The relationship between emotional disorders and heart rate variability: A Mendelian randomization study.

OBJECTIVE: Previous studies have shown that emotional disorders are negatively associated with heart rate variability (HRV), but the potential causal relationship between genetic susceptibility to emotional disorders and HRV remains unclear. We aimed to perform a Mendelian randomization (MR) study to investigate the potential association between emotional disorders and HRV. METHODS: The data used for this study were obtained from publicly available genome-wide association study datasets. Five models, including the inverse variance weighted model (IVW), the weighted median estimation model (WME), the weighted model-based method (WM), the simple model (SM) and the MR-Egger regression model (MER), were utilized for MR. The leave-one-out sensitivity test, MR pleiotropy residual sum and outlier test (MR-PRESSO) and Cochran's Q test were used to confirm heterogeneity and pleiotropy. RESULTS: MR analysis revealed that genetic susceptibility to broad depression was negatively correlated with HRV (pvRSA/HF) (OR = 0.380, 95% CI 0.146-0.992; p = 0.048). However, genetic susceptibility to irritability was positively correlated with HRV (pvRSA/HF, SDNN) (OR = 2.017, 95% CI 1.152-3.534, p = 0.008) (OR = 1.154, 95% CI 1.000-1.331, p = 0.044). Genetic susceptibility to anxiety was positively correlated with HRV (RMSSD) (OR = 2.106, 95% CI 1.032-4.299; p = 0.041). No significant directional pleiotropy or heterogeneity was detected. The accuracy and robustness of these findings were confirmed through a sensitivity analysis. CONCLUSIONS: Our MR study provides genetic support for the causal effects of broad depression, irritable mood, and anxiety on HRV.

Why does HER2-positive breast cancer metastasize to the brain and what can we do about it?

Breast cancer is the most frequent malignancy in women. However, in the middle and late stages, some people develop distant metastases, which considerably lower the quality of life and life expectancy. The brain is one of the sites where metastasis frequently happens. According to epidemiological research, brain metastases occur at a late stage in 30-50% of patients with HER2-positive breast cancer, resulting in a poor prognosis. Additionally, few treatments are available for HER2-positive brain metastatic breast cancer, and the mortality rate is remarkable owing to the complexity of the brain's anatomical structure and physiological function. In this review, we described the stages of the brain metastasis of breast cancer, the relationship between the microenvironment and metastatic cancer cells, and the unique molecular and cellular mechanisms. It involves cancer cells migrating, invading, and adhering to the brain; penetrating the blood-brain barrier; interacting with brain cells; and activating signal pathways once inside the brain. Finally, we reviewed current clinically used treatment approaches for brain metastasis in HER2-positive breast cancer; summarized the traditional treatment, targeted treatment, immunotherapy, and other treatment modalities; compared the benefits and drawbacks of each approach; discussed treatment challenges; and emphasized the importance of identifying potential targets to improve patient survival rates and comprehend brain metastasis in breast cancer.

First-line CDK4/6 inhibitor-based combinations for HR+/HER2- advanced breast cancer: A Bayesian network meta-analysis.

BACKGROUND: International guidelines recommend cyclin-dependent kinase 4/6 inhibitor (CDK4/6i)-based first-line therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). However, direct drug comparisons are lacking. We aimed to identify the most effective and safe therapy through network meta-analysis (NMA). METHODS: We searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and OpenGrey up to September 30, 2023. Eligible studies included randomized controlled trials (RCTs) assessing endocrine therapy alone or in combination with CDK4/6i as first-line endocrine treatment for HR+/HER2- ABC patients. The hazard ratios for progression-free survival (PFS) and overall survival (OS) and relative risks for objective response rate and adverse events (AEs) were available in selected trials. We performed a Bayesian NMA following PRISMA guidelines. RESULTS: Thirteen RCTs, involving 10 treatments, were included. Most studies were at low risk of bias. Regarding PFS, ribociclib+fulvestrant ranked first with a surface under the cumulative ranking curve (SUCRA) of 85.0%, followed by dalpiciclib+nonsteroidal aromatase inhibitor (NSAI) (SUCRA = 78.9%). Considering OS, the top three ranked treatments were ribociclib+fulvestrant (SUCRA = 94.1%), abemaciclib+NSAI (SUCRA = 69.9%), and ribociclib+NSAI (SUCRA = 68.5%). Out of four CDK4/6is, ribociclib minimized the grade 3/4 AEs, while dalpiciclib demonstrated the worst safety. Publication bias could not be ignored in our analyses, and the certainty of evidence was downgraded primarily due to imprecision. CONCLUSIONS: Ribociclib+fulvestrant probably represents the best option in a first-line setting. When combined with NSAI, dalpiciclib likely showed the best efficacy but the worst safety. Abemaciclib+NSAI and ribociclib+NSAI could also be promising treatments, while palbociclib presented inferiority. (PROSPERO Registration No. CRD42022370271).

