MLH1 Inhibits Metastatic Potential of Pancreatic Ductal Adenocarcinoma via Downregulation of GPRC5C.

DNA mismatch repair gene MutL homolog-1 (MLH1) has divergent effects in many cancers; however, its impact on the metastasis of pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, MLH1 stably overexpressed (OE) and knockdowned (KD) sublines were established. Wound healing and transwell assays were used to evaluate cell migration/invasion. In vivo metastasis was investigated in orthotopic implantation models (severe combined immunodeficiency mice). RT-qPCR and western blotting were adopted to show gene/protein expression. MLH1 downstream genes were screened by transcriptome sequencing. Tissue microarray-based immunohistochemistry was applied to determine protein expression in human specimens. In successfully generated sublines, OE cells presented weaker migration/invasion abilities, compared with controls, whereas in KD cells, these abilities were significantly stronger. The metastasis-inhibitory effect of MLH1 was also observed in mice. Mechanistically, G protein-coupled receptor, family C, group 5, member C (GPRC5C) was a key downstream gene of MLH1 in PDAC cells. Subsequently, transient GPRC5C silencing effectively inhibited cell migration/invasion and remarkably reversed the proinvasive effect of MLH1 knockdown in KD cells. In animal models and human PDAC tissues, tumoral GPRC5C expression, negatively associated with MLH1 expressions, was positively correlated with histologic grade, vessel invasion, and poor cancer-specific survival. In conclusion, MLH1 inhibits the metastatic potential of PDAC via downregulation of GPRC5C.

Diagnosis, Genetics, and Management of 24 Patients With Cardiac Paragangliomas: Experience From a Single Center.

Context: Paragangliomas located within the pericardium represent a rare yet challenging clinical situation. Objective: The current analysis aimed to describe the clinical characteristics of cardiac paragangliomas, with emphasis on the diagnostic approach, genetic background, and multidisciplinary management. Methods: Twenty-four patients diagnosed with cardiac paraganglioma (PGL) in Peking Union Medical College Hospital, Beijing, China, between 2003 and 2021 were identified. Clinical data was collected from medical record. Genetic screening and succinate dehydrogenase subunit B immunohistochemistry were performed in 22 patients. Results: The median age at diagnosis was 38 years (range 11-51 years), 8 patients (33%) were females, and 4 (17%) had familial history. Hypertension and/or symptoms related to catecholamine secretion were present in 22 (92%) patients. Excess levels of catecholamines and/or metanephrines were detected in 22 (96%) of the 23 patients who have completed biochemical testing. Cardiac PGLs were localized with 131I-metaiodobenzylguanidine scintigraphy in 11/22 (50%), and 99mTc-hydrazinonicotinyl-tyr3-octreotide scintigraphy in 24/24 (100%) patients. Genetic testing identified germline SDHx mutations in 13/22 (59%) patients, while immunohistochemistry revealed succinate dehydrogenase (SDH) deficiency in tumors from 17/22 (77%) patients. All patients were managed by a multidisciplinary team through medical preparation, surgery, and follow-up. Twenty-three patients received surgical treatment and perioperative death occurred in 2 cases. Overall, 21 patients were alive at follow-up (median 7.0 years, range 0.6-18 years). Local recurrence or metastasis developed in 3 patients, all of whom had SDH-deficient tumors. Conclusion: Cardiac PGLs can be diagnosed based on clinical manifestations, biochemical tests, and appropriate imaging studies. Genetic screening, multidisciplinary approach, and long-term follow-up are crucial in the management of this disease.

Prevalence, Genetic Background, and Clinical Phenotype of Congenital Thrombophilia in Chronic Thromboembolic Pulmonary Hypertension.

Background: The role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved. Objectives: The purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH. Methods: In total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia. Results: A total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients. Conclusions: Congenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.

