Successful live birth of thin endometrium: A case report.

RATIONALE: The success of pregnancy depends on various factors, with the endometrial receptivity being a crucial component. Endometrial thickness (EMT) serves as a direct indicator for assessing endometrial receptivity. Previous studies have suggested that a thin endometrium is associated with lower pregnancy rates, especially in patients with an EMT of less than 4 mm. Even in assisted reproductive technology cycles with high success rates, clinical pregnancy cases in patients with such thin endometrium are reported to be very few, let alone in natural conception cycles. Therefore, a thin endometrium poses significant challenges for infertility patients. In this study, patients with an extremely thin endometrium were able to achieve clinical pregnancy and successful live births through natural conception, highlighting the possibility of success even in challenging cases. PATIENT CONCERNS: The patient presented with polycystic ovary syndrome and ovulation disorders. She underwent a natural cycle of letrozole-induced ovulation. On the day of the human chorionic gonadotropin trigger, she had an EMT of 3.8 mm. DIAGNOSES: Polycystic ovary syndrome, ovulation disorders, thin endometrium. INTERVENTIONS: The patient received medications including Progynova, Aspirin, and Dydrogesterone. OUTCOMES: The patient achieved spontaneous conception and subsequently had a live birth. LESSONS: This case report underscores the significance of managing a thin endometrium during letrozole-induced ovulation. While EMT is traditionally pivotal for predicting embryo implantation success, our findings indicate that endometrial receptivity extends beyond thickness alone. Factors such as endometrial morphology, type, and blood supply play crucial roles. Successful pregnancies with a 3.8 mm EMT are rare, making this case a beacon of hope for such patients. It highlights that, with appropriate interventions, successful pregnancies remain attainable. For those with a thin endometrium, emphasis should extend beyond thickness, addressing ways to enhance both endometrial blood supply and morphology for improved pregnancy rates.

Application of a modified lateral thoracic artery perforator flap in partial breast defects.

Background: Breast cancer has become the most frequently diagnosed cancer in the world. Detection at an early stage, frequently allows women to benefit from breast conserving surgery. However, some patients are not satisfied with the breast shape after breast-conserving surgery, and autologous tissue flaps are needed to fill the defect in the resection area. The modified lateral thoracic artery perforator (LTAP) flap isn't one of the commonly used flaps in breast surgery and has the advantages of a reliable blood supply, simple operation and few postoperative complications. In this study, we aimed to evaluate the feasibility and effectiveness of a modified LTAP flap for repairing partial breast defects after breast-conserving surgery. Methods: In this study, we retrospectively analyzed the clinical data of 126 patients treated with LTAP flaps to repair local breast defects at Affiliated Hospital of Guangdong Medical University between January 2020 and June 2021. Data were collected on the demographic characteristics of these patients, tumor size and location, type of axillary lymph node surgery, availability of adjuvant chemotherapy and radiotherapy, and postoperative complications. Results: The median weight of the tumor specimen was 185 g (range, 170-320 g), and this glandular tissue accounted for 30% to 40% of the total breast volume. The average flap size was 10.5 cm ×2.5 cm (length range, 8-15 cm, width range: 2-4 cm). The minimum follow-up time was 6 months, with an average of 10 months (range, 6-22 months). The mean operative time was 130 minutes (range: 90-180 minutes), and the mean hospital stay was 3 days (range, 2-5 days). All modified LTAP flaps survived completely without donor site complications. None of the patients required revision surgery on the postoperative breast. Conclusions: The modified LTAP flap is a reliable method for repairing partial breast defects after breast-conserving surgery. It has the advantages of a simple operation, a reliable blood supply, fewer postoperative complications, and a high flap survival rate. It is especially suitable for Asian women with small breast volumes and can achieve good breast contouring effects.

COVID-19 vaccination and the risk of autoimmune diseases: a Mendelian randomization study.

