BACKGROUND: High temperatures are known to be associated with an increased risk of self-harm, but the influence of demographic changes and country-level indicators on the burden of heat-related self-harm remains unclear. This study examined the key factors driving changes in self-harm mortality linked to high temperatures and explored their impact at the country level. METHODS: This is an ecological study that analyzes data from the 2021 Global Burden of Disease (GBD) study, the World Bank, and the Climate Research Unit (CRU) were analyzed. Decomposition analyses were used to identify key factors driving changes in high temperature-related self-harm mortality between 1990 and 2021. A panel data model assessed the impact of national indicators on heat-related self-harm mortality. RESULTS: In 2021, 14,885 deaths globally were attributed to heat-related self-harm, a 41.94% increase from 1990, with low-middle SDI regions accounting for 47.84% of these deaths. While the global death rate from heat-related self-harm declined slightly over this period, South Asia and low-middle SDI regions contributed most to the decline. However, population aging exacerbated mortality rates. Demographic and meteorological factors were also linked to heat-related self-harm. CONCLUSION The global decline in heat-related self-harm mortality is largely driven by reductions in females, low-middle SDI regions, and South Asia. However, population aging and growth in these regions have added to the mortality burden, slowing the overall decline. Factors such as population density are also associated with heat-related self-harm. Targeted measures are needed to mitigate heat-induced self-harm more effectively in future.
Humans ; Self-Injurious Behavior/etiology* ; Hot Temperature/adverse effects* ; Global Health/statistics & numerical data* ; Female ; Male ; Adult ; Middle Aged ; Aged ; Young Adult ; Adolescent

Protein liquid-liquid phase separation (LLPS), a pivotal phenomenon intricately linked to cellular processes, is regulated by various other proteins. However, there is still a lack of high-throughput methods for screening protein regulators of LLPS in target proteins. Here, we developed a CRISPR/Cas9-based screening method to identify protein phase separation regulators by integrating bimolecular fluorescence complementation (BiFC) and fluorescence-activated cell sorting (FACS). Using this newly developed method, we screened the RNA-binding proteins that regulate PABPN1 phase separation and identified the tumor suppressor QKI as a promoter of PABPN1 phase separation. Furthermore, QKI exhibits decreased expression levels and diminished nuclear localization in colorectal cancer cells, resulting in reduced PABPN1 phase separation, which, in turn, promotes alternative polyadenylation (APA), cell proliferation, and migration in colorectal cancer.
Humans ; Colorectal Neoplasms/genetics* ; RNA-Binding Proteins/genetics* ; Poly(A)-Binding Protein I/genetics* ; CRISPR-Cas Systems ; Flow Cytometry ; Cell Proliferation ; Cell Line, Tumor ; Cell Movement

Humans ; Glycated Hemoglobin ; Diabetes Mellitus, Type 1 ; Blood Glucose ; Diabetes Mellitus, Type 2

Background::Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Methods::Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-cateninΔ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. Results::MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. Conclusion::MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

Objective To explore the role of MAPK4 in cervical squamous cell carcinoma(CSCC)for the identification of candidate prognostic prediction biomarkers and molecular therapeutic targets.Methods The TCGA cohort was subjected to Kaplan-Meier survival analysis.Immunohistochemistry experiments were conducted on clinical samples to explore the correlation between MAPK4 and patient prognosis.A nomogram was constructed based on MAPK4 mRNA levels.Western blot,CCK-8,colony formation,and Transwell cell function experiments were performed to clarify the abnormal expression and role of MAPK4 in CSCC.DIA proteome sequencing was used to identify effector molecules regulated by MAPK4.Combined with the above cell function experiments,the knockdown of MAPK4 and the overexpression of effector molecules revealed that MAPK4 regulated effector molecules to mediate tumor progression.Results CSCC patients with elevated MAPK4 mRNA levels and high protein expression have a worse prognosis.The constructed nomogram based on MAPK4 can accurately predict the 1-,3-,and 5-year survival rates of patients.Compared with that in normal cervical tissues,MAPK4 protein expre-ssion was up-regulated in tumors.MAP-K4 knockdown substantially inhibited the proliferation,colony formation,mig-ration,and invasion of CSCC ME180 and SiHa cells.SLC3A2 is a downs-tream effector molecule of MAPK4.Overexpression SLC3A2 can weaken the inhibitory effect of MAPK4 knockdown on cell proliferation,colony formation,migration,and invasion.Conclusion MAPK4 is a candidate prognostic biomarker for patients with CSCC.MAPK4 positively regulates SLC3A2 protein expression and accelerates tumor progression,making it a potential molecular therapeutic target for patients with CSCC.