Predictive value of suprasellar extension for intracranial infection after endoscopic transsphenoidal pituitary adenoma resection.

OBJECTIVE: To investigate the relationship between suprasellar extension (SSE) and intracranial infection after endoscopic endonasal transsphenoidal approach (EETA) for pituitary adenoma resection. METHODS: We retrospectively analyzed 94 patients with suprasellar extended pituitary adenoma admitted to the Department of Neurosurgery of the Affiliated Hospital of Guilin Medical College from January 2018 to December 2021. We measured the preoperative magnetic resonance sagittal SSE and collected clinical data and divided the patients into groups according to the presence of postoperative intracranial infection. The critical value for the SSE was calculated by using a working characteristic curve for the subjects. The risk factors for intracranial infection after EETA resection of pituitary adenomas were analyzed by multivariate regression analysis. RESULTS: Among the 94 patients, 12 cases (12.8%) were placed in the infection group and 82 cases (87.2%) in the non-infection group. The cut-off value for the SSE in the sagittal position was 15.6 mm, the sensitivity was 75%, the specificity was 87.8%, and the area under the curve (AUC) was 0.801. The coronary cut-off value for the SSE was 15.8 mm, the sensitivity was 66.7%, the specificity was 79.3%, and the AUC was 0.787. The SSE values in the sagittal and coronal positions were correlated with postoperative intracranial infection (P < 0.05). After univariate analysis, those with significant differences were included in the multivariate regression analysis. It was concluded that the extension distance of the tumor above the sella in the sagittal position was ≥ 15.6 mm, the tumor texture was hard, and the postoperative cerebrospinal fluid leakage were the independent risk factors for intracranial infection after EETA resection of suprasellar extended pituitary tumors (P < 0.05). CONCLUSIONS: The value of SSE on sagittal MRI can predict intracranial infection in patients with suprasellar extended pituitary adenoma after endoscopic endonasal transsphenoidal resection. This finding recommends neurosurgeons pay more attention to the imaging characteristics of pituitary adenomas and select appropriate treatment plans in combination with the intraoperative conditions to reduce the incidence of intracranial infection.

A bibliometric analysis of cardiomyocyte apoptosis from 2014 to 2023: A review.

Cardiomyocyte apoptosis is an important factor in cardiac function decline observed in various cardiovascular diseases. To understand the progress in the field of cardiomyocyte apoptosis research, this paper uses bibliometrics to statistically analyze publications in this field. A total of 5939 articles were retrieved from the core Web of Science database, and then VOSviewer and Citespace were used to conduct a scientometric analysis of the authors, countries, institutions, references and keywords included in the articles to determine the cooperative relationships between researchers that study cardiomyocyte apoptosis. At present, the research hotspots in this field mainly include experimental research, molecular mechanisms, pathophysiology and cardiac regeneration of cardiomyocyte apoptosis-related diseases. NOD-like receptor thermal protein domain associated protein 3 inflammasome, circular RNA, and sepsis are the research frontiers in this field and are emerging as new areas of research focus. This work provides insight into research directions and the clinical application value for the continued advancement of cardiomyocyte apoptosis research.

Predictive Significance of Systemic Immune-Inflammation Index in Patients with Breast Cancer: A Retrospective Cohort Study.

Background: Peripheral blood inflammation indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), have become research hotspots in the diagnosis, treatment, and prognosis prediction of breast cancer, whereas existing research findings remain controversial. Methods: Data pertaining to 1808 breast cancer patients were collected retrospectively to analyze the predictive value of NLR/PLR/SII for breast cancer clinicopathological characteristics, chemotherapy response, and relapse. 1489, 258, and 53 eligible breast cancer patients entered into the three analyses, respectively. Logistic regression analyses were used to assess the correlation between these indices and poor response to chemotherapy. A predictive scoring model was established to predict chemotherapeutic responses based upon the odds ratio values of significant variables identified in logistic regression analyses. Results: Higher pretherapeutic NLR/PLR/SII values were significantly correlated with higher tumor stage, triple-negative breast cancer, premenopausal status, and younger age. Logistic regression analyses indicated that pretherapeutic high SII (as a continuous variable or with a cut-off value of 586.40) and HER2-negative status were independent predictors of poor response to neoadjuvant chemotherapy. A first-in-class SII-based predictive scoring model well distinguished patients who might not benefit from neoadjuvant chemotherapy, with an area under the curve of 0.751. In HR-positive cancers, SII was more strongly associated with clinicopathological features and chemotherapy response. In addition, a receiver operating characteristic curve analysis indicated that the specificity of follow-up SII in identifying cancer relapse was greater than 98.0% at a cut-off value of 900. Conclusion: As a predictor of breast cancer, especially in the HR-positive subtype, SII may eclipse NLR/PLR. SII-high patients are more likely to have a worse chemotherapy response and a higher risk of recurrence.

