Exploring the role of m6A methylation regulators in glioblastoma multiforme and their impact on the tumor immune microenvironment.

Although the role of N6-Methyladenosine (m6A) methylation factors has been established in multiple cancer types, its involvement in glioblastoma multiforme (GBM) remains limited. This study aims to explore the involvement of m6A regulators in GBM and examine their association with the tumor immune microenvironment (TIME). A comprehensive set of 24 candidate m6A RNA regulators was procured. Consensus clustering was performed based on these regulators to identify distinct GBM clusters. PD-L1 and PD-1 levels, immune cell infiltration, and immune scores were evaluated between two clusters. Prognostic signatures and correlation analysis with TIME were analyzed using Lasso and Spearman's analysis. GBM tissue was collected to verify the correlations. Eighteen m6A regulators (WTAP, YTHDF2, HNRNPC, CAPRIN1, YTHDF3, METTL14, GNL3, ZCCHC4, HNRNPD, YTHDF1, RBM15, PCIF1, RBM27, KIAA1429, MSI2, FTO, ALKBH5, and METTL3), PD-L1, and PD-1 were significantly upregulated in GBM tissue. These regulators were divided into two distinct molecular subtypes (clusters 1 and 2). Cluster 2 exhibited a significant increase in immune score, monocytes, M1 macrophages, activated mast cells, and eosinophils. HNRNPC, YWHAG, and ALKBH5 were significantly associated with TIME and positively correlated with PD-L1. Immune cell invasiveness profiles dynamically changed with copy number changes of these three m6A regulators. Finally, YWHAG and ALKBH5 were found to be independent prognostic indicators of GBM through risk analysis and were experimentally verified with clinical samples. YWHAG and ALKBH5 may be used as prognostic markers for patients with GBM. m6A methylation regulators may play an important role in regulating PD-L1/PD-1 expression and immune infiltration, thus having a significant impact on GBM TIME.

Combined 4-1BB and ICOS co-stimulation improves anti-tumor efficacy and persistence of dual anti-CD19/CD20 chimeric antigen receptor T cells.

Chimeric antigen receptor (CAR) T-cell therapy is a promising therapeutic strategy against lymphoma. However, post-treatment relapses due to antigen loss remain a challenge. Here the authors designed a novel bicistronic CAR construct and tested its functions in vitro and in vivo. The CAR construct consisted of individual anti-CD19 and anti-CD20 single-chain fragment variables equipped with ICOS-CD3ζ and 4-1BB-CD3ζ intracellular domains, respectively. The CD19 and CD20 bicistronic CAR T cells exhibited tumor lytic capacities equivalent to corresponding monospecific CAR T cells. Moreover, when stimulated with CD19 and CD20 simultaneously, the bicistronic CAR T cells showed prolonged persistence and enhanced cytokine generation compared with single stimulations. Interestingly, the authors found that the 4-1BB signal was predominant in the signaling profiles of ICOS and 4-1BB doubly activated CAR T cells. In vivo study using a CD19/CD20 double-positive tumor model revealed that the bicistronic CAR T cells were more efficient than monospecific CD19 CAR T cells in eradicating tumors and prolonging mouse survival. The authors' novel bicistronic CD19/CD20 CAR T cells demonstrate improved anti-tumor efficacy in response to dual antigen stimulations. These data provide optimism that this novel bicistronic CAR construct can improve treatment outcomes in patients with relapsed/refractory B cell malignancy.

Chitosan Hydrogel Enhances the Therapeutic Efficacy of Bone Marrow-Derived Mesenchymal Stem Cells for Myocardial Infarction by Alleviating Vascular Endothelial Cell Pyroptosis.