Background: In recent times, reports have emerged suggesting that a variety of autoimmune disorders may arise after the coronavirus disease 2019 (COVID-19) vaccination. However, causality and underlying mechanisms remain unclear. Methods: We collected summary statistics of COVID-19 vaccination and 31 autoimmune diseases from genome-wide association studies (GWAS) as exposure and outcome, respectively. Random-effects inverse variance weighting (IVW), MR Egger, weighted median, simple mode, and weighted mode were used as analytical methods through Mendelian randomization (MR), and heterogeneity and sensitivity analysis were performed. Results: We selected 72 instrumental variables for exposure (p < 5 × 10-6; r2 < 0.001, genetic distance = 10,000 kb), and MR analyses showed that COVID-19 vaccination was causally associated with an increased risk of multiple sclerosis (MS) (IVW, OR: 1.53, 95% CI: 1.065-2.197, p = 0.026) and ulcerative colitis (UC) (IVW, OR: 1.00, 95% CI: 1.000-1.003, p = 0.039). If exposure was refined (p < 5 × 10-8; r2 < 0.001, genetic distance = 10,000 kb), the associations became negative. No causality was found for the remaining outcomes. These results were robust to sensitivity and heterogeneity analyses. Conclusion: Our study provided potential evidence for the impact of COVID-19 vaccination on the risk of MS and UC occurrence, but it lacks sufficient robustness, which could provide a new idea for public health policy.

Acupuncture therapies for relieving pain in pelvic inflammatory disease: A systematic review and meta-analysis.

BACKGROUND: Studies investigating the effectiveness of acupuncture therapies in alleviating pain in pelvic inflammatory disease (PID) have gained increasing attention. However, to date, there have been no systematic reviews and meta-analyses providing high-quality evidence regarding the efficacy and safety of acupuncture therapies in this context. OBJECTIVE: The objective of this review was to assess the efficacy and safety of acupuncture therapies as complementary or alternative treatments for pain relief in patients with PID. METHOD: A comprehensive search was conducted in eight databases from inception to February 20, 2023: PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and Chinese Biomedical Literature Database. Randomized controlled trials (RCTs) investigating acupuncture therapies as complementary or additional treatments to routine care were identified. Primary outcomes were pain intensity scores for abdominal or lumbosacral pain. The Cochrane risk of bias criteria was applied to assess the methodological quality of the included trials. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system was used to evaluate the quality of evidence. Data processing was performed using RevMan 5.4. RESULT: This systematic review included twelve trials comprising a total of 1,165 patients. Among these, nine trials examined acupuncture therapies as adjunctive therapy, while the remaining three did not. Meta-analyses demonstrated that acupuncture therapies, whether used alone or in combination with routine treatment, exhibited greater efficacy in relieving abdominal pain compared to routine treatment alone immediately after the intervention (MD: -1.32; 95% CI: -1.60 to -1.05; P < 0.00001). The advantage of acupuncture therapies alone persisted for up to one month after the treatment (MD: -1.44; 95% CI: -2.15 to -0.72; P < 0.0001). Additionally, acupuncture therapies combined with routine treatment had a more pronounced effect in relieving lumbosacral pain after the intervention (MD: -1.14; 95% CI: -2.12 to -0.17; P < 0.00001) in patients with PID. The incidence of adverse events did not increase with the addition of acupuncture therapies (OR: 0.56; 95% CI: 0.21 to 1.51; P = 0.25). The findings also indicated that acupuncture therapies, as a complementary treatment, could induce anti-inflammatory cytokines, reduce pro-inflammatory cytokines, alleviate anxiety, and improve the quality of life in patients with PID. CONCLUSION: Our findings suggest that acupuncture therapies may effectively reduce pain intensity in the abdomen and lumbosacral region as complementary or alternative treatments, induce anti-inflammatory cytokines, decrease pro-inflammatory cytokines, alleviate anxiety, and enhance the quality of life in patients with PID, without increasing the occurrence of adverse events. However, due to the low quality of the included trials, the conclusion should be interpreted with caution, highlighting the need for further high-quality trials to establish more reliable conclusions.

Risk factors for acute kidney injury in pediatric patients after hematopoietic stem cell transplantation: a systematic review and meta-analysis.

