CLEC6A, (C-type lectin domain family 6, member A), plays a prominent role in regulating innate immunity and adaptive immunity. CLEC6A has shown great potential as a target for cancer immunotherapy. This study aims to explore the prognostic value of CLEC6A, and analyze the relationship associated with the common hematological parameters in breast cancer patients. We performed a retrospective analysis on 183 breast cancer patients data in hospital information system from January 2013 to December 2015. The expression of CLEC6A was recorded via semiquantitative immunohistochemistry in breast cancer. The association between expression of CLEC6A and relative parameters were performed by Chi-square test and Fisher's exact test. Kaplan-Meier assay and Log-rank test were performed to evaluate the survival time. The Cox proportional hazards regression analysis was applied to identify prognostic factors. Nomograms were conducted to predict 1-, 3-, and 5-year disease free survival (DFS) and overall survival (OS) for breast cancer, which could be a good reference in clinical practice. The nomogram model was estimated by calibration curve analysis for its function of discrimination. The accuracy and benefit of the nomogram model were appraised by comparing it to only CLEC6A via decision curve analysis (DCA). The prediction accuracy of CLEC6A was also determined by time-dependent receiver operating characteristics (TDROC) curves, and the area under the curve (AUC) for different survival time. There were 94 cases in the CLEC6A low-expression group and 89 cases in CLEC6A high-expression group. Compared to CLEC6A low-expression group, the CLEC6A high-expression group had better survival (DFS: 56.95 vs. 70.81 months, P = 0.0078 and OS: 67.98 vs. 79.05 months, P = 0.0089). The CLEC6A was a potential prognostic factor in multivariate analysis (DFS: P = 0.023, hazard ratio (HR): 0.454, 95 % confidence interval (CI): 0.229-0.898; OS: P = 0.020, HR: 0.504, 95 %CI: 0.284-0.897). The nomogram in accordance with these potential prognostic factors was constructed to predict survival and the calibration curve analysis had indicated that the predicted line was well-matched with reference line in 1-, 3-, and 5-year DFS and OS category. The 1-, 3-, and 5-year DCA curves have revealed that nomogram model yielded larger net benefits than CLEC6A alone. Finally, the TDROC curve indicated that CLEC6A could better predict 1-year DFS and OS than others. Furthermore, we combined these potential independent prognostic factors to analyze the relationship among these hematologic index and oxidative stress indicators, and indicated that higher CLEC6A level, higher CO2 level or low CHOL level or high HDL-CHO level would have survived longer and better prognosis. In breast cancer, high expression of CLEC6A can independently predict better survival. Our nomogram consisted of CLEC6A and other indicators has good predictive performance and can facilitate clinical decision-making.
Hybrid nanogenerators (HNGs) represent a promising avenue for water energy harvesting, yet their commercial viability faces hurdles such as limited power output, poor coupling, and constrained operational lifespans. Here, a highly coupled triboelectric-electromagnetic magnetic-levitation hybrid nanogenerator (ML-HNG) is introduced that shows great potential for water energy harvesting. The ML-HNG fulfills the challenges of high power output, strong coupling, and long operational lifespans. During the contact-separation process of the triboelectric nanogenerator (TENG), the changing magnetic flux in the electromagnetic generator's coils generates a potential difference between the coils and Cu electrodes. The unique design of the ML-HNG employs a shared coil electrode configuration, which enhances the coupling without adding extra volume. This integration allows the ML-HNG to achieve multi-frequency vibrations and multiple output cycles per external longitudinal movement, a phenomenon known as the frequency multiplication effect. With an average power density of 1.69 W m-3 in water, the ML-HNG provides continuous power for a thermo-hygrometer and can quickly drive a wireless water level alarm system within a minute. This groundbreaking hybrid nanogenerator design holds significant promise for the efficient and consistent harvesting of low-frequency ocean wave energy, marking a substantial advancement in blue energy technology.