Myocardial infarction (MI) is one of the higher mortality rates, and current treatment can only delay the progression of the disease. Experiments have shown that cell therapy could improve cardiac function and mesenchymal stem cells (MSCs)-based therapies provide a great promising approach in the treatment of MI. However, low cell survival and engraftment restricts the successful application of MSCs for treating MI. Here, we explored whether co-transplantation of a chitosan (CS) thermosensitive hydrogel with bone marrow-derived MSCs (BMSCs) could optimize and maximize the therapeutic of BMSCs in a mouse model of MI. The fate of transplanted BMSCs was monitored by bioluminescence imaging, and the recovery of cardiac function was detected by echocardiogram. Our results proved that CS hydrogel enhanced the BMSCs' survival and the recovery of cardiac function by protecting the vascular endothelial cells. Further studies revealed that the increased number of vascular endothelial cells was due to the fact that transplanted BMSCs inhibited the inflammatory response and alleviated the pyroptosis of vascular endothelial cells. In conclusions, CS hydrogel improved the engraftment of transplanted BMSCs, ameliorated inflammatory responses, and further promoted functional recovery of heart by alleviating vascular endothelial cell pyroptosis.

Retraction: Zhao et al. Protective Effect of Glycyrrhizic Acid on Alcoholic Liver Injury in Rats by Modulating Lipid Metabolism. Molecules 2018, 23(7), 1623.

As the authors of the title paper [...].

Protective Effect of Glycyrrhizic Acid on Alcoholic Liver Injury in Rats by Modulating Lipid Metabolism.

Glycyrrhhizic acid (GA), including 18α-glycyrrhizic acid (18α-GA) and 18ß-glycyrrhizic acid (18ß-GA), is the main active ingredient of licorice. GA is generally considered an effective pharmacological strategy protecting against hepatic disease; however, the optimal compatibility proportion of 18α-GA and 18ß-GA against alcoholic liver disease (ALD) and the underlying mechanism are not well established. Hence, this study was designed to explore the optimal compatibility proportion of 18α-GA and 18ß-GA against ALD, followed by investigating the underlying mechanisms. SD rats were administered 40% ethanol once a day, accompanied by treatment with different proportions of 18α-GA and 18ß-GA for four weeks. Then all rats were anesthetized with chloral hydrate and blood samples were taken from the abdominal aorta for biochemical assay. Livers were also collected and the liver function, lipid profile, ROS production, and mRNA and protein levels of related genes involved in lipid metabolism were assessed. The results showed that 18α-GA and 18ß-GA, particularly at a proportion of 4:6, significantly reduced liver damage, lipid accumulation, and oxidative stress in ethanol-induced rats, as indicated by the decreased levels of alanine aminotransferase (ALT) and aminotransferase (AST) in serum, improvement of liver histopathological changes, regulation of total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), and modulation of superoxide dismutase (SOD), glutathione (GSH), and malonaldehyde (MDA). Moreover, the combination treatment with 18α-GA and 18ß-GA substantially reduced the mRNA and protein levels of sterol regulatory element-binding protein-1c (SREBP-1c) and acetyl-coal carboxylase (ACC); meanwhile, increased levels of peroxisome proliferators activated receptor-α (PPAR-α) and carnitine palmitoy transferase-1 (CTP-1) in the liver tissues of ethanol-induced rats. In conclusion, our results indicated that the optimal compatibility proportion of 18α-GA and 18ß-GA protecting against ALD was 4:6, and the mechanism was associated with the regulation of oxidative stress and lipid metabolism.

Intact endothelial and contractile function of coronary artery after 8 hours of heart preservation.

OBJECTIVES: The aim of the study was to investigate if adequate preservation of coronary artery endothelium-dependent relaxation and contractility may be obtained after 8 hours of non-ischemic heart preservation. DESIGN: Porcine hearts were perfused for 8 hours at 8 °C, either in cycles of 15 minutes perfusion and 60 minutes non-perfusion, or by continuous perfusion. The perfusate consisted of a cardioplegic, hyperoncotic nutrition solution with oxygenated red cells, and the perfusion pressure was 20 mmHg. In organ baths, coronary artery segments from the preserved hearts were studied and compared to fresh controls. RESULTS: Endothelium-dependent relaxation and contractility were fully preserved after both intermittent and continuous perfusion, as compared to fresh controls. No myocardial edema was seen; water content of the myocardium was 79.5 ± 0.2%, 79.0 ± 0.4% and 79.0 ± 0.3% (ns) for fresh controls, intermittently perfused, and continuously perfused hearts, respectively. CONCLUSION: Intact endothelial and contractile function of coronary artery may be obtained after 8 hours of non-ischemic heart preservation.

