Gender Differences in Clinical Outcomes of Patients with Coronary Artery Disease after Percutaneous Coronary Intervention

With the increasing incidence of coronary artery disease, the percutaneous coronary intervention (PCI) has become one of the most effective treatments for coronary artery disease. After more than 40 years of clinical application, development and research, and continuous improvement, it has been widely used around the world. In recent years, due to the continuous innovation of drug-eluting stents, equipment, drugs, and interventional technology, the indications for treatment have been continuously broadened, many heart centers can deal with complete revascularization for high-risk indicated patient session, and the efficacy has been further improved. However, studies have shown that there are gender differences in the clinical prognosis of patients with coronary artery disease after percutaneous coronary intervention, which are affected by many related risk factors of gender differences, but there is lack of systematic and comprehensive review of relevant factors. The purpose of this review is to evaluate the possible causes of gender differences in the clinical outcomes of patients after percutaneous coronary intervention and to put forward recommendations for primary prevention and secondary prevention

Radial Basis Function Neural Network Based on an Improved Exponential Decreasing Inertia Weight-Particle Swarm Optimization Algorithm for AQI Prediction

This paper proposed a novel radial basis function (RBF) neural network model optimized by exponential decreasing inertia weight particle swarm optimization (EDIW-PSO). Based on the inertia weight decreasing strategy, we propose a new Exponential Decreasing Inertia Weight (EDIW) to improve the PSO algorithm. We use the modified EDIW-PSO algorithm to determine the centers, widths, and connection weights of RBF neural network. To assess the performance of the proposed EDIW-PSO-RBF model, we choose the daily air quality index (AQI) of Xi’an for prediction and obtain improved results

Mice with a Mutation in the Mdm2 Gene That Interferes with MDM2/Ribosomal Protein Binding Develop a Defect in Erythropoiesis

MDM2, an E3 ubiquitin ligase, is an important negative regulator of tumor suppressor p53. In turn the Mdm2 gene is a transcriptional target of p53, forming a negative feedback loop that is important in cell cycle control. It has recently become apparent that the ubiquitination of p53 by MDM2 can be inhibited when certain ribosomal proteins, including RPL5 and RPL11, bind to MDM2. This inhibition, and the resulting increase in p53 levels has been proposed to be responsible for the red cell aplasia seen in Diamond-Blackfan anemia (DBA) and in 5q- myelodysplastic syndrome (MDS). DBA and 5q- MDS are associated with inherited (DBA) or acquired (5q- MDS) haploinsufficiency of ribosomal proteins. A mutation in Mdm2 causing a C305F amino acid substitution blocks the binding of ribosomal proteins. Mice harboring this mutation (Mdm2C305F), retain a normal p53 response to DNA damage, but lack the p53 response to perturbations in ribosome biogenesis. While studying the interaction between RP haploinsufficiency and the Mdm2C305F mutation we noticed that Mdm2C305F homozygous mice had altered hematopoiesis. These mice developed a mild macrocytic anemia with reticulocytosis. In the bone marrow (BM), these mice showed a significant decrease in Ter119hi cells compared to wild type (WT) littermates, while no decrease in the number of mature erythroid cells (Ter119hiCD71low) was found in the spleen, which showed compensated bone marrow hematopoiesis. In methylcellulose cultures, BFU-E colonies from the mutant mice were slightly reduced in number and there was a significant reduction in CFU-E colony numbers in mutant mice compared with WT controls (p < 0.01). This erythropoietic defect was abrogated by concomitant p53 deficiency (Trp53ko/ko). Further investigation revealed that in Mdm2C305F animals, there was a decrease in Lin-Sca-1+c-Kit+ (LSK) cells, accompanied by significant decreases in multipotent progenitor (MPP) cells (p < 0.01). Competitive BM repopulation experiments showed that donor BM harboring the Mdm2C305F mutation possessed decreased repopulation capacity compared to WT BM, suggesting a functional stem cell deficit. These results suggest that there is a fine tuned balance in the interaction of ribosomal proteins with the MDM2/p53 axis which is important in normal hematopoiesis

