Anti-pancreatic cancer activity of cassane diterpenoids isolated from the seeds of Caesalpinia sappan mediated by autophagy activation via ROS/AMPK/mTORC1 pathway.

Three undescribed cassane diterpenoids, caesalpanins D-F (1-3), and seven known ones were isolated from the seeds of Caesalpinia sappan. Structures and absolute configurations of 1-3 were elucidated based on the extensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and ECD calculations. Structurally, compound 1 was the first example of 18-norcassane diterpenoid and 2 was a rare 20-norcassane diterpenoid having an unusual five-membered oxygen bridge between C-10/C-18. The anti-proliferative activity of 1, 3, and 4-10 against PANC-1 cells (pancreatic ductal adenocarcinoma cell line) was evaluated, and phanginin H (4) was found to exhibit anti-cancer activity with IC50 value of 18.13 ± 0.63 µM. Compound 4 inhibited PANC-1 cell growth by arresting the cell cycle at G2/M phase via regulation of cyclin-dependent kinases, and the self-renewal and metastasis of PANC-1 cells by suppressing cancer cell stemness. Furthermore, compound 4 induced ROS generation and subsequently activated autophagy, which was demonstrated by the formation of autophagic vacuoles and dynamic change of autophagic flux. The induced ROS accumulation resulted in AMPK activation and subsequently regulation of mTORC1 activity and ULK phosphorylation, indicating that 4 triggered autophagy through ROS/AMPK/mTORC1 pathway. These findings suggested that 4 might potentially be an autophagy inducer for the therapy of pancreatic cancer.

The Role of Cerebellar Intrinsic Neuronal Excitability, Synaptic Plasticity, and Perineuronal Nets in Eyeblink Conditioning.

Evidence is strong that, in addition to fine motor control, there is an important role for the cerebellum in cognition and emotion. The deep nuclei of the mammalian cerebellum also contain the highest density of perineural nets-mesh-like structures that surround neurons-in the brain, and it appears there may be a connection between these nets and cognitive processes, particularly learning and memory. Here, we review how the cerebellum is involved in eyeblink conditioning-a particularly well-understood form of learning and memory-and focus on the role of perineuronal nets in intrinsic membrane excitability and synaptic plasticity that underlie eyeblink conditioning. We explore the development and role of perineuronal nets and the in vivo and in vitro evidence that manipulations of the perineuronal net in the deep cerebellar nuclei affect eyeblink conditioning. Together, these findings provide evidence of an important role for perineuronal net in learning and memory.

LncRNA SNHG12 regulated by WTAP aggravated the oxygen-glucose deprivation/reperfusion-induced injury in bEnd.3 cell.

OBJECTIVES: Previous studies have identified abnormal expression of lncRNA SNHG12 in ischemic stroke, but the underlying molecular mechanism remains unclear. MATERIALS AND METHODS: Through database predictions, m6A methylation sites were found on SNHG12, suggesting post-transcriptional modification. To further elucidate the role of SNHG12 and m6A methyltransferase WTAP in oxygen-glucose deprivation/reperfusion (OGD/R)-induced damage in cerebral microvascular endothelial cells, we conducted investigations. Additionally, we examined the impact of m6A methyltransferase WTAP on SNHG12 expression. RESULTS: Overexpressing SNHG12 in bEnd.3 cells was found to inhibit cell proliferation and promote apoptosis, as well as activate the production of reactive oxygen species and inflammatory cytokines (E-selectin, IL-6 and MCP-1), along with angiogenic proteins (VEGFA and FGFb). Conversely, SNHG12 knockdown alleviated OGD/R-induced damage to BEnd.3 cells, resulting in improved cell proliferation, reduced apoptosis, decreased ROS and LDH production, as well as diminished expression of inflammatory cytokines (E-selectin, IL-6 and MCP-1) and angiogenic proteins (VEGFA and FGFb). Furthermore, WTAP was found to positively regulate SNHG12 expression, and WTAP knockdown in bEnd.3 cells under the OGD/R conditions inhibited cell proliferation, promoted apoptosis, and increased ROS and LDH production. CONCLUSION: These findings suggest that WTAP may play a crucial role in SNHG12-mediated OGD/R-induced damage in bEnd.3 cells. More molecular experiments are needed to further analyze its mechanism. Overall, our study helps to enrich our understanding of the dysregulation of SNHG12 in ischemic stroke.