INTRODUCTION AND HYPOTHESIS: Catheterization is a common treatment for postpartum urinary retention (PUR); however, its application before diagnosis of PUR remains unclear. The aim was to give an overview of the existing literature on the effectiveness and safety of intrapartum or postpartum catheterization in the prevention of PUR. METHODS: This scoping review followed a methodological framework. PubMed, the Cochrane Library, Embase, Web of Science, the China National Knowledge Infrastructure, WanFang, the China Science and Technology Journal Database, and the China Biomedical Literature Database were searched from the inception of each database to 21 May 2023. RESULTS: The search revealed 16 studies examining three different catheterization methodologies, including 12 intrapartum studies. Ten studies concluded that intrapartum or postpartum catheterization prevented PUR, two of which were only for overt or covert PUR. In 4 out of 13 experimental studies, no significant difference was found: one for intrapartum catheterization versus routine nursing, the other for intrapartum or postpartum intermittent versus indwelling catheterization. However, one found that postpartum disposable catheterization after ineffective targeted care reduced the incidence of PUR compared with indwelling catheterization. One out of the 3 case-control studies concluded that prenatal catheterization ≥2 times was a risk factor for PUR. CONCLUSIONS: Based on the findings in this scoping review, catheterization prior to the diagnosis of PUR appears to play a role in preventing PUR and is safe. Preliminary evidence is accumulating on the effectiveness of three types of catheterization methods in preventing PUR, but more comprehensive studies are needed to establish these findings.
This study aimed to identify characteristic proteins in infantile epileptic spasm syndrome (IESS) patients' plasma, offering insights into potential early diagnostic biomarkers and its underlying causes. Plasma samples were gathered from 60 patients with IESS and 40 healthy controls. Data-independent acquisition proteomic analysis was utilized to identify differentially expressed proteins (DEPs). These DEPs underwent functional annotation through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Gene set enrichment analysis (GSEA) was employed for both GO (GSEA-GO) and KEGG (GSEA-KEGG) analyses to examine the gene expression profiles. Receiver operating characteristic (ROC) curves assessed biomarkers' discriminatory capacity. A total of 124 DEPs were identified in IESS patients' plasma, mainly linked to pathways, encompassing chemokines, cytokines, and oxidative detoxification. GSEA-GO and GSEA-KEGG analyses indicated significant enrichment of genes associated with cell migration, focal adhesion, and phagosome pathways. ROC curve analysis demonstrated that the combination of PRSS1 and ACTB, PRSS3, ACTB, and PRSS1 alone exhibited AUC values exceeding 0.7. This study elucidated the significant contribution of cytokines, chemokines, oxidative detoxification, and phagosomes to the IESS pathogenesis. The combination of PRSS1 and ACTB holds promise as biomarkers for the early diagnosis of IESS.
BACKGROUND: Psilocybin-assisted psychotherapy (PAP) is a promising treatment option for depression, with randomized controlled trials (RCTs) providing preliminary support for its safety and efficacy. However, there is a lack of consistency across existing treatment protocols and psychotherapeutic approaches. The objective of this review is to summarize and compare current psychotherapy methods of PAP in treating depression and distress in life-threatening illnesses. We sought to comprehensively summarize published psychotherapy protocols from clinical trials to provide insights for future practices. METHODS: A systematic search of four databases (Embase, MEDLINE, PsycINFO, CINAHL) for data relating to psychotherapy protocols was conducted by two independent reviewers. RESULTS: In total, our search identified 1869 articles; after removing duplicates, we screened 1107 articles. We included 70 articles in the full-text review and determined that 28 were eligible for the final review. All protocols include sessions before (preparatory) and after (integration) the psychedelic dosing session with supportive monitoring. However, there was substantial variability and inconsistencies in all other aspects of therapy protocols (e.g., duration and number of sessions, model of therapy). Additionally, significant limitations were identified in the frequent need for more clarity in the description of therapeutic approaches. CONCLUSION: In published clinical trials, PAP has consisted of preparation, supportive dosing, and integration sessions. Beyond this basic framework, significant heterogeneity and lack of clarity were identified in reported psychotherapy protocols, meaning a validated and universally agreed upon protocol for PAP currently does not exist. Future studies should more clearly define and report psychotherapeutic components to identify the safest and most efficacious approaches to PAP.