Potentially functional genetic variants in RPS6KA4 and MAP2K5 in the MAPK signaling pathway predict HBV-related hepatocellular carcinoma survival.

Hepatocellular carcinoma (HCC) ranks the third leading cause of cancer deaths with a dismal 5-year survival rate. The mitogen-activated protein kinase (MAPK) signaling pathway is abnormally activated in HCC to promote growth and aggressive metastatic potential of cancer cells. Therefore, genetic variants in the MAPK signaling pathway may serve as potential predictors of Hepatitis B virus (HBV)-related HCC survival. In the present study, we performed a two-stage survival analysis to evaluate the associations between 10,912 single nucleotide polymorphisms (SNPs) in 79 MAPK signaling pathway genes and the overall survival (OS) of 866 HBV-related HCC patients, followed by functional annotation. In combined datasets, we identified two novel and potential functional SNPs (RPS6KA4 rs600377 T>G and MAP2K5 rs17300363 A>C) as prognostic factors for HBV-related HCC, with adjusted allelic hazards ratios of 1.24 (95% confidence interval [CI] = 1.05-1.46, p = 0.010) and 1.48 (1.15-1.91, p = 0.001), respectively. Furthermore, their combined risk genotypes also predicted a poor survival in a dose-response manner in the combined data set (Ptrend < 0.001). Additional functional analysis showed that RPS6KA4 rs600377 G and MAP2K5 rs17300363 C alleles were associated with elevated mRNA expression levels of the corresponding genes in normal tissues. These results provide new insights into the role of genetic variants in the MAPK signaling pathway genes in HBV-related HCC survival.

A prognostic signature associated with cell senescence predicts survival outcomes and strongly associates with immunotherapy and chemotherapy response in breast cancer.

The objective of this study is to assess the predictive potency of cell senescence-related genes (CSRGs) in breast cancer (BC) and establish a risk signature. Trascriptome data of CSRGs were obtained from the TCGA and GEO databases. Consensus clustering was used to generate CSRGs-based molecular clusters for BC patients. A CSRGs-derived risk signature was built using multiple Cox regression analyses of differentially expressed genes (DEGs) between clusters. The prognosis, immune infiltration, chemotherapy and immunotherapy response between different risk groups were analyzed and compared. Two molecular clusters of BC patients were generated on the basis of 79 differentially expressed CSRGs, which showed distinct prognosis and immune infiltration. A total of 1403 DEGs between the CSRGs-derived clusters were found, and 10 of them were independent prognostic genes that used to construct a risk signature. The results demonstrated that patients with older age and advanced stage presented with a higher risk scores. In addition, the risk signature was found to be associated with outcomes, immune infiltration, chemotherapy and immunotherapy response. Patients in the low-risk group showed a favorable prognosis and higher immunotherapy response than those in the high-risk group. Finally, we developed a highly stable nomogram that incorporates risk signature, chemotherapy, radiotherapy, and stage variables, enabling accurate prediction of the overall survival (OS) of individual patients. To conclude, the signature derived from CSRGs holds great promise as a biomarker for prognostic assessment of BC and may serve as a valuable tool in guiding immunotherapy.

Pathologic complete response of hepatoid adenocarcinoma of the stomach after chemo-immunotherapy: A rare case report and literature review.

Background: Hepatoid adenocarcinoma of the stomach (HAS) is a highly malignant subtype of gastric carcinoma with specific clinicopathological features and extremely poor prognosis. We present an exceedingly rare case of complete response after chemo-immunotherapy. Case Description: A 48-year-old woman with highly elevated serum alpha-fetoprotein (AFP) level was found to have HAS verified by pathological examination based on gastroscopy. Computed tomography scan was done and TNM staging of the tumor was T4aN3aMx. Programmed cell death ligand-1 (PD-L1) immunohistochemistry was performed, revealing a negative PD-L1 expression. Chemo-immunotherapy including oxaliplatin plus S-1 and PD-1 inhibitor terelizumab was given to this patient for 2 months until the serum AFP level decreased from 748.5 to 12.9 ng/mL and the tumor shrank. D2 radical gastrectomy was then performed and histopathology of the resected specimen revealed that the cancerous cells had disappeared. Pathologic complete response (pCR) was achieved and no evidence of recurrence has been found after 1 year of follow-up. Conclusions: We, for the first time, reported an HAS patient with negative PD-L1 expression who achieved pCR from the combined chemotherapy and immunotherapy. Although no consensus has been reached regarding the therapy, it might provide a potential effective management strategy for HAS patient.