Search

Abstract Background Hepatitis B virus (HBV) infection can exacerbate liver disease progression through multiple mechanisms, eventually leading to hepatocellular carcinoma (HCC). HBV-encoded oncogene X protein (HBx), a key regulatory protein of HBV infection, serves as a positive regulator of hepatocarcinogenesis. The indispensability of the M2 subunit of ribonucleotide-diphosphate reductase (RRM2) lies in its role in facilitating DNA replication and repair processes. In our previous investigation, it was postulated that the gene RRM2 exhibits elevated expression levels in several categories of malignant tumors, particularly in HBV-related HCC. Additionally, it was observed that RRM2 is present within protein complexes that are centered on HBx. In the present investigation, the objective of this work was to investigate the potential relationship between the elevated expression of RRM2 in HBV-related HCC and the influence of HBx on this expression. The study attempted to determine the specific mechanism by which RRM2 is implicated in the promotion of hepatocarcinogenesis by HBx. There have been multiple scholarly proposals suggesting that the induction of autophagy by HBx is a significant intermediary factor in the development of HCC. However, the precise carcinogenic function of HBx-induced autophagy remains a subject of debate. Results This work initially investigated the impact of suppressing cellular autophagy on the malignant biological behaviors of HBx-promoted cells using an in vitro cellular model. The findings revealed that the suppression of cellular autophagy partially disrupted the oncogenic effects of HBx. In light of this, we proceeded to conduct more investigations into the regulatory association between RRM2 and HBx-induced autophagy in the upstream-downstream context. Our data indicate that HBx proteins increase the expression of RRM2. Suppression of RRM2 expression not only hinders HBx-induced autophagy, but also worsens the cellular G1/S blockage and reduces the HBx-induced malignant growth of hepatocellular carcinoma tumors, while stimulating apoptosis. Conclusions Therefore, we hypothesised that RRM2 is a potential downstream target of HBx-induced hepatocarcinogenesis, and mining the oncogenic mechanism of RRM2 is significant in exploring the preventive treatment of HBV-related HCC.

Abstract Objectives This study aimed to compare plasma concentrations of anesthetic drugs administered during Cesarean section with low Apgar score in neonates deliveried under general anesthesia and analyze associated risk factors. Methods Data from 76 neonates undergoing Cesarean section under general anesthesia with blood concentrations of anesthetic drugs were analyzed. A low Apgar score was defined as ≤ 7. Perioperative maternal and neonatal data were collected and analyzed. Neonates were divided into a control group (Group CON, n = 65) and a low Apgar score group (Group LAS, n = 11) based on Apgar score. Results There were no significant differences in the plasma concentrations of anesthetic drugs in maternal artery, umbilical vein or umbilical artery blood between the two groups. Risk factors for neonatal low Apgar scores during Cesarean section under general anesthesia were premature delivery (aOR 10.2, 95% CI = 1.8–56.9) and preoperative fetal distress (aOR 9.6, 95% CI = 1.3–69.0). The prediction model was: probability = 1/(e‑Y), Y= -4.607 + 2.318× (premature delivery) + 2.261× (fetal distress) (yes = 1, no = 0). The Hosmer–Lemeshow test showed χ²= 9.587, P = 0.213, and the area under the curve (AUC) was 0.850 (0.670 ~ 1.000). With a cutoff value of 0.695, sensitivity and specificity were 81.8% and 87.7%, respectively. Conclusions There was no correlation between blood concentration of general anesthetic drugs and Apgar score or occurrence of neonatal low Apgar scores. Premature delivery and preoperative fetal distress were identified as independent risk factors for neonatal low Apgar scores after Cesarean section under general anesthesia.

Abstract The heterogeneous molecular subtypes of gliomas demonstrate varied responses to chemotherapy and distinct prognostic outcomes. Gliomas with Isocitrate dehydrogenase 1 (IDH1) mutation are associated with better outcomes and are more responsive to temozolomide (TMZ) compared to those without IDH1 mutation. IDH1-mutant gliomas elevate D-2-hydroxyglutarate (D-2HG) levels, with potential dual effects on tumor progression. Limited research has explored the potential anti-glioma effects of D-2HG in combination with TMZ. Clinical data from over 2500 glioma patients in our study confirms that those with IDH1 mutations exhibit enhanced responsiveness to TMZ chemotherapy and a significantly better prognosis compared to IDH1 wild-type patients. In subsequent cellular experiments, we found that the IDH1-mutant metabolite D-2HG suppresses Integrin subunit beta 4 (ITGB4) expression, and down-regulate the phosphorylation levels of PI3K and AKT, ultimately inhibiting cell proliferation while promoting apoptosis, thereby improving glioma prognosis. Additionally, we have demonstrated the synergistic effect of D-2HG and TMZ in anti-glioma therapy involved inhibiting the proliferation of glioma cells and promoting apoptosis. Finally, by integrating data from the CGGA and TCGA databases, it was validated that ITGB4 expression was lower in IDH1-mutant gliomas, and patients with lower ITGB4 expression were associated with better prognosis. These findings indicate that ITGB4 may be a promising therapeutic target for gliomas and D-2HG inhibits proliferation and sensitizes glioma to temozolomide via down-regulating ITGB4/PI3K/AKT. These findings drive theoretical innovation and research progress in glioma therapy.

ABSTRACT Objectives Despite high levels of mental ill‐health amongst young people (aged 15–30), this group demonstrates low help‐seeking and high drop‐out from mental health services (MHS). Whilst shared decision‐making can assist people in receiving appropriate and effective health care, young people frequently report that they do not feel involved in treatment decisions. The current study focused on co‐design of a clinical education and participant information programme for the Brain and Mind Centre Youth Model of Care. This model, which articulates a youth‐focused form of highly personalised and measurement‐based care, is designed to promote shared decision‐making between young people and clinical service providers. Methods We conducted workshops with 24 young people (16–31; MAge = 21.5) who had accessed mental health services. Participants were asked what advice they would give to young people entering services, before giving advice on existing materials. Workshops were conducted and transcripts were coded using thematic analysis by two lived experience researchers and a clinical researcher. Results Young people found it empowering to be educated on transdiagnostic models of mental illness, namely clinical staging, which gives them a better understanding of why certain treatments may be inappropriate and ineffective, and thus reduce self‐blame. Similarly, young people had limited knowledge of links between mental health and other life domains and found it helpful to be educated on multidisciplinary treatment options. Measurement‐based care was seen as an important method of improving shared decision‐making between young people and health professionals; however, to facilitate shared decision‐making, young people also wanted better information on their rights in care and more support to share their expertise in their own needs, values and treatment preferences. Conclusions These findings will inform the delivery of the further development and implementation of a youth‐specific clinical education and participant information programme for the BMC Youth Model. Patient or Public Contribution Workshops were facilitated by researchers with lived expertise in mental ill‐health (A.H. and/or C.G.) and a clinical researcher (who has expertise as an academic and a clinical psychologist). A.H. and C.G. were also involved in conceptualisation, analysis, interpretation, review and editing of this paper.

