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Shaojie Bi,1 Juan Zhang,1 Ning Wei,2 Qingbo Zhou,3,4 Chunyan Wang3 1Department of Cardiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Information Center, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Department of Geriatrics, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 4School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Chunyan Wang, Email 201062013735@email.sdu.edu.cnIntroduction: Anemia, characterized by low hemoglobin or erythrocyte levels, is a significant global health issue with severe implications for public health. Recent studies have explored the potential link between anemia and 25-hydroxyvitamin D [25(OH)D], yet the precise mechanisms remain unclear. This study aims to clarify the possible causal relationship between 25(OH)D levels and anemia risk.Methods: We conducted a comprehensive investigation combining observational and Mendelian randomization (MR) analyses. The observational study included detailed demographic, comorbidities, and laboratory data collected from 7160 hospitalized patients in China. For the MR analysis, genetic polymorphisms were utilized to assess causal effects.Results: Observational analysis revealed an inverse relationship between 25(OH)D levels and the risk of anemia, with stratified analysis indicating a nonlinear association and a threshold of 48.716 nmol/L. The MR analysis confirmed a protective causal relationship between higher 25(OH)D levels and a reduced risk of anemia. Bidirectional MR analysis found no evidence that anemia influences 25(OH)D levels.Discussion: This study provides strong evidence of a causal link between increased 25(OH)D levels and a lower incidence of anemia. The findings highlight the potential role of vitamin D in anemia prevention, supporting the need for further research into vitamin D supplementation as a strategy to reduce anemia risk.Conclusion: Our findings support the hypothesis that higher 25(OH)D levels are causally associated with a reduced risk of anemia, suggesting vitamin D’s potential role in anemia prevention and public health strategies.Keywords: anemia, 25-hydroxyvitamin D, Mendelian randomization

Jing Yang, Chengsen Shu, Xianfu Shang, Hao Xu, Ning Wei Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, People’s Republic of ChinaCorrespondence: Ning Wei, Email weiningjieru2006@163.comPurpose: This study aimed to investigate the prognostic value of systemic immune-inflammation index (SII) in patients with extrahepatic cholangiocarcinoma (EHCC) treated by percutaneous transhepatic biliary stenting (PTBS) combined with 125I seed intracavitary irradiation and further develop a predictive model related to SII.Methods: A total of 145 patients with EHCC who received PTBS combined with 125I seed implantation were retrospectively analyzed. The optimal cut-off value of SII was identified by receiver operating characteristic (ROC) curve analysis. Kaplan–Meier curves and Cox regression were applied to estimate the prognostic value of SII and identify other significant factors of overall survival (OS). Additionally, a novel nomogram was constructed. The concordance index (C-index), calibration plots and decision curve analysis were used to evaluate the performance of the nomogram model.Results: The optimal cut-off value for preoperative SII of 890.2 stratified the patients into High-SII (H-SII) and Low-SII (L-SII) groups. Univariate and multivariate analyses demonstrated that SII was an independent factor for OS. We also found that better therapeutic effect could be obtained with combined postoperative chemotherapy (P < 0.001). Moreover, we revealed that elevated preoperative CA19-9 (P = 0.038) and TBIL level (P = 0.024) were reason for poor prognosis of EHCC. A well-discriminated and calibrated nomogram was developed to predict the 1-year and 2-year OS of EHCC (C-index: 0.709).Conclusion: The SII may be a feasible and convenient prognosis predictor for EHCC. The comprehensive nomogram based on SII presented in this study is a promising model for predicting OS in EHCC patients after PTBS combined with 125I seed intracavitary irradiation.Keywords: extrahepatic cholangiocarcinoma, biliary stenting, 125I seed, systemic immune-inflammation index, nomogram