Effects of different Chinese traditional exercises on sleep quality and mental health of adults: systematic review and meta-analysis.

OBJECTIVE: To evaluate the effects of traditional Chinese exercises on sleep quality and mental health in adults with different health statuses. METHOD   : This review was registered a priori (CRD42023382188) and executed according to PRISMA statement guidelines. We searched the databases CNKI, China Biology Medicine disc (CBM), Wangfang, PubMed, Web of Science, and Embase from the date of database creation to March 2023. Two researchers independently screened the literature, extracted the data, evaluated the methodological quality of the included literature, and then used Revman 5.4 and Stata 17.0 for the corresponding statistical analysis and graphing. RESULTS: Thirty-four randomized controlled trials (RCTs) were included, with a total sample of 2563 adults (1276 in the experimental group and 1287 in the control group). The meta-analysis results showed that traditional Chinese exercise significantly improved sleep quality in different groups [WMD = - 1.58, 95% CI = - 2.17, - 1.00, P < 0.00001] and that Badaanjin was better than Taijiquan in improving sleep quality. For mental health, traditional Chinese exercise had good effects on anxiety [WMD = - 1.66, 95% CI = - 2.64, - 0.69, P = 0.0009] and depression [WMD = - 1.67, 95% CI = - 3.23, - 0.11, P = 0.04]. CONCLUSION: Traditional Chinese exercises can improve the quality of sleep and mental health in different groups of people and are highly recommended for good health effects.

XPS Investigation of the Oxidation States of the As-Deposited Ta Films Prepared by Magnetron Sputtering Technology.

Due to their versatile and unique properties, tantalum-based thin films have been extensively studied. However, tantalum is susceptible to oxidation due to its higher chemical activity, which is crucial regardless of whether oxidations of Ta are beneficial or detrimental. Therefore, the oxidation of Ta during material processing, especially without conscious means, should be taken seriously. In this study, pure Ta films were fabricated by magnetron sputtering under set procedure parameters. The effects of base pressure and substrate temperature on the degree of oxidation of Ta films were investigated. The results revealed that the magnitude of the base pressure directly affects the oxidation state of the as-deposited Ta films. When preferably avoiding the oxidation of sputtered Ta films, the base pressure should be controlled below 4.4 × 10-4 Pa. The substrate temperature has little effect on the oxidation state of the as-deposited Ta films under a base pressure ranging from about 10-2 Pa to 10-4. We hope that this study can provide some references for controlling the oxidation states of Ta involved in relevant film preparation.

A Novel Compute-and-Forward Relaying Method for Multi-Antenna Wireless Relay Networks.

Compute-and-Forward (CoF) is an innovative physical layer network coding strategy, designed to enable receivers in wireless communications to effectively utilize interference. The key idea of CoF is to implement integer combinations based on the codewords from multiple transmitters, rather than decoding individual source codewords. Although CoF is widely used in wireless relay networks, there are still some problems to be solved, such as rank failure, single antenna reception, and the shortest vector problem. In this paper, we introduce a successive extended CoF (SECoF) as a pioneering solution tailored for multi-source, multi-relay, and multi-antenna wireless relay networks. First, we analyze the traditional CoF, and design a SECoF method combining the concepts of matrix projection and successive interference cancellation, which overcomes the problem of CoF rate tending to zero and rank failure and improves the network performance. Secondly, we obtain an approximate solution to the integer-value coefficient vectors by using the LLL lattice-based resolution algorithm. In addition, we deduce the corresponding concise formulas of SECoF. Simulation results show that the SECoF has strong robustness and the approaches outperform the state-of-the-art methods in terms of computation rate, rank failure probability, and outage probability.

Changes in the global burden of foreign body aspiration among under-5 children from 1990 to 2019.

