Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To establish and evaluate a confirmation method for hepatitis B surface antigen(HBsAg)based on chemiluminescent immunoassay and neutralization test.Methods:①Detection procedure of the confirmation method:Initially,optimal concentration of neutralizing antibody was determined through a preliminary trial.During the confirmation of HBsAg,in the detection cups and control cups already containing test serum,neutralizing antibody and pre-test four items(hepatitis B serological markers,HCV antibody,syphilis spiral body antibody,HIV antibody)negative serum were added in a 1∶1 ratio(100 μl∶100 μl),respectively.After thorough mixing,the mixture was incubated at 37℃for 30 min,and the pre-treated serum was tested using the Siemens Atellica IM HBsAg detection program.②Reliability evaluation of the confirmation method:Coincidence rate of the confirmation method results and the Siemens confirmation reagent test results for 64 serum samples with different concentrations of HBsAg reactivity was compared and analyzed.③Determination of the diagnostic value and positive judgment value of the confirmation method:Taking the Siemens confirmation reagent test results for 64 HBsAg reactive serum samples as"the gold standard",neutralization rate of the confirmation method test results was statistically analyzed using ROC curve.Results:①In the preliminary trial,when the concentration of HBsAb was≥1 285.12 mU/ml,neutralization rate of the test results was>50%,and the neutralization rate was increased with the concentra-tion of HBsAb.After the same concentration of HBsAb neutralized different concentrations of HBsAg,trend of the neutralization rate change was not significant.②Coincidence rate of the two methods was 100.00%.③Area under the curve(AUC)was 0.993 4,the pos-itive judgment value was neutralization rate≥47.93%,with a sensitivity of 98.15%and specificity of 100.00%.Conclusion:This de-tection method is simple,easy-to-use,cost-effective,and has high diagnostic value,suitable for confirming HBsAg at different con-centrations.

Objective To explore the protective effect of exercise-induced metabolite-3 (EIM-3) on myocardial ischemia-reperfusion (I/R) injury and explore its underlying molecular mechanisms. Methods The physicochemical properties and half-life of EIM-3 were analyzed using the Human Metabolome Database (HMDB, https://hmdb.ca/). A primary rat cardiomyocyte hypoxia/reoxygenation (H/R) injury model was established. Cell apoptosis and viability were assessed using TUNEL assay and cell counting kit-8, respectively. Lactate dehydrogenase (LDH) levels in the cell culture supernatant were measured. Intracellular reactive oxygen species (ROS) levels were detected. Transcriptomic analysis was performed to identify potential signaling pathways and targets of EIM-3. Results Plasma levels of EIM-3 were elevated post-exercise. EIM-3 was characterized as a phospholipid small-molecule compound with a partition coefficient (logP) of 5.58 and a solubility (logS) of −7.6, indicating favorable lipophilicity and cell membrane permeability. In cardiomyocytes H/R injury modles, EIM-3 significantly inhibited apoptosis, increased cell viability, reduced intracellular ROS levels, and decreased LDH release (P＜0.01). Transcriptomic analysis suggested that EIM-3 exerts its protective function potentially by regulating glucose metabolim. Quantitative real-time polymerase chain reaction results confirmed that EIM-3 significantly upregulated the transcriptional level of pyruvate kinase M2 (PKM2) in a dose-dependent manner (P＜0.001). Conclusions EIM-3 protects cardiomyocytes against I/R injury by modulating glucose metabolim. This study provides foundational insights into the mechanisms underlying exercise-induced cardioprotection.

Radiotherapy plays a pivotal role in the treatment of malignant tumors. The emergence of radiation resistance in malignant tumors, contributing to tumor recurrence, progression, or distant metastasis, remains a significant treatment challenge. Exploring the mechanisms underlying radiation resistance and overcoming the radio-resistance of tumors have become urgent problems in oncological practice. Cuproptosis, a copper-dependent form of regulated cell death, is driven by the aggregation of lipoylated proteins and the reduction of Fe-S cluster proteins, etc. Copper and cuproptosis are not only intricately related to the incidence and development of tumors, but also participate in radiation resistance of tumor cells. Strategic interventions targeting copper and inducing cuproptosis will present promising avenues for overcoming radiation resistance and further improving the prognosis of tumor patients. This review comprehensively delineates established and potential mechanisms governing the intricate crosstalk between radiation resistance and cuproptosis, aiming to provide reference for overcoming radiation resistance in malignant tumor cells.