An electrochemical sensor based on porous aromatic cages was reported, which can achieve chiral sensing of DOPA enantiomers. The prepared sensor can achieve a recognition efficiency of up to 2.6 for DOPA enantiomers. The enhanced recognition efficiency could be attributed to the cooperation of intermolecular interactions, and the efficient charge transfer process.
BACKGROUND AND OBJECTIVES: This study aimed to examine the associations between breastfeeding duration and metabolic syndrome (MetS) in adolescents and to further investigate the role of birth weight for gestational age (GA) on these associations. METHODS: A total of 10 275 participants aged 7 to 18 years were included applying multistage cluster random sampling from a Chinese national survey. Birth weight was classified into small for GA (SGA), appropriate for GA (AGA) and large for GA (LGA). Information was collected through a self-administered questionnaire, physical examination and blood biochemical examination. Multivariable linear regression, logistic regression models, restricted cubic spline models were applied to assess the relationships of breastfeeding duration and MetS with different birth weight for GA. RESULTS: The prevalence of non-breastfeeding, 0-5, 6-12 and >12 months groups were 16.2%, 23.1%, 42.5% and 18.2%, and the prevalence of SGA and LGA was 11.9% and 12.7%, respectively. Prolonged breastfeeding duration was associated with higher odds of MetS (ß: 0.08, 95% CI: 0.03, 0.13), WC (ß: 3.49, 95% CI: 2.82, 4.16) and SBP (ß: 2.34, 95% CI: 1.80, 2.89). SGA and prolonged breastfeeding synergistically increased MetS risks, but LGA appeared to offset the adverse effects of prolonged breastfeeding. CONCLUSION: Prolonged breastfeeding may increase children's MetS risks. SGA synergies with prolonged breastfeeding increased MetS burden in children and adolescents, while LGA mitigated the risks. This reminds us that intensive attention should be paid to both early birth weight and subsequent living environment for children and adolescents' lifelong health.
The main rice planting areas in the middle and lower reaches of the Yangtze River are primarily affected by two types of rice seedling diseases: bakanae disease and seedling rot disease. These diseases lead to considerable losses. Seed coating technology effectively protects rice from these diseases and mitigates environmental pollution. We determined the antifungal activity of six fungicides, including phenamacril, azoxystrobin, fludioxonil, metconazole, thifluzamide and prothioconazole against Fusarium moniliforme Sheldon and Curvularia lunata in this study. In addition, the impact of fungicides and surfactants on rice seed germination were determined. Furthermore, phenamacril and fludioxonil were selected as the active components of suspension concentrate for seed coating. The antifungal activity of phenamacril against F. moniliforme Sheldon was 0.139 mg/L and fludioxonil against C. lunata was 0.110 mg/L. PEG-2000 was selected as the surfactant due to its promoting effect on rice seedling. Based on the above findings, 6% phenamacril fludioxonil FS was developed via the wet sand grinding method. The toxicity of 6% phenamacril fludioxonil FS to zebrafish was verified, and field experiments were conducted in five different regions of the Yangtze River Basin. The results indicated minimal toxicity of 6% phenamacril fludioxonil FS to zebrafish. Relative to the control agent consisting of 6.25% phenamacril metalaxyl-M FS, 6% phenamacril fludioxonil FS showed better control effect and exhibited superior efficacy in promoting growth and increasing yield in all five regions. Specifically, the control effect of 6% phenamacril fludioxonil FS on bakanae exceeded 84.83% with the highest yield increasing value recorded at 30.48%. Currently, the market offers a limited selection of suspension concentrate for seed coating of rice. The findings of this study may offer a viable alternative formulation and directions for further research concerning the application of suspension concentrate for seed coating of rice.
