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Abstract Background and purpose The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in directing folate species towards nucleotide synthesis or DNA methylation. The MTHFR polymorphisms C677T and A1298C have been linked to cancer susceptibility, but the evidence supporting this association has been equivocal. To investigate the individual and joint associations between MTHFR C677T, A1298C, and digestive system cancer in a Chinese hypertensive population, we conducted a population-based case–control study involving 751 digestive system cancer cases and one-to-one matched controls from the China H-type Hypertension Registry Study (CHHRS). Methods We utilized the conditional logistic regression model to evaluate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of digestive system cancer. Results The analysis revealed a significantly lower risk of digestive system cancer in individuals with the CT genotype (adjusted OR: 0.71; 95% CI 0.52, 0.97; P = 0.034) and TT genotype (adjusted OR: 0.57; 95% CI 0.40, 0.82; P = 0.003; P for trend = 0.003) compared to those with the 677CC genotype. Although A1298C did not show a measurable association with digestive system cancer risk, further stratification of 677CT genotype carriers by A1298C homozygotes (AA) and heterozygotes (AC) revealed a distinct trend within these subgroups. Conclusion These findings indicate a potential protective effect against digestive system cancer associated with the T allele of MTHFR C677T. Moreover, we observed that the presence of different combinations of MTHFR polymorphisms may contribute to varying susceptibilities to digestive system cancer.

BackgroundCoinfection with the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) occurs in 5–67% of patients with HIV. HIV weakens the human immune system and leads to various tumors. Patients with unresectable hepatocellular carcinoma (HCC) and HIV experience poor treatment efficacy and have a short survival period. Approximately 70% of cases of HCC are diagnosed at advanced stages due to the subtle onset of the disease. As a result, most cases are not suits for curative therapy. Transcatheter arterial chemoembolization (TACE) is the first-line treatment for intermediate-stage HCC and is commonly used to treat unresectable HCC in China. Recent advancements in systemic treatments have significantly enhanced the effectiveness of unresectable HCC treatment. Several previous study showed that combination treatment combination therapy can enhance the efficacy. Notably, studies proposed that TACE combined targeted drugs with immune checkpoint inhibitors results in a high objective response rate and overall survival. However, the novelty of this study lies in its report of a complete response using a triple combination in patients with HIV and HCC with main trunk portal vein tumor thrombus.Case presentationA 57-year-old woman was diagnosed with HCC with a main trunk portal vein tumor thrombus combined with HIV infection, cirrhosis, and chronic viral hepatitis. She underwent TACE and was administered donafenib and tislelizumab. This triple therapy treatment regimen resulted in a clinical complete response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) based on contrast-enhanced computed tomography.ConclusionWe first used TACE combined with donafenib and tislelizumab for HCC patients with main trunk portal vein tumor thrombus and HIV-HBV coinfection and achieved complete response.

Abstract Background This study aimed to evaluate the association of triglyceride-glucose (TyG) index, an insulin resistance surrogate biomarker, with first stroke in a hypertensive population and to explore potential influencing factors. Methods This study, a cohort study among a rural Chinese hypertensive population, utilized data from the China Stroke Primary Prevention Trial (CSPPT). The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate analysis using Cox proportional hazards models was conducted. Results A total of 7569 hypertensive patients were included in this study. When TyG index was assessed as quartiles, compared with the reference group (Quartile 1), the hazard ratio of stroke was 1.04 in Quartile 2, 1.43 in Quartile 3, and 1.45 in Quartile 4, with a significant trend test (P = 0.013). When Quartiles 3 and 4 were combined (≥ 8.8), the hazard ratio was 1.41 compared with combined Quartiles 1 and 2 (

Abstract Transarterial chemoembolisation (TACE) is a standard therapy for hepatocellular carcinoma (HCC). However, adverse events, including abdominal pain, are common. This study aimed to investigate and verify the feasibility of a nomogram model to predict severe abdominal pain after first conventional TACE (cTACE) among patients with HCC. Patients with HCC treated with cTACE between October 28, 2019, and August 5, 2022, at a single centre were enrolled (n = 216). Patients were divided into training and validation cohorts (ratio, 7:3). A visual analogue scale score between 7 and 10 was considered severe abdominal pain. A total of 127 (58.8%) patients complained of severe abdominal pain after first cTACE treatment. The nomogram considered age and tumour number and size. The nomogram demonstrated good discrimination, with a C-index of 0.749 (95% confidence interval [CI], 0.617, 0.881). Further, the C-index in the validation cohort reached 0.728 (95% CI 0.592, 0.864). The calibration curves showed ideal agreement between the prediction and real observations, and the nomogram decision curve analysis performed well. The nomogram model can provide an accurate prediction of severe abdominal pain in patients with HCC after first cTACE, aiding in the personalization of pain management and providing novel insights into hospital nursing.