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.

In recent years, with the development of power battery technology, an increasing number of manufacturers have favored lithium batteries as forklift power sources. However, there has been a lack of relevant research on the safety performance of lithium batteries for forklifts, especially on the nondestructive inspection of faulty batteries, which is rarely performed. Therefore, this study adopted high-resolution industrial computed tomography (CT) to study faulty lithium batteries for forklifts, scanning the internal structure and analyzing the relationship between the performance attenuation of the lithium battery and the internal structure, thereby combining with the charging and discharging conditions, to provide a solution for the nondestructive inspection of lithium batteries in forklifts.

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 Few studies have been designed to investigate the effect of serum choline on the risk of incident cancer. This study aims to explore the association between serum choline and the risk of new-onset cancer. We conducted a case–control study, including 199 patients with incident cancer and 199 matched controls during a median of 3.9 years of follow-up, nested within the China Stroke Primary Prevention Trial. Cubic spline regression (RCS) and conditional logistic regression analysis was used to assess the association of serum choline and incident cancer risk. We observed a positive dose–response association between serum choline levels and the risk of overall (p for overall = 0.046) and digestive system cancer (p for overall = 0.039). Compared with patients with the lowest choline levels (Q1 group), patients in the highest levels of choline (Q4) had a 3.69-fold and 6.01-fold increased risk of overall (OR = 3.69, 95% CI 1.17–11.63) and digestive system cancer (OR = 6.01, 95% CI 1.14–31.67). Elevated choline levels (per SD, 11.49 μg/mL) were associated with a higher risk of overall cancer among participants who were older, male, and smokers in the subgroup analyses. We found a positive association between elevated levels of serum choline with increased risk of incident cancer. Our findings have critical clinical implications for cancer prevention and diagnosis. Trial registration CSPPT, NCT00794885. Registered: November 20, 2008. https://www.clinicaltrials.gov/ct2/show/study/NCT00794885 https://www.clinicaltrials.gov/ct2/show/study/NCT00794885.

Abstract Background Forsythia suspensa (Thunb.) Vahl is a valuable ornamental and medicinal plant. Although the nuclear and chloroplast genomes of F. suspensa have been published, its complete mitochondrial genome sequence has yet to be reported. In this study, the genomic DNA of F. suspensa yellowish leaf material was extracted, sequenced by using a mixture of Illumina Novaseq6000 short reads and Oxford Nanopore PromethION long reads, and the sequencing data were assembled and annotated. Result The F. suspensa mitochondrial genome was obtained in the length of 535,692 bp with a circular structure, and the GC content was 44.90%. The genome contains 60 genes, including 36 protein-coding genes, 21 tRNA genes, and three rRNA genes. We further analyzed RNA editing of the protein-coding genes, relative synonymous codon usage, and sequence repeats based on the genomic data. There were 25 homologous sequences between F. suspensa mitochondria and chloroplast genome, which involved the transfer of 8 mitochondrial genes, and 9473 homologous sequences between mitochondrial and nuclear genomes. Analysis of the nucleic acid substitution rate, nucleic acid diversity, and collinearity of protein-coding genes of the F. suspensa mitochondrial genome revealed that the majority of genes may have undergone purifying selection, exhibiting a slower rate of evolution and a relatively conserved structure. Analysis of the phylogenetic relationships among different species revealed that F. suspensa was most closely related to Olea europaea subsp. Europaea. Conclusion In this study, we sequenced, assembled, and annotated a high-quality F. suspensa mitochondrial genome. The results of this study will enrich the mitochondrial genome data of Forsythia, lay a foundation for the phylogenetic development of Forsythia, and promote the evolutionary analysis of Oleaceae species.

Abstract Regulating electron transport rate and ion concentrations in the local microenvironment of active site can overcome the slow kinetics and unfavorable thermodynamics of CO2 electroreduction. However, simultaneous optimization of both kinetics and thermodynamics is hindered by synthetic constraints and poor mechanistic understanding. Here we leverage laser-assisted manufacturing for synthesizing CuxO bipyramids with controlled tip angles and abundant nanograins, and elucidate the mechanism of the relationship between electron transport/ion concentrations and electrocatalytic performance. Potassium/OH− adsorption tests and finite element simulations corroborate the contributions from strong electric field at the sharp tip. In situ Fourier transform infrared spectrometry and differential electrochemical mass spectrometry unveil the dynamic evolution of critical *CO/*OCCOH intermediates and product profiles, complemented with theoretical calculations that elucidate the thermodynamic contributions from improved coupling at the Cu+/Cu2+ interfaces. Through modulating the electron transport and ion concentrations, we achieve high Faradaic efficiency of 81% at ~900 mA cm−2 for C2+ products via CO2RR. Similar enhancement is also observed for nitrate reduction reaction (NITRR), achieving 81.83 mg h−1 ammonia yield rate per milligram catalyst. Coupling the CO2RR and NITRR systems demonstrates the potential for valorizing flue gases and nitrate wastes, which suggests a practical approach for carbon-nitrogen cycling.

Background: Systemic immune-inflammation index (SII) is a novel biomarker of growing interest in predicting stroke. The aim of this study was to investigate its predictive value and explore its effect modification on folic acid supplement for stroke primary prevention in a Chinese population with hypertension. Methods: A total of 10,013 participants from the China Stroke Primary Prevention Trial with available neutrophil, platelet and lymphocyte count were included, including 5,019 subjects in the enalapril group and 4,994 in the enalapril-folic acid group. SII was calculated as (platelet × neutrophil)/lymphocyte. The primary endpoint was first stroke. Cox proportional hazards models were used to evaluate the association between SII and first stroke. Results: A U-shape association between SII and first stroke risk was observed in enalapril group. Compared with the reference group (Quartile 2: 335.1 to

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

The maintenance of the root stem cell niche identity in Arabidopsis relies on the delicate balance of reactive oxygen species (ROS) levels in root tips; however, the intricate molecular mechanisms governing ROS homeostasis within the root stem cell niche remain unclear. In this study, we unveil the role of ATP hydrolase superfamily protein 1 (ASP1) in orchestrating root stem cell niche maintenance through its interaction with the redox regulator cystathionine β-synthase domain-containing protein 3 (CBSX3). ASP1 is exclusively expressed in the quiescent center (QC) cells and governs the integrity of the root stem cell niche. Loss of ASP1 function leads to enhanced QC cell division and distal stem cell differentiation, attributable to reduced ROS levels and diminished expression of SCARECROW and SHORT ROOT in root tips. Our findings illuminate the pivotal role of ASP1 in regulating ROS signaling to maintain root stem cell niche homeostasis, achieved through direct interaction with CBSX3.