Investigating adolescent mental health of Chinese students during the COVID-19 pandemic: Multicenter cross-sectional comparative investigation.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused significant challenges for adolescent mental health. AIM: To survey adolescent students in China to determine the effects of the COVID-19 pandemic on their mental health. METHODS: A multicenter cross-sectional comparative investigation was conducted in March 2022. We collected demographic information and survey data related to the COVID-19 pandemic. The Patient Health Questionnaire-9 and Generalized Anxiety Disorder Screener scales were used for objective assessment of depression and anxiety. RESULTS: We collected mental health questionnaires from 3184 students. The investigation demonstrated that adolescents most strongly agreed with the following items: Increased time spent with parents, interference with academic performance, and less travel. Conversely, adolescents most strongly disagreed with the following items: Not having to go to school, feeling an increase in homework, and not socializing with people; 34.6% of adolescents were depressed before COVID-19, of which 1.9% were severely depressed. After COVID-19, 26.3% of adolescents were prone to depression, of which 1.4% were severely depressed. 24.4% of adolescents had anxiety before COVID-19, with severe anxiety accounting for 1.6%. After COVID-19, 23.5% of adolescents were prone to anxiety, of which 1.7% had severe anxiety. CONCLUSION: Chinese adolescents in different grades exhibited different psychological characteristics, and their levels of anxiety and depression were improved after the COVID-19 pandemic. Changes in educational management practices since the COVID-19 pandemic may be worth learning from and optimizing in long-term educational planning.

KLF14 potentiates oxidative adaptation via modulating HO-1 signaling in castrate-resistant prostate cancer.

Insights into the mechanisms by which key factors stimulate cell growth under androgen-depleted conditions is a premise to the development of effective treatments with clinically significant activity in patients with castration-resistant prostate cancer (CRPC). Herein, we report that, the expression of Krüppel-like factor 14 (KLF14), a master transcription factor in the regulation of lipid metabolism, was significantly induced in castration-insensitive PCa cells and tumor tissues from a mouse xenograft model of CRPC. KLF14 upregulation in PCa cells, which was stimulated upstream by oxidative stress, was dependent on multiple pathways including PI3K/AKT, p42/p44 MAPK, AMPK and PKC pathways. By means of ectopic overexpression and genetic inactivation, we further show that KLF14 promoted cell growth via positive regulation of the antioxidant response under androgen-depleted conditions. Mechanistically, KLF14 coupled to p300 and CBP to enhance the transcriptional activation of HMOX1, the gene encoding the antioxidative enzyme heme oxygenase-1 (HO-1) that is one of the most important mechanisms of cell adaptation to stress. Transient knockdown of HMOX1 is sufficient to overcome KLF14 overexpression-potentiated PCa cell growth under androgen-depleted conditions. From a pharmacological standpoint, in vivo administration of ZnPPIX (a specific inhibitor of HO-1) effectively attenuates castration-resistant progression in the mouse xenograft model, without changing KLF14 level. Together, these results provide comprehensive insight into the KLF14-dependent regulation of antioxidant response and subsequent pathogenesis of castration resistance and indicate that interventions targeting the KLF14/HO-1 adaptive mechanism should be further explored for CRPC treatment.

Outcomes of surgery for functional cardiac paragangliomas: A single-center experience of 17 patients.

OBJECTIVE: Cardiac paragangliomas are rare neuroendocrine tumors. Early surgical treatment improves clinical symptoms and prolongs survival. We review our experience in 17 patients who underwent surgical resection for functional cardiac paraganglioma. METHODS: Seventeen patients underwent surgery for functional cardiac paraganglioma from 2004 to 2017 were identified. Clinical data and long-term outcomes were extracted and analyzed. RESULTS: All 17 patients with cardiac paraganglioma (11 males) with a median age of 35 years (range, 11 to 51 years) were hormonally functional and underwent operations. A 24-hour urine catecholamine assay documented elevation of norepinephrine, epinephrine, and dopamine. Tumors were determined with octreotide scintiscan in all 17 patients and metaiodoben-zylguanidine scintigraphy in 10 of 15 patients. Tumor sites were right atrioventricular groove in 4 patients, between the main arteries in 10 patients, and interatrial groove in 4 patients. All patients underwent complete resection. Concomitant surgeries were: structural reconstruction in 16 patients (94%) and coronary artery bypass graft in 8 patients (47%). One patient had a history of incomplete resection of an intra-atrial tumor. One patient died postoperatively. Operative mortality is 5.8%. During follow-up (mean, 6.5 years; range, 1.5 to 14.2 years), 16 patients are alive in functional class I or II. Two patients developed tumor recurrence and 14 remained symptom-free with normal urinary catecholamines. CONCLUSIONS: With a multidisciplinary treatment, early diagnosis, complete resection for the tumor along with complex reconstruction is achievable for most patients, and it offers promising long-term survival.