IntroductionMalnutrition is prevalent among individuals with gastric cancer and notably decreases their quality of life (QOL). However, the factors impacting QOL are yet to be clearly defined. This study aimed to identify essential factors impacting QOL in malnourished patients suffering from gastric cancer.MethodsBy using the Patient-Generated Subjective Global Assessment (PG-SGA) to assess the nutritional status (≥4 defined malnutrition) of hospitalized cancer patients, 4,586 gastric cancer patients were ultimately defined as malnourished. Spearman method was used to calculate the relationship between clinical features and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Then, univariate and multivariate logistic regression were used to observe which factors affected QOL, and subgroup analysis was performed in young and old population respectively. In addition, we used univariate and multivariate logistic regression to explore whether and how self-reported frequent symptoms in the last 2 weeks of the PG-SGA score affected QOL.ResultsIn multivariate logistic regression analysis of clinical features of patients with malnourished gastric cancer, women, stage II, stage IV, WL had an independent correlation with a low global QOL scores. However, BMI, secondary education, higher education, surgery, chemotherapy, HGS had an independent correlation with a high global QOL scores. In multivariate logistic regression analysis of symptoms in self-reported PG-SGA scores in patients with malnourished gastric cancer, having no problem eating had an independent correlation with a high global QOL scores. However, they have no appetite, nausea, vomiting, constipation and pain had an independent correlation with a lower global QOL scores. The p values of the above statistical results are both < 0.05.ConclusionThis study demonstrates that QOL in malnourished patients with gastric cancer is determined by female sex, stage II, stage IV, BMI, secondary and higher education or above, surgery, chemotherapy, WL, and HGS. Patients’ self-reported symptoms of nearly 2 weeks, obtained by using PG-SGA, are also further predictive of malnourished gastric cancer patients. Detecting preliminary indicators of low QOL could aid in identifying patients who might benefit from an early referral to palliative care and assisted nursing.

Abstract Evidence from epidemiologic studies on the association of circulating betaine levels with the incident risk of cancer has been inconsistent. We aimed to investigate the prospective association of serum betaine concentrations with the risk of cancer. We performed two, nested, case-control studies utilizing data from the “H-type Hypertension Prevention and Control Public Service Project” (HHPCP) and the China Stroke Primary Prevention Trial (CSPPT), with 2782 participants (1391 cancer cases and 1391 matched controls) in the discovery cohort, and 228 participants (114 cancer cases and 114 matched controls) in the validation cohort. Odds ratios (OR) of the association between betaine and cancer were calculated using conditional logistic regression models. There was an association between serum betaine as a continuous variable and total cancer (OR = 1.03, 95%CI = 0.99–1.07, p = 0.097). Among cancer subtypes, a positive association was found between serum betaine and the risk of lung cancer, and an inverse association was found with other cancers. Interestingly, a U-shaped association was observed between serum betaine and digestive cancers, with a turning point of 5.01 mmol/L for betaine (betaine

Background and aimThe purpose of this study was to investigate and validate the efficacy of a nomogram model in predicting early objective response rate (ORR) in u-HCC patients receiving a combination of TACE, Lenvatinib, and anti-PD-1 antibody treatment after 3 months (triple therapy).MethodThis study included 169 u-HCC cases from five different hospitals. As training cohorts (n = 102), cases from two major centers were used, and external validation cohorts (n = 67) were drawn from the other three centers. The clinical data and contrast-enhanced MRI characteristics of patients were included in this retrospective study. For evaluating MRI treatment responses, the modified revaluation criteria in solid tumors (mRECIST) were used. Univariate and multivariate logistic regression analyses were used to select relevant variables and develop a nomogram model. Our as-constructed nomogram was highly consistent and clinically useful, as confirmed by the calibration curve and decision curve analysis (DCA); an independent external cohort also calibrated the nomogram.ResultsThe ORR was 60.9% and the risk of early ORR was independently predicted by AFP, portal vein tumor thrombus (PVTT), tumor number, and size in both the training (C-index = 0.853) and test (C-index = 0.800) cohorts. The calibration curve revealed that the nomogram-predicted values were consistent with the actual response rates in both cohorts. Furthermore, DCA indicated that our developed nomogram performed well in clinical settings.ConclusionThe nomogram model accurately predicts early ORR achieved by triple therapy in u-HCC patients, which aids in individual decision-making and modifying additional therapies for u-HCC cases.