BACKGROUND: Risk factors for acute kidney injury (AKI) in pediatric patients after hematopoietic stem cell transplantation (HSCT) remain controversial. OBJECTIVES: This study aimed to identify risk factors for AKI following HSCT in the pediatric population. DATA SOURCES: PubMed, Embase, Web of Science, Cochrane Library, and Scopus databases were searched from inception to February 8, 2023. STUDY ELIGIBILITY CRITERIA: Studies meeting the following criteria were included: (1) The study was a case-control, cohort study, or cross-sectional design, (2) the study was performed among pediatric and young patients aged 21 years or younger undergoing HSCT, (3) the study measured at least one related factor for AKI after pediatric HSCT, (4) the study included a sample of at least ten patients, and (5) original articles published in English in peer-reviewed scientific journals. PARTICIPANTS AND INTERVENTIONS: Children who were undergoing pediatric HSCT. STUDY APPRAISAL AND SYNTHESIS METHODS: We assessed the quality of the included studies and analyzed them with a random-effect model. RESULTS: Fifteen studies with a total of 2,093 patients were included. All were cohort studies of high quality. The overall pooled incidence of AKI was 47.4% (95%CI 0.35, 0.60). We found significant associations between post-transplant AKI in pediatric patients and unrelated donor [odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.09-2.79], cord blood stem cell transplantation (OR = 3.14, 95%CI 2.14-4.60), and veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) (OR = 6.02, 95%CI 1.40-25.88). Other controversial factors such as myeloablative conditioning (MAC), acute graft vs. host disease (aGVHD), and the use of calcineurin inhibitors (CNI) were not found to be related to AKI after pediatric HSCT. LIMITATIONS: Results were limited mainly by heterogeneity in the characteristics of patients and transplantation. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Posttransplant AKI in children is a common complication. Unrelated donors, cord blood stem cell transplantation, and VOD/SOS might be risk factors for AKI after pediatric HSCT. Further large-scale studies are still needed to draw firm conclusions. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42022382361 A higher resolution version of the Graphical abstract is available as Supplementary information.

Global, regional and national burden of male infertility in 204 countries and territories between 1990 and 2019: an analysis of global burden of disease study.

BACKGROUND: Many countries and regions have experienced male fertility problems due to various influencing factors, especially in less developed countries. Unlike female infertility, male infertility receives insufficient attention. Understanding the changing patterns of male infertility in the world, different regions and different countries is crucial for assessing the global male fertility and reproductive health. METHODS: We obtained data on prevalence, years of life lived with disability (YLD), age-standardized rates of prevalence (ASPR) and age-standardized YLD rate (ASYR) from the Global Burden of Disease Study 2019. We analyzed the burden of male infertility at all levels, including global, regional, national, age stratification and Socio-demographic Index (SDI). RESULTS: In 2019, the global prevalence of male infertility was estimated to be 56,530.4 thousand (95% UI: 31,861.5-90,211.7), reflecting a substantial 76.9% increase since 1990. Furthermore, the global ASPR stood at 1,402.98 (95% UI: 792.24-2,242.45) per 100,000 population in 2019, representing a 19% increase compared to 1990. The regions with the highest ASPR and ASYR for male infertility in 2019 were Western Sub-Saharan Africa, Eastern Europe, and East Asia. Notably, the prevalence and YLD related to male infertility peaked in the 30-34 year age group worldwide. Additionally, the burden of male infertility in the High-middle SDI and Middle SDI regions exceeded the global average in terms of both ASPR and ASYR. CONCLUSION: The global burden of male infertility has exhibited a steady increase from 1990 to 2019, as evidenced by the rising trends in ASPR and ASYR, particularly in the High-middle and Middle SDI regions. Notably, the burden of male infertility in these regions far exceeds the global average. Additionally, since 2010, there has been a notable upward trend in the burden of male infertility in Low and Middle-low SDI regions. Given these findings, it is imperative to prioritize efforts aimed at improving male fertility and reproductive health.

In vitro study of piwi interaction RNA-31106 promoting breast carcinogenesis by regulating METTL3-mediated m6A RNA methylation.