Dadi Xie,1,&ast; Fengfeng Li,1,&ast; Deshui Pang,1 Shiyuan Zhao,2 Meihua Zhang,1 Zhongfa Ren,1 Chunmei Geng,2 Changshui Wang,3 Ning Wei,4 Pei Jiang2 1Tengzhou Central People’s Hospital, Tengzhou, 277500, People’s Republic of China; 2Jining First People’s Hospital, Jining Medical University, Jining, 272000, People’s Republic of China; 3Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272000, People’s Republic of China; 4Shanting District People’s Hospital, Zaozhuang, 277200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meihua ZhangTengzhou Central People’s Hospital, Xingtan Road, Tenzhou, 277500, People’s Republic of ChinaTel/Fax +86 0632-5512227Email meihua_zhang@126.comPei JiangJining First People’s Hospital, Jning Medical University, Jiankang Road, Jining, 272000, People’s Republic of ChinaTel/Fax + 86 0537-2106208Email jiangpeicsu@sina.comPurpose: Inflammatory bowel diseases (IBD) are a chronic inflammatory disease, which affects almost all tissues in the body. Previous studies mainly focused on breathing, fecal, and urine samples of patients with IBD. However, there is no comprehensive metabolomic analysis of the serum, colon, heart, liver, kidney, cortex, hippocampus, and brown fat tissues. Therefore, the aim of our study is to evaluate the utility metabolomic analysis of target tissues in the pathogenesis of IBD in exploring new biomarkers for early diagnosis and treatment.Methods: Male Sprague–Dawley rats were randomly allocated to control and DSS-treated groups (n = 7). Dextran sulfate sodium (DSS) was orally administered for 6 weeks. Gas chromatography-mass spectrometry (GC-MS) was used for metabolite determination, multivariate statistical analysis was used to identify metabolites that were differentially expressed in two groups.Results: Our results showed that 3, 11, 12, 6, 5, 13, 13, and 11 metabolites were differentially expressed between the DSS treatment group and the control group in the serum, colon, heart, liver, kidney, cortex, hippocampus, and brown fat tissues, respectively. The most significant change of metabolites in the study was amino acid (L-alanine, L-glutamic acid, L-phenylalanine, L-proline, L-lysine, L-isoleucine, L-tryptophan, L-norleucine, L-valine, glycine, serine, L-threonine), organic acid (citric acid, 3-hydroxybutyric acid, propanoic acid), glucide (D-arabinose, D-fructose) and purine (9H-purin-6-ol, D-ribose) profiles. Several pathways were affected according to the integrated pathway analysis. These pathways ranged from amino acid metabolism (such as alanine, aspartate, and glutamate metabolism, glutathione metabolism) to purine metabolism (aminoacyl-tRNA biosynthesis).Conclusion: Using GC-MS-based profiling of metabolite changes, these results may provide a more comprehensive view for IBD and IBD-related diseases and improve the understanding of IBD pathogenesis.Keywords: inflammatory bowel disease, metabolite, GC-MS, dextran sodium sulfate, biomarker

Theresa Gillis, Megan Crane, Carly Hinkle, Nathan Wei Arthritis Treatment Center, Frederick, MD, USA Objective: Many types of treatment are available for patients with rheumatoid arthritis (RA), however, some patients fail to achieve remission. This report aims to determine the safety and efficacy of using repository corticotropin injection (RCI) as an adjunctive therapy in patients with RA refractory to at least three therapeutics with different mechanisms of action. Method: In this open-label, interventional, single-group study, patients received 80 U RCI twice weekly via subcutaneous injection over 12 weeks. Changes in the Ritchie–Camp Articular Index and health assessment questionnaire scores were monitored for changes from baseline measures. Results: Eight patients were enrolled and consisted of seven females and one male with an average age of 64.6 years and disease duration of 20.9 years. Use of RCI resulted in significant improvement in swollen and tender joint counts. The disease activity score 28 and the physician and patient visual analog scale scores were significantly reduced at treatment week 12. The reduction in health assessment questionnaire scores did not reach statistical significance after RCI treatment. Once RCI therapy was discontinued, all improvements in disease activity score 28, physician and patient visual analog scale, and tender and swollen joint counts achieved during treatment were lost by the week 16 follow-up visit. Conclusion: While larger clinical trials are necessary to further confirm the efficacy of RCI in patients with refractory RA, the response of patients with refractory RA in this study suggests that RCI can be an effective add-on therapy for patients who have exhausted several classes of treatments. Furthermore, this study suggests that RCI has an alternative mode of action, compared to other available antirheumatic drugs. Keywords: refractory rheumatoid arthritis, rheumatoid arthritis, adrenocorticotropic hormone, repository corticotropin injection

Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the TATA-box binding protein gene (TBP). The disease has a varied age at onset and clinical presentation. It is distinct from other SCAs for its association with dementia, psychiatric symptoms, and some patients presenting with chorea. For this reason, it is also called Huntington’s disease-like 4 (HDL-4). Here we examine the distribution of SCA17 allele repeat sizes in a United Kingdom-based cohort with ataxia and find that fully penetrant pathogenic alleles are very rare (5 in 1,316 chromosomes; 0.38%). Phenotype-genotype correlation was performed on 30 individuals and the repeat structure of their TBP genes was examined. We found a negative linear correlation between total CAG repeat length and age at disease onset and, unlike SCA1, there was no correlation between the longest contiguous CAG tract and age at disease onset. We were unable to identify any particular phenotypic trait that segregated with particular CAG/CAA repeat tract structures or repeat lengths. One individual within the cohort was homozygous for variable penetrance range SCA17 alleles. This patient had a similar age at onset to heterozygotes with the same repeat sizes, but also presented with a rapidly progressive dementia. A pair of monozygotic twins within the cohort presented 3 years apart with the sibling with the earlier onset having a more severe phenotype with dementia and chorea in addition to the ataxia observed in their twin. This appears to be a case of variable expressivity, possibly influenced by other environmental or epigenetic factors. Finally, there was an asymptomatic father with a severely affected child with an age at onset in their twenties. Despite this, they share the same expanded allele repeat sizes and sequences, which would suggest that there is marked difference in the penetrance of this 51-repeat allele. We therefore propose that the variable penetrance range extend from 48 repeats to incorporate this allele. This study shows that there is variability in the presentation and penetrance of the SCA17 phenotype and highlights the complexity of this disorder.

A great deal of progress has been made over the last three decades in research on pheromone-mediated mating disruption technology for the oriental fruit moth, Grapholita molesta (Busck). Pheromones can interrupt normal orientation, and the most likely mechanism of pheromone disruption, competitive-attraction (false-plume following), invokes competition between point sources of pheromone formulation and females for males. This technology, performed by broadcasting pheromones into orchards to disrupt mate finding, has been successfully implemented in oriental fruit moth control. Reservoir-style dispensers made of polyethylene tubes, which release pheromone throughout the full growing season, are the current industry standard. Although reasonably effective, they require labor-intensive hand application. Recently, a new formulation, paraffin wax, which maximizes competition between point sources of synthetic pheromone and feral females for males, was shown to have high disruption performance. As this formulation is highly effective, inexpensive, and easy to produce, further study and development are advisable. Increased understanding of the principles of mating disruption will aid in the design of more effective dispensers. Continued research is needed to meet grower concerns with regard to risk, efficacy, and cost and to identify other semiochemicals that can be applied to this delivery system. Greater knowledge of the integration of different biological control methods is therefore essential.