Background: To evaluate the changes in the global burden of foreign body aspiration (FBA) among children under 5 years old at regional, age, sex, and socio-demographic index (SDI) levels between 1990 and 2019. Methods: Data on FBA was derived from the Global Burden of Disease (GBD) Study 2019 database on pulmonary aspiration and foreign body in airway. The means and 95% uncertainty intervals (UIs) were calculated for incidence, and disability-adjusted life-years (DALYs). The temporal trends were represented by estimated annual percentage change (EAPC) using Joinpoint regression. Results: Globally, FBA caused 109.6 (95% UI: 69.5, 175.7) per 100,000 incidence and 317.9 (95% UI: 270.7, 372.4) per 100,000 DALYs under 5 years old in 2019. Many European countries (such as Italy, Netherlands, Iceland, etc.) showed a high incidence rate, but did not cause a large disease burden (DALYs all less than 200 per 100,000). Compared to 1990, although a decrease in both incidence and DALYs occurred in 2019, the Joinpoint regression showed an increasing trend in incidence rate from 2014 to 2019 [APC: both (2.10), female (2.25), male (1.98), P < 0.05)], especially China, Netherlands, and Malta. Despite the lower incidence rate in early neonatal group and middle SDI areas, they instead resulted in higher DALYs than other age groups and areas. Conclusion: Although declines occurred in incidence and DALYs of FBA among children under 5 years of age from 1990 to 2014, an upward trend began to emerge from 2014 to 2019. The incidence and DALY rates were correlated with age and SDI. Increased efforts are needed to improve the necessary monitoring and reporting systems, hazard assessment, and public education activities.

Reducing airborne transmission of SARS-CoV-2 by an upper-room ultraviolet germicidal irradiation system in a hospital isolation environment.

Upper-room ultraviolet germicidal irradiation (UVGI) technology can potentially inhibit the transmission of airborne disease pathogens. There is a lack of quantitative evaluation of the performance of the upper-room UVGI for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) airborne transmission under the combined effects of ventilation and UV irradiation. Therefore, this study aimed to explore the performance of the upper-room UVGI system for reducing SARS-CoV-2 virus transmission in a hospital isolation environment. Computational fluid dynamics and virological data on SARS-CoV-2 were integrated to obtain virus aerosol exposure in the hospital isolation environment containing buffer rooms, wards and bathrooms. The UV inactivation model was applied to investigate the effects of ventilation rate, irradiation flux and irradiation height on the upper-room UVGI performance. The results showed that increasing ventilation rate from 8 to 16 air changes per hour (ACH) without UVGI obtained 54.32% and 45.63% virus reduction in the wards and bathrooms, respectively. However, the upper-room UVGI could achieve 90.43% and 99.09% virus disinfection, respectively, with the ventilation rate of 8 ACH and the irradiation flux of 10 µW cm-2. Higher percentage of virus could be inactivated by the upper-room UVGI at a lower ventilation rate; the rate of improvement of UVGI elimination effect slowed down with the increase of irradiation flux. Increase irradiation height at lower ventilation rate was more effective in improving the UVGI performance than the increase in irradiation flux at smaller irradiation height. These results could provide theoretical support for the practical application of UVGI in hospital isolation environments.

Surgical management of broad-based sessile vocal cord polyps: Transnasal vocal fold polypectomy versus microlaryngoscopic surgery: Our experience in 159 cases.

OBJECTIVES: In this study, we retrospectively reviewed and compared the treatment outcomes and complications of office transnasal vocal fold polypectomy (TVFP) with those of microplarygoscopic surgery (MLS) for different clinical and histopathological features of broad-based sessile vocal fold polyps. METHODS: We retrospectively reviewed the records of 159 consecutive patients with broad-based sessile vocal fold polyps treated by TVFP or MLS. The differences in efficacy and complication between these two surgical techniques were compared according to the different types of vocal fold polyps. RESULTS: Satisfactory outcomes of both TVFP and MLS treatments were reported in patients with oedematous, gelatinous and vascular types of vocal fold polyps (p > .05). The efficacy of TVFP was slightly worse than MLS in fibrous polyps group (p < .05). The TVFP-treated patients did not exhibit obvious complications, whereas several MLS-treated patients had suffered different complications. CONCLUSION: The therapeutic effects of both TVFP and MLS on the treatment of broad-based sessile vocal cord polyps are related to their clinical characteristics and histological types. Satisfactory outcomes are achieved in oedematous, gelatinous, and vascular types of polyps after either surgical procedure. TVFP has fewer surgical complications than MLS which can be a preferred option for the treatment of broad-based sessile vocal cord polyps at outpatient setting. TVFP also can be an alternative surgery option for patients who could not tolerate general anaesthesia or laryngeal suspension. In contrast, MLS has proven to be a particularly advantageous treatment in patients who have fibrous type of polyps.