Background: Breast cancer is the most common gynecological malignancy and the leading cause of cancer-related deaths in women. P-element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are novel non-coding RNAs whose abnormal expressions have been closely associated with multiple cancers. This study explored the roles and possible mechanisms of piRNA-31106 in breast cancer. Methods: The expression of piRNA-31106 in breast cancer tissues and cells was detected by reverse transcription polymerase chain reaction (RT-PCR). The pcDNA vector containing piRNA-31106 (pcDNA-piRNA-31106) and a short hairpin (sh)RNA containing piRNA-31106 (shRNA-piRNA-31106) were used to interfere with piRNA-31106 expression in breast cancer cells. The effects on cell proliferation, apoptosis/cell cycle, invasion, and metastasis were detected via Cell Counting Kit-8 (CCK-8), flow cytometry, transwell assays, and scratch tests, respectively. The protein expressions of murine double minute 2 (MDM2), cyclin-dependent kinase 4 (CDK4), and cyclinD1 were detected by Western blot analysis. The N6-methyladenosine (m6A) RNA methylation level and the binding relationship between piRNA-31106 and METTL3 were analyzed. The role of METTL3 in the regulation of breast cancer by piRNA-31106 was further analyzed by using small interfering (si)RNA targeting METTL3. Results: PiRNA-31106 was highly expressed in breast cancer tissues and cell lines MDA-MB-231 and MCF-7. Overexpression of piRNA-31106 promoted the viability, invasion, and migration of breast cancer, inhibited apoptosis, and promoted the expressions of MDM2, CDK4, and cyclinD1. Inhibition of piRNA-31106 showed the opposite effect. In addition, piRNA-31106 promoted the m6A methylation levels and facilitated methyltransferase-like 3 (METTL3) expression in MDA-MB-231 and MCF-7 cells. RNA immunoprecipitation (RIP) assays confirmed the binding relationship between piRNA-31106 and METTL3. Further experiments demonstrated that si-METTL3 could inhibit the regulatory effects of piRNA-31106 on breast cancer. Conclusions: PiRNA-31106 was significantly highly expressed in breast cancer and could promote breast cancer progression by regulating METTL3-mediated m6A RNA methylation.

A Dynamic Prediction Model Supporting Individual Life Expectancy Prediction Based on Longitudinal Time-Dependent Covariates.

In the field of clinical chronic diseases, common prediction results (such as survival rate) and effect size hazard ratio (HR) are relative indicators, resulting in more abstract information. However, clinicians and patients are more interested in simple and intuitive concepts of (survival) time, such as how long a patient may live or how much longer a patient in a treatment group will live. In addition, due to the long follow-up time, resulting in generation of longitudinal time-dependent covariate information, patients are interested in how long they will survive at each follow-up visit. In this study, based on a time scale indicator-restricted mean survival time (RMST)-we proposed a dynamic RMST prediction model by considering longitudinal time-dependent covariates and utilizing joint model techniques. The model can describe the change trajectory of longitudinal time-dependent covariates and predict the average survival times of patients at different time points (such as follow-up visits). Simulation studies through Monte Carlo cross-validation showed that the dynamic RMST prediction model was superior to the static RMST model. In addition, the dynamic RMST prediction model was applied to a primary biliary cirrhosis (PBC) population to dynamically predict the average survival times of the patients, and the average C-index of the internal validation of the model reached 0.81, which was better than that of the static RMST regression. Therefore, the proposed dynamic RMST prediction model has better performance in prediction and can provide a scientific basis for clinicians and patients to make clinical decisions.

Identification of shared fatty acid metabolism related signatures in dilated cardiomyopathy and myocardial infarction.

Aim: It is to be elucidated the risk-predictive role of differentially expressed fatty acid metabolism related genes (DE-FRGs) in dilated cardiomyopathy (DCM) and myocardial infarction. Materials & methods: Four gene enrichment analyses defined DE-FRGs' biological functions and pathways. Three strategies were applied to identify risk biomarkers and construct a nomogram. The 4-DE-FRG correlation with immune cell infiltration, drugs, and ceRNA was explored. Results: DE-FRGs were enriched in lipid metabolism. A risk nomogram was established by ACSL1, ALDH2, CYP27A1 and PPARA, demonstrating a good ability for DCM and myocardial infarction prediction. PPARA was positively correlated with adaptive immunocytes. Thirty-five drugs are candidate therapeutic targets. Conclusion: A nomogram and new biological targets for early diagnosis and treatment of DCM and myocardial infarction were provided.