BACKGROUND: In Asia, adjuvant chemotherapy after gastrectomy with D2 or more extensive lymph-node dissection is standard treatment for people with pathological stage III gastric or gastro-oesophageal junction (GEJ) cancer. We aimed to assess the efficacy and safety of adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy administered in this setting. METHODS: ATTRACTION-5 was a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial conducted at 96 hospitals in Japan, South Korea, Taiwan, and China. Eligible patients were aged between 20 years and 80 years with histologically confirmed pathological stage IIIA-C gastric or GEJ adenocarcinoma after gastrectomy with D2 or more extensive lymph-node dissection, with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 and available tumour tissue for PD-L1 expression analysis. Patients were randomly assigned (1:1) to receive either nivolumab plus chemotherapy or placebo plus chemotherapy via an interactive web-response system with block sizes of four. Investigational treatment, either nivolumab 360 mg or placebo, was administered intravenously for 30 min once every 3 weeks. Adjuvant chemotherapy was administered as either tegafur-gimeracil-oteracil (S-1) at an initial dose of 40 mg/m2 per dose orally twice per day for 28 consecutive days, followed by 14 days off per cycle, or capecitabine plus oxaliplatin consisting of an initial dose of intravenous oxaliplatin 130 mg/m2 for 2 h every 21 days and capecitabine 1000 mg/m2 per dose orally twice per day for 14 consecutive days, followed by 7 days off treatment. The primary endpoint was relapse-free survival by central assessment. The intention-to-treat population, consisting of all randomly assigned patients, was used for analysis of efficacy endpoints. The safety population, defined as patients who received at least one dose of trial drug, was used for analysis of safety endpoints. This trial is registered with ClinicalTrials.gov (NCT03006705) and is closed. FINDINGS: Between Feb 1, 2017, and Aug 15, 2019, 755 patients were randomly assigned to receive either adjuvant nivolumab plus chemotherapy (n=377) or adjuvant placebo plus chemotherapy (n=378). 267 (71%) of 377 patients in the nivolumab group and 263 (70%) of 378 patients in the placebo group were male; 110 (29%) of 377 patients in the nivolumab group and 115 (31%) of 378 patients in the placebo group were female. 745 patients received assigned treatment (371 in the nivolumab plus chemotherapy group; 374 in the placebo plus chemotherapy group), which was the safety population. Median time from first dose to data cutoff was 49·1 months (IQR 43·1-56·7). 3-year relapse-free survival was 68·4% (95% CI 63·0-73·2) in the nivolumab plus chemotherapy group and 65·3% (59·9-70·2) in the placebo plus chemotherapy group; the hazard ratio for relapse-free survival was 0·90 (95·72% CI 0·69-1·18; p=0·44). Treatment-related adverse events occurred in 366 (99%) of 371 patients in the nivolumab plus chemotherapy group and 364 (98%) of 374 patients in the placebo plus chemotherapy group. Discontinuation due to adverse events was more frequent in the nivolumab plus chemotherapy group (34 [9%] of 371 patients) than the placebo plus chemotherapy group (13 [4%] of 374 patients). The most common treatment-related adverse events were decreased appetite, nausea, diarrhoea, neutrophil count decreased, and peripheral sensory neuropathy. INTERPRETATION: The results of this trial do not support the addition of nivolumab to postoperative adjuvant therapy for patients with untreated, locally advanced, resectable gastric or GEJ cancer. FUNDING: Ono Pharmaceutical and Bristol Myers Squibb.
BACKGROUND: Oxaliplatin- and fluoropyrimidine-based triplet regimens have demonstrated feasibility and efficacy in the treatment of upper gastrointestinal (UGI) cancers. Herein, we evaluate the feasibility and preliminary efficacy of biweekly nab-paclitaxel plus oxaliplatin and S-1/leucovorin (SOLAR) in chemonaïve UGI cancers. METHODS: A 3â +â 3 phase 1 study was conducted to determine the maximal tolerated dose (MTD) of oxaliplatin in SOLAR (nab-paclitaxel [150 mg/m2 in D1], oxaliplatin [60, 75, or 85 mg/m2 in D1], and oral S-1/leucovorin [35 mg/m2 and 30 mg bid from D1 to D7]). The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Thirteen and 6 accruals were in the dose-escalation and MTD expansion cohorts, respectively. One of 6 patients at level III experienced dose-limiting toxicity (grade 3 diarrhea), which revealed that the MTD of oxaliplatin was 85 mg/m2. After a mean of 15.9 cycles of treatment, the most common treatment-related grade 3/4 toxicities were neutropenia (57.9%) and diarrhea (21.1%). The ORR was 63.2%. The median PFS and OS were 12.5 and 24.7 months, respectively. CONCLUSION: The current study revealed the MTD of oxaliplatin and demonstrated the preliminary efficacy of SOLAR in UGI cancers, which deserves further investigation. CLINICALTRIALS.GOV IDENTIFIER: NCT03162510.
