miR-34b-3p-mediated regulation of STC2 and FN1 enhances chemosensitivity and inhibits proliferation in cervical cancer.

Dysregulation of microRNA (miRNA) expression in cancer is a significant factor contributing to the progression of chemoresistance. The objective of this study is to explore the underlying mechanisms by which miR-34b-3p regulates chemoresistance in cervical cancer (CC). Previous findings have demonstrated low expression levels of miR-34b-3p in both CC chemoresistant cells and tissues. In this study, we initially characterize the behavior of SiHa/DDP cells which are CC cells resistant to the chemotherapeutic drug cisplatin (DDP). Subsequently, miR-34b-3p mimics are transfected into SiHa/DDP cells. It is observed that overexpression of miR-34b-3p substantially inhibits the proliferation, migration, and invasion abilities of SiHa/DDP cells and also enhances their sensitivity to DDP-induced cell death. Quantitative RT-PCR and western blot analysis further reveal elevated expression levels of STC2 and FN1 in SiHa/DDP cells, contrary to the expression pattern of miR-34b-3p. Moreover, STC2 and FN1 contribute to DDP resistance, proliferation, migration, invasion, and decreased apoptosis in CC cells. Through dual-luciferase assay analysis, we confirm that STC2 and FN1 are direct targets of miR-34b-3p in CC. Finally, rescue experiments demonstrate that overexpression of either STC2 or FN1 can partially reverse the inhibitory effects of miR-34b-3p overexpression on chemoresistance, proliferation, migration and invasion in CC cells. In conclusion, our findings support the role of miR-34b-3p as a tumor suppressor in CC. This study indicates that targeting the miR-34b-3p/STC2 or FN1 axis has potential therapeutic implications for overcoming chemoresistance in CC patients.

Melatonin alleviates valproic acid-induced neural tube defects by modulating Src/PI3K/ERK signaling and oxidative stress.

Neural tube defects (NTDs) represent a developmental disorder of the nervous system that can lead to significant disability in children and impose substantial social burdens. Valproic acid (VPA), a widely prescribed first-line antiepileptic drug for epilepsy and various neurological conditions, has been associated with a 4-fold increase in the risk of NTDs when used during pregnancy. Consequently, urgent efforts are required to identify innovative prevention and treatment approaches for VPA-induced NTDs. Studies have demonstrated that the disruption in the delicate balance between cell proliferation and apoptosis is a crucial factor contributing to NTDs induced by VPA. Encouragingly, our current data reveal that melatonin (MT) significantly inhibits apoptosis while promoting the restoration of neuroepithelial cell proliferation impaired by VPA. Moreover, further investigations demonstrate that MT substantially reduces the incidence of neural tube malformations resulted from VPA exposure, primarily by suppressing apoptosis through the modulation of intracellular reactive oxygen species levels. In addition, the Src/PI3K/ERK signaling pathway appears to play a pivotal role in VPA-induced NTDs, with significant inhibition observed in the affected samples. Notably, MT treatment successfully reinstates Src/PI3K/ERK signaling, thereby offering a potential underlying mechanism for the protective effects of MT against VPA-induced NTDs. In summary, our current study substantiates the considerable protective potential of MT in mitigating VPA-triggered NTDs, thereby offering valuable strategies for the clinical management of VPA-related birth defects.

Open Chest Duration Following Congenital Cardiac Surgery Increases Risk for Surgical Site Infection.

Surgical site infections (SSI) following congenital heart surgery (CHS) remain a significant source of morbidity. Delayed sternal closure (DSC) is often required to minimize the potential for hemodynamic instability. The purpose of this study was to determine the incidence of SSI among patients undergoing DSC versus primary chest closure (PCC) and to define a potential inflection point for increased risk of SSI as a function of open chest duration (OCD).A retrospective review of our institutional Society of Thoracic Surgeons dataset is to identify patients undergoing CHS at our institution between 2015 and 2020. Incidences of SSI were compared between DSC and PCC patients. DSC patients were evaluated to determine the association of OCD and the incidence of SSI.2582 operations were performed at our institution between 2015 and 2020, including 195 DSC and 2387 PCC cases. The incidence of SSI within the cohort was 1.8% (47/2,582). DSC patients had significantly higher incidences of SSI (17/195, 8.7%) than PCC patients (30/2387, 1.3%, p < 0.001). Further, patients with an OCD of four or more days had a significantly higher incidence of SSI (11/62, 17.7%, p = 0.006) than patients with an OCD less than 4 days (6/115, 5.3%).The incidence of SSI following CHS is higher in DSC patients compared to PCC patients. Prolonged OCD of 4 days or more significantly increases the risk of SSI and represents a potentially modifiable risk factor for SSI predisposition. These data support dedicated, daily post-operative assessment of candidacy for chest closure to minimize the risk of SSI.

Evaluating the risk of spinal cord ischemia in zone 2 frozen elephant trunk replacement.