Effect Of Type And Quantity Of Inherent Alkali Cations On Alkali-silica Reaction

In this study, the macroscopical expansion induced by alkali-silica reaction (ASR) and its corresponding ASR products are investigated using ordinary Portland cement (OPC) mortar specimens with a gradient of boosted alkalis. Experimental results show that the expansion increases with the concentration of inherent alkalis. Sodium-boosted samples expand approximately three times as much as potassium-boosted samples. ASR gels that are present in aggregate veins are calcium-free and amorphous; the atomic ratios of ASR gels are nearly independent of the type and quantity of alkali cations. Aggregate ASR gel exudation occurs in high (≥2.5 %) sodium cases and produces potential Na-shlykovite. Crystalline and amorphous calcium-containing ASR products are present in aggregate vicinities in either Na- or K-boosted samples. The higher hydrophilicity of Na-gel in aggregate veins accounts for the larger expansion. Boosted alkali cations are more effective in ASR products formation than in exposing solution. A new observation that NaOH exposure inhibits ASR in K-boosted samples (zero expansion) is reported

Prevalence of Postpartum Depression Based on Diagnostic Interviews:A Systematic Review and Meta-Analysis

Background. Postpartum depression (PPD) is common after childbirth. Previous reviews on the prevalence of PPD have mainly included results that relied on screening instruments or a mixture of such instruments and diagnostic interviews. In this study, we aimed to assess the prevalence of PPD based exclusively on studies using diagnostic interviews, as they provide the most reliable and valid approach for defining “caseness.” Methods. Using PubMed, Web of Science, Cochrane Library, Embase, CNKI, WANFANG DATA, and CBM up to September 18, 2022, we searched for original articles reporting data that could be used to calculate the prevalence of PPD based on diagnostic interviews. A random-effect meta-analysis model was then used to estimate the pooled prevalence. In addition, we assessed quality, heterogeneity, and publication bias across studies. Also, we did subgroup analyses to explore the pooled prevalence at different time points and settings. This study was registered with PROSPERO, CRD42021244539. Results. Of 17,115 articles retrieved, 54 studies were included (total sample size=15,586 women). The pooled prevalence of all depression and major depression within one year postpartum was 12.1% (95% CI 10.3%-14.1%; I2=91.0%) and 7.0% (95% CI 5.7%-8.4%; I2=83.0%), respectively. The peaks of all depression occurred during the first 6 months postpartum, especially 2-3 weeks and 6-8 weeks. Subgroup analyses showed that the prevalence of major depression was associated with the income level of countries (higher in low- and middle-income countries (LMICs) than in high-income countries (HICs)) and diagnostic criteria (higher using ICD than using DSM and RDC). No evidence of publication bias was found. Conclusions. Approximately one in eight postpartum women experiences a depressive condition, with one in fifteen suffering major depression. The pooled prevalence based on diagnostic interviews was lower than the existing consensus, which was largely based on self-reported screening instruments. The higher prevalence in LMICs underlines the importance of strengthening research and service provision among these populations

Multi-Stage Tuberculosis Subunit Vaccine Candidate LT69 Provides High Protection against Mycobacterium tuberculosis Infection in Mice

Effective tuberculosis (TB) vaccine should target tubercle bacilli with various metabolic states and confer long-term protective immunity. In this study, we constructed a novel multi-stage TB subunit vaccine based on fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-HspX (LT69 for short) which combined early expressed antigens and latency-associated antigen. The fusion protein was mixed with an adjuvant being composed of N, N’-dimethyl-N, N’-dioctadecylammonium bromide (DDA) and polyriboinosinic polyribocytidylic acid (PolyI:C) to construct subunit vaccine, whose immunogenicity and protective ability were evaluated in C57BL/6 mice. The results showed that LT69 had strong immunogenicity and high protective effect against Mycobacterium tuberculosis (M. tuberculosis) H37Rv aerosol challenge. Low-dose (2 μg) of LT69 generated long-term immune memory responses and provided effective protection, which was even higher than traditional vaccine BCG did at 30 weeks post the last vaccination. In conclusion, multistage subunit vaccine LT69 showed high and long-term protection against M. tuberculosis infection in mice, whose effect could be enhanced by using a relative low dosage of antigen.National Major Science and Technology Projects (China) (2012ZX10003-008-006)National Natural Science Foundation (China) (31470895)National Natural Science Foundation (China) (81072499)China. Ministry of Education (Doctoral Fund 20120211110038

Development and validation of prognostic dynamic nomograms for hepatitis B Virus-related hepatocellular carcinoma with microvascular invasion after curative resection