BACKGROUND & AIM: Smoking is a major risk factor for multiple gastrointestinal cancers, and adversely affects peptic ulcer disease, gastroesophageal reflux, pancreatitis and Crohn's disease. Despite key recommendations for diagnosing and treating tobacco use disorder in healthcare settings, the degree to which this is implemented in Gastroenterology (GI) clinics is unknown. We aimed to assess our providers' practices, identify barriers for implementing evidence-based smoking cessation treatments, and address these barriers by implementing a novel low-burden point of care Electronic health record-enabled evidence-based tobacco treatment (ELEVATE), in GI clinics. METHODS: An online survey was distributed to clinic gastroenterologists. ELEVATE module training was implemented in 1/2021. Data were evaluated during pre (7/2020-12/2020) and post (1/2021-12/2021) implementation periods to evaluate the reach and effectiveness of ELEVATE. Generalized estimating equations (GEE) were used to generate rate ratios (RR) to evaluate the intervention. RESULTS: 91% (20/22) of GI physicians responded to our survey, and only 20% often assisted patients who smoke with counseling. Lack of a systematic program to offer help to patients was reported by 80% of providers as an extremely/very important barrier limiting their smoking cessation practices. The proportion of current patients who smoke receiving cessation treatment increased from pre-ELEVATE to post-ELEVATE (14.36-27.47%, RR = 1.90, 95% CI 1.60-2.26, p < .001). Post-ELEVATE, 14.4% (38/264) of patients with treatment quit smoking, compared to 7.9% (55/697) of patients without treatment (RR = 1.89, 95% CI 1.26-2.82, p = .0021). CONCLUSION: Smoking practices are frequently assessed in GI clinics but barriers limiting cessation treatment exist. The use of a low burden point of care EHR enabled smoking cessation treatment module has led to a significant improvement in the treatment of smoking and subsequent cessation in our clinics. This study sheds light on an often under-recognized source of morbidity in GI patients and identifies an efficient, effective, and scalable strategy to combat tobacco use and improve clinical outcomes in our patients.
Point-of-Care Systems , Smoking Cessation , Humans , Smoking Cessation/methods , Male , Female , Gastroenterology , Middle Aged , Adult , Surveys and Questionnaires , Electronic Health Records , Practice Patterns, Physicians'/statistics & numerical data , Tobacco Use Disorder/therapy
Isoprenoid metabolism and its derivatives took part in photosynthesis, growth regulation, signal transduction, and plant defense to biotic and abiotic stresses. However, how aluminum (Al) stress affects the isoprenoid metabolism and whether isoprenoid metabolism plays a vital role in the Citrus plants in coping with Al stress remain unclear. In this study, we reported that Al-treatment-induced alternation in the volatilization rate of monoterpenes (α-pinene, ß-pinene, limonene, α-terpinene, γ-terpinene and 3-carene) and isoprene were different between Citrus sinensis (Al-tolerant) and C. grandis (Al-sensitive) leaves. The Al-induced decrease of CO2 assimilation, maximum quantum yield of primary PSII photochemistry (Fv/Fm), the lower contents of glucose and starch, and the lowered activities of enzymes involved in the mevalonic acid (MVA) pathway and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway might account for the different volatilization rate of isoprenoids. Furthermore, the altered transcript levels of genes related to isoprenoid precursors and/or derivatives metabolism, such as geranyl diphosphate (GPP) synthase (GPPS) in GPP biosynthesis, geranylgeranyl diphosphate synthase (GGPPS), chlorophyll synthase (CHS) and GGPP reductase (GGPPR) in chlorophyll biosynthesis, limonene synthase (LS) and α-pinene synthase (APS) in limonene and α-pinene synthesis, respectively, might be responsible for the different contents of corresponding products in C. grandis and C. sinensis. Our data suggested that isoprenoid metabolism was involved in Al tolerance response in Citrus, and the alternation of some branches of isoprenoid metabolism could confer different Al-tolerance to Citrus species.