Objective To investigate the association between 8 insulin resistance(IR)surrogate markers and incident atherosclerotic cardiovascular disease(ASCVD)in population with cardiovascular-kidney-metabolic syndrome(CKM)of stages 0-3,and to identify the surrogate marker with the best predictive performance.Methods A study was conducted on 20121 community residents classified as CKM stages 0-3 from the Chengdu cohort of the China Multi-Ethic Cohort.A Cox proportional hazards model was used to calculate hazard ratios(HRs)between each IR surrogate marker and incident ASCVD.Cubic spline regression was employed to explore the dose-response relationships between these markers and incident ASCVD.The relative relationships between different markers and incident ASCVD were examined through the ratio of HRs(RHRs).Time-dependent area under the receiver operating characteristic curve(TDAUC)and Uno's C-statistic were calculated to compare the predictive performance of each marker for incident ASCVD.Based on the PREVENT equation components and the 8 surrogate markers under analysis,random forest feature selection was used to determine the contribution of each marker to accurate prediction.Results During a follow-up period of82 741.93 person-years,1447 incident cases of ASCVD were recorded,with an incidence density of 17.49 per 1000 person-years.Association analyses indicated that the triglyceride to high-density lipoprotein cholesterol ratio(TG/HDL)and the TyG/(TG/HDL)index were not associated with incident ASCVD(P＞0.05).The TyG index combined with obesity measurement parameters emerged as a reliable predictor of ASCVD incidence.The most promising indicator,TyG index with waist-to-height ratio(TyG_WHtR),exhibited an inverted J-shaped association with incident ASCVD(P for nonlinearity=0.045;TDAUC=0.640;C=0.634),while the TyG index with body mass index(TyG_BMI),waist circumference(TyG_WC),and waist-to-hip ratio(TyG_WHR)showed positive linear associations(all P for trend＜0.05),with relatively lower predictive performance(C=0.564,0.588,and 0.598,respectively).Although both the TyG index and the metabolic score for insulin resistance(METS-IR)were associated with increased ASCVD risk(TyG:Q2 vs.Q1,HR=1.23 and Q4 vs.Q1,HR=1.24;METS-IR:P for non-linearity=0.045),they exhibited poor predictive performance for incident ASCVD.Conclusion The TyG index combined with obesity measurement parameters is an ideal IR surrogate marker for predicting incident ASCVD in populations with stages 0-3 CKM.Monitoring these markers will facilitate the prevention and control of cardiovascular diseases in CKM populations.

Objective To investigate the association between rest-activity rhythm(RAR)and the risks of rheumatoid arthritis(RA),and to evaluate whether genetic susceptibility modifies this relationship.Methods This prospective cohort study utilized data from the UK Biobank,including 88 060 participants who did not have RA at baseline.RAR parameters(e.g.,relative amplitude)were calculated using data obtained through wrist-worn accelerometers.The participants'genetic susceptibility to RA was assessed using a polygenic risk score.Cox proportional hazards models were employed to analyze the association between RAR and RA risk,with interaction terms incorporated to evaluate the effect modification by genetic susceptibility.Results Over a median follow-up period of 7.97 years,660 incident RA cases were identified.After adjusting for age,sex,ethnicity,educational attainment,Townsend deprivation index,drinking status,smoking status,dietary score,body mass index,and polygenic risk score for incident RA,the dose-response analysis revealed a linear relationship between the RAR-related parameters,including the average amplitude during the most active 10 h(M10),interdaily stability(IS),intradaily variability(IV),and the risk of developing RA(P>0.05).In contrast,relative amplitude and the average amplitude during the least active 5 h(L5)showed a nonlinear relationship with the risk of developing RA(P<0.05).Compared to those in the the highest quartile of relative amplitude,participants in the lowest quartile had a 49%increase in the risk of developing RA(hazard ratio[HR]=1.49;95%CI,1.17-1.90).Compared to those in the lowest quartile,participants in the highest quartile of L5 had a 40%increased risk of developing RA(HR=1.40;95%CI,1.12-1.75).Every time M10 increased by one standard deviation,the risk of developing RA decreased by 12%(HR=0.88;95%CI,0.80-0.96).No evidence of effect modification by genetic susceptibility was observed in the RAR-RA association(P>0.05).Conclusion Disrupted rest-activity rhythm is associated with an increased risk of RA,which is independent of genetic susceptibility to RA.Our findings suggest that improving rest-activity rhythm may help reduce RA