Surgical treatment of active native mitral infective endocarditis: A meta-analysis of current evidence.

BACKGROUND: The native mitral lesion of active infective endocarditis implies a poor prognosis and is associated with adverse short- or long-term results without surgical treatment. Both mitral valvuloplasty (MVP) and mitral valve replacement (MVR) have been performed in the treatment of active native mitral infective endocarditis (ANMIE). However, the outcomes of the two approaches remain unclear. The aim of this study was to systematically review the two procedures with mortality and survival as the primary endpoints. METHODS: A systematic review of the literature was conducted to identify all relevant studies with comparative data on MVP versus MVR for the treatment of ANMIE. Information on baseline characteristics of patients, operation method, quality of literature, follow-up, and so forth was abstracted using standardized protocols. Pooled odds ratio (OR) or hazard ratio (HR) was calculated and possible publication bias was tested. RESULTS: Nine comparative observational studies with a total of 633 patients (MVP = 265, MVR = 368) were identified for qualitative assessment, data extraction, and analysis. The summary OR for operative mortality, comparing repair with replacement, was 0.37 (95% CI 0.0.18-0.80; p = 0.0005). Summary 1- and 5-year HRs for event-free survival were 0.43 (95% CI 0.20-0.92; p = 0.03) and 0.44 (95% CI 0.25-0.77, p = 0.004), respectively (repair vs. replacement). Summary 1- and 5-year survival HRs were 0.51 (95% CI 0.24-1.08; p = 0.08) and 0.55 (95% CI 0.32-0.96; p = 0.004), respectively (repair vs. replacement). No heterogeneity was revealed between studies, and possible publication bias was insignificant. CONCLUSIONS: This meta-analysis suggests that MVP may be associated with superior postoperative survival outcomes compared with MVR. MVP is desirable, if possible, as a durable alternative to replacement. However, we must consider the influence of different patient characteristics and surgeons' preferences on the choice of surgical approach, and additional powered clinical trials will be required to confirm these findings.

Regulation of Docetaxel Sensitivity in Prostate Cancer Cells by hsa-miR-125a-3p via Modulation of Metastasis-Associated Protein 1 Signaling.

OBJECTIVE: To identify the potential downstream targets of hsa-miR-125a-3p, a mature form of miR-125a, during the pathogenesis of chemoresistance in prostate cancer (PCa). MATERIALS AND METHODS: The expression levels of hsa-miR-125a-3p were assessed in chemoresistant PCa tissues and experimentally established chemoresistant cells using quantitative reverse transcription-polymerase chain reaction. The effect of hsa-miR-125a-3p knockdown or hsa-miR-125a-3p overexpression on the Dox-induced cell death was evaluated using apoptosis ELISA in chemosensitive PC-3 cells or in chemoresistant PC-3 cells (PC-3R). Finally, using multiple assays, the regulation of metastasis-associated protein 1 (MTA1), an essential component of the Mi-2-nucleosome remodeling deacetylation complex, by hsa-miR-125a-3p was studied at both molecular and functional levels. RESULTS: The expression of hsa-miR-125a-3p was significantly downregulated in chemoresistant PCa tissues and cells. Inhibition of hsa-miR-125a-3p significantly increased docetaxel (Dox) resistance in PC-3 cells, whereas upregulation of hsa-miR-125a-3p effectively reduced Dox resistance in PC-3R, suggesting that this microRNA (miRNA) may act as a tumor suppressor along the pathogenesis of drug resistance. Mechanistically, hsa-miR-125a-3p induced apoptosis and Dox sensitivity in PCa cells through regulating MTA1. CONCLUSION: Our results collectively indicate that miRNA-MTA1 can form a delicate regulatory loop to maintain a bistable state in the Dox chemosensitivity, and future endeavor in this filed should provide important clues to develop miRNA-based therapies that benefit advanced PCa patients through modulating the functional status of MTA1.

Surgical Treatment Strategies of Intravenous Leiomyomatosis withRight Cardiac Cavities Extension.