Dilated cardiomyopathy (DCM) and myocardial infarction (MI) are two common types of heart disease. This study investigated the fatty acid metabolism related genes to predict the risk of DCM or MI. Four of them (ACSL1, ALDH2, CYP27A1 and PPARA) were effective in predicting disease risk. Additionally, PPARA was found to be associated with immune cell infiltration, and 35 drugs emerged as potential therapeutic targets for these diseases. This study may provide insights into the early diagnosis and treatment of DCM and MI.

A cross-sectional study of the association between heavy metals and pan-cancers associated with sex hormones in NHANES 1999-2018.

Given the complexity of tumorigenesis, numerous studies have also shown that excessive exposure to heavy metals increases the risk of cancers and disrupts the secretion of sex hormones. However, the specific effects of heavy metals on cancers remain to be proven. To confirm the association between heavy metals and pan-cancer sex hormone levels among adults, 94,337 individuals from the National Health and Nutrition Examination Survey were assessed. We examined the associations between pan-cancers associated with sex hormones (ovarian, testicular, breast, and prostate cancers) and heavy metals in blood/urine. The methods (the WQS (weighted quantile sums) and SVYGLM (survey generalized linear model) regressions) were used to evaluate the association between sex hormone-related cancers and each metal category by incorporating covariates. To evaluate the overall effect of heavy metals and detect the dose-response relationship between the prevalence of pan-cancers associated with sex hormones and heavy metals, RCS (restricted cubic splines) were applied. Environmental exposure to heavy metals may be associated with pan-cancers associated with sex hormones in adults in the USA. Prostate cancer was inversely associated with blood cadmium while positively associated with blood lead, urinary tin, and thallium. Breast cancer was inversely associated with blood lead. Ovarian cancer was positively associated with blood cadmium. We also found a non-linear dose-response relationship between pan-cancers associated with sex hormones and heavy metals, which was non-parametric, using RCS models. The OR for breast cancer decreased along with the increase in lead concentration under approximately 20 µg/dl, while the OR for prostate cancer increased between urine thallium levels of approximately 0.17-1.1 ng/ml. Pan-cancers associated with sex hormones are associated with exposure to heavy metals. Considering the design of the NHANES study, further studies need to be conducted on other nationally representative surveys.

Dynamic effects of prognostic factors and individual survival prediction for amyotrophic lateral sclerosis disease.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons, with broad heterogeneity in disease progression and survival in different patients. Therefore, an accurate prediction model will be crucial to implement timely interventions and prolong patient survival time. METHODS: A total of 1260 ALS patients from the PRO-ACT database were included in the analysis. Their demographics, clinical variables, and death reports were included. We constructed an ALS dynamic Cox model through the landmarking approach. The predictive performance of the model at different landmark time points was evaluated by calculating the area under the curve (AUC) and Brier score. RESULTS: Three baseline covariates and seven time-dependent covariates were selected to construct the ALS dynamic Cox model. For better prognostic analysis, this model identified dynamic effects of treatment, albumin, creatinine, calcium, hematocrit, and hemoglobin. Its prediction performance (at all landmark time points, AUC ≥ 0.70 and Brier score ≤ 0.12) was better than that of the traditional Cox model, and it predicted the dynamic 6-month survival probability according to the longitudinal information of individual patients. INTERPRETATION: We developed an ALS dynamic Cox model with ALS longitudinal clinical trial datasets as the inputs. This model can not only capture the dynamic prognostic effect of both baseline and longitudinal covariates but also make individual survival predictions in real time, which are valuable for improving the prognosis of ALS patients and providing a reference for clinicians to make clinical decisions.

Identification of a Novel Cuproptosis-Related Gene Signature in Eutopic Endometrium of Women with Endometriosis.