C,N co-doped TiO2 hollow nanofibers coated stainless steel meshes for oil/water separation and visible light-driven degradation of pollutants.

Complex pollutants are discharging and accumulating in rivers and oceans, requiring a coupled strategy to resolve pollutants efficiently. A novel method is proposed to treat multiple pollutants with C,N co-doped TiO2 hollow nanofibers coated stainless steel meshes which can realize efficient oil/water separation and visible light-drove dyes photodegradation. The poly(divinylbenzene-co-vinylbenzene chloride), P(DVB-co-VBC), nanofibers are generated by precipitate cationic polymerization on the mesh framework, following with quaternization by triethylamine for N doping. Then, TiO2 is coated on the polymeric nanofibers via in-situ sol-gel process of tetrabutyl titanate. The functional mesh coated with C,N co-doped TiO2 hollow nanofibers is obtained after calcination under nitrogen atmosphere. The resultant mesh demonstrates superhydrophilic/underwater superoleophobic property which is promising in oil/water separation. More importantly, the C,N co-doped TiO2 hollow nanofibers endow the mesh with high photodegradation ability to dyes under visible light. This work draws an affordable but high-performance multifunctional mesh for potential applications in wastewater treatment.

An immune-related prognostic model predicts neoplasm-immunity interactions for metastatic nasopharyngeal carcinoma.

Background: The prognosis of nasopharyngeal carcinoma (NPC) has been recognized to improve immensely owing to radiotherapy combined with chemotherapy. However, patients with metastatic NPC have a poor prognosis. Immunotherapy has dramatically prolonged the survival of patients with NPC. Hence, further research on immune-related biomarkers is imperative to establish the prognosis of metastatic NPC. Methods: 10 NPC RNA expression profiles were generated from patients with or without distant metastasis after chemoradiotherapy from the Fujian Cancer Hospital. The differential immune-related genes were identified and validated by immunohistochemistry analysis. The method of least absolute shrinkage and selection operator (LASSO)was used to further establish the immune-related prognostic model in an external GEO database (GSE102349, n=88). The immune microenvironment and signal pathways were evaluated in multiple dimensions at the transcriptome and single-cell levels. Results: 1328 differential genes were identified, out of which 520 were upregulated and 808 were downregulated. Notably, most of the immune genes and pathways were down-regulated in the metastasis group. A prognostic immune model involving nine hub genes. Patients in low-risk group were characterized by survival advantage, hot immune phenotype and benefit from immunotherapy. Compared with immune cells, malignant cell exhibited the most active levels of risk score by ssGSEA. Accordingly, intercellular communications including LT, CD70, CD40 and SPP1, and the like, between high-risk and low-risk were explored by the R package "Cellchat". Conclusion: We have constructed a model based on immunity of metastatic NPC and determined its prognostic value. The model identified the level of immune cell infiltration, cell-cell communication, along with potential immunotherapy for metastatic NPC.

Human Endogenous Retrovirus, SARS-CoV-2, and HIV Promote PAH via Inflammation and Growth Stimulation.

Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease characterized by the progressive elevation of pulmonary arterial pressures. It is becoming increasingly apparent that inflammation contributes to the pathogenesis and progression of PAH. Several viruses are known to cause PAH, such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), human endogenous retrovirus K(HERV-K), and human immunodeficiency virus (HIV), in part due to acute and chronic inflammation. In this review, we discuss the connections between HERV-K, HIV, SARS-CoV-2, and PAH, to stimulate research regarding new therapeutic options and provide new targets for the treatment of the disease.

Isobavachalcone ameliorates the progression of osteoarthritis by suppressing NF-κB signaling pathway.