ANGPTL4 Stabilizes Bone Morphogenetic Protein 7 Through Deubiquitination and Promotes HCC Proliferation via the SMAD/MAPK Pathway.

This study aimed to determine the function of angiopoietin-related protein 4 (ANGPTL4) and bone morphogenetic protein 7 (BMP7) on hepatocellular carcinoma (HCC). Overexpressing plasmids were cotransfected into HepG2 cells to determine the interaction between ANGPTL4 and BMP7. The effect of ANGPTL4 on the stability of BMP7 is examined by detecting the expression and ubiquitination levels. In vitro and in vivo experiments of knocking down ANGPTL4 while overexpressing BMP7 were performed to investigate whether the effects of ANGPTL4 on HCC proliferation, migration, and downstream signaling pathways were dependent on BMP7. ANGPTL4 is able to interact with BMP7, and knockdown of ANGPTL4 increased BMP7 expression and ubiquitination. Overexpression of BMP7 reversed the inhibition of HCC proliferation and migration as well as the decrease in the expression levels of Smad1/5/8 and MAPK14 caused by knockdown of ANGPTL4. ANGPTL4 promotes the proliferation and migration of HCC by inhibiting the ubiquitination degradation of BMP7 and the Smad/MAPK pathway, providing a novel mechanism and a potential therapeutic target for the treatment of HCC.

Effect of Deletion of ANGPTL4 Gene on Viability, Migration and Invasion Ability and Apoptosis of Hepatocellular Carcinoma Cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor that impacts individuals worldwide and is particularly prevalent in Asia. Angiopoietin-like protein 4 (ANGPTL4) plays an important role in regulating glucose and lipid metabolism in mouse liver. We sought to explore the effects of the ANGPTL4 gene on cell viability, migration, invasive capacity, and apoptosis of HCC cells. METHODS: The expression of ANGPTL4 in HCC and paracancerous tissues was determined by immunohistochemistry and immunofluorescence assays. The ANGPTL4 knockdown cells were established by shRNA transfection. The effect of ANGPTL4 knockdown on HepG2 and Huh7 cells was determined by Cell Count Kit-8 (CCK-8), wound healing and transwell assays. Cell apoptosis was determined by flow cytometry. RESULTS: The ANGPTL4 expression was dramatically enhanced in HCC tissues than in paracancerous tissues (p < 0.001). HCC cell lines HepG2 and Huh7 with knockdown of ANGPTL4 gene showed lower cell viability, migration, and invasion ability while inducing higher apoptosis levels than the control group (p < 0.001). CONCLUSIONS: High expression of ANGPTL4 is closely related to HCC. Knockdown of ANGPTL4 significantly inhibits the proliferation of HCC cells. This study provides a rationale for the ANGPTL4 gene, a molecular marker of HCC.

Angiopoietin-Related Protein 4-Transcript 3 Increases the Proliferation, Invasion, and Migration of Hepatocellular Carcinoma Cells and Inhibits Apoptosis.

To investigate the functional differences of angiopoietin-related protein 4 (ANGPTL4) transcripts in hepatocellular carcinoma (HCC) cells. By transfecting ANGPTL4-Transcript 1 and ANGPTL4-Transcript 3 overexpression vectors into HepG2 and Huh7 cell lines with ANGPTL4 knockdown, the effects of overexpression of two transcripts on cell viability, invasion, migration, and apoptosis were analyzed. The expression of two transcripts was compared in human liver cancer tissue, and their effects on tumor development were validated in vivo experiments in mice. Compared with control, the overexpression of ANGPTL4-Transcript 1 had no significant effect on viability, invasion, healing, and apoptosis of HepG2 and Huh7 cells. However, these two cell lines overexpressing ANGPTL4-Transcript 3 showed remarkably enhanced cell viability, invasive and healing ability, and decreased apoptosis ability. Furthermore, the mRNA level of ANGPTL4-Transcript 3 was significantly increased in human HCC tissues and promoted tumor growth compared with Transcript 1. Different transcripts of gene ANGPTL4 have distinct effects on HCC. The abnormally elevated Transcript 3 with the specific ability of promoting HCC proliferation, infiltration, and migration is expected to become a new biological marker and more precise intervention target for HCC.