Endometriosis (EMs) is a life-long endocrine disorder and a common cause for female infertility and pelvic pain. The key characteristics of eutopic endometrium of EMs patients are high proliferative and migratory potentials. Cuproptosis is a recently identified copper- and-mitochondrial-dependent regulated cell death. Regretfully, its role in EMs remains unclear. In this study, Kyoto Encyclopedia of Genes and Genomes analyses of differentially expressed genes (DEGs) indicated strong activation of the PI3K-Akt-mTOR pathway and biological process analysis reported positive regulation of kinase activity. Next, we screened 11 cuproptosis-related DEGs and found all of them were downregulated in the EMs group, which indicated the suppression of cuproptosis in EMs. One key cuproptosis-related gene, PDHA1, was selected via support vector machine, random forest algorithm and lasso regularization to build a risk-scoring model, which was tested in both internal and external validations. In conclusion, the downregulation and kinase activity of PDHA1 may function with the PI3K-Akt-mTOR pathway in some way, which could suppress the cuproptosis level and account for the cancer-like pathology in EMs.

Polycystic ovary syndrome: Identification of novel and hub biomarkers in the autophagy-associated mRNA-miRNA-lncRNA network.

Introduction: Polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder prevalent among women of reproductive age. Recent studies show that autophagy participated in the pathogenesis of PCOS, including anovulation, hyperandrogenism, and metabolic disturbances. This study was designed to screen autophagy-related genes (ATGs) that may play a pivotal role in PCOS, providing potential biomarkers and identifying new molecular subgroups for therapeutic intervention. Methods: Gene expression profiles of the PCOS and control samples were obtained from the publicly available Gene Expression Omnibus database. The gene lists of ATGs from databases were integrated. Then, the weighted gene co-expression network analysis was conducted to obtain functional modules and construct a multifactorial co-expression network. Gene Ontology and KEGG pathway enrichment analyses were performed for further exploration of ATG's function in the key modules. Differentially expressed ATGs were identified and validated in external datasets with the Limma R package. To provide guidance on PCOS phenotyping, the dysfunction module consists of a co-expression network mapped to PCOS patients. A PCOS-Autophagy-related co-expression network was established using Cytoscape, followed by identifying molecular subgroups using the Limma R package. ps. RNA-sequencing analysis was used to confirm the differential expression of hub ATGs, and the diagnostic value of hub ATGs was assessed by receiver operating characteristic curve analysis. Results: Three modules (Brown, Turquoise, and Green) in GSE8157, three modules (Blue, Red, and Green) in GSE43264, and four modules (Blue, Green, Black, and Yellow) in GSE106724 were identified to be PCOS-related by WGCNA analysis. 29 ATGs were found to be the hub genes that strongly correlated with PCOS. These hub ATGs were mainly enriched in autophagy-related functions and pathways such as autophagy, endocytosis, apoptosis, and mTOR signaling pathways. The mRNA-miRNA-lncRNA multifactorial network was successfully constructed. And three new molecular subgroups were identified via the K-means algorithm. Discussion: We provide a novel insight into the mechanisms behind autophagy in PCOS. BRCA1, LDLR, MAP1B, hsa-miR-92b-3p, hsa-miR-20b-5p, and NEAT1 might play a considerably important role in PCOS dysfunction. As a result, new potential biomarkers can be evaluated for use in PCOS diagnosis and treatment in the future.

Individual dynamic prediction and prognostic analysis for long-term allograft survival after kidney transplantation.

BACKGROUND: Predicting allograft survival is vital for efficient transplant success. With dynamic changes in patient conditions, clinical indicators may change longitudinally, and doctors' judgments may be highly variable. It is necessary to establish a dynamic model to precisely predict the individual risk/survival of new allografts. METHODS: The follow-up data of 407 patients were obtained from a renal allograft failure study. We introduced a landmarking-based dynamic Cox model that incorporated baseline values (age at transplantation, sex, weight) and longitudinal changes (glomerular filtration rate, proteinuria, hematocrit). Model performance was evaluated using Harrell's C-index and the Brier score. RESULTS: Six predictors were included in our analysis. The Kaplan-Meier estimates of survival at baseline showed an overall 5-year survival rate of 87.2%. The dynamic Cox model showed the individual survival prediction with more accuracy at different time points (for the 5-year survival prediction, the C-index = 0.789 and Brier score = 0.065 for the average of all time points) than the static Cox model at baseline (C-index = 0.558, Brier score = 0.095). Longitudinal covariate prognostic analysis (with time-varying effects) was performed. CONCLUSIONS: The dynamic Cox model can utilize clinical follow-up data, including longitudinal patient information. Dynamic prediction and prognostic analysis can be used to provide evidence and a reference to better guide clinical decision-making for applying early treatment to patients at high risk.

