Objective: To explore the longitudinal associations between dietary macronutrients and lung function in schoolaged children, so as to provide the nutritional research evidence for promoting children s lung health. Methods: In November 2021, two primary schools located in Chengdu, Sichuan Province were selected from the Southwest China Childhood Nutrition and Growth (SCCNG) cohort by a stratified cluster random sampling method, enrolling a total of 1 112 school aged children aged 8 to 13 years. At baseline, the dietary and sociodemographic characteristics of the children were assessed. One year later, the forced vital capacity (FVC) of the children was measured and converted into Z scores (FVC- Z ), while the vital capacity index (VCI) was also calculated. Generalized linear regression analysis was employed to examine the associations between dietary macronutrients and lung function, considering interactions with gender and age, followed by stratified analysis. Results: After adjusting for confounding factors, the analysis results of the generalized linear regression model showed that the carbohydrate energy ratio was negatively correlated with FVC- Z ( β =-0.02) and VCI ( β =-0.16), while the fat energy ratio showed a positive correlation with FVC- Z ( β =0.03) and VCI ( β =0.23) ( P <0.05). The protein energy ratio was positively correlated with FVC- Z ( β =0.09) and VCI ( β =0.60) specifically in girls ( P <0.05). Additionally, there was an interaction effect of age on the associations between macronutrients and lung function ( P <0.01); in children aged 8-9 and 10-11, the carbohydrate energy supply ratio was negatively correlated with FVC- Z ( β =-0.04, -0.03) and VCI ( β =-0.29, -0.21), and fat energy supply ratio was positively correlated with FVC- Z ( β =0.07, 0.05) and VCI ( β =0.46, 0.32) ( P <0.05). Conclusions There are age and sex differences in the association of dietary macronutrients with lung function, with a low carbohydrate, high fat diet promoting lung function in children. Additionally, protein intake appears to have a positive influence on the lung function of girls. The early school age period may represent a critical window for dietary interventions aimed at promoting lung health.

Community general practitioners are the main force of primary health care, however, the lack of effective incentive mechanisms would affect their work enthusiasm. Therefore, to enhance incentive mechanisms,particularly from the perspective of the career development,will improve the work enthusiasm and post competeny of general practitioners in primary health care services. This article summarizes five major influencing factors of the incentives for community general practitioners, namely salary and benefits, performance evaluation, promotion and development, working conditions and interpersonal relationships, and proposes the operational strategies of incentive improvement, to provide reference for improving working conditions and strengthening incentive measures for community general practioners in primary community hospitals.

Objective To explore the correlation of neutrophil/lymphocyte ratio(NLR),monocyte/high density lipoprotein cholesterol ratio(MHR)and mild cognitive impairment(MCI)in patients with type 2 diabetes mellitus(T2DM).Methods 159 T2DM patients hospitalized in the Department of Endocrinology,Affiliated Hospital of Xuzhou Medical University from February 2023 to April 2023 were selected.The subjects were divided into normal cognitive function(Con,n=72)group and MCI group(n=87)based on score of Montreal cognitive assessment scale(MoCA).NLR and MHR were calculated and compared between the two groups.Spearman correlation analysis was used to analyze the correlation between NLR,MHR and MoCA score.Logistic regression analysis of the factors influencing the association between T2DM with MCI.Receiver operator characteristic(ROC)curve was used to evaluate the predictive value of NLR and MHR for DM complicated with MCI.Results Compared with Con group,MCI group showed a significant increase in hemoglobin A1c(HbA1c),fasting plasma glucose,NLR,MHR,neutrophil count,monocyte count,serum creatinine,cystatin C,while high density lipoprotein cholesterol lymphocytes,visual space and executive function,naming,attention,language ability,abstract thinking,delayed memory,orientation and MoCA score decreased(P＜0.05).Spearman correlation analysis showed that there was a negative correlation between MHR,NLR and MoCA score,visuospatial and executive function,delayed recall and attention.Logistic regression analysis showed that NLR,MHR,HbA1c were all risk factors for MCI in T2DM.ROC curve analysis showed that the area under the curve of NLR combined with MHR for diagnosing T2DM with MCI was 0.872,with corresponding sensitivity of 81.6%and specificity of 87.5%.Conclusions NLR and MHR are closely related to MCI in T2DM patients.The combination of NLR and MHR have certain efficacy in prediction T2DM with MCI.