BACKGROUND: The appropriate stent length in frozen elephant trunk replacements (FET) remains debated relative to the risk for paraplegia. However, landing the distal end of the stent beyond the curve of the arch facilitates distal reintervention, which is commonly beyond the 10 cm stent coverage when deployed proximal to the left subclavian artery. The aim of this study was to evaluate outcomes following the use of 15 cm stent grafts in zone 2 (z2, distal to the left common carotid). METHODS: Using our single institution-maintained database, 103 zone 2 FET performed from 2016 to 2020 were reviewed. RESULTS: Of the 103 z2, a 15 cm stent graft was used in 51 operations. The indications for FET included acute and chronic aortic dissection, arch aneurysms, and pseudoaneurysms. The incidence of SCI was 0%. Seven deaths (13.7%) occurred. CONCLUSIONS: The data demonstrates the incidence of post-operative paraplegia to be 0% with 15 cm z2 FET. The understanding of SCI in FET should not only include the stent length but also from where it begins.

Risk factors and long-term prognosis of beyond-Milan recurrence after hepatectomy for BCLC stage 0/A hepatocellular carcinoma: A large-scale multicenter study.

BACKGROUND: Data on recurrence are important to inform surveillance and improve long-term surgical outcomes for patients with hepatocellular carcinoma. We sought to identify risk factors and long-term prognosis among patients who experienced beyond-Milan recurrence after hepatectomy for early-stage hepatocellular carcinoma. METHODS: Patients who underwent hepatectomy for Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma were identified from a multi-institutional database. Predictors of beyond-Milan recurrence and risk factors associated with post-recurrence survival among patients with beyond-Milan recurrence were assessed using univariate and multivariate Cox regression analyses. RESULTS: Among 753 patients (median follow-up, 51.8 months), 138 (18.3%) developed beyond-Milan recurrence. Regular surveillance (interval follow-up ≤3 months within 1 year and ≤6 months in subsequent years after surgery) was not carried out for 53 (38.4%) patients who developed beyond-Milan recurrence. On multivariate analysis, increased risk of beyond-Milan recurrence was independently associated with preoperative alpha-fetoprotein level >400 ng/mL, tumor size >5.0 cm, multifocal disease, microvascular invasion, and no/irregular recurrence surveillance. Median post-recurrence survival among patients with beyond-Milan recurrence was only 8.4 months (95% confidence interval: 7.0-9.8 months). Among patients who developed beyond-Milan recurrence, Child-Pugh grade B/C, early recurrence within 1 year after surgery, macrovascular invasion/distant metastasis, and noncurative treatment of recurrence were independent risk factors associated with worse post-recurrence survival. CONCLUSION: Nearly 1 in 5 patients developed beyond-Milan recurrence after hepatectomy for early-stage hepatocellular carcinoma. Patients with beyond-Milan recurrence had a median survival of less than 1 year after diagnosis of the recurrence. Regular surveillance is an important and actionable measure to decrease beyond-Milan recurrence and, in turn, improve long-term survival among patients treated with hepatectomy for hepatocellular carcinoma.

CLEC1B is a Promising Prognostic Biomarker and Correlated with Immune Infiltration in Hepatocellular Carcinoma.

Purpose: C-type lectin domain family 1 member B (CLEC1B) is a protein-coding gene involved in various processes, such as platelet activation, tumor cell metastasis and separation of blood/lymphatic vessels. However, how CLEC1B plays its role in hepatocellular carcinoma (HCC) has not been well studied. The purpose of this study was to investigate the clinical significance and biological function of CLEC1B in HCC. Patients and Methods: Based on (The Cancer Genome Atlas) TCGA database, CLEC1B expression matrix and corresponding clinical information were extracted. ROC curves and Kaplan-Meier method were generated to evaluate the value of CLEC1B as a diagnostic and prognostic biomarker. Moreover, single-gene difference analysis constructed by DESeq2 method and then the related genes were used to predict CLEC1B-related signaling pathways. The ssGSEA algorithm was conducted for studies related to immune infiltration. CLEC1B protein expression was evaluated and immunohistochemistry in HCC tissues through tissue microarray. Finally, the relationship between CLEC1B expression and T cell infiltration was assessed according to tissue microarray. Results: The mRNA and protein levels of CLEC1B were significantly down-regulated in HCC compared to paired normal tissues, which were further verified in clinical tissue samples. ROC curves and Kaplan-Meier survival analysis suggested the significant diagnostic and clinical prognostic value of CLEC1B. Meanwhile, downregulation of CLEC1B was significantly associated with clinical parameters such as clinical tumor vascular invasion and distant metastasis. Moreover, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment (GSEA) analysis indicated that CLEC1B has significant association with immune function. Finally, immune infiltration analysis indicated that CLEC1B was significantly associated with immune cell subsets and affected the efficacy of immunotherapy in cancer patient. Conclusion: Collectively, our findings suggested that CLEC1B could be a promising prognostic biomarker in HCC and its expression was related to immune cell infiltration.

Association of Preoperative Body Mass Index with Surgical Textbook Outcomes Following Hepatectomy for Hepatocellular Carcinoma: A Multicenter Study of 1206 Patients.