Objective To investigate the diagnosis and surgical treatment strategies of intravenous leiomyomatosis(IVL)extending through inferior vena cava into the right cardiac cavities. Methods Thirty patients of IVL extending through inferior vena cava into the right cardiac cavities were treated in Peking Union Medical College Hospital from November 2002 to January 2015.The following variables were studied: age,cardiopulmonary bypass time,deep hypothermic circulatory arrest time,origins of IVL,blood loss,duration of post-operative hospital stay,hospitalization expenses,edema of lower extremity,blood transfusion,postoperative complication,residual IVL,and re-grow or recurrence. Results Thirteen of 30 patients reported double lower limb edema. The cardiopulmonary bypass was applied in 27 cases,and the average duration of cardiopulmonary bypass was(106.9±53.7)min. Then,21 patients were treated with the deep hypothermic circulatory arrest,and the mean time was(28.2±11.6) min. The tumors originated from the genital veins in 9 cases,the iliac vein in 13 cases,and both veins in 8 cases. The average intra-operative blood loss volume was (2060.5±2012.3)ml,and 21 patients received blood transfusion. The average hospitalization time was(18.9±8.3)days and the average hospitalization expenses was (80 840.4±28 264.2)RMB yuan. While 14 patients had postoperative complications,there was no serious postoperative complication or death.All patients have shown a favorable outcome.Conclusions Tumor embolus extending through inferior vena cava into the right cardiac cavities should be suspected in patients with multiple hysteromyoma. Successful therapy for IVL with right cardiac cavities extension is dependent on reasonable surgical treatment strategies. Surgical removal of the ovaries is vital to avoid IVL re-grow or recurrence.

Surgical treatment of pulmonary artery aneurysm: an institutional experience and literature review.

OBJECTIVES: The occurrence of pulmonary artery aneurysm (PAA) is extremely rare in the clinical setting. Careful treatment should be considered because of the possibility of fatal complications including rupture, dissection, pulmonary embolism and heart failure. Our goal is to contribute a better understanding of this disease and its treatment. METHODS: Information on patients diagnosed with PAA was retrieved from the institute's database. The detailed data including aetiology, clinical presentation, diagnostic methods, operation methods and long-term outcomes of the surgical cases were outlined and analysed. RESULTS: In total, 21 patients were diagnosed with PAA in Peking Union Medical College Hospital from 1980 to 2015, among whom 5 patients received surgical treatment, including 2 patients with giant PAAs. The complete remission rate of surgical cases was 80%, and the average postoperative hospital stay was 8.5 ± 1.29 days. One postoperative death occurred due to distributive shock. CONCLUSIONS: PAAs must be seriously classified by aetiology to be treated appropriately. Patients with giant-size PAAs, and those with pulmonary hypertension, anatomical anomalies, and rapid growth and compression of neighbouring critical structures, are proper candidates for surgery. Surgical options include aneurysm repair and replacement with allogeneic/synthetic grafts, depending on the situation. Additionally, the correction of associated abnormalities should be performed simultaneously during surgery. Surgical outcomes are effective, and long-term prognoses are satisfactory.

Effect of Right Heart Systolic Function on Outcomes in Patients with Constrictive Pericarditis Undergoing Pericardiectomy.

BACKGROUND: To determine the influence of right ventricular function in patients with constrictive pericarditis (CP) undergoing surgery and to compare the outcomes of patients who received surgery with those managed medically. METHODS: Patients with the diagnosis of CP and healthy volunteers were recruited from January 2006 to November 2011. Patients with CP chose to either receive pericardiectomy or medical management. Echocardiographic measurements were performed to evaluate heart function, and survival was recorded. RESULTS: A total of 58 patients with CP (36 received pericardiectomy, 22 managed medically), and 43 healthy volunteers were included. CP patients who received surgery had a higher survival rate than those managed medically (P = 0.003), and higher survival was also seen in the subgroup of CP patients with severely impaired right systolic function. Albumin level, left ventricular end-diastolic dimension, and tricuspid regurgitation velocity were associated with survival in CP patients who received surgery. CONCLUSIONS: Preoperative right heart function does not affect surgical outcomes. Patients with severely impaired preoperative right systolic function obtain a greater survival advantage with surgery than with medical treatment.