Isobavachalcone (IBC), an active component isolated from Psoralea corylifolia L., has been used extensively to treat a wide range of inflammation-associated diseases. However, little is known regarding the potential effect of IBC in the treatment of osteoarthritis (OA). The purpose of this research was to investigate the potential therapeutic effectsof IBC on OA by performingin vitroand in vivo experiments. Meanwhile, the underlying mechanism responsibles for that effect was also explored. Primary rat chondrocytes were isolated from the knee cartilage, and then pretreated with various concentrations of IBC followed by stimulation with or without LPS (1 µg/ml) for the indicated times. In vitro, the expression levels of iNOS, COX-2, MMP3, MMP13, ADAMTS5, aggrecan, and collagen II were determined by qRT-PCR, western blot, and immunofluorescence staining. In addition, western blot analysis and immunofluorescence were used to assess alterations to the NF-κB signaling pathway. In vivo, an ACLT-induced rat OA model was established in order to determine the protective effect of IBC. The results showed that IBC treatment inhibited the upregulation of inflammatory factors such as iNOS and COX-2 in response to LPS stimulation. Moreover, IBC significantly suppressed the expression of MMP-3, MMP-13, and ADAMTS5 induced by LPS in a dose-dependent manner. Furthermore, the LPS-induced reduction of collagen II and aggrecan was reversed by IBC. Mechanistically, IBC significantly decreased LPS-induced p65 phosphorylation and IκBα degradation as well as suppressed nuclear translocation of p65 in rat chondrocytes as evidenced by western blot analysis and immunofluorescence staining, indicating that IBC effectively inhibited the LPS-induced activation of the NF-κB pathway. In vivo, IBC treatment prevented cartilage degeneration in the ACLT-induced rat model. In summary, our results suggest that IBC may be able to act as a promising therapeutic drug for treating OA.

Transoral CO2 laser-modified posterior cordotomy combined with plasma ablation subtotal arytenoidectomy for bilateral vocal fold paralysis: A retrospective study.

OBJECTIVES: To investigate the effect of transoral CO2 laser-modified posterior cordotomy combined with plasma ablation subtotal arytenoidectomy for bilateral vocal fold paralysis (BVFP). DESIGN: A retrospective study with medical records from 2017 to 2021 in our hospital. SETTING: A single-centre study. PARTICIPANTS: This retrospective study included 22 patients with BVFP. They underwent transoral CO2 laser-modified posterior cordotomy combined with plasma ablation subtotal arytenoidectomy in our hospital from 2017 to 2021. MAIN OUTCOME MEASURES: Preoperative and postoperative swallowing and phonation functions were evaluated in all patients. RESULTS: All 22 patients with a tracheostomy were successfully decannulated within 6 months after surgery without subsequent revision operations, and the width of the posterior glottis was more than 3.9 mm in all patients when they inspired. The statistical analysis showed that there was no difference in vocal function and swallowing function in all patients compared to preoperative (p > .05). CONCLUSION: Transoral CO2 laser-modified posterior cordotomy combined with plasma ablation subtotal arytenoidectomy enlarges the posterior glottis in patients with BVFP, which maintains airway patency without significant worsening in voice and swallowing function.

Injectable adhesive carboxymethyl chitosan-based hydrogels with self-mending and antimicrobial features for the potential management of periodontal diseases.

Treating periodontal diseases is a great challenge owing to the motion and wet conditions, bacterial infection, and tissue defects. Therefore, designing bioactive materials with outstanding wet-tissue adhesion, antimicrobial features, as well as favorable cell responses, is highly desirable to meet practical necessity. In this work, bio-multifunctional melatonin-loaded carboxymethyl chitosan/polyaldehyde dextran (CPM) hydrogels have been developed through the dynamic Schiff-base reaction. Our results demonstrate that the CPM hydrogels display injectability, structural stability, and high tissue adhesion in the wet and motional state, as well as self-healing features. In addition, the designed hydrogels show great antibacterial properties and excellent biocompatibility. The prepared hydrogels display a slow release of melatonin. Moreover, the in vitro cellular assay indicates that the developed hydrogels containing 10 mg per mL melatonin significantly promote cell migration. Thus, the synthesized bio-multifunctional hydrogels show great promise in the treatment of periodontal disease.

Between-Class Adversarial Training for Improving Adversarial Robustness of Image Classification.