Abstract We studied the effectiveness of movie character analysis for teaching psychotic symptomatology to medical undergraduates. We randomly selected two of six medical schools in Shandong Province, China, then randomly assigned eight undergraduate classes at those schools to intervention or control groups. The intervention group (n = 162) participated in seminars in which psychotic symptoms were explored through analysis of movie characters. The control group (n = 165) participated in conventional seminars. The participants in both groups were surveyed with a custom-designed questionnaire, and their knowledge was assessed using a written exam. Compared to the control group, the intervention group showed greater interest in the topic (t = 5.63, p

Background Little is known about the relationship between sleep quality and lung cancer incidence. Thus, this study was conducted to investigate the potential connection between sleep quality and lung cancer incidence. Methods We performed and selected a nested case–control study that included 150 lung cancer cases and 150 matched controls based on the Lianyungang cohort. Univariate and multivariate logistic regression was utilized to investigate the connection between potential risk factors and lung cancer incidence risk. Results In this study, the average age of participants was 66.5 ± 9.1 years, with 58.7% being male, and 52.7% reportedly experiencing sleep quality problems. The results of multivariate logistic regression showed that poor sleep quality was connected to an increased lung cancer incidence risk (P = 0.033, odds ratio = 1.83, 95% confidence interval = [1.05–3.19]) compared with those with good sleep quality. The stratified analyses showed a significantly positive connection between poor sleep quality (vs. good sleep quality) and cancer risk in smokers (vs. non-smoker, P for interaction = 0.085). The combined effect analysis indicated that smokers with poor sleep quality suffered from a 2.79-fold increase in cancer incidence rates when compared with non-smokers with good sleep quality. Conclusions Poor sleep quality was positively connected to an increased lung cancer incidence risk. In addition, among those individuals with poor sleep quality, smoking increased the lung cancer incidence risk.

Abstract All‐solid‐state sodium‐ion batteries have the potential to improve safety and mitigate the cost bottlenecks of the current lithium‐ion battery system if a high‐performance electrolyte with cost advantages can be easily synthesized. In this study, a one‐step dehydrogenation‐assisted strategy to synthesize the novel thio‐borohydride (Na‐B‐H‐S) electrolyte is proposed, in which both raw material cost and preparation temperature are significantly reduced. By using sodium borohydride (NaBH4) instead of B as a starting material, B atoms can be readily released from NaBH4 with much less energy and thus became more available to generate thio‐borohydride. The synthesized Na‐B‐H‐S (NaBH4/Na‐B‐S) electrolyte exhibits excellent compatibility with current cathode materials, including FeF3 (1.0–4.5 V), Na3V2(PO4)3 (2.0–4.0 V), and S (1.2–2.8 V). This novel Na‐B‐H‐S electrolyte will take a place in mainstream electrolytes because of its advantages in preparation, cost, and compatibility with various cathode materials.

Background: The association between changes in estimated glomerular filtration rate (eGFR) over time and the risk of stroke remains inconclusive. We aimed to evaluate the relation of eGFR change during the China Stroke Primary Prevention Trial (CSPPT) with the risk of first stroke during the subsequent post-trial follow-up. Methods: A total of 11,742 hypertensive participants with two eGFR measurements (median measure interval, 4.4; interquartile range, 4.2–4.6 years) and without a history of stroke from the CSPPT were included in this analysis. Results: Over a median post-trial follow-up of 4.4 years, 729 first strokes were identified, of which 635 were ischemic, 88 were hemorrhagic, and 6 were uncertain types of strokes. Compared with those with 1 to

The Main protease of SARS-CoV-2 is key for viral replication, but its maturation process is still not completely understood. Here, the authors not only reveal unique details from the first step of maturation, but also demonstrate how different classes of inhibitor can block this step.

Abstract Background Airway epithelium is the first barrier against environmental insults, and epithelial barrier dysfunction caused by cigarette smoke (CS) is particularly relevant to chronic obstructive pulmonary disease (COPD) progression. Our study was to determine whether Azithromycin (AZI) ameliorates CS-induced airway epithelial barrier dysfunction and the underlying mechanisms. Methods Primary bronchial epithelial cells (PBECs), human bronchial epithelial cells (HBECs), Sprague Dawley rats and nuclear factor erythroid 2-related factor 2 (Nrf2)−/− mice were pretreated with AZI and subsequently exposed to CS. Transepithelial electronic resistance (TEER), junction proteins as well as pro-inflammatory cytokines and apoptosis markers were examined to assess epithelial barrier dysfunction. Metabolomics study was applied to explore the underlying mechanism of AZI. Results CS-induced TEER decline and intercellular junction destruction, accompanied with inflammatory response and cell apoptosis in PBECs were restored by AZI dose-dependently, which were also observed in CS-exposed rats. Mechanistically, GSH metabolism pathway was identified as the top differentially impacted pathway and AZI treatment upregulated the activities of glutamate cysteine ligase (GCL) and the contents of metabolites in GSH metabolic pathway. Furthermore, AZI apparently reversed CS-induced Nrf2 suppression, and similar effects on airway epithelial barrier dysfunction were also found for Nrf2 agonist tert-butylhydroquinone and vitamin C. Finally, deletion of Nrf2 in both HBECs and C57BL/6N mice aggravated CS-induced GSH metabolism imbalance to disrupt airway epithelial barrier and partially deprived the effects of AZI. Conclusion These findings suggest that the clinical benefits of AZI for COPD management are related with the protection of CS-induced airway epithelial barrier dysfunction via activating Nrf2/GCL/GSH pathway, providing potential therapeutic strategies for COPD. Graphical abstract

We systematically investigate the strain-engineered magnon states in two-dimensional (2D) ferromagnetic monolayers. By suitable engineering of an inhomogeneous strain, we demonstrate the emergence of magnon Landau levels and magnon snake states in 2D ferromagnetic monolayers. We show a magnon valley Hall effect and valley filter without relying on any external fields. Our proposal offers us another way to manipulate magnon valley transport and construct different types of flexible spintronic devices, and is experimentally feasible for 2D ferromagnetic materials by using state-of-art techniques.

