rats with pulmonary hypertension, in an effort to understand mechanisms underlying pulmonary vascular remodeling. A total of 40 male Sprague-Dawley rats were randomly divided into normal group, model group, captopril group, and losartan group. After 5 weeks, the mean pulmonary arterial pressure (mPAP), right ventricular index, and neointima formation in each group were determined. Immunohistochemical analysis was performed to determine the degree of pulmonary arterial muscularization as well as MMP-2, MMP-9, and TIMP-1 protein expression in lung tissue. Real-time fluorescent quantitative PCR was used to detect MMP2, MMP9, TIMP1, COL1A1, and COL4A1 mRNA expression. Picro-sirius red staining was performed to detect collagen protein expression. Neointima formation was observed in the model group. Moreover, the mPAP, right ventricular index, degree of arterial muscularization, and collagen deposition, as well as mRNA and protein expression of MMP2, MMP9, and TIMP1 were significantly higher than those in the other groups (P < 0.05). The mPAP, right ventricular index, degree of arterial muscularization, and mRNA and protein expression in the captopril and losartan groups were significantly decreased compared with those of the model group (P < 0.05). AngII regulates MMP-2, MMP-9, and TIMP-1 expression and affects collagen deposition. Thus, this hormone is involved in pulmonary vascular remodeling, indicating a possible mechanism that can be targeted in pulmonary hypertension intervention.

Electroluminescence enhancement in InGaN light-emitting diode during the electrical stressing process.

This study of the optoelectronic properties of blue light-emitting diodes under direct current stress. It is found that the electroluminescence intensity increases with duration of stress, and the efficiency droop curves illustrated that the peak-efficiency and the peak-efficiency-current increases and decreases, respectively. We hypothesize that these behaviors mainly result from the increased internal quantum efficiency.

The expression of UNC5D is abnormal in the early stage of colorectal tumors associated with its proliferation and migration.

OBJECTIVE: Colorectal adenomas are an important precancerous lesion of colorectal adenoma with a high incidence. This study aims to explore new prognostic targets for colorectal adenomas through bioinformatics techniques. MATERIALS AND METHODS: In this study, data from 29 colonic adenomas and 38 normal colonic mucosa in GSE37364 were analyzed to screen for differentially expressed genes (DEGs). Then, batch survival analysis, construction of risk model, mutation analysis, Cox regression analysis and expression analysis were performed on DEGs to determine the hub genes of this study. Finally, immune correlation analysis and cell experiments were carried out on the hub gene to explore its potential mechanism. RESULTS: In our study, a total of 431 up-regulated and 809 down-regulated differentially expressed genes (DEGs) were identified. Among these, Unc-5 Netrin Receptor D (UNC5D) emerged as a pivotal gene associated with colorectal adenoma. Notably, UNC5D expression levels were found to be significantly higher in normal tissues compared to colorectal adenoma tissues. Furthermore, our analysis demonstrated that UNC5D showed promising diagnostic potential for patients with colon adenocarcinoma. In vitro experiments revealed that the overexpression of UNC5D had a profound impact on the behavior of colorectal tumor cells. Specifically, it led to a substantial reduction in the proliferation, motility, and invasion of these tumor cells. Additionally, UNC5D was shown to exert control over STAT1/STAT3 phosphorylation, which in turn regulated the expression of PD-L1 in response to interferon (IFN) stimulation. These findings highlight the significant role of UNC5D in modulating immune responses and the development of colorectal adenoma. UNC5D emerges as a potential diagnostic biomarker and an attractive immunotherapeutic target in the context of colorectal malignancies. These results call for further exploration of UNC5D-based strategies for the diagnosis and treatment of colorectal adenoma and adenocarcinoma. CONCLUSIONS: In addition to having the potential to be used as a diagnostic biomarker and an immunotherapeutic target in colorectal malignancies, UNC5D is necessary for the growth of colorectal adenomas. Additionally, UNC5D controlled STAT1/STAT3 phosphorylation to suppress the growth of colorectal cancers by regulating IFN-induced PD-L1 expression.

Efficacy and safety of ipilimumab in metastatic melanoma patients surviving more than 2 years following treatment in a phase III trial (MDX010-20).

BACKGROUND: In a phase III trial (ClinicalTrials.gov registration ID: NCT00094653), ipilimumab significantly improved survival versus a vaccine control in pretreated patients with metastatic melanoma. Here, we characterize outcomes of those patients who survived ≥ 2 years. METHODS: Patients were randomized (3 : 1 : 1) to receive ipilimumab 3 mg/kg + gp100 vaccine, ipilimumab 3 mg/kg + placebo, or gp100 vaccine alone. Baseline demographic data, duration of survival, responses, and safety among patients with ≥ 2 years' survival were analyzed. RESULTS: Among 676 randomized patients, 474 and 259 patients had at least 2 or 3 years of potential follow-up, respectively, and were eligible for analysis. Among these, 94 (20%) and 42 (16%) survived ≥ 2 and ≥ 3 years, respectively. Survival rates at 2 and 3 years were 25% (24 of 95) and 25% (13 of 53) with ipilimumab alone and 19% (54 of 284) and 15% (24 of 156) with ipilimumab plus gp100. Safety among patients with ≥ 2 years' survival was comparable with the overall study population, with the onset of new ipilimumab-related toxic effect (all grades) reported in 6 of 78 (8%) patients. CONCLUSIONS: Ipilimumab results in survival of ≥ 2 years in one-fifth of pretreated patients with 2 years potential follow-up in a phase III trial. New onset, low-grade events starting after administration of the last dose were infrequent. TRIAL REGISTRATION ID: NCT00094653.