ObjectiveThe effect of arginine on tumors appears to be bidirectional. The association of serum arginine with the risk of incident cancer remains uncovered at present. We aimed to investigate the prospective relationship of baseline serum arginine concentrations with the risk of incident cancer in hypertensive participants.Materials and methodsA nested, case-control study with 1,389 incident cancer cases and 1,389 matched controls was conducted using data from the China H-Type Hypertension Registry Study (CHHRS). Conditional logistic regression analyses were performed to evaluate the association between serum arginine and the risk of the overall, digestive system, non-digestive system, and site-specific cancer.ResultsCompared with matched controls, cancer patients had higher levels of arginine (21.41 μg/mL vs. 20.88 μg/mL, p < 0.05). When serum arginine concentrations were assessed as quartiles, compared with participants in the lowest arginine quartile, participants in the highest arginine quartile had a 32% (OR = 1.32, 95% CI: 1.03 to 1.71), and 68% (OR = 1.68, 95% CI: 1.09 to 2.59) increased risk of overall and digestive system cancer, respectively, in the adjusted models. In the site-specific analysis, each standard deviation (SD) increment of serum arginine was independently and positively associated with the risk of colorectal cancer (OR = 1.35, 95% CI: 1.01 to 1.82) in the adjusted analysis.ConclusionWe found that hypertensive individuals with higher serum arginine levels exhibited a higher risk of overall, digestive system, and colorectal cancer.

BackgroundThe status of circulating tumor cells (CTCs) is related to the recurrence of hepatocellular carcinoma (HCC), which is also one of the reasons for the poor prognosis of HCC. The purpose of this study was to explore whether CTCs can help guide the choice of treatment methods for HCC.MethodsThis study is a multicenter retrospective study, including 602 patients with HCC. CTCs were detected in the overall cohort before operation. There were 361 patients in the training cohort and 241 patients in the validation cohort. Patients were divided into CTC-negative group (CTCs = 0/5 mL) and the CTC-positive group (CTCs ≥ 1/5 mL) according to CTCs status. Subgroup analysis was performed according to CTCs status. We compared overall survival, and recurrence outcomes for HCC patients with different CTC statuses after undergoing radiofrequency ablation (RFA) or surgical resection (SR)ResultsThere was no significant difference in overall survival (OS) and recurrence-free survival (RFS) between the RFA group and SR group for CTC-negative patients in both the training cohort and the validation cohort (P > 0.05). However, among CTC-positive patients, the clinical outcome of patients in the SR group was significantly better than those in the RFA group. CTC-positive patients who underwent RFA had increased early recurrence compared to those who underwent SR. RFA is an independent risk factor for survival and recurrence in CTC-positive HCC patientsConclusionsThe CTC status could serve as an indicator to guide the choice between surgical resection or radiofrequency ablation for early hepatocellular carcinoma. Surgical resection is recommended for CTC-positive patients.

Accurate atmospheric temperature and moisture profiles are essential for weather forecasts and research. Satellite-based hyperspectral infrared observations are meaningful in detecting atmospheric profiles, especially over oceans where conventional observations can seldom be used. In this study, a HIRAS (Hyperspectral Infrared Atmospheric Sounder) Atmospheric Sounding System (HASS) was introduced, which retrieves atmospheric temperature and moisture profiles using a one-dimension variational scheme based on HIRAS observations. A total of 274 channels were optimally selected from the entire HIRAS spectrum through information entropy analyses, and a group of retrieval experiments were independently performed for different HIRAS fields of views (FOVs). Compared with the ECMWF reanalysis data version-5 (ERA5), the RMSEs of temperature (relative humidity) for low-, mid-, and high-troposphere layers were 1.5 K (22.3%), 1.0 K (33.2%), and 1.3 K (38.5%), respectively, which were similar in magnitude to those derived from other hyperspectral infrared sounders. Meanwhile, the retrieved temperature RMSEs with respect to the satellite radio occultation (RO) products increased to 1.7 K, 1.8 K, and 1.9 K for the low-, mid-, and high-troposphere layers, respectively, which could be attributed to the accurate RO temperature products in the upper atmospheres. It was also found that the RMSE varied with the FOVs and latitude, which may be caused by the current angle-dependent bias correction and unique background profiles.

Abstract Trap formation is the key indicator of carnivorous lifestyle transition of nematode‐trapping fungi (NTF). Here, the DNA methylation profile was explored during trap induction of Arthrobotrys oligospora, a typical NTF that captures nematodes by developing adhesive networks. Whole‐genome bisulfite sequencing identified 871 methylation sites and 1979 differentially methylated regions (DMRs). This first‐of‐its‐kind investigation unveiled the widespread presence of methylation systems in NTF, and suggested potential regulation of ribosomal RNAs through DNA methylation. Functional analysis indicated DNA methylation's involvement in complex gene regulations during trap induction, impacting multiple biological processes like response to stimulus, transporter activity, cell reproduction and molecular function regulator. These findings provide a glimpse into the important roles of DNA methylation in trap induction and offer new insights for understanding the molecular mechanisms driving carnivorous lifestyle transition of NTF.