BackgroundIron is an essential element for organismal health but excessive iron is potentially toxic. However, few observational studies link plasma iron (PI) concentrations and cancer risk, and the results are inconsistent.ObjectiveThis study aimed to explore the associations of PI concentrations with cancer risk in Chinese adults with hypertension.MethodsWe conducted a nested, case-control study, including 223 pairs of incident cancer cases and matched controls from the China Stroke Primary Prevention Trial. The median time between blood sample collection and subsequent cancer event occurrence was 2.13 years. The odds ratio (OR) and 95% confidence interval (CI) for the risk of cancer by PI were estimated from multivariable conditional logistic regression models.ResultsThere was a nonlinear association between PI concentrations and total cancer risk. When compared with participants in tertile 2 of PI, the ORs of total cancer were 2.17 (95%CI: 1.25-3.85) and 1.29 (95%CI: 0.77-2.19) in participants in PI tertiles 3 and 1, respectively. Furthermore, higher PI was associated with increased digestive system cancer risk (OR=3.25, 95%CI:1.29-8.90), while lower PI was associated with increased risk of non-digestive system cancer (OR=3.32, 95%CI: 1.39-8.71). In a sensitivity analysis, the increases in total cancer risk or digestive system cancer risk were still observed with higher PI after excluding cancer cases occurring within the first year.ConclusionOur results showed an increased risk of cancer related to higher PI or lower PI in Chinese adults with hypertension. Higher iron levels were linked to an increased risk of digestive system cancers, whereas lower iron levels were linked to an increased risk of non-digestive system cancers.

BackgroundThere is growing concern regarding elevated levels of circulating unmetabolized folic acid (UMFA) due to excessive intake of folic acid (FA). However, no randomized clinical trial has been conducted to examine the FA-UMFA dose-response relationship.ObjectiveThis study aimed to investigate the FA-UMFA dose-response relationship in Chinese adults with hypertension and elevated homocysteine (H-type hypertension), a population with clear clinical indication for FA treatment.MethodsThe data for this study were derived from a randomized, double-blind, multicenter clinical trial of 8 FA dosages on efficacy of homocysteine (Hcy) lowering. The parent trial had three 3 stages: screening period (2–10 days), run-in period (0–2 weeks, baseline visit), and double-blind treatment period (8 weeks) with follow-up visits at the end of the 2nd, 4th, 6th, and 8th weeks of treatment. Participants were randomly assigned to 8 treatment groups corresponding to FA dosages of 0, 0.4, 0.6, 0.8, 1.2, 1.6, 2.0 mg to 2.4 mg.ResultsThis study included 1,567 Chinese adults aged ≥45 years with H-type hypertension. There was a positive but non-linear association between FA supplementation and UMFA levels in the dosage range of 0 mg to 2.4 mg. In the regression analysis, the coefficients for the linear and quadratic terms of FA dosage were both statistically significant (P < 0.001). Notably, the slope for UMFA was greater for FA dosages >0.8 mg (ß = 11.21, 95% CI: 8.97, 13.45) compared to FA dosages ≤0.8 mg (ß = 2.94, 95% CI: 2.59, 3.29). Furthermore, FA dosages higher than 0.8 mg did not confer additional benefits in terms of increasing 5-methyl tetrahydrofolic acid (5-MTHF, active form of folate) or reducing homocysteine (Hcy).ConclusionIn Chinese adults with H-type hypertension, this study showed a positive, non-linear, dosage-response relationship between FA supplementation ranging from 0 to 2.4 mg and circulating UMFA levels. It revealed that 0.8 mg FA is an optimal dosage in terms of balancing efficacy (increasing 5-MTHF and lowering Hcy) while minimizing undesirable elevation of UMFA.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03472508?term=NCT03472508&draw=2&rank=1, identifier NCT03472508.

ObjectiveIt was unknown whether a regimen of aspirin plus ticagrelor (aspirin-ticagrelor) attenuates ischemic vascular events without increasing bleeding risk in patients who had undergone intracranial stenting compared with an aspirin plus clopidogrel (aspirin-clopidogrel) regimen. This article compares the efficacy and safety outcomes of the two double antibody regimens in patients undergoing intracranial stent and investigates whether aspirin-ticagrelor could be an alternative antiplatelet agent without increasing the risk of bleeding.MethodsWe conducted a retrospective analysis of our database for patients who had undergone intracranial stenting. From January 2017 to May 2021, consecutive patients treated with endovascular stenting were identified and dichotomized by whether aspirin-ticagrelor or aspirin-clopidogrel were used. The outcomes were compared by propensity score matching.ResultsA total of 340 patients treated with intracranial stent were included. Of all, 132 patients were matched. At 180 days, ischemic vascular events occurred in one patient (1.5%) in the aspirin-ticagrelor group and in six patients (9.1%) in the aspirin-clopidogrel group. Although the absolute incidence of ischemic vascular events [1.5% (1/66) vs. 9.1% (6/66), p = 0.125] was lower in the aspirin-ticagrelor group than in the aspirin-clopidogrel group, there were no statistical differences. There were no statistical differences in ischemic vascular events, ischemic stroke, or death up to 180 days between the two groups. In addition, the incidence of bleeding did not differ. No intracranial hemorrhage or mild bleeding occurred. No statistically significant difference was noted in restenosis and symptomatic restenosis at follow-up.ConclusionIn our study involving patients with acute ischemic stroke who had undergone intracranial stenting, aspirin-ticagrelor was not found to be superior to aspirin-clopidogrel in reducing the rate of ischemic vascular events. The risk of bleeding did not differ between the two groups. Aspirin-ticagrelor does not lower total restenosis and symptomatic restenosis risk at follow-up.

Pyelolymphatic backflow is a rare type of pyelolymphatic fistula that occurs in cases of urinary obstruction. This phenomenon may help to decompress an acutely obstructed kidney, and therefore, alleviate renal function from deteriorating. Pyelolymphatic backflow has specific imaging characteristics best shown on CT urography. Our case study aims to improve the understanding and diagnosis of pyelolymphatic backflow by presenting a case of pyelolymphatic backflow seen on CT urography, including discussions on the pathophysiology, clinical relevance and management of this phenomenon. Our case study demonstrates the opacification of landmark lymphatic structures including the retroperitoneal para-aortic lymphatic chain, cisterna chyli and thoracic duct, which have not been demonstrated previously.