Objective To explore the correlation of neutrophil/lymphocyte ratio(NLR),monocyte/high density lipoprotein cholesterol ratio(MHR)and mild cognitive impairment(MCI)in patients with type 2 diabetes mellitus(T2DM).Methods 159 T2DM patients hospitalized in the Department of Endocrinology,Affiliated Hospital of Xuzhou Medical University from February 2023 to April 2023 were selected.The subjects were divided into normal cognitive function(Con,n=72)group and MCI group(n=87)based on score of Montreal cognitive assessment scale(MoCA).NLR and MHR were calculated and compared between the two groups.Spearman correlation analysis was used to analyze the correlation between NLR,MHR and MoCA score.Logistic regression analysis of the factors influencing the association between T2DM with MCI.Receiver operator characteristic(ROC)curve was used to evaluate the predictive value of NLR and MHR for DM complicated with MCI.Results Compared with Con group,MCI group showed a significant increase in hemoglobin A1c(HbA1c),fasting plasma glucose,NLR,MHR,neutrophil count,monocyte count,serum creatinine,cystatin C,while high density lipoprotein cholesterol lymphocytes,visual space and executive function,naming,attention,language ability,abstract thinking,delayed memory,orientation and MoCA score decreased(P＜0.05).Spearman correlation analysis showed that there was a negative correlation between MHR,NLR and MoCA score,visuospatial and executive function,delayed recall and attention.Logistic regression analysis showed that NLR,MHR,HbA1c were all risk factors for MCI in T2DM.ROC curve analysis showed that the area under the curve of NLR combined with MHR for diagnosing T2DM with MCI was 0.872,with corresponding sensitivity of 81.6%and specificity of 87.5%.Conclusions NLR and MHR are closely related to MCI in T2DM patients.The combination of NLR and MHR have certain efficacy in prediction T2DM with MCI.

Community general practitioners are the main force of primary health care, however, the lack of effective incentive mechanisms would affect their work enthusiasm. Therefore, to enhance incentive mechanisms,particularly from the perspective of the career development,will improve the work enthusiasm and post competeny of general practitioners in primary health care services. This article summarizes five major influencing factors of the incentives for community general practitioners, namely salary and benefits, performance evaluation, promotion and development, working conditions and interpersonal relationships, and proposes the operational strategies of incentive improvement, to provide reference for improving working conditions and strengthening incentive measures for community general practioners in primary community hospitals.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

The angiogenic microenvironment is a new blood vessel with different molecular and functional characteristics that sprouts on the original blood vessels through different mechanisms,which directly affects the process of tumor cell growth,proliferation,and migration and has an important impact on the occurrence and development of precancerous lesions of gastric cancer.Correa mode has shown that precancerous lesions of gastric cancer is the key pathological stage before the occurrence of gastric cancer,and it is of great significance to advance the prevention and treatment strategy to this stage.TCM believes that qi deficiency and blood stasis is the key pathogenesis of precancerous lesions of gastric cancer,and its basic treatment is to replenish qi and remove blood stasis,and based on the syndrome differentiation,drugs with the efficacy of nourishing yin and tonifying stomach,soothing the liver and regulating qi,resolving phlegm and dispersing lumps,and clearing heat and dampness for treatment.This article discussed the correlation between precancerous lesions of gastric cancer and angiogenic microenvironment and its regulatory pathways,and summarized the methods and mechanisms of TCM in the treatment of precancerous lesions of gastric cancer from the perspective of regulating angiogenic microenvironment-related pathways,in order to provide a reference for the treatment of precancerous lesions of gastric cancer with TCM.

Objective To study the effect of cobalt-60 gamma-ray (⁶⁰Co-γ) radiation on the structure of Nialamide, compare the anti-inflammatory activity of irradiation products, and explore the mechanism of action. Methods After ⁶⁰Co-γ irradiation of nialamide at a dose of 50 kGy, five known compounds were obtained (2-6). The viability of RAW 264.7 (mouse mononuclear macrophage leukemia) cells treated with these compounds was determined by CCK-8 assay. The secretion of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE₂) and the content of nitric oxide (NO) were measured using enzyme-linked immunosorbent assay and Griess method. The production of reactive oxygen species (ROS) was detected using DCFH-DA fluorescent probe. The expression levels of cell-induced nitric oxide synthase (iNOS), cyclooxygenase (COX-2), nuclear transcription factor-κB (NF-κB), and IκB were detected using Western blot. Results The products of nialamide after irradiation did not significantly affect RAW264.7 cell viability (P > 0.05) but showed a strong anti-inflammatory effect (P < 0.01). Compared with nialamide, compounds 2, 3, 4, 6 significantly reduced NO content in LPS-induced RAW 264.7 cells (P < 0.01), and compound 4 had the most significant effect. Moreover, compound 4 significantly reduced the content of IL-6, TNF-α, PGE₂, and ROS (P < 0.05) as well as the expression of iNOS, COX-2, NF-κB, and IκB (P < 0.05) in LPS-induced RAW 264.7 cells. Conclusion The chemical structure of nialamide is changed after irradiation with ⁶⁰Co-γ, and its product compound 4 shows strong anti-inflammatory activity, which may be related to inhibiting the activation of NF-κB signaling pathway and reducing the release of inflammatory factors. Radiation technology can provide new insights into the changes of molecular structures and physiological properties of natural products.