ObjectiveEvaluate the efficacy and safety/tolerability of cryoneurolysis for reduction of pain and symptoms associated with knee osteoarthritis (OA).DesignRandomized, double-blind, sham-controlled, multicenter trial with a 6-month follow-up in patients with mild-to-moderate knee OA. Patients were randomized 2:1 to cryoneurolysis targeting the infrapatellar branch of the saphenous nerve (IPBSN) or sham treatment. The primary endpoint was the change from baseline to Day 30 in the Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain score adjusted by the baseline score and site. Secondary endpoints, including visual analogue scale (VAS) pain score and total WOMAC score, were tested in a pre-defined order.ResultsThe intent-to-treat (ITT) population consisted of 180 patients (n = 121 active treatment, n = 59 sham treatment). Compared to the sham group, patients who received active treatment had a statistically significant greater change from baseline in the WOMAC pain subscale score at Day 30 (P = 0.0004), Day 60 (P = 0.0176), and Day 90 (P = 0.0061). Patients deemed WOMAC pain responders at Day 120 continued to experience a statistically significant treatment effect at Day 150. Most expected side effects were mild in severity and resolved within 30 days. The incidence of device- or procedure-related adverse events was similar in the two treatment groups with no occurrence of serious or unanticipated adverse device effects (ADE).ConclusionsCryoneurolysis of the IPBSN resulted in statistically significant decreased knee pain and improved symptoms compared to sham treatment for up to 150 days, and appeared safe and well tolerated.

ObjectiveTofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). The pathways affected by tofacitinib and the effects on gene expression in situ are unknown. Therefore, tofacitinib effects on synovial pathobiology were investigated.MethodsA randomised, double-blind, phase II serial synovial biopsy study (A3921073; NCT00976599) in patients with RA with an inadequate methotrexate response. Patients on background methotrexate received tofacitinib 10 mg twice daily or placebo for 28 days. Synovial biopsies were performed on Days -7 and 28 and analysed by immunoassay or quantitative PCR. Clinical response was determined by disease activity score and European League Against Rheumatism (EULAR) response on Day 28 in A3921073, and at Month 3 in a long-term extension study (A3921024; NCT00413699).ResultsTofacitinib exposure led to EULAR moderate to good responses (11/14 patients), while placebo was ineffective (1/14 patients) on Day 28. Tofacitinib treatment significantly reduced synovial mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-3 (p

The future Sixth-Generation (6G) wireless systems are expected to encounter emerging services with diverse requirements. In this paper, 6G network resource orchestration is optimized to support customized network slicing of services, and place network functions generated by heterogeneous devices into available resources. This is a combinatorial optimization problem that is solved by developing a Particle Swarm Optimization (PSO) based scheduling strategy with enhanced inertia weight, particle variation, and nonlinear learning factor, thereby balancing the local and global solutions and improving the convergence speed to globally near-optimal solutions. Simulations show that the method improves the convergence speed and the utilization of network resources compared with other variants of PSO.

Abstract In recent years, under the background of exam-oriented physical education reform, the government has issued a lot of physical education documents and policies. As a result, many schools have made fundamental changes in physical education activities. These policies are mainly aimed at getting young people to be more active and autonomous in school sports. This requires physical education training teachers must adhere to the people-oriented, student-oriented, so as to highlight the subject status of students. Based on this, students should establish a good sports values and ethics and form a good habit of lifelong sports, so as to further promote the sustainable development of youth sports activities. Based on the ecological theory of sustainable development as the background, this study constructs a unified theory of Unified Theory of Acceptance and Use of Technology (UTAUT) model for the sustainable training and development of youth skating sports training institutions. This study selects the youth skating sports training institutions in Beijing, China as the investigation object, covering small, medium and large institutions of different sizes, and analyzes based on the statistical data in 2023 and the results of field research. The results show that the application of this model not only increases the willingness of youth skating training institutions to continue to participate by 3.66%, but also promotes the diversified development of youth skating training. In addition, this study also discusses the environmental protection measures implemented in the process of skating training to ensure that the training activities are sustainable while reducing the impact on the environment, so as to build a sustainable development of the new ecology of skating sports training.