Abstract Background Bupleurum chinense(B. chinense) is a plant that is widely distributed globally and has strong pharmacological effects. Though the chloroplast(cp) genome of B. chinense has been studied, no reports regarding the mitochondrial(mt) genome of B. chinense have been published yet. Results The mt genome of B.chinense was assembled and functionally annotated. The circular mt genome of B. chinense was 435,023 bp in length, and 78 genes, including 39 protein-coding genes, 35 tRNA genes, and 4 rRNA genes, were annotated. Repeat sequences were analyzed and sites at which RNA editing would occur were predicted. Gene migration was observed to occur between the mt and cp genomes of B. chinense via the detection of homologous gene fragments. In addition, the sizes of plant mt genomes and their GC content were analyzed and compared. The sizes of mt genomes of plants varied greatly, but their GC content was conserved to a greater extent during evolution. Ka/Ks analysis was based on code substitutions, and the results showed that most of the coding genes were negatively selected. This indicates that mt genes were conserved during evolution. Conclusion In this study, we assembled and annotated the mt genome of the medicinal plant B. chinense. Our findings provide extensive information regarding the mt genome of B. chinense, and help lay the foundation for future studies on the genetic variations, phylogeny, and breeding of B. chinense via an analysis of the mt genome.

Particulate methane monooxygenase (pMMO) is the main enzyme used by methanotrophs. Here, the authors determined the native structure of pMMO by cryo-electron tomography, revealing lipid-stabilized features and a higher-order hexagonal array arrangement in intact cells.

Abstract Background The analgesic effects of erector spinae plane block in general anesthesia for cesarean section and recovery from puerperae remain unclear. Methods Sixty patients with contraindications for spinal anesthesia who required general anesthesia for cesarean section were enrolled and randomly divided into the erector spinal plane block (ESPB) combined with the general anesthesia group (group E) and general anesthesia group (group G). Group E received bilateral ESPB (20 ml of 0.25% ropivacaine on each side) under ultrasound guidance 30 min before general anesthesia. The primary outcomes were the number of patient-controlled intravenous analgesia (PCIA) boluses, and Bruggemann comfort scale (BCS) scores at 2 h, 6 h, 12 h, and 24 h after operation. The second outcome was intraoperative anesthesia dosage, fetal delivery time, puerperae emergence time, visual analog scale (VAS) at 2 h, 6 h, 12 h, and 24 h after operation, and incidence of nausea and vomiting. Heart rate (HR) and mean arterial pressure (MAP) were recorded 10 min before the start of anesthesia (T0), at the induction of anesthesia (T1), at skin incision (T2), and fetal delivery (T3), and immediately after surgery (T4). Results The number of PCIA boluses was lower in group E than in group G (P

As the penetration of renewables increases, air conditioners (ACs), whose electricity consumptions account for a large share, present tremendous potential in providing load regulating service to maintain the power supply–demand balance. In this paper, an analytical model for the dynamic aggregated power and schedulable capacity of ACs is presented, where the safe protocol (SP) is utilized to eliminate the power oscillations caused by temperature setpoint shifting. Based on this, the response potential of ACs is quantified by the evaluation indexes in the dimensions of capacity and time. Besides, an optimal dispatch strategy is proposed to implement the coordination of air conditioning resources in the response stage and recovery stage, by which not only the reliable load regulation service can be provided, but also the influences on users can be minimized. Simulation studies demonstrate the effectiveness of the proposed method.

ObjectiveThe histological conversion of lung adenocarcinoma (LUAD) into small-cell lung cancer (SCLC) is an important resistance mechanism for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-resistant LUAD. Anlotinib has been recommended as the third-line treatment for SCLC patients. The efficacy of etoposide/platinum (EP) as the main treatment is very limited for patients with transformed SCLC. However, little is known about EP plus anlotinib for transformed SCLC. The present study retrospectively explored the clinical response to EP combined with anlotinib in patients with transformed SCLC from LUAD after EGFR-TKI failure.MethodsA total of 10 patients who underwent SCLC transformation from EGFR-TKI-resistant LUAD were retrospectively reviewed from September 1, 2019, to December 31, 2022, in three regional hospitals. All of the patients were treated with the combination regimen of EP and anlotinib for four to six cycles, followed by anlotinib maintenance therapy. The clinical efficacy indices including objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and toxicities were evaluated.ResultsThe median time from EGFR-TKI treatment to SCLC conversion was 20.1 ± 2.76 months (17–24 months). Genetic examination after transformation showed that 90% of the patients retained their original EGFR gene mutations. Additional driver genes were found, including BRAF mutation (10%), PIK3CA mutation (20%), RB1 loss (50%), and TP53 mutation (60%). The ORR and DCR were 80% and 100%, respectively. The mPFS was 9.0 months (95% CI, 7.9–10.1 months), and the mOS was 14.0 months (95% CI, 12.0–15.9 months). Less than 10% of grade 3 toxicities were observed, and no grade 4 toxicity and death events were reported.ConclusionThe EP plus anlotinib regimen appears to be a promising and safe strategy in transformed SCLC patients after EGFR-TKI resistance, which warrants further investigation.

Plants, as sessile organisms, uptake nutrients from the soil. Throughout their whole life cycle, they confront various external biotic and abiotic threats, encompassing harmful element toxicity, pathogen infection, and herbivore attack, posing risks to plant growth and production. Plants have evolved multifaceted mechanisms to cope with exogenous stress. The element defense hypothesis (EDH) theory elucidates that plants employ elements within their tissues to withstand various natural enemies. Notably, essential and non-essential trace metals and metalloids have been identified as active participants in plant defense mechanisms, especially in nanoparticle form. In this review, we compiled and synthetized recent advancements and robust evidence regarding the involvement of trace metals and metalloids in plant element defense against external stresses that include biotic stressors (such as drought, salinity, and heavy metal toxicity) and abiotic environmental stressors (such as pathogen invasion and herbivore attack). We discuss the mechanisms underlying the metals and metalloids involved in plant defense enhancement from physiological, biochemical, and molecular perspectives. By consolidating this information, this review enhances our understanding of how metals and metalloids contribute to plant element defense. Drawing on the current advances in plant elemental defense, we propose an application prospect of metals and metalloids in agricultural products to solve current issues, including soil pollution and production, for the sustainable development of agriculture. Although the studies focused on plant elemental defense have advanced, the precise mechanism under the plant defense response still needs further investigation.