Deep neural networks (DNNs) have been known to be vulnerable to adversarial attacks. Adversarial training (AT) is, so far, the only method that can guarantee the robustness of DNNs to adversarial attacks. However, the robustness generalization accuracy gain of AT is still far lower than the standard generalization accuracy of an undefended model, and there is known to be a trade-off between the standard generalization accuracy and the robustness generalization accuracy of an adversarially trained model. In order to improve the robustness generalization and the standard generalization performance trade-off of AT, we propose a novel defense algorithm called Between-Class Adversarial Training (BCAT) that combines Between-Class learning (BC-learning) with standard AT. Specifically, BCAT mixes two adversarial examples from different classes and uses the mixed between-class adversarial examples to train a model instead of original adversarial examples during AT. We further propose BCAT+ which adopts a more powerful mixing method. BCAT and BCAT+ impose effective regularization on the feature distribution of adversarial examples to enlarge between-class distance, thus improving the robustness generalization and the standard generalization performance of AT. The proposed algorithms do not introduce any hyperparameters into standard AT; therefore, the process of hyperparameters searching can be avoided. We evaluate the proposed algorithms under both white-box attacks and black-box attacks using a spectrum of perturbation values on CIFAR-10, CIFAR-100, and SVHN datasets. The research findings indicate that our algorithms achieve better global robustness generalization performance than the state-of-the-art adversarial defense methods.

Prognostic Value of Controlling Nutritional Status Score in Advanced Hypopharyngeal Cancer.

OBJECTIVE: The purpose of this study was to investigate the prognostic significance of the preoperative controlling nutritional status (CONUT) score in patients with resectable advanced hypopharyngeal cancer. METHODS: This retrospective study included 113 advanced hypopharyngeal cancer patients who underwent curative resection in our hospital from 2013 to 2017. The association between the CONUT score and clinicopathological variables was evaluated. The association between CONUT score and survival was analyzed using Kaplan-Meier survival curves and Cox regression. The efficacy of the CONUT score and other immune-nutritional markers to predict prognosis was compared using a time-dependent receiver operating characteristic (ROC). RESULTS: Patients were divided into the high-CONUT score group (≥3) and the low-CONUT score group (≤2) according to ROC analysis. The CONUT score was associated with body mass index (p = 0.047), monocyte (p = 0.021), pharyngocutaneous fistula (p = 0.045), flap repairment (p = 0.034), tumor (T) classification (p = 0.034), node (N) classification (p = 0.036), subsite of tumor (p = 0.035), and negative pathologic factors (p < 0.001). Tumor, node, metastasis (TNM) stage, negative pathologic factors, adjuvant radiotherapy, postoperative chemoradiotherapy, and CONUT score were independent prognostic factors for survival. Patients with a higher CONUT score had worse overall survival (OS) (hazard ratio: 2.76, 95% confidence interval [CI]: 1.44-5.29, p = 0.002) and disease-free survival (hazard ratio: 2.51, 95% CI: 1.28-4.91, p = 0.007). The area under the curve of the CONUT score (0.799) to predict 5-year OS was greater than those of Preoperative Nutritional Index (0.769), platelet-to-lymphocyte ratio (0.643), neutrophil-to-lymphocyte ratio (0.565), and lymphocyte-to-monocyte ratio (0.577). CONCLUSION: The CONUT score is a prognostic marker for patients with resectable advanced hypopharyngeal cancer. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2613-2620, 2023.

Number of positive lymph nodes combined with the logarithmic ratio of positive lymph nodes predicts long-term survival for patients with node-positive parotid gland carcinoma after surgery: a SEER population-based study.

PURPOSE: To evaluate the prognostic value of the number of positive lymph nodes (NPLN), the ratio of positive lymph nodes (pLNR), and the logarithmic ratio of positive lymph nodes (LODDS) in patients with parotid gland carcinoma. On this basis, establishing and validating an optimal nomogram. METHODS: A total of 895 patients with T1-4N1-3M0 parotid gland carcinoma were included in our study from the Surveillance, Epidemiology, and End Results (SEER) database. Patients' data were randomly assigned to the training cohort and the validation cohort by a ratio of 7:3. Univariate and multivariate COX regression analysis were used to explore the relationship between the study factors and the prognosis of parotid gland carcinoma, including overall survival (OS) and cause-specific survival (CSS). The Akaike Information Criterion (AIC) was used to evaluate model fit. Harrell's concordance index (C-index), integrated discrimination improvement (IDI), and net reclassification index (NRI) were used to evaluate the predictive ability of these models. The decision curve analysis was used to evaluate the clinical benefit of the nomograms compared with the TNM stage. RESULTS: NPLN, pLNR, and LODDS are independent risk factors for the prognostic of PGC. According to the AIC, C index, IDI, and NRI, the models combined with NPLN and LODDS were the best. The decision curves suggested that our nomograms had good predictive abilities for the prognosis of parotid gland carcinoma. CONCLUSION: The two nomograms which contained NPLN and LODDS had the potential to predict OS and CSS in patients with parotid gland carcinoma.