Preliminary analysis of stimulation parameters for sacral neuromodulation in different indications: a multicenter retrospective cohort study from China.

BACKGROUND: Sacral neuromodulation (SNM) is an effective approach for treating lower urinary tract dysfunction (LUTD), and stimulation programming is essential for successful treatment. However, research on SNM programming for various indications is limited. Thus, the authors aimed to determine whether there were differences in the stimulation parameters for different SNM indications and the appropriate programming recommendations. MATERIALS AND METHODS: Clinical data were retrospectively collected from patients with LUTD who underwent SNM and completed internal pulse generator implantation. The parameters with the highest patient satisfaction or the most symptom improvement during the test period were considered optimal and used to set the programming after internal pulse generator implantation. RESULTS: After screening, 282 patients were enrolled and categorized into four groups based on the following indications: refractory overactive bladder (OAB) ( n =61), neurogenic lower urinary tract dysfunction (nLUTD) ( n =162), interstitial cystitis/painful bladder syndrome (IC/BPS) ( n =24), and idiopathic nonobstructive urinary retention (NOUR) ( n =35). When analyzing the optimal stimulus parameters, disparities in the stimulation amplitude and pulse frequency were noted among the four groups. The stimulation amplitude in the nLUTD group was higher than that in the idiopathic NOUR group ( P =0.013). Differences in pulse frequency were observed between the refractory OAB and nLUTD groups ( P <0.001) and between the refractory OAB and idiopathic NOUR groups ( P =0.001). No differences in the electrode configuration or pulse width settings existed among the four groups. CONCLUSIONS: The stimulation parameters for SNM varied among the different indications. For the initial programming of stage I, most patients are recommended to start with stimulation amplitudes below 2 V, although patients with nLUTD may benefit from higher amplitudes. A standard pulse width of 210 µs is recommended for all patients. However, for individuals experiencing nLUTD or idiopathic NOUR, the pulse frequency can begin above the standard 14 Hz but not exceed 50 Hz.

Complete optical throughput analysis of the static polarization wind imaging interferometer.

The basic principle of the static polarization wind imaging interferometer (SPWII) is expounded in this paper. By using trigonometric function and complex amplitude methods, the complex vibration amplitude of each polarization device with deviation from its ideal direction is calculated. The variations of the fringe visibility and optical throughput with deviation angles are given analytically and simulated numerically. According to the design parameters of the SPWII, the air-equivalent length L is equal to 16.14 cm and the total transmissivity is greater than 0.4. When the polarization directions of each polarization device are all in the ideal directions, the total optical throughput can be maintained at about 16.4% of the incident optical intensity. When the polarization directions of each polarization device are all 2° deviated from the ideal positions, the total optical throughput is decreased by 0.08%. This work would be useful for the realization and data processing of the SPWII.

Application of targeted diagnosis of PSMA in the modality shift of prostate cancer diagnosis: a review.

Prostate cancer (PCa) is a serious threat to the health of men all over the world. The progression of PCa varies greatly among different individuals. In clinical practice, some patients often progress to advanced PCa. Therefore, accurate imaging for diagnosis and staging of PCa is particularly important for clinical management of patients. Conventional imaging examinations such as MRI and CT cannot accurately diagnose the pathological stages of advanced PCa, especially metastatic lymph node (LN) stages. As a result, developing an accurate molecular targeted diagnosis is crucial for advanced PCa. Prostate specific membrane antigen (PSMA) is of great value in the diagnosis of PCa because of its specific expression in PCa. At present, researchers have developed positron emission tomography (PET) targeting PSMA. A large number of studies have confirmed that it not only has a higher tumor detection rate, but also has a higher diagnostic efficacy in the pathological stage of advanced PCa compared with traditional imaging methods. This review summarizes recent studies on PSMA targeted PET in PCa diagnosis, analyzes its value in PCa diagnosis in detail, and provides new ideas for urological clinicians in PCa diagnosis and clinical management.