The abuse of antibiotics is becoming more serious as antibiotic use has increased. The sulfa antibiotics, sulfamerazine (SM1) and sulfamethoxazole (SMZ), are frequently detected in a wide range of environments. The interaction between SM1/SMZ and bacterial diversity in drinking water was investigated in this study. The results showed that after treatment with SM1 or SMZ at four different concentrations, the microbial community structure of the drinking water changed statistically significantly compared to the blank sample. At the genus level, the proportions of the different bacteria in drinking watermay affect the degradation of the SM1/SMZ. The growth of bacteria in drinking water can be inhibited after the addition of SM1/SMZ, and bacterial community diversity in drinking water declined in this study. Furthermore, the resistance gene sul2 was induced by SM1 in the drinking water. [ABSTRACT FROM AUTHOR]

Therapies for patients with unresectable hepatocellular carcinoma (uHCC) are currently popular. Current first-line standard-of-care treatments for uHCC are systematic therapies. However, treatments that combine locoregional therapy with systemic therapy are widely accepted in China and have demonstrated high rates of tumor response and conversion to resection with manageable toxicity. A literature review was performed by searching published literature in PubMed and Web of Science up to December 2023 for relevant articles on the use of triple therapy (transarterial chemoembolization combined with lenvatinib and anti--PD-1 antibodies) in uHCC. This review concentrates on the efficacy and safety of triple therapy with Chinese characteristics in patients with uHCC and describes the outcome of conversion surgery, degree of pathological necrosis, and effect prediction. This article will contribute to a comprehensive understanding of the role of triple therapy with Chinese characteristics in patients with uHCC. [ABSTRACT FROM AUTHOR]

Summary: Understanding how fungi interact with other organisms has significant medical, environmental, and agricultural implications. Nematode-trapping fungi (NTF) can switch to pathogens by producing various trapping devices to capture nematodes. Here we perform comparative genomic analysis of the NTF with four representative trapping devices. Phylogenomic reconstruction of these NTF suggested an evolutionary trend of trapping device simplification in morphology. Interestingly, trapping device simplification was accompanied by expansion of gene families encoding adhesion proteins and their increasing adhesiveness on trap surfaces. Gene expression analysis revealed a consistent up-regulation of the adhesion genes during their lifestyle transition from saprophytic to nematophagous stages. Our results suggest that the expansion of adhesion genes in NTF genomes and consequential increase in trap surface adhesiveness are likely the key drivers of fungal adaptation in trapping nematodes, providing new insights into understanding mechanisms underlying infection and adaptation of pathogenic fungi.

Nematode-trapping fungi are "carnivorous" and attack their hosts using specialized trapping devices. The morphological development of these traps is the key indicator of their switch from saprophytic to predacious lifestyles. Here, the genome of the nematode-trapping fungus Arthrobotrys oligospora Fres. (ATCC24927) was reported. The genome contains 40.07 Mb assembled sequence with 11,479 predicted genes. Comparative analysis showed that A. oligospora shared many more genes with pathogenic fungi than with non-pathogenic fungi. Specifically, compared to several sequenced ascomycete fungi, the A. oligospora genome has a larger number of pathogenicity-related genes in the subtilisin, cellulase, cellobiohydrolase, and pectinesterase gene families. Searching against the pathogen-host interaction gene database identified 398 homologous genes involved in pathogenicity in other fungi. The analysis of repetitive sequences provided evidence for repeat-induced point mutations in A. oligospora. Proteomic and quantitative PCR (qPCR) analyses revealed that 90 genes were significantly up-regulated at the early stage of trap-formation by nematode extracts and most of these genes were involved in translation, amino acid metabolism, carbohydrate metabolism, cell wall and membrane biogenesis. Based on the combined genomic, proteomic and qPCR data, a model for the formation of nematode trapping device in this fungus was proposed. In this model, multiple fungal signal transduction pathways are activated by its nematode prey to further regulate downstream genes associated with diverse cellular processes such as energy metabolism, biosynthesis of the cell wall and adhesive proteins, cell division, glycerol accumulation and peroxisome biogenesis. This study will facilitate the identification of pathogenicity-related genes and provide a broad foundation for understanding the molecular and evolutionary mechanisms underlying fungi-nematodes interactions.