Background and purpose:Esophageal carcinoma(ESCA)is one of the malignant tumors with high mortality rate,and the underlying mechanism of its development is largely unknown.CDC20 plays an important role in tumorigenesis,and its dysregulated expression is closely related to tumor occurrence and development.The expression of CDC20 is increased in a variety of tumors,and knocking down CDC20 can inhibit tumor cell proliferation.NLRP3 is the main component of the inflammasome,and inflammasome is also closely related to tumor occurrence and development.Here,our study aimed to investigate whether CDC20 promotes the proliferation of ESCA cells through NLRP3 and its regulatory mechanism.Methods:The expression levels of CDC20 and NLRP3 genes in ESCA patients were analyzed using The Cancer Genome Atlas(TCGA)detabase and GTEx public database.We collected clinical and pathological data and tissues from 80 ESCA patients at the First Affiliated Hospital of Xinxiang Medical College,and detected the protein expression of NLRP3 in ESCA patients through immunohistochemistry staining.This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College(Number:EC-021-137).We studied the effects of knocking down CDC20 and NLRP3 gene on the proliferation ability of esophageal squamous cell carcinoma cells EC9706 and KYSE150 using short hairpin RNA(shRNA)technology.Co-immunoprecipitation(Co-IP),proteasome inhibitors and ubiquitination experiments were used to detect whether CDC20 interacts with NLRP3,and to elucidate whether CDC20 regulates NLRP3 expression through the ubiquitination pathway.This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College(Number:EC-021-137).Results:The TCGA database analysis showed that the expression levels of CDC20 and NLRP3 mRNA were significantly higher in the cancer tissues of ESCA patients than in the adjacent tissues.The immunohistochemistry results further showed that compared with adjacent tissues,the protein expression levels of CDC20 and NLRP3 were increased in ESCA tissues.Knocking down CDC20 and NLRP3 genes inhibited the proliferation of ESCA cells.Co-IP,proteasome inhibitors and ubiquitination experiments confirmed that CDC20 interacted with NLRP3 through its leucine-rich repeat(LRR),and CDC20 stabilized its expression by promoting NLRP3 ubiquitination.Conclusion:CDC20 and NLRP3 are upregulated in ESCA tissues,and CDC20 stabilizes their expression through ubiquitination of NLRP3,promoting ESCA cell proliferation.This suggests that CDC20 and NLRP3 may be potential diagnostic targets for ESCA.

Objective To explore the correlation between thyroid antibody levels and early renal injury in patients with type 2 diabetes mellitus(T2DM)combined with Hashimoto's thyroiditis(HT).Methods A total of 375 T2DM patients hospitalized in The Affiliated Hospital of Xuzhou Medical University from January 2018 to December 2022 were selectedas the study subjects,and 197 healthy people were selected as the control subjects.The patients with T2DM were divided into simple T2DM group(n=191)and T2DM combined with HT group(HT,n=184).According to the urinary albumin/creatinine ratio(UACR)level,T2DM patients with HT were divided into microalbuminuria subgroup(MUAlb,30≤UACR≤300 mg/g,n=70)and normal albuminuria subgroup(NUAlb,UACR<30 mg/g,n=114).According to whether the thyroid antibody was positive,they were divided into thyroid peroxides antibody[TPOAb(+)]subgroup(n=56),thyroglobulin antibody[TGAb(+)]subgroup(n=40)and TGAb and TPOAb double antibody positive subgroup(n=88).Results Compared with the NC group,the smoking,drinking,urinary creatinine,alpha 1-microglobulin,UACR,FPG,HbA1c,LDL-C,TC,and TG in the HT and T2DM groups increased(P<0.05),while HDL-C decreased(P<0.05).Compared with the NUAlb subgroup,the MUAlb subgroup showed age,DM duration,FPG,HbA1c,TGAb,TPOAb,thyroid stimulating hormone(TSH)increased(P<0.05),while FT3 and eGFR decreased(P<0.05).Spearman correlation analysis showed that UACR was positively correlated with age,HbA1c,TPOAb,TGAb,TSH(P<0.01),and negatively correlated with FT3(P<0.01).The UACR of the TGAb(+)+TPOAb(+)subgroup was higher than that of the TGAb(+)and TPOAb(+)subgroups(P<0.05).Logistic regression analysis showed that TSH,TGAb,TPOAb,and HbA1c were risk factors for MUAlb,while FT3 was a protective factor for MUAlb.Conclusions In T2DM with HT patients with normal thyroid function,TPOAb and TGAb are closely related to the occurrence of early renal injury.