Construction and validation of a cuproptosis-related lncRNA prognosis signature in bladder carcinoma.

BACKGROUND: Bladder cancer (BLCA) is a prevalent urological tumor with high morbidity and mortality. However, BLCA treatment remains challenging due to a lack of effective biomarkers. Long non-coding RNAs (lncRNAs), as active participants in tumor progression are involved in multiple biological regulatory mechanisms, and cuproptosis-related genes participate in the development of cancer. It is important to discover cuproptosis- related lncRNAs for BLCA diagnosis and treatment. METHODS: A predictive signature was constructed based on least absolute shrinkage and selection operator regression (LASSO) and Cox regression analyses of the 9 cuproptosis-related lncRNAs. Samples were divided into high-risk group and low-risk group based on their median risk scores to explore their prognosis. RESULTS: This signature is well predictive, as evidenced by the receiver operating characteristic curves (ROC curves) and K-M curves. Based on the nomogram, we were able to visually forecast the survival rates of patients with BLCA at 1-, 3-, and 5-year, and the calibration plots displayed that the actual results were well matched with the predicted 1-, 3-, and 5-year survival rates. Furthermore, BLCA patients in the high-risk group had a higher Tumor Immune Dysfunction and Exclusion (TIDE) score and lower TMB. Finally, we investigated the response of antitumor drugs for BLCA patients in different risk groups, and a statistically significant difference was observed in the sensitivity of those drugs between low- and the high-risk groups. CONCLUSION: According to the 9 cuproptosis-related lncRNAs, we constructed a signature which can be served as a promising prognostic biomarker for BLCA patients.

Postoperative pathological complete response in a patient with PD­L1­negative stage IIIB lung squamous cell carcinoma following neoadjuvant tislelizumab treatment combined with chemotherapy: A case report and literature review.

The utilization of immune checkpoint inhibitors in oncological treatment has increased in recent years. The therapeutic strategy of targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway has altered the management of advanced non-small cell lung carcinoma (NSCLC). Tislelizumab, a novel anti-PD-1 monoclonal antibody developed in China, has demonstrated efficacy in treating advanced NSCLC. However, its potential role as a neoadjuvant therapy for locally advanced NSCLC has not been definitively established. Current guidelines do not specify which patient populations may gain the most benefit from neoadjuvant immunotherapy coupled with chemotherapy, nor do they indicate the optimal timing, dose or duration of adjuvant maintenance therapy post-NSCLC surgery. Similarly, data concerning the safety and practicability of surgical resection following neoadjuvant tislelizumab treatment for NSCLC remain limited. The present study describes the case of a patient diagnosed with stage IIIB NSCLC, which was initially deemed unresectable. A preoperative biopsy of the tumor mass revealed squamous cell carcinoma and a negative PD-L1 gene test. Notably, after two cycles of neoadjuvant tislelizumab treatment coupled with chemotherapy, the tumor exhibited marked shrinkage. This permitted the patient to undergo thoracoscopic radical lung cancer resection, which resulted in a pathological complete response. Postoperative pathology identified a large infiltration of lymphoplasmacytic cells and foamy histiocytes. The patient experienced grade 2 myelosuppression, a condition that was successfully addressed with the administration of recombinant human granulocyte colony-stimulating factor. The present case indicates the safety and feasibility of neoadjuvant immunotherapy integrated with chemotherapy for patients with locally advanced, PD-L1-negative NSCLC prior to surgical intervention. Moreover, the case suggests the potential of this therapeutic combination to alter the tumor microenvironment. However, the generalization of these findings necessitates further validation through randomized multicenter trials.

A preliminary evaluation of targeted nanopore sequencing technology for the detection of Mycobacterium tuberculosis in bronchoalveolar lavage fluid specimens.