[Endoscopic Saphenous Vein Harvesting versus Open Vein Harvesting Techniques].

OBJECTIVE: To investigate whether endoscopic saphenous vein harvesting (EVH )reduces leg wound morbidity and improves rehabilitation of lower extremity as compared to open vein harvesting (OVH) in patients with coronary artery disease. METHODS: The clinical data of 333 patients who underwent isolated coronary artery bypass graft surgery (CABG) between January 2007 and December 2011 were retrospectively analyzed.These patients were divided into EVH group (n=210) and OVH group (n=123). Parameters including age,sex,with/without diabetes mellitus,leg wound complications rate,postoperative hospital stay,hospitalization expense,and vein graft patency were analyzed. RESULTS: The age,sex,with/without diabetes mellitus were not significantly different between two groups (P>0.05). However,the incidences of leg wound complications, poor wound healing, wound infections, wound pain,wound numbness, and edema of lower extremity were significantly lower in the EVH group than the OVH group (P<0.05). The ecchymoma and deep vein thrombosis incidences were not significantly different between these two groups (P>0.05). The postoperative hospital stay showed no significant difference (P>0.05), while the hospitalization expense was significantly higher in the EVH group than in the OVH group (P<0.05). There was no statistical difference of vein graft patency (P>0.05). CONCLUSION: The EVH system is a safe and effective alternative to OVH because it can markedly reduce postoperative leg wound morbidity and the EVH vein graft has good patency.

Angiosarcoma of the pericardium: a case report.

BACKGROUND: Primary malignant tumors of the pericardium are rare, and most primary malignant pericardium tumors are mesotheliomas. Primary pericardial angiosarcoma is extremely rare, and it is associated with a poor prognosis. CASE PRESENTATION: We report of a 47-year-old woman who complained of activity-related chest tightness and shortness of breath. Computed tomography, magnetic resonance imaging, and transesophageal echocardiography revealed an enlarged pericardium with hematic and solid components. An exploratory pericardiotomy was performed, and the results of the histological examination were suggestive of spindle cell hemangioendothelioma. She survived for 9 months after surgery without chemotherapy and radiotherapy, and she had a relatively good quality of life. CONCLUSION: Primary pericardial angiosarcoma is difficult to diagnose, and it has a poor prognosis. Pericardiotomy, radiation therapy, and chemotherapy were associated with a prolongation of survival.

[Investigation of FTIR spectra analysis on carbon dioxide absorption with improved amine solution].

Carbon dioxide is a major sort of greenhouse gas as well as important carbon resource. With the developments of industries, emission of carbon dioxide has increased sharply. Hence, controls of carbon dioxide emission and resource transformation have become the hotspot of current study. As a new kind of carbon resource, the fields of CO2 research and application are very extensive. Among those methods, the amine absorption has good qualities of faster absorption rate, higher efficiency and so on, so it has been widely studied. But organic amine have such shortcomings: high consumption of heat energy, strong corrosive and easy oxidated, now pursuer mainly focused on the organic amine modified. The results showed that, when the time the amount of antioxidant 1010 is 0.152, the absorption capacity is 2503.53 mL. the volume of analysis is 982.00 mL, and the absorption rate changes more slowly, by FTIR, Samples of its renewable-OH associating is not apparent that the antioxidant content in 1010, oxidation products of the MEA is acid or less oxidation and antioxidant 1010 product in early to respond fully to form stable non-radical compounds. Therefore, the best dosage of antioxidant 1010 is 0.15%. When the time that the amount of Na2SO3 is 0.15%, the absorption capacity is 2922.88 mL. Analysis of the volume is 723.00 mL, by FTIR, which reveals the oxidation products of the MEA is amide -C=O which in alkaline solution can be transiting into primary amine, and be easy absorbing CO2. Comparing the antioxygenic proerty of antioxidant 1010 with Na2SO3, from the absorption rate, the amount of absorption , Na2SO3's antioxidant properties is superior than antioxidant 1010; by infrared spectral analysis, 1010/20% MEA solution's oxidation products is the acid, Na2SO3/20% MEA solutions, the oxidation product is amide, amide solution is advantaged for absorbing CO2, So Na2SO3's antioxidant properties is superior than antioxidant 1010.