Aluminum , Bicyclic Monoterpenes , Citrus , Limonene , Photosynthesis , Plant Leaves , Terpenes , Aluminum/toxicity , Terpenes/metabolism , Citrus/metabolism , Citrus/drug effects , Limonene/metabolism , Photosynthesis/drug effects , Bicyclic Monoterpenes/metabolism , Plant Leaves/metabolism , Plant Leaves/drug effects , Stress, Physiological/drug effects , Monoterpenes/metabolism , Hemiterpenes/metabolism , Cyclohexenes/metabolism , Sugar Phosphates/metabolism , Butadienes/metabolism , Erythritol/analogs & derivatives , Erythritol/metabolism , Mevalonic Acid/metabolism , Cyclohexane Monoterpenes , Citrus sinensis/metabolism , Citrus sinensis/drug effects , Citrus sinensis/genetics , Chlorophyll/metabolism , Alkyl and Aryl Transferases/metabolism , Alkyl and Aryl Transferases/genetics , Volatilization
Manganese (Mn) exposure is a common environmental risk factor for Parkinson's disease (PD), with pathogenic mechanisms associated with dopaminergic neuron damage and neuroinflammation. Mesenchymal stem cells (MSCs)-derived small extracellular vesicles (sEVs) have emerged as a novel therapeutic approach for neural damage repair. The functional sEVs released from MSCs when they are induced into dopaminergic progenitors may have a better repair effect on neural injury. Therefore, we collected sEVs obtained from primary human nasal mucosal mesenchymal stem cells (hnmMSC-sEVs) or cells in the process of dopaminergic progenitor cell differentiation (da-hnmMSC-sEVs), which were cultured in a 3D dynamic system, and observed their repair effects and mechanisms of Mn-induced neural damage by intranasal administration of sEVs. In Mn-exposed mice, sEVs could reach the site of brain injury after intranasal administration, da-hnmMSC enhanced the repair effects of sEVs in neural damage and behavioral competence, as evidenced by restoration of motor dysfunction, enhanced neurogenesis, decreased microglia activation, up-regulation of anti-inflammatory factors, and down-regulation of pro-inflammatory factors. The transcriptomics of hnmMSC-sEVs and da-hnmMSC-sEVs revealed that miRNAs, especially miR-494-3p in sEVs were involved in neuroprotective and anti-inflammatory effects. Overexpression of miR-494-3p in sEVs inhibited Mn-induced inflammation and neural injury, and its repair mechanism might be related to the down-regulation of CMPK2 and NLRP3 in vitro experiments. Thus, intranasal delivery of da-hnmMSC-sEVs is an effective strategy for the treatment of neural injury repair.
Cell Differentiation , Dopaminergic Neurons , Extracellular Vesicles , Mesenchymal Stem Cells , MicroRNAs , Nasal Mucosa , Animals , MicroRNAs/genetics , Mice , Humans , Cell Differentiation/drug effects , Dopaminergic Neurons/drug effects , Manganese/toxicity , Male , Administration, Intranasal , Cells, Cultured , Mice, Inbred C57BL
Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.
Background: The triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women. Methods: This cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer. Results: Multivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19-2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13-17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09-1.68), 1.27 (1.05-1.54), 1.26 (1.05-1.52), and 1.32 (1.08-1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44-3.87). Conclusion: The TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.