Objective: To evaluate the efficacy of targeted nanopore sequencing technology for the detection of Mycobacterium tuberculosis(M.tb.) in bronchoalveolar lavage fluid(BALF) specimens. Methods: A prospective study was used to select 58 patients with suspected pulmonary tuberculosis(PTB) at Henan Chest Hospital from January to October 2022 for bronchoscopy, and BALF specimens were subjected to acid-fast bacilli(AFB) smear, Mycobacterium tuberculosis MGIT960 liquid culture, Gene Xpert MTB/RIF (Xpert MTB/RIF) and targeted nanopore sequencing (TNS) for the detection of M.tb., comparing the differences in the positive rates of the four methods for the detection of patients with different classifications. Results: Among 58 patients with suspected pulmonary tuberculosis, there were 48 patients with a final diagnosis of pulmonary tuberculosis. Using the clinical composite diagnosis as the reference gold standard, the sensitivity of AFB smear were 27.1% (95% CI: 15.3-41.8); for M.tb culture were 39.6% (95% CI: 25.8-54.7); for Xpert MTB/RIF were 56.2% (95% CI: 41.2-70.5); for TNS were 89.6% (95% CI: 77.3-96.5). Using BALF specimens Xpert MTB/RIF and/or M.tb. culture as the reference standard, TNS showed 100% (30/30) sensitivity. The sensitivity of NGS for pulmonary tuberculosis diagnosis was significantly higher than Xpert MTB/RIF, M.tb. culture, and AFB smear. Besides, P values of <0.05 were considered statistically significant. Conclusion: Using a clinical composite reference standard as a reference gold standard, TNS has the highest sensitivity and consistency with clinical diagnosis, and can rapidly and efficiently detect PTB in BALF specimens, which can aid to improve the early diagnosis of suspected tuberculosis patients.

Genome-wide analysis revealed the dysregulation of RNA binding protein-correlated alternative splicing events in myocardial ischemia reperfusion injury.

BACKGROUND: Myocardial ischemia reperfusion injury (MIRI), the tissue damage which is caused by the returning of blood supply to tissue after a period of ischemia, greatly reduces the therapeutic effect of treatment of myocardial infarction. But the underlying functional mechanisms of MIRI are still unclear. METHODS: We constructed mouse models of MIRI, extracted injured and healthy myocardial tissues, and performed transcriptome sequencing experiments (RNA-seq) to systematically investigate the dysregulated transcriptome of MIRI, especially the alternative splicing (AS) regulation and RNA binding proteins (RBPs). Selected RBPs and MIRI-associated AS events were then validated by RT-qPCR experiments. RESULTS: The differentially expressed gene (DEG) analyses indicated that transcriptome profiles were changed by MIRI and that DEGs' enriched functions were consistent with MIRI's dysregulated pathways. Furthermore, the AS profile was synergistically regulated and showed clear differences between the mouse model and the healthy samples. The exon skipping events significantly increased in MIRI model samples, while the opposite cassette exon events significantly decreased. According to the functional analysis, regulated alternative splicing genes (RASGs) were enriched in protein transport, cell division /cell cycle, RNA splicing, and endocytosis pathways, which were associated with the development of MIRI. Meanwhile, 493 differentially expressed RBPs (DE RBPs) were detected, most of which were correlated with the changed ratios of AS events. In addition, nine DE RBP genes were validated, including Eif5, Pdia6, Tagln2, Vasp, Zfp36l2, Grsf1, Idh2, Ndrg2, and Uqcrc1. These nine DE RBPs were correlated with RASGs enriched in translation process, cell growth and division, and endocytosis pathways, highly consistent with the functions of all RASGs. Finally, we validated the AS ratio changes of five regulated alternative splicing events (RASEs) derived from important regulatory genes, including Mtmr3, Cdc42, Cd47, Fbln2, Vegfa, and Fhl2. CONCLUSION: Our study emphasized the critical roles of the dysregulated AS profiles in MIRI development, investigated the potential functions of MIRI-associated RASGs, and identified regulatory RBPs involved in AS regulation. We propose that the identified RASEs and RBPs could serve as important regulators and potential therapeutic targets in MIRI treatment in the future.

Green credit and market expansion strategy of high pollution enterprises-Evidence from China.