BACKGROUND:A pathophysiological feature of septic organ failure is endothelial dysfunction in sepsis(EDS).The physiological and pathological mechanism of sepsis is considered to be vascular leakage caused by endothelial dysfunction.These pathological changes lead to systemic organ injury.However,an analysis using bibliometric methods has not yet been conducted in the field of EDS.This study was conducted to provide an overview of knowledge structure and research trends in the field of EDS. METHODS:Based on previous research,a literature search was performed in the Web of Science Core Collection(WoSCC)for publications associated with EDS published between the year 2003 and 2023.Various types of data from the publications,such as citation frequency,authorship,keywords and highly cited articles,were extracted.The"Create Citation Report"feature in the WoSCC was employed to calculate the Hirsch index(h-index)and average citations per item(ACI)of authors,institutions,and countries.To conduct bibliometric and visualization analyses,three bibliometric tools were used,including R-bibliometrix,CiteSpace(co-citation analysis of references),and VOSviewer(co-authorship analysis of institutions,co-authorship analysis of authors,co-occurrence analysis of keywords). RESULTS:After excluding invalid records,the study finaly included 4,536 publications with 135,386 citations.Most of these publications originated in the USA,China,Germany,Canada,and Japan.Harvard University emerged as the most prolific institution,while professor Jong-Sup Bae and his research team at Kyungpook National University emerged as authors with the greatest influence.The"protein C","tissue factor","thrombin","glycocalyx","acute kidney injury","syndecan-1"and"biomarker"were identified as prominent areas of research.Future research may focus on molecular mechanisms(such as as vascular endothelial[VE]-cadherin regulation)and therapeutic interventions to enhance endothelial repair and function. CONCLUSION:Our findings show a growing interest in EDS research.Key areas for future research include signaling pathways,molecular mechanisms,endothelial repair,and interactions between endothelial cells and other cell types in sepsis.

Objective To establish a differential model of phlegm and blood stasis pattern and qi deficiency and blood stasis pattern in stable angina pectoris using radiomics.Methods A total of 91 patients with stable angina pectoris who underwent coronary artery CT angiography in Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 2021 to January 2022 were collected,including 47 cases of phlegm and blood stasis pattern and 44 cases of qi deficiency and blood stasis pattern.The patients were divided into train set(64 cases)and test set(27 cases)according to the ratio of 7∶3 by stratified random sampling method.3D-slicer software was used to extract the radiomics features of pericoronary adipose tissue(PCAT)images.Principal component analysis was used to visualize the distribution of radiomics features of pattern of phlegm and blood stasis and pattern of qi deficiency and blood stasis.The least absolute shrinkage and selection operator regression analysis and support vector machine decreasing feature elimination were used for feature selection.The multinomial logistics regression was used for model construction.The receiver operating characteristic(ROC)curve was used to verify the model in the train set and the test set to evaluate the effectiveness of the radiomics features in differentiating phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.Finally,Spearman coefficient was used to analyze the correlation between the differential features and clinical physicochemical data.Results A total of 837 radiomics features were extracted from PCAT images by 3D-slicer software.In the principal component analysis,PC1 and PC2 explained 77.9%and 8.1%of the total variance,respectively,and there was a relatively obvious separation trend between the two pattern groups.After feature screening,7 radiomics features were used to construct the differential model of phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.The area under the ROC curve(AUC)of the differential model was 0.844 in the train set and 0.834 in the test set.Spearman correlation analysis showed that the differential features were significantly correlated with cTnI,neutrophil,triglyceride,total cholesterol,and leukocyte.Conclusion The CT radiomics model based on PCAT has a high discrimination efficiency for stable angina pectoris with phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.