Development and validation of a novel ubiquitination-related gene prognostic signature based on tumor microenvironment for colon cancer.

Background: Colon cancer (CC) is one of the most common cancers with high morbidity globally. Ubiquitination is involved in the characterization of multiple biological processes, and some ubiquitinated enzymes are associated with the prognosis of CC. However, the prognostic model associated with ubiquitination-related genes (URGs) for CC is unavailable. Methods: Gene expression data, somatic mutations, transcriptome profiles, microsatellite instability status (MSI) status, and clinical information for CC were obtained from The Cancer Genome Atlas (TCGA) dataset. Seven URGs were used for establishing a prognostic prediction model, which was constructed and validated in GSE17538. Besides, genomic variance analysis (GSVA) was used to explore further the differences in biological pathway activation status between the high-risk and low-risk groups. Finally, the single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithm analysis were used to characterize the cellular infiltration in the microenvironment. Results: A seven-URG prognostic signature was established, based on which patients in the training and test groups could be divided into high-risk and low-risk groups. The results demonstrated that the model has a solid ability to predict the prognosis of CC patients. Conclusions: We established a prognostic prediction model for CC based on ubiquitination. Then we analyzed the genetic characteristics associated with ubiquitination and the tumor microenvironment (TME) cell infiltration in CC. These results are worthy of exploring new clinical treatment strategies for CC.

Astragaloside IV Regulates Insulin Resistance and Inflammatory Response of Adipocytes via Modulating CTRP3 and PI3K/AKT Signaling.

INTRODUCTION: Emerging evidence showed that adipocytes are important regulators in controlling insulin resistance in type 2 diabetes mellitus (T2DM). So far, compounds isolated from natural plants have been widely studied for their roles in alleviating T2DM-associated complications. This work evaluated the actions of astragaloside IV (AS-IV) on insulin resistance and inflammatory biomarker expression in adipocytes and explored the potential mechanisms. METHODS: Glucose consumption of the adipocytes was determined by a glucose assay kit; the mRNA expression levels of glucose transporter type 4 (GLUT-4), interleukin-6 (IL-6), TNF-α and C1q tumor necrosis factor-related protein 3 (CTRP3) were measured by quantitative real-time PCR (qRT-PCR); the protein levels were determined by western blot assay and enzyme-linked immunosorbent assay. RESULTS: AS-IV concentration-dependently increased glucose consumption in the insulin resistance adipocytes. Further qRT-PCR results showed that AS-IV concentration-dependently reduced adipocyte IL-6 and TNF-α expression. Moreover, GLUT-4 expression in adipocytes was also significantly upregulated by AS-IV. Furthermore, we found that AS-IV concentration-dependently increased CTRP3 expression in adipocytes. CTRP3 silence decreased glucose consumption, upregulated IL-6 and TNF-α expression and downregulated GLUT-4 mRNA expression in 200 µM AS-IV-treated adipocytes. Moreover, AS-IV treatment enhanced the activity of phosphoinositide 3-kinase (PI3K)/AKT signaling in adipocytes, which was markedly attenuated by CTRP3 silencing. Importantly, inhibition of PI3K/AKT signaling also attenuated AS-IV induced an increase in glucose consumption and GLUT-4 expression and a decrease in IL-6 and TNF-α expression of adipocytes. CONCLUSIONS: Collectively, our data indicated that AS-IV attenuated insulin resistance and inflammation in adipocytes via targeting CTRP3/PI3K/Akt signaling.

Restricted mean survival time regression model with time-dependent covariates.