Abstract Manganese (Mn) is an essential trace metal element that is associated with diabetes; however, the results of previous studies are inconsistent. Furthermore, few studies have been conducted in a hypertensive population. The purpose of this study is to explore the relationship between manganese and diabetes in a population with hypertension. A cross‐sectional study was conducted, including 2575 hypertensive individuals from 14 provinces in China. Serum manganese concentrations were measured by the inductively coupled plasma mass spectrometry (ICP‐MS) method. And logistic regression models were used to analyze the association between serum manganese and the risk of diabetes. The prevalence of diabetes was 27.0% in this hypertensive population. In logistic regression models, the odds ratios (95% confidence interval) for diabetes in tertile subgroups were 1.40 (1.12, 1.76) and 1.32 (1.05, 1.65) for tertiles 1 and tertiles 3, respectively, compared to tertile 2 (reference). Additionally, an interaction between sex and manganese was observed. The odds ratios (95% confidence interval) for diabetes were 1.29 (0.95, 1.75) and 0.96 (0.70, 1.31) for tertiles 1 and tertiles 3 among males, and 1.44 (1.01, 2.04) and 1.81 (1.29, 2.55) for tertiles 1 and tertiles 3 among females, respectively, compared to tertile 2. In conclusion, a U‐shaped association between serum manganese and diabetes was observed in a Chinese population with hypertension, and the association was modified by sex.

Abstract We aimed to evaluate the prospective association of vitamin B5 with all‐cause mortality and explore its potential modifiers in Chinese adults with hypertension. A nested, case‐control study was conducted in the China Stroke Primary Prevention Trial, including 505 deaths of all causes and 505 matched controls. The median follow‐up duration was 4.5 years. The primary outcome measure in this investigation was all‐cause mortality, which encompassed deaths for any reason. The mean plasma vitamin B5 concentration for cases (43.7 ng/mL) was higher than that in controls (40.9 ng/mL) (p = .001). When vitamin B5 was further assessed as quintiles, compared with the reference group (Q1:

Introduction: Biofungicides with low toxicity and high efficiency are a global priority for sustainable agricultural development. Phytohormone salicylic acid (SA) is an ancient medicine against various diseases in humans and activates the immune system in plants, but little is known of its function as a biofungicide. Objectives: Here, Fusarium oxysporum, the causal agent of devastating Fusarium wilt and immunodepressed patients, was used as a model system to explore whether SA can enter the pathogen cells and suppress key targets of the pathogen. Methods: Oxford Nanopore MinION sequencing and high-throughput chromosome conformation capture (Hi-C) sequencing were used to analyzed the genome of F. oxysporum. In addition, RNA-seq, qRT-PCR, and western blotting were conducted to detect gene and protein expression levels. Results: We isolated and sequenced the genome of F. oxysporum from potato dry rot, and the F. oxysporum included 12 chromosomes and 52.3 Mb genomic length. Pharmacological assays showed that exogenous application of SA can efficiently arrest hyphal growth, spore production, and pathogenicity of F. oxysporum, whereas endogenous salicylate hydroxylases significantly detoxify SA. The synergistic growth inhibition of F. oxysporum was observed when SA was combined with rapamycin. Kinase assays showed that SA inhibits FoTOR complex 1 (FoTORC1) by activating FoSNF1 in vivo. Transgenic potato plants with the interference of FoTOR1 and FoSAH1 genes inhibited the invasive growth of hyphae and significantly prevented the occurrence of Fusarium wilt. Conclusion: This study revealed the underlying mechanisms of SA against F. oxysporum and provided insights into SA in controlling various fungal diseases by targeting the SNF1-TORC1 pathway of pathogens.

Abstract Background Surgical treatment is currently the only way to achieve the clinical cure for Klatskin tumor. However, whether combined vascular resection should be combined during surgeries is still controversial. The aim of this article was to analyze the effect of portal vein resection (PVR) and hepatic artery resection (HAR) on the long-term survival after surgery for Klatskin tumor. Methods Articles about Klatskin tumor with PVR and HAR, which were published from 2000 to 2020, were searched using PubMed, Embase, and EBSCO. HR with a 95% CI of overall survival, recurrence-free survival, disease-free survival, 3- and 5-year survival rate, and median survival time were reported to evaluate prognosis. Results A total of 17 articles were included. The total case number of these studies was 3150 (685 in the PVR group, 345 in the HAR group, and 2120 in the control group). Survival analyses showed that both vascular resection types were poor prognostic factors (PVR: HR = 1.50, 95% CI = 1.24–1.81, P < 0.001; HAR: HR = 1.68, 95% CI = 1.26–2.24, P < 0.001; the pooled effect size of the two groups: HR = 1.55, 95% CI = 1.32–1.82, P < 0.001). In general, the analyses of 3- and 5-year survival and median survival time showed that both vascular resection types tended to be poor prognostic factors, but most of recent researches showed that the PVR did not lead to a poor prognosis. Conclusion PVR should be used when necessary to achieve R0 resection of Klatskin tumor and improve the long-term survival of patients. Whether HAR should be performed or not is still need to be evaluated.

Abstract Background and aims Clarifying the association between 5-methyltetrahydrofolate and homocysteine and the effect pattern of methylene tetrahydrofolate reductase (MTHFR C677T) may contribute to the management of homocysteine and may serve as a significant reference for a randomized controlled trial of 5-methyltetrahydrofolate intervention. This study aimed to reveal the association between these two biochemical indices. Methods Study population was drawn from the baseline data of the China Stroke Primary Prevention Trial (CSPPT), including 2328 hypertensive participants. 5-methyltetrahydrofolate and homocysteine were determined by stable-isotope dilution liquid chromatography-tandem mass spectrometry and automatic clinical analyzers, respectively. MTHFR C677T polymorphisms were detected using TaqMan assay. Multiple linear regression was performed to evaluate the association between serum 5-methyltetrahydrofolate and homocysteine. Results There was a significant inverse association between 5-methyltetrahydrofolate and homocysteine when 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T (per 1-ng/mL increment; All: β = − 0.50, P

Background and objectiveThe optimal treatment for patients with symptomatic non-acute atherosclerotic intracranial large artery occlusion (ILAO) despite medical treatment is not well established. We aimed to assess the safety, efficacy, and feasibility of angioplasty and stenting for these patients.MethodsA total of 251 consecutive patients with symptomatic non-acute atherosclerotic ILAO treated with interventional recanalization were retrospectively collected in our center from March 2015 to August 2021. The rate of successful recanalization, perioperative complications, and follow-up outcomes were evaluated.ResultsSuccessful recanalization was achieved in 88.4% (222/251) of the patients. A total of 24 (24/251, 9.6%) symptomatic complications occurred among 251 procedures. In the 193 patients with clinical follow-up during 19.0 ± 14.7 months, 11 (11/193, 5.7%) patients developed ischemic stroke and four (4/193, 2.1%) patients developed transient ischemic attack (TIA). In the 106 patients with vascular imaging follow-up during 6.8 ± 6.6 months, seven (7/106, 6.6%) patients had restenosis and 10 (10/106, 9.4%) patients had reocclusion.ConclusionThis study suggests that interventional recanalization may be a feasible, basically safe, and an effective alternative in carefully selected patients with symptomatic non-acute atherosclerotic ILAO who have failed medical management.