This paper uses the Difference-in-Differences method to test the impact of the promulgation of Green Credit Guidelines, a market-oriented environmental regulation, on the enterprise market expansion strategy, based on the panel data of Chinese A-share listed companies from 2008 to 2015. We find that the promulgation of Green Credit Guidelines significantly inhibited the market expansion strategy of high pollution enterprises. Two channels through which the Green Credit Guidelines affect the market expansion strategies of high polluters are increasing the cost of financing and promoting green R&D. Heterogeneity analysis finds that the impact of Green Credit Guidelines on the market expansion of highly polluting enterprises is more significant in non-state-owned enterprises and enterprises without equity incentive. Further analysis shows that the promulgation of Green Credit Guidelines damages the corporate image and profitability of high polluting enterprises, but it doesn't increase the risk of high polluting enterprises. The results of this research could help relevant government departments to formulate practical environmental regulations and promote sustainable economic development.

Exposure to Abnormally Hot Temperature and the Demand for Commercial Health Insurance.

Using the China Health and Retirement Longitudinal Study, this paper studies the impact of abnormal hot temperature on residents' demand for commercial health insurance. The results show that for every 1°F rise in abnormal temperature, the probability of people buying commercial health insurance increased by 6%. Furthermore, the abnormal hot temperature has a more significant impact on the commercial health insurance demand of women, residents in the South and residents in the East. Channel analysis shows that abnormal hot temperature affects the demand for commercial health insurance through two channels: increasing residents' concern about climate risk and affecting health. This paper provides evidence for actively promoting sustainable development and improving the construction of medical security system.

Impact of Drinking Water Source and Sanitation Facility on Malnutrition Prevalence in Children under Three: A Gender-Disaggregated Analysis Using PDHS 2017-18.

OBJECTIVES: The proposed research studied the determinants of male and female child malnutrition in Pakistan. More specifically, it observed the role of the sanitation facility and drinking water source as important determinants of malnutrition in a gender analysis. METHODS: Novel data of 1010 children under three years of age from PDHS 2017-18 were used. A CIAF (Cumulative Index for Anthropometric Failure) was established to assess malnourishment in the children. Discrete-choice logistic methodology was applied in this empirical research to study the likelihood of malnourishment in children. RESULTS: The logistic regression results depicted that factors such as a child belonging to a deprived area, the status of home wealth, and the education of the mother were common determinants of malnutrition in children. Factors such as a child having diarrhea (OR = 1.55, CI = 0.96-2.50) and the drinking water source (OR = 0.62, CI = 0.37-1.03) were separate prominent predictors of malnutrition in male children whereas the sanitation facility was the main determinant of malnutrition in female children (OR = 0.64, CI = 0.43-0.95). CONCLUSION: This study concludes that important links exist between the drinking water source and male child malnutrition and between sanitation facilities and female child malnutrition.

The Role of ANGPTL Gene Family Members in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is highly aggressive with a poor prognosis and survival rate. Certain ANGPTL members have been implicated in tumor progression. However, the relevance of the ANGPTL gene family to HCC remains poorly understood. In this study, we explored the role of ANGPTLs in the prognosis of HCC. Methods: From the CCLE database, we studied the expression of ANGPTLs in a range of cancer cell lines. The UCSC, HCCDB, and Human Protein Atlas databases were used to analyze the differences in mRNA and protein expression of ANGPTLs in HCC tissues. Additionally, the correlation between ANGPTL mRNA and methylation levels and clinicopathological features were assessed in the TCGA database. The correlation between ANGPTL mRNA and overall survival was determined by the Kaplan-Meier plotter. cBioPortal database was used to analyze ANGPTL genomic alterations. Genes associated with ANGPTLs were determined by enrichment with KEGG. Moreover, the differentially expressed genes of ANGPTLs were analyzed by the LinkedOmics database, and the KEGG pathway and miRNA targets of ANGPTLs were also enriched. Results: There was a significant correlation between the ANGPTL members (excluding ANGPTL2) and the prognosis of HCC patients according to the Kaplan-Meier plotter analysis (p < 0.05). ANGPTL1 was the gene with the highest mutation frequency. ANGPTLs are involved in certain pathways that may influence the development of HCC. Conclusion: In summary, the expression of some members of ANGPTLs was significantly correlated with HCC prognosis, suggesting that the ANGPTL gene family members may be promising molecular markers for HCC treatment and prognosis.