BACKGROUND: Assessment of quality in the perioperative period is critical to ensure good patient care. Textbook outcomes (TO) have been proposed to combine several parameters into a single defined quality metric. The association of preoperative body mass index (BMI) with incidences of achieving or not achieving TO (non-TO) among patients undergoing hepatectomy for hepatocellular carcinoma (HCC) was characterized. METHODS: Patients who underwent curative-intent hepatectomy for HCC between 2015 and 2018 were identified from a multicenter database. These patients were divided into three groups based on preoperative BMI: low-BMI (≤ 18.4 kg/m2), normal-BMI (18.5-24.9 kg/m2), and high-BMI (≥ 25.0 kg/m2). The incidences of non-TO among these three groups were compared. Multivariate analyses were performed to identify whether there was any independent association between preoperative BMI and non-TO. RESULTS: Among 1206 patients, 100 (8.3%), 660 (54.7%), and 446 (37.0%) were in the low-BMI, normal-BMI, and high-BMI groups, respectively. The incidence of non-TO was 65.6% in the whole cohort. The incidence of non-TO was significantly higher among patients in the low- and high-BMI cohorts versus the normal-BMI cohort (75.0% and 74.7% versus 58.0%, both P < 0.01). After adjustment of other confounding factors on multivariate analysis, low-BMI and high-BMI were independently associated with higher incidences of non-TO compared with normal-BMI (OR: 1.98 and 2.27, both P < 0.05). CONCLUSIONS: Two out of three patients did not achieve TO after hepatectomy for HCC. Both preoperative low-BMI and high-BMI were independently associated with lower odds to achieve optimal TO following HCC resection.

Clinical Features of Recurrence After Hepatic Resection for Early-Stage Hepatocellular Carcinoma and Long-Term Survival Outcomes of Patients with Recurrence: A Multi-institutional Analysis.

BACKGROUND: A potentially curative hepatic resection is the optimal treatment for hepatocellular carcinoma (HCC), but most HCCs, even at an early stage, eventually recur after resection. This study investigates clinical features of initial recurrence and long-term prognosis of patients with recurrence after curative resection for early-stage HCC. PATIENTS AND METHODS: From a multicenter database, patients who underwent curative hepatic resection for early-stage HCC [Barcelona Clinic Liver Cancer (BCLC) stage 0/A] were extracted. Time to initial recurrence, patterns of initial recurrence, and treatment modalities for recurrent tumors were investigated. Univariate and multivariate analysis were used to identify independent risks associated with postoperative recurrence, as well as post-recurrence survival (PRS) for patients with recurrence. RESULTS: Among 1424 patients, 679 (47.7%) developed recurrence at a median follow-up of 54.8 months, including 408 (60.1%) early recurrence (≤ 2 years after surgery) and 271 (39.9%) late recurrence (> 2 years). Independent risks of postoperative recurrence included cirrhosis, preoperative alpha-fetoprotein level > 400 ug/L, tumor size > 5 cm, multiple tumors, satellites, microvascular invasion, and intraoperative blood transfusion. Multivariate analysis revealed that receiving irregular recurrence surveillance, initial tumor beyond Milan criteria, early recurrence, BCLC stage B/C of the recurrent tumor, and noncurative treatments were independently associated with poorer PRS. CONCLUSIONS: Nearly half of patients with early-stage HCC experienced recurrence after resection. Understanding recurrence risks may help identify patients at high risk of recurrence who may benefit from future adjuvant therapies. Meaningful survival even after recurrence can still be achieved by postoperative regular surveillance and curative treatment.

1-Nitropyrene exposure impairs embryo implantation through disrupting endometrial receptivity genes expression and producing excessive ROS.

Haze problem is an important factor threatening human health. PM2.5 is the main culprit haze. 1-Nitropyrene (1-NP) is the main nitrated polycyclic aromatic hydrocarbon, the toxic component of PM2.5 particles. The effects of 1-NP on various organs and reproductive health have been extensively and deeply studied, but the effects of 1-NP on embryo implantation and endometrial receptivity remain to be determined. The purpose of this study was to investigate the adverse effects of 1-NP on mouse embryo implantation and human endometrial receptivity. In early pregnancy, CD1 mice were given 2 mg/kg 1-NP by oral gavage, which resulted in a decreased embryo implantation number on day 5, inhibited leukemic inhibitory factor (LIF)/STAT3 pathway, decreased expression of estrogen receptor and progesterone receptor, and disrupted regulation of uterine cell proliferation. In addition, in a human in vitro implantation model, 1-NP was found to significantly inhibit the adhesion rate between trophoblast spheroids and endometrial epithelial cells, possibly by inhibiting the expression of receptivity molecules in Ishikawa cells. Promoting reactive oxygen species (ROS) production may be an additional mechanism by which it inhibits trophoblast spheroid adhesion. In this study, we used an in vivo mouse pregnancy model and an in vitro human embryo implantation model to demonstrate that 1-NP can impair endometrial receptivity and compromise embryo implantation.