Blood Glucose , Breast Neoplasms , Triglycerides , Humans , Female , Breast Neoplasms/blood , Breast Neoplasms/epidemiology , Middle Aged , Triglycerides/blood , Cross-Sectional Studies , China/epidemiology , Adult , Blood Glucose/analysis , Blood Glucose/metabolism , Aged , Risk Factors , Longitudinal Studies , East Asian People
Importance: It is unclear whether cannabis use is associated with adverse health outcomes in patients with COVID-19 when accounting for known risk factors, including tobacco use. Objective: To examine whether cannabis and tobacco use are associated with adverse health outcomes from COVID-19 in the context of other known risk factors. Design, Setting, and Participants: This retrospective cohort study used electronic health record data from February 1, 2020, to January 31, 2022. This study included patients who were identified as having COVID-19 during at least 1 medical visit at a large academic medical center in the Midwest US. Exposures: Current cannabis use and tobacco smoking, as documented in the medical encounter. Main Outcomes and Measures: Health outcomes of hospitalization, intensive care unit (ICU) admission, and all-cause mortality following COVID-19 infection. The association between substance use (cannabis and tobacco) and these COVID-19 outcomes was assessed using multivariable modeling. Results: A total of 72â¯501 patients with COVID-19 were included (mean [SD] age, 48.9 [19.3] years; 43â¯315 [59.7%] female; 9710 [13.4%] had current smoking; 17â¯654 [24.4%] had former smoking; and 7060 [9.7%] had current use of cannabis). Current tobacco smoking was significantly associated with increased risk of hospitalization (odds ratio [OR], 1.72; 95% CI, 1.62-1.82; P < .001), ICU admission (OR, 1.22; 95% CI, 1.10-1.34; P < .001), and all-cause mortality (OR, 1.37, 95% CI, 1.20-1.57; P < .001) after adjusting for other factors. Cannabis use was significantly associated with increased risk of hospitalization (OR, 1.80; 95% CI, 1.68-1.93; P < .001) and ICU admission (OR, 1.27; 95% CI, 1.14-1.41; P < .001) but not with all-cause mortality (OR, 0.97; 95% CI, 0.82-1.14, P = .69) after adjusting for tobacco smoking, vaccination, comorbidity, diagnosis date, and demographic factors. Conclusions and Relevance: The findings of this cohort study suggest that cannabis use may be an independent risk factor for COVID-19-related complications, even after considering cigarette smoking, vaccination status, comorbidities, and other risk factors.
COVID-19 , Hospitalization , Intensive Care Units , SARS-CoV-2 , Humans , COVID-19/mortality , COVID-19/epidemiology , Female , Male , Middle Aged , Retrospective Studies , Hospitalization/statistics & numerical data , Adult , Risk Factors , Intensive Care Units/statistics & numerical data , Aged , Tobacco Use/adverse effects , Tobacco Use/epidemiology , Tobacco Smoking/adverse effects , Tobacco Smoking/epidemiology , Marijuana Smoking/epidemiology , Marijuana Smoking/adverse effects
Clarifying current situation of farmers' fertilization and yield in citrus producing areas and the effects of different fertilization measures can provide a scientific basis for improving the yield and quality of citrus in China. We retrieved 92 literatures on citrus fertilization from the CNKI and Web of Science to examine the impacts of nitrogen (N), phosphorus (P or P2O5), and potassium (K or K2O) fertilizer dosage and partial productivity under farmers' conventional fertilization and experts' optimized fertilization, as well as the effects of optimized fertilization measures on citrus yield and quality by using meta-analysis approach. The average conventional application rates of N, P2O5, and K2O were 507.3, 262.2, and 369.3 kg·hm-2 in citrus production in China. Compared with conventional fertilization, optimized fertilization resulted in a reduction of N and P2O5 by 14.7% and 8.3%, an increase in K2O application by 6.6%, which promoted partial productivity of N, P2O5, and K2O fertilizers by 7.8%, 18.4%, and 14.7%, correspondingly. The optimized fertilization resulted in 11.9% and 2.8% increase in fruit yield and single fruit weight, while improved vitamin C content (Vc, 3.1%), total soluble solids (TSS, 5.9%) and total sugar content (TSC, 8.6%). Additionally, it also led to a reduction in titratable acid (TA, -3.4%) and total acid content (TAC, -3.6%), and consequently elevated the TSS/TA (14.0%) and TSC/TAC (9.5%). Among different optimized fertilization methods, the effect of optimized NPK + medium and/or micro element fertilizer on citrus yield and fruit quality was the best, especially NPK decrement ≤25% between optimized NPK measures. The effect of conventional NPK + organic fertilizer was higher than conventional NPK + medium and/or micro element fertilizer. However, different citrus varieties, including mandarins, pomelos, and oranges, showed different responses to optimized fertilization. Optimized fertilization management could synergistically improve citrus yield, fertilizer use efficiency, and fruit quality. Therefore, the strategy of integrated nutrient management1 with reducing NPK fertilizer, balancing medium and/or micro nutrient fertilizer and improving soil fertility by organic fertilizer should be adopted according to local conditions in citrus producing areas of China.