Analysis of m7G methylation modification patterns and pulmonary vascular immune microenvironment in pulmonary arterial hypertension.

Background: M7G methylation modification plays an important role in cardiovascular disease development. Dysregulation of the immune microenvironment is closely related to the pathogenesis of PAH. However, it is unclear whether m7G methylation is involved in the progress of PAH by affecting the immune microenvironment. Methods: The gene expression profile of PAH was obtained from the GEO database, and the m7G regulatory factors were analyzed for differences. Machine learning algorithms were used to screen characteristic genes, including the least absolute shrinkage and selection operator, random forest, and support vector machine recursive feature elimination analysis. Constructed a nomogram model, and receiver operating characteristic was used to evaluate the diagnosis of disease characteristic genes value. Next, we used an unsupervised clustering method to perform consistent clustering analysis on m7G differential genes. Used the ssGSEA algorithm to estimate the relationship between the m7G regulator in PAH and immune cell infiltration and analyze the correlation with disease-characteristic genes. Finally, the listed drugs were evaluated through the screened signature genes. Results: We identified 15 kinds of m7G differential genes. CYFIP1, EIF4E, and IFIT5 were identified as signature genes by the machine learning algorithm. Meanwhile, two m7G molecular subtypes were identified by consensus clustering (cluster A/B). In addition, immune cell infiltration analysis showed that activated CD4 T cells, regulatory T cells, and type 2 T helper cells were upregulated in m7G cluster B, CD56 dim natural killer cells, MDSC, and monocyte were upregulated in the m7G cluster A. It might be helpful to select Calpain inhibitor I and Everolimus for the treatment of PAH. Conclusion: Our study identified CYFIP1, EIF4E, and IFIT5 as novel diagnostic biomarkers in PAH. Furthermore, their association with immune cell infiltration may facilitate the development of immune therapy in PAH.

CYP4 subfamily V member 2 (CYP4V2) polymorphisms were associated with ischemic stroke in Chinese Han population.

BACKGROUND: CYP4 subfamily V member 2 (CYP4V2) polymorphisms are related to venous thromboembolism. However, the influence of CYP4V2 polymorphisms on the susceptibility to ischemic stroke (IS) remains undetermined. METHODS: We selected and genotyped five polymorphisms of CYP4V2 in 575 cases and 575 controls to test whether CYP4V2 variants were associated with the risk for IS in a Chinese Han population. Genotyping of CYP4V2 polymorphisms was performed using the Agena MassARRAY platform. Logistic regression analysis was used to assess the association between CYP4V2 polymorphisms and IS risk by calculating odds ratios (ORs) and 95% confidence interval (CI). False-positive report probability analysis was applied to assess the noteworthy relationship of the significant findings. RESULTS: CYP4V2 rs1398007 might be a risk factor for IS (OR = 1.34, 95% CI 1.05-1.71, p = 0.009). Specially, confounding factors (age, gender, smoking and drinking status) might affect the relationship between rs1398007 and IS susceptibility. Moreover, rs1053094 and rs56413992 were associated with IS risk in males. Multifactor dimensionality reduction analysis showed the combination of rs13146272 and rs3736455 had the strongest interaction effect (information gain value of 0.40%). Furthermore, genotypes of rs1398007 (p = 0.006) and rs1053094 (p = 0.044) were associated with the levels of high-density lipoprotein cholesterol (HDL-C) among healthy controls. CONCLUSION: Our results first provided evidence that CYP4V2 rs1398007 might be a risk factor for IS, which provides instructive clues for studying the mechanisms of CYP4V2 to the pathogenesis of IS.