People's emotions may be affected by the sound environment in court. A courtroom's sound environment usually consists of the people's voices, such as the judge's voice, the plaintiff's voice, and the defendant's voice. The judge, plaintiff, and defendant usually express their emotions through their voices. Human communication is heavily reliant on emotions. Emotions may also reflect a person's condition. Therefore, People's emotions at the Court must be recognized, especially for vulnerable groups, and the impact of the sound on the defendant's motions and judgment must be inferred. However, people's emotions are difficult to recognize in a courtroom. In addition, as far as we know, no existing study deals with the impact of sound on people in court. Based on sound perception, we develop a deep neural network-based model to infer people's emotions in our previous work. In the proposed model, we use the convolutional neural network and long short-term memory network to obtain features from speech signals and apply a dense neural network to infer people's emotions. Applying the model for emotion prediction based on sound at court, we explore the impact of sound at court on the defendant. Using the voice data collected from fifty trail records, we demonstrate that the voice of the judge can affect the defendant's emotions. Angry, neutrality and fear are the top three emotions of the defendant in court. In particular, the judge's voice expressing anger usually induces fear in the defendant. The plaintiff's angry voice may not have a substantial impact on the defendant's emotions.

Glycogen synthase kinase 3 (GSK3) family members are evolutionally conserved Ser/Thr protein kinases in mammals and plants. In plants, the GSK3s function as signaling hubs to integrate the perception and transduction of diverse signals required for plant development. Despite their role in the regulation of plant growth and development, emerging research has shed light on their multilayer function in plant stress responses. Here we review recent advances in the regulatory network of GSK3s and the involvement of GSK3s in plant adaptation to various abiotic and biotic stresses. We also discuss the molecular mechanisms underlying how plants cope with environmental stresses through GSK3s-hormones crosstalk, a pivotal biochemical pathway in plant stress responses. We believe that our overview of the versatile physiological functions of GSK3s and underlined molecular mechanism of GSK3s in plant stress response will not only opens further research on this important topic but also provide opportunities for developing stress-resilient crops through the use of genetic engineering technology.

Abstract Electrochemical CO2 reduction reaction (CO2RR) to produce value‐added products has received tremendous research attention in recent years. With research efforts across the globe, remarkable advancement has been achieved, including the improvement of selectivity for the reduction products, the realization of efficient reduction beyond two electrons, and the delivery of industrially relevant current densities. In this review, we introduce the recent development of nanomaterials for CO2RR, including the zero‐dimensional graphene quantum dots, two‐dimensional materials such as metal chalcogenides and metal/covalent organic framework, single‐atom catalysts, and nanostructured metal catalysts. The engineering of materials into three‐dimensional structure will also be discussed. Finally, we will provide a summary of the catalytic performance and perspectives on future development.

Abstract Background Serum choline levels were associated with multiple chronic diseases. However, the association between serum choline and all-cause mortality in Chinese adults with hypertension remains unclear. The purpose of this study is to explore the association between serum choline concentrations and all-cause mortality risk in Chinese adults with hypertension, a high-risk population. Methods A nested, case–control study was conducted that included 279 patients with all-cause death, and 279 matched, living controls, derived from the China Stroke Primary Prevention Trial (CSPPT). Baseline serum choline concentrations were measured by liquid chromatography with tandem quadrupole mass spectrometry (LC–MS/MS). Multivariate logistic regression analysis was used to assess the association of serum choline levels and all-cause mortality risk, with adjustment of pertinent covariables, including folic acid and homocysteine. Results The median age of all participants was 64.13 years [interquartile range (IQR), 57.33–70.59 years]. The median serum choline concentration for cases (9.51 μg/mL) was higher than that in controls (7.80 μg/mL) (P = 0.009). When serum choline concentration was assessed as a continuous variable (per SD increased), there was a positive relation between serum choline levels and all-cause mortality risk [odds ratios (OR), 1.29; 95% confidence intervals (95%CI), 1.06–1.57; P = 0.010]. There was an increased all-cause mortality risk for participants in quartiles 2–4 (≥ 4.00 μg/mL; OR, 1.79; 95%CI, 1.15–2.78 compared with quartile 1 (

Abstract Background The purpose of this study was to examine the correlation between fasting blood glucose and new-onset hypertension and examine any synergistically effect modification with multiple risk factors. Methods We conducted post-hoc analyses of repeated-measures data in the original Dongzhi osteoporosis cohort study. In total, 3985 participants without hypertension aged 25–64 years were included in the current analyses. Generalized estimating equation models were used to assess the relationship between fasting blood glucose and risk of new-onset hypertension after adjusting for pertinent covariates and autocorrelations among siblings. Results 393 men (19.4%) and 398 women (20.3%) without hypertension at the baseline developed hypertension by the end of the study period. Compared to lower baseline fasting blood glucose levels (Q1–Q3:

Abstract Objective To explore the influence of childhood trauma and family alcohol use on male alcohol use disorder. Methods We conducted a case-control study using Childhood Trauma Questionnaire (CTQ) and a structured interview involving 129 men with alcohol use disorder and 129 healthy male volunteers. The two groups were compared in terms of childhood trauma, parental drinking behavior, and attitudes toward childhood drinking. Results Patients showed higher scores of CTQ than controls on childhood trauma experiences, including on the subscales of physical abuse, emotional abuse, sexual abuse, and emotional neglect. Higher proportions of patients than controls had fathers who drank seven or more times a week, and had mothers who were opposed to childhood drinking. Conversely, a smaller proportion of patients than controls had fathers who opposed childhood drinking. Patients were more likely than controls to have been induced to drink as children. Logistic regression analysis identified three risk factors for alcohol use disorder: induced drinking during childhood [odds ratio (OR) 6.09, 95% confidence interval (CI) 2.56–14.51], the father’s weekly alcohol consumption during the respondent’s childhood (OR 4.40, 95%CI 2.94–6.58) and history of smoking (OR 3.39, 95%CI 1.48–7.77). Conversely, more years of education were a protective factor against alcohol use disorder (OR 0.88, 95% CI 0.78–0.99). Conclusions Men whose fathers drank frequently during their childhood and were encouraged to drink may be at increased risk of alcohol use disorder in adulthood. In fact these factors of family alcohol use appear to increase risk of alcohol use disorder among adult men more than exposure to childhood trauma does.