Citrus , Fertilizers , Fruit , Nitrogen , Phosphorus , Fertilizers/analysis , Citrus/growth & development , China , Phosphorus/analysis , Nitrogen/analysis , Fruit/growth & development , Fruit/chemistry , Nutrients/analysis , Agriculture/methods , Potassium/analysis , Biomass , Crop Production/methods
The Wnt/ß-catenin signaling pathway plays a crucial role in various physiological processes, encompassing development, tissue homeostasis, and cell proliferation. Under normal physiological conditions, the Wnt/ß-catenin signaling pathway is meticulously regulated. However, aberrant activation of this pathway and downstream target genes can occur due to mutations in key components of the Wnt/ß-catenin pathway, epigenetic modifications, and crosstalk with other signaling pathways. Consequently, these dysregulations contribute significantly to tumor initiation and progression. Therapies targeting the Wnt/ß-catenin signaling transduction have exhibited promising prospects and potential for tumor treatment. An increasing number of medications targeting this pathway are continuously being developed and validated. This comprehensive review aims to summarize the latest advances in our understanding of the role played by the Wnt/ß-catenin signaling pathway in carcinogenesis and targeted therapy, providing valuable insights into acknowledging current opportunities and challenges associated with targeting this signaling pathway in cancer research and treatment.
Carcinogenesis , Neoplasms , Wnt Signaling Pathway , Humans , Wnt Signaling Pathway/drug effects , Neoplasms/metabolism , Neoplasms/drug therapy , Neoplasms/genetics , Carcinogenesis/genetics , Carcinogenesis/metabolism , Animals , beta Catenin/metabolism , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Molecular Targeted Therapy/methods
CrRLK1L subfamily members are involved in diverse growth- and development-related processes in Arabidopsis. However, the functions of their counterparts in rice are unknown. Here, OsANX expression was detected in developing inflorescences, mature pollen grains, and growing pollen tubes, and it was localized to the plasma membrane in pollen grains and tobacco epidermal cells. Homozygous osanx progeny could not be segregated from the CRISPR/Cas9-edited mutants osanx-c1+/- and osanx-c2+/-, and such progeny were segregated only occasionally from osanx-c3+/-. Further, all three alleles showed osanx male but not female gamete transmission defects, in line with premature pollen tube rupture in osanx-c3. Additionally, osanx-c3 exhibited precocious flowering, excessively branched inflorescences, and an extremely low seed setting rate of 1.4â¯%, while osanx-c2+/- and osanx-c3+/- had no obvious defects in inflorescence development or the seed setting rate compared to wild-type Nipponbare (Nip). Consistent with this, the complemented line pPS1:OsANX-GFP/osanx-c2 (PSC), in which the lack of OsANX expression was inflorescence-specific, showed slightly earlier flowering and overly-branched panicles. Multiple inflorescence meristem transition-related and inflorescence architecture-related genes were expressed at higher levels in osanx-c3 than in Nip; thus, they may partially account for the aforementioned mutant phenotypes. Our findings broaden our understanding of the biological functions of OsANX in rice.