Objective:To review the scope of research on the application of managing cancer and living meaningfully (CALM) in cancer patient populations, and provide reference for follow-up research and clinical promotion and application.Methods:Using the research method of scope review, two evidence-based trained researchers independently conducted a blind literature search. A total of 12 databases were searched, including CNKI, Wanfang, VIP, China Biomedical Literature Database, Cochrane Library, PubMed, Web of Science, CTNAHL, Embase, Scopus, Medline and EBSCO. The search time limit was from database establishment to September 26, 2022. Collected relevant literature on the application of CALM therapy to cancer patients, extracted data included in the literature, summarize and report research results.Results:A total of 2 089 articles were retrieved, and 13 were eventually included through the inclusion criteria, including 8 randomized controlled studies, 2 quasi experimental studies and 3 qualitative studies. The results showed that CALM therapy included 4 themes, 3 to 8 separate psychotherapy sessions, each lasting for 3 to 6 months for 30 to 60 minutes. It was a short and flexible evidence-based personalized psychotherapy method that was easily accepted by patients, could alleviate the negative emotions of patients with advanced cancer, and promote their mental health. There was no literature reports on the occurrence of adverse events related to CALM therapy.Conclusions:CALM therapy has a positive impact on cancer patients, with safety and feasibility. In the future, it is necessary to construct a specific, standard, and localized CALM therapy program, conduct large sample, high-quality research to verify the application effect of CALM therapy in cancer patients, and provide evidence-based basis for formulating the best CALM therapy program for cancer patients.

Objective:To evaluate the effect of preventive application of PEG-rhG-CSF on the prevention of neutropenia during concurrent chemoradiotherapy in patients with lung cancer.Methods:A total of 149 patients with lung cancer who received concurrent chemoradiotherapy at Peking University Cancer Hospital from April 2020 to April 2021 were retrospectively analyzed. There were 79 cases in the prevention group, including 48 cases of primary prevention group (preventive application of PEG-rhG-CSF in all concurrent chemoradiotherapy cycles) and 31 cases of secondary prevention group (preventive application of PEG-rhG-CSF in the concurrent chemoradiotherapy cycles after neutropenia occurred). There were 70 cases in non-prevention group. The incidence of grade 3-4 neutropenia, the completion rate of concurrent chemoradiotherapy, the rate of chemoradiotherapy dose reduction and treatment delay, and the rate of hematological toxicities related hospitalization were compared between the prevention group and the non-prevention group.Results:The incidence of grade 3-4 neutropenia in the whole group was 32.2% (48/149), including 6.3% (3/48) in the primary prevention group, 9.7% (3/31) in the secondary prevention group, and 35.7% (25/70) in the non-prevention group. The difference was statistically significant ( χ2=17.81, P<0.001) in the incidence of grade 3-4 neutropenia. The incidence of febrile neutropenia was 3.4% (5/149) in the whole group, but none of them occurred in the primary prevention group. The full completion rate of concurrent chemotherapy was 96.2% (76/79) in the prevention group, which was significantly higher than 82.9% (58/70) in the non-prevention group ( χ2=7.30, P=0.007). The incidence of treatment delayed and dose reduction of chemoradiotherapy was 19.0% (15/79) in the prevention group and 40.0% (28/70) in the non-prevention group, and the difference was statistically significant ( χ2=7.98, P=0.005). Conclusions:The preventive application of PEG-rhG-CSF can effectively reduce the incidence of neutropenia and better ensure the concurrent chemoradiotherapy in lung cancer patients on schedule.

A case of suppurative meningitis caused by Streptococcus suis infection is reported. The patient was an elderly female with an atypical epidemiological history. The common symptoms included fever, headache and cervicodynia. According to the results of blood bacterial culture and next-generation sequencing of cerebrospinal fluid, the patient was considered purulent meningitis caused by Streptococcus suis. After treatment with the third generation cephalosporins, the symptoms improved significantly. One week after the onset of the disease, herpes labialis occurred, followed by hearing loss about 1 week later. The patient was treated with antiviral and hormone therapy, and was discharged after improvement.