Background Recent studies have identified ribonucleotide reductase subunit M2 (RRM2) as a putative promoter of tumors. However, no systematic analysis of its carcinogenicity has been conducted. Methods The potential functions of RRM2 in various tumor types were investigated using data from the Genotype-Tissue Expression (GTEx), the Clinical Proteomic Tumor Analysis Consortium (CPTAC), the Cancer Genome Atlas (TCGA), the Human Protein Atlas (HPA), cBioPortal, GEPIA, String, and Gene Set Enrichment Analysis (GSEA). We analyzed the difference in mRNA and protein expression, pathological stage, survival, mutation, tumor microenvironment (TME), and immune cell infiltration in relation to RRM2. Meanwhile, using TCGA and the Tumor Immune Estimation Resource 2 (TIMER 2), the associations between RRM2 expression, immune infiltration, and immune-related genes were assessed. Additionally, CCK-8, Edu and RT-PCR assays were used to validate that RRM2 acts as an oncogene in liver cancer cells and its association with HBx. A cohort of liver hepatocellular carcinoma (LIHC) patients (n=154) from Huashan Hospital was analyzed for the expression of RRM2 and the association between RRM2 and immune infiltration. Results Using the GTEx and TCGA databases, we discovered that 28 tumors expressed RRM2 at significantly higher levels than the corresponding normal tissues. Increased RRM2 expression may be predictive of a poor overall survival (OS) in patients with seven different cancers. GO, KEGG, and GSEA analyses revealed that the biological process of RRM2 was associated with the regulation of carcinogenic processes and immune pathways in a variety of tumor types. The expression of RRM2 was highly correlated with maker genes involved in immune activation and immunosuppression, immune checkpoints, DNA mismatch repair system (MMR), and the infiltration levels of Tregs and macrophages (TAMs), suggesting that the carcinogenic effect of RRM2 may be achieved by regulating immune related genes. Moreover, as demonstrated by CCK-8 and Edu assays, RRM2 was an oncogene in liver cancer cells. We confirmed for the first time that RRM2 was significantly upregulated by HBx, suggesting that RRM2 may be a key regulator of LIHC induced by HBV. IHC analysis validated the upregulated expression of RRM2 protein and its correlation with immune infiltration makers in a LIHC patient cohort. Conclusion RRM2 may be a valuable molecular biomarker for predicting prognosis and immunotherapeutic efficacy in pan-cancer, particularly in LIHC.

BackgroundThe prospective association between plasma Se and stroke risk remains inconclusive. The relationship between Se and ischemic stroke among a low circulating Se status population deserves more attention, especially for Chinese people who were a high-risk group for Se deficiency.ObjectiveThe relationship between plasma Se concentration and ischemic stroke risk in a large-scale Chinese community-based population and any potential effect modifiers were investigated.MethodsA nested, case-control study, using data from the “China H-type Hypertension Registry Study” were conducted. A total of 1,904 first ischemic stroke cases and 1,904 controls matched for age, sex, and village were included in this study. The association between plasma Se and first ischemic stroke was evaluated by conditional logistic regression analyses.ResultsThe median value of plasma Se was 65.8 μg/L among total participants. Overall, a significant inverse relationship between plasma Se and first ischemic stroke risk was found (per SD increment; adjusted OR: 0.87; 95% CI: 0.80 and 0.95). Accordingly, a significantly lower risk of first ischemic stroke was found in participants in quartile 3 (65.8−

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.

Abstract Periprocedural antithrombotic management with glycoprotein IIb/IIIa inhibitors (GPI) for intracranial artery stenting is still controversial. We sought to assess the safety and efficacy of prophylactic tirofiban infusion for acute intracranial intraprocedural stent thrombosis in routine clinical practice. From January 2013 to December 2019, consecutive patients treated with endovascular stenting for symptomatic intracranial atherosclerotic stenosis (ICAS) were identified and dichotomized by whether tirofiban was used. The efficacy and safety outcomes were compared by propensity score matching. A total of 160 consecutive patients in the tirofiban group and 177 patients in the non-tirofiban group were enrolled. Propensity score matching analysis selected 236 matched patients. One acute intraprocedural stent thrombosis (AIST) occurred in patients receiving prophylactic tirofiban, while 8 in the non-tirofiban group. The incidence of AIST in the tirofiban group was significantly lower than that in the non-tirofiban group (0.8% vs 6.8%, P = 0.039). The periprocedural ischemic events (8.5% vs 5.1%, P = 0.424), periprocedural intracranial hemorrhage (4.2% vs 0.8%, P = 0.219) and 30-day total mortality (3.4% vs 0%, P = 0.125) were not statistically different between the two groups. Compared with conventional stenting angioplasty without tirofiban, tirofiban prophylactic infusion can lower the incidence of AIST, without increasing the risk of periprocedural intracranial hemorrhage and 30-day total mortality. However, there is no superiority in reducing periprocedural ischemic events. The current study adds more important insights to the available clinical evidence on the use of tirofiban during stenting of ICAS.

BackgroundEvidence from epidemiologic studies has been limited and inconsistent regarding the role of serum calcium in stroke incidence risk. We aimed to evaluate the association between serum albumin-corrected calcium and the risk of the first stroke in the Chinese community-dwelling population.MethodsThe study sample population was drawn from the “H-type Hypertension and Stroke Prevention and Control Project.” Using a nested case-control study, a total of 1,255 first-stroke cases and 1,255 controls matched for age, sex, and village were included in the final data analysis. We measured the serum calcium by inductively coupled plasma mass spectrometry and assessed the associations between serum albumin-corrected calcium and first stroke using conditional logistic regression.ResultsThe overall mean (SD) serum albumin-corrected calcium was 8.9 (0.6) mg/dl. Compared with the middle tertile (8.7–9.1 mg/dl), the multivariate-adjusted odds ratios (95% CIs) of first total stroke associated with the lowest tertile and the highest tertile of serum albumin-corrected calcium were 1.37 (1.10, 1.70) and 1.30 (1.04, 1.62), respectively. Similar trends were observed for the first ischemic stroke. Consistently, restricted cubic spline showed a U-shaped association between serum albumin-corrected calcium and risk of total stroke and ischemic stroke. However, serum albumin-corrected calcium had no significant effect on first hemorrhagic stroke. No significant effect modification was observed in the subgroup analysis.ConclusionsOur results suggested a U-shaped association between serum calcium and first stroke; both low and high serum calcium levels were associated with an increased risk of the first stroke in the Chinese population.