BackgroundCurrently， there has been a gradual increase in the incidence of mental diseases， becoming a problem that has attracted great concern of the general public. Zhuhai is a core city of the Guangdong-Hong Kong-Macao Greater Bay Area， and the local government have attached great importance to the mental health of residents. The systematic study on the mental health has focused largely on pregnant women and medical workers， yet few are on the adult residents.ObjectiveTo investigate the prevalence and its influencing factors of anxiety and depression among adult residents in Zhuhai， so as to provide references for formulating targeted psychological intervention strategies.MethodsFrom September 1 to December 1， 2021， a cohort of 5 600 permanent residents aged 18 years and above in Zhuhai were selected through multistage sampling. All participants were subjected to complete Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， Generalized Anxiety Disorder Scale-7 item （GAD-7） and National Mental Health Literacy Questionnaire based on Wenjuanxing software. Then Logistic regression was employed to identify the factors associated with anxiety and depression among the residents.ResultsAmong the 5 600 residents， depressive symptoms were detected in 842 （15.04%） residents and anxiety symptoms in 579 （10.34%） residents. Logistic regression analysis yielded that female gender （OR=1.488）， living in Doumen district （OR=1.942）， junior college/undergraduate level （OR=3.602）， postgraduate and above （OR=5.904）， irregular meal pattern （OR=3.320）， comorbid chronic diseases （OR=3.244）， disqualification of self-assessment （OR=3.414） and disqualification of mental health skill （OR=2.131） were risk factors for depression symptoms， whereas age ≥25 years old （of all age groups OR20 000 yuan （OR=0.438） and exercising ≥3 times a week （OR=0.431） were protective factors for depression symptoms. Age of 25~34 years old （OR=2.051）， living in Jinwan district （OR=1.729） or Doumen district （OR=1.901）， junior college/undergraduate level （OR=2.955）， postgraduate and above （OR=6.662）， irregular meal pattern （OR=2.741）， comorbid chronic diseases （OR=3.535）， disqualification of self-assessment （OR=3.325） and disqualification of mental health skill （OR=1.838） were risk factors for anxiety symptoms， while monthly per capita income of 6 001~9 000 yuan （OR=0.665） and exercising ≥3 times a week （OR=0.572） were protective factors for anxiety symptoms.ConclusionThe mental health status of adult residents in Zhuhai is affected by various factors， including gender， age， region of residence， education level， meal pattern， exercise frequency and chronic diseases. ［Funded by 2023 Zhuhai Medical Research Project （number， 2220009000227）］

Abstract Background The association of body mass index (BMI) with survival outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with first-line chemotherapy, immunotherapy, or chemoimmunotherapy is controversial. We aimed to investigate these associations, including associations in male and female patients specifically, in a multicenter cohort study. Methods We retrospectively analyzed data from seven cohorts comprising 7021 advanced non-small cell lung cancer patients who received chemotherapy (three cohorts), immunotherapy (two cohorts), and chemoimmunotherapy (two cohorts) from five data sources, including a de-identified nationwide (US-based) NSCLC clinico-genomic database and two randomized, double-blind, phase 3 clinical trials. BMI was categorized as underweight, normal weight, overweight, or obese. Underweight patients were excluded because of their small proportion. The primary endpoints were the associations between BMI and progression-free survival (PFS) and overall survival (OS) stratified by treatment type and sex, which were assessed using Kaplan–Meier methods and adjusted Cox modeling. Meta-analyses were performed to combine the adjusted hazard ratios. Results In the pooled analysis, obesity was significantly associated with improved OS in patients receiving chemotherapy (hazard ratios [HR] = 0.84, 95% confidence interval (CI) 0.76–0.93), but there was no association with PFS (HR = 0.91, 95% CI 0.82–1.02). The association of BMI with OS for patients receiving chemotherapy differed by sex, with an inverse association in men (HR = 0.74, 95% CI 0.64–0.84), but no association observed in women (HR = 0.96, 95% CI 0.81–1.13, Pinteraction = 0.018). No impact of BMI on OS or PFS was detected in patients receiving immunotherapy or chemoimmunotherapy. Obese patients had the lowest level of tumor mutational burden, similar level of programmed death-ligand 1 expression and ESTIMATE scores. Conclusions Obesity may be associated with an increased overall survival among male patients treated with chemotherapy, whereas not associated with the outcomes in patients treated with immunotherapy or chemoimmunotherapy.