Background and AimThe prediction models of postoperative survival for hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) with microvascular invasion (MVI) have not been well established. The study objective was the development of nomograms to predict disease recurrence and overall survival (OS) in these patients.MethodsData were obtained from 1046 HBV-related MVI-positive HCC patients who had undergone curative resection from January 2014 to December 2017. The study was approved by the Eastern Hepatobiliary Surgery Hospital and Jinling Hospital ethics committee, and patients provided informed consent for the use of their data. Nomograms for recurrence and OS were created by Cox regression model in the training cohort (n=530). The modes were verified in an internal validation cohort (n= 265) and an external validation cohort (n= 251).ResultsThe nomograms of recurrence and OS based on preoperative serological indicators (HBV-DNA, neutrophil-lymphocyte ratio, a-fetoprotein), tumor clinicopathologic features (diameter, number), surgical margin and postoperative adjuvant TACE achieved high C-indexes of 0.722 (95% confidence interval [CI], 0.711-0.732) and 0.759 (95% CI, 0.747-0.771) in the training cohort, respectively, which were significantly higher than conventional HCC staging systems (BCLC, CNLC, HKLC).The nomograms were validated in the internal validation cohort (0.747 for recurrence, 0.758 for OS) and external validation cohort(0.719 for recurrence, 0.714 for OS) had well-fitted calibration curves. Our nomograms accurately stratified patients with HBV-HCC with MVI into low-, intermediate- and high-risk groups of postsurgical recurrence and mortality. Prediction models for recurrence-free survival (https://baishileiehbh.shinyapps.io/HBV-MVI-HCC-RFS/) and OS (https://baishileiehbh.shinyapps.io/HBV-MVI-HCC-OS/) were constructed.ConclusionsThe two nomograms showed good predictive performance and accurately distinguished different recurrence and OS by the nomograms scores for HBV-HCC patients with MVI after resection

Rap2B promotes proliferation, migration and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway

Rap2B, a member of GTP-binding proteins, is widely upregulated in many types of tumors and promotes migration and invasion of human suprarenal epithelioma. However, the function of Rap2B in breast cancer is unknown. Expression of Rap2B was examined in breast cancer cell lines and human normal breast cell line using Western blot analysis. Using the CCK-8 cell proliferation assay, cell cycle analysis, and transwell migration assay, we also elucidated the role of Rap2B in breast cancer cell proliferation, migration, and invasion. Results showed that the expression of Rap2B is higher in tumor cells than in normal cells. Flow cytometry and Western blot analysis revealed that Rap2B elevates the intracellular calcium level and further promotes extracellular signal-related kinase (ERK) 1/2 phosphorylation. By contrast, calcium chelator BAPTM/AM and MEK inhibitor (U0126) can reverse Rap2B-induced ERK1/2 phosphorylation. Furthermore, Rap2B knockdown inhibits cell proliferation, migration, and invasion abilities via calcium related-ERK1/2 signaling. In addition, overexpression of Rap2B promotes cell proliferation, migration and invasion abilities, which could be neutralized by BAPTM/AM and U0126. Taken together, these findings shed light on Rap2B as a therapeutic target for breast cancer

Serial Monitoring of Circulating Tumor DNA in Patients With Metastatic Colorectal Cancer to Predict the Therapeutic Response

Early biomarkers of therapeutic responses can help optimize the treatment of metastatic colorectal cancers (mCRC). In this prospective exploratory study, we examined serial changes of plasma-circulating tumor DNA (ctDNA) in 41 mCRC patients receiving first-line chemotherapies and tested its association with treatment outcomes according to radiological assessments. Using next-generation sequencing technologies, we profiled somatic mutations in 50 cancer-related genes in ctDNA before each of the first four treatment cycles. We observed mutations in 95.7% of pre-treatment ctDNA samples. Using mutations of the maximal frequency in each pre-treatment plasma ctDNA sample as the candidate targets, we computed log2 fold changes of ctDNA levels between adjacent treatment cycles. We found that ctDNA reductions as early as prior to cycle 2 predicted responses after cycle 4. Log2 fold changes of ctDNA after cycle 1 (ctDNA log2 (C1/C0)) &gt; −0.126 predicted progressive disease, with an accuracy of 94.6%. These patients also showed significantly worse progression-free survival than those with ctDNA log2 (C1/C0) ≤ −0.126 (median 2.0 vs. 9.0 months; P = 0.007). Together, the present exploratory study suggests that early changes in ctDNA levels detected via targeted sequencing are potential biomarkers of future treatment responses in mCRCs