Missing data and censoring in the analysis of progression-free survival in oncology clinical trials.

Progression-free survival (PFS) is increasingly used as a primary endpoint in oncology clinical trials. However, trial conduct is often such that PFS data on some patients may be partially missing either due to incomplete follow-up for progression, or due to data that may be collected but confounded by patients stopping randomized therapy or starting alternative therapy prior to progression. Regulatory guidance on how to handle these patients in the analysis and whether to censor these patients differs between agencies. We present results of a reanalysis of 28 Phase III trials from 12 companies or institutions performed by the Pharmaceutical Research and Manufacturers Association-sponsored PFS Expert Team. We show that analyses not adhering to the intention-to-treat principle tend to give hazard ratio estimates further from unity and describe several factors associated with this shift. We present illustrative simulations to support these findings and provide recommendations for the analysis of PFS.

Genetic relationships between Lolium (Poaceae) species revealed by RAPD markers.

The genus Lolium is one of the most important groupings of temperate forage grasses, including about eight recognized species that are native to some temperate and subtropical regions of the northern hemisphere. We examined genetic relationships among 18 accessions representing all Lolium species using RAPD markers. Among 50 random primers that we screened, 13 gave reproducible amplification banding patterns. Each of these 13 primers generated 19-43 scorable fragments. A total of 367 RAPD fragments were detected, of which 95.9% were polymorphic across all the Lolium accessions. Dice's coefficient of dissimilarity ranged from 0.016 to 0.622, which is indicative of substantial genetic variations in these Lolium accessions. A neighbor-joining cluster analysis, with bootstrap permutation, produced an unrooted dendrogram, which grouped 18 accessions into two main clades, supporting high bootstrap values (98 and 96%). The first clade included the self-pollinated species, L. persicum, L. temulentum, L. remotum, and L. subulatum. The cross-pollinated species, i.e., L. multiflorum, L. perenne, L. rigidum, and L. canariense, composed the second clade, in which L. canariense formed a distinct subclade, indicating its higher genetic separation from other allogamous species. The value of r = 0.97 in the Mantel test for cophenetic correlation applied to the cluster analysis indicated the high degree of fit of the accessions to a group. A principal coordinate analysis, whose first three coordinates explained 72.6% of the variation, showed similar groupings as in the cluster analysis. The genetic relationships estimated by the polymorphism of RAPD markers are basically in agreement with those previously inferred with other genetic markers.

[Research and discovery of "inner GPS" of brain].

Since the 20th century, with the progress of brain science research, scientists have discovered the brain GPS, revealing the mechanism of brain spatial cognition. The discovery process of brain GPS has gone through three stages. In 1971, John O'Keefe discovered the position cells in the hippocampus of the brain, which was the beginning of the research on the GPS in the brain; In 1900, James Rank discovered the head direction cells in the medial entorhinal cortex of the brain, and the research on the GPS in the brain made a breakthrough; In 2005, Edvard I. Moser and his wife discovered grid cells, marking the maturity of the research on GPS in the brain. The discovery of intracerebral GPS not only reveals the spatial cognitive function of the brain at the cellular level, but also provides a theoretical basis for the study of diseases related to the nervous system.

Gene-gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics.

The use of atypical antipsychotics (AAPs) is associated with increasing the risk of the metabolic syndrome (MetS), which is an important risk factor for cardiovascular disease and diabetes. Two insulin-induced gene (INSIG) isoforms, designated INSIG-1 and INSIG-2 encode two proteins that mediate feedback control of lipid metabolism. In this genetic case-control study, we investigated whether the common variants in INSIG1 and INSIG2 genes were associated with MetS in schizophrenic patients treated with atypical antipsychctics. The study included 456 schizophrenia patients treated with clozapine (n=171), olanzapine (n=91) and risperidone (n=194), for an average of 45.5±27.6 months. The prevalence of MetS among all subjects was 22.8% (104/456). Two single-nucleotide polymorphisms (SNPs) of the INSIG1 gene and seven SNPs of the INSIG2 gene were chosen as haplotype-tagging SNPs. In single-marker-based analysis, the INSIG2 rs11123469-C homozygous genotype was found to be more frequent in the patients with MetS than those without MetS (P=0.001). In addition, haplotype analysis showed that the C-C-C haplotype of rs11123469-rs10185316- rs1559509 of the INSIG2 gene significantly increased the risk of MetS (P=0.0023). No significant associations were found between polymorphisms of INSIG1 gene and MetS, however, INSIG1 and INSIG2 interactions were found in the significant 3-locus and 4-locus gene-gene interaction models (P=0.003 and 0.012, respectively). The results suggest that the INSIG2 gene may be associated with MetS in patients treated with AAPs independently or in an interactive manner with INSIG1.

Analysis of genetic diversity among wild bermudagrass germplasm from southwest China using SSR markers.

Fifty-five wild accessions of bermudagrass (Cynodon dactylon) were collected from southwest China (Sichuan, Chongqing, Yunnan, Guizhou, and Tibet), and their genetic diversity was analyzed using simple sequence repeat markers. A total of 267 polymorphic bands were detected with 18 primer combinations. The genetic similarity among the accessions ranged from 0.688 to 0.894 with an average of 0.797. All 55 wild accessions were clustered into 7 eco-geographic groups. Our data showed that the dendrogram was almost in accordance with geographic distribution, and accessions from the same collection sites tended to be clustered into the same group. A genetic differentiation analysis revealed that the percentage of genetic variance was 70.07 and 29.93% within and among groups, respectively. Finally, we discuss the implications of these results for C. dactylon in southwest China.