Abstract The photothermal conversion properties of tellurium (Te) nanoparticles have been extensively investigated, rendering them a promising candidate for tumor photothermal therapy. However, there is still room for improvement in the development of efficient Te-based drug delivery systems. Here, Te nanoparticles are mineralized with bioactive molecules within attenuated Salmonella (S-Te), which are subsequently taken up by macrophages (RAW264.7) to construct a double-camouflaged delivery platform (RS-Te). Remarkably, RS-Te retains superior photothermal properties under near-infrared irradiation. The mineralization process eliminates bacterial proliferation potential, thereby mitigating the risk of excessive bacterial growth in vivo. Furthermore, the uptake of bacteria by macrophages not only polarizes them into M1 macrophages to induce an anti-tumor immune response but also circumvents any adverse effects caused by complex antigens on the bacterial surface. The results show that RS-Te can effectively accumulate and retain in tumors. RS-Te-mediated photothermal immunotherapy largely promotes the maturation of dendritic cells and priming of cytotoxic T cells induced by near-infrared laser irradiation. Moreover, RS-Te can switch the activation of macrophages from an immunosuppressive M2 phenotype to a more inflammatory M1 state. The double-camouflaged delivery system may offer highly efficient and safe cancer treatment.

Objective The objective of this experiment was to determine the standard ileal digestibility (SID) of amino acid (AA) in 10 different sources of wheat bran fed to broilers and establish the SID AA prediction based on the chemical composition. Methods A total of 660 1-day-old broilers were randomly divided into 11 treatments with 6 replicates of 10 chickens each. Diets included 10 semi-purified mash diets and 1 nitrogen-free diet. Titanium dioxide (TiO2) 0.50% was used as an indigestible index. On day 13, 6 chickens from each replicate were selected for slaughter to collect ileal contents. On day 28, 4 chickens from each replicate were selected for slaughter to collect ileal contents. Results Results showed that the coefficient of variation of the conventional nutrients (except for gross energy, and dry matter) and all AAs was greater than 8.00%. The average SID of essential AA in wheat bran for 13-day-old broilers was 37.24% and the average SID of nonessential AA was 42.02%; the average SID of essential AA for 28-day-old broilers was 67.13% and the average SID of nonessential AA was 69.51%. A correlation was observed (p

Abstract In food circular economy, the utilization of food manufacturing side streams (FMSS) offers significant potential instead of being discarded. However, reincorporating FMSS into the food value chain raises food safety concerns due to potential food hazards. This perspective explores food safety risks associated with circular management of FMSS by using a ‘Quad-Modal hazard dynamic’ approach with case studies. Future research and advancements in food safety control strategies are also discussed.

Objective: To investigate whether angiotensin II type 1 receptor (AGTR1 A1166C) gene polymorphism was associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension. Methods: This retrospective analysis included 198 patients (⩾18 years of age) who received valsartan monotherapy (80 mg/day) for newly developed essential hypertension at the authors’ center between January 1, 2020 and December 31, 2023. Genotyping for AGTR1 A1166C gene polymorphism was done by polymerase chain reaction (PCR)-melting curve analysis of genomic DNA from peripheral blood samples. A dominant genetic model for AGTR1 A1166C (AA genotype versus AC + CC genotype) was used. Multivariate regression analysis of baseline variables and AGTR1 polymorphism was conducted to identify predictors of target blood pressure attainment (

This study aimed to compare the effects of dietary methionine (Met) and 2-hydroxy-4-(methylthio)-butanoate (HMTBA) on the eggshell quality of broiler breeder hens and elucidate the mechanism of Met in improving eggshell quality from the perspectives of eggshell microstructure and shell gland physiological function. A total of 720 WOD188 broiler breeder hens at 40 weeks old were assigned to 3 groups, with 8 replicates per group and 30 birds per replicate. Over 7 weeks, birds were fed a basal diet or the same diet supplemented with 0.15% Met or 0.17% HMTBA. Our findings revealed significant improvements in the Met group for egg shape index, shell thickness, breaking strength, and fracture toughness (P 0.05). Met supplementation increased calcium and phosphorus levels in both serum and shell gland tissue (P