In clinical or epidemiological follow-up studies, methods based on time scale indicators such as the restricted mean survival time (RMST) have been developed to some extent. Compared with traditional hazard rate indicator system methods, the RMST is easier to interpret and does not require the proportional hazard assumption. To date, regression models based on the RMST are indirect or direct models of the RMST and baseline covariates. However, time-dependent covariates are becoming increasingly common in follow-up studies. Based on the inverse probability of censoring weighting (IPCW) method, we developed a regression model of the RMST and time-dependent covariates. Through Monte Carlo simulation, we verified the estimation performance of the regression parameters of the proposed model. Compared with the time-dependent Cox model and the fixed (baseline) covariate RMST model, the time-dependent RMST model has a better prediction ability. Finally, an example of heart transplantation was used to verify the above conclusions.

Reconstruction of complex chest wall defects: A case report.

BACKGROUND: Chronic radiative chest wall ulcers are common in patients undergoing radiation therapy. If not treated early, then symptoms such as erosion, bleeding and infection will appear on the skin. In severe cases, ulcers invade the ribs and pleura, presenting a mortality risk. Small ulcers can be repaired with pedicle flaps. Because radioactive ulcers often invade the thorax, surgeons need to remove large areas of skin and muscle, and sometimes ribs. Repairing large chest wall defects are a challenge for surgeons. CASE SUMMARY: A 74-year-old female patient was admitted to our department with chest wall skin ulceration after radiation therapy for left breast cancer. The patient was diagnosed with chronic radioactive ulceration. After multidisciplinary discussion, the authors performed expansive resection of the chest wall ulcers and repaired large chest wall defects using a deep inferior epigastric perforator (DIEP) flap combined with a high-density polyethylene (HDPE) patch. The patient was followed-up 6 mo after the operation. No pigmentation or edema was found in the flap. CONCLUSION: DIEP flap plus HDPE patch is one of the better treatments for radiation-induced chest wall ulcers.

A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile.

Although epilepsy is one of the most common neurologic disorders, there is still a lack of effective therapeutic drugs for it. Recently, we synthesized a novel hydrogen sulfide (H2S) donor, which is found to reduce seizures in animal models effectively. But it remains to be determined for its mechanism. In the present study, we found that the novel H2S donor could reduce pilocarpine-induced seizures in mice. It alleviated the epileptic behavior, the hippocampal electroencephalography (EEG) activity of seizures, and the damage of hippocampal neurons in status epilepticus mice. In addition, the novel H2S donor could reduce microglial inflammatory response. It not only reduced the upregulation of pro-inflammatory markers [inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)] in status epilepticus mice, but also increased the levels of microglial anti-inflammatory marker arginase-1 (Arg-1). In lipopolysaccharide-treated microglia BV2 cells, administration of the H2S donor also significantly reduced the lipopolysaccharide-induced upregulation of the expression of the pro-inflammatory markers and increased the expression of the anti-inflammatory markers. Thus, the novel H2S donor regulates microglial inflammatory profile in status epilepticus mice and in vitro. These results suggested that the novel H2S donor can reduce seizures and regulate microglial inflammatory profile, which may be a novel mechanism and potential therapeutic strategy of the H2S donor anti-seizures.

Strategies for the selection of oncoplastic techniques in the treatment of early-stage breast cancer patients.

BACKGROUND: In recent years, breast cancer is the most common malignancy in women. The traditional method of surgery is to remove a woman's breast completely, which has a negative impact on her work and life. Today, women have a fiery pursuit to maintain their perfect figure, which has forced breast surgeon to find a new surgical approach to maintain the shape of the breast after surgery. METHODS: This study systematically analyzed and summarized the incision design and repair of glandular defects in early-stage breast cancer patients by oncoplastic breast techniques. By summarizing the methods of oncoplastic breast surgery (OBS) in different quadrants, it could help beginners to master this technology more quickly, so as to provide better help for breast cancer patients. RESULTS: A total of 216 breast cancer patients who underwent OBS from January 2016 to June 2020 at the Affiliated Hospital of Guangdong Medical University were included in this study. In patients treated with the volume-displacement method and the volume-replacement method, 92.6% and 86.2% of patients achieved excellent breast shape, respectively. CONCLUSIONS: OBS is a safe and effective way to treat early-stage breast cancer while obtaining better breast shape, reducing postoperative psychological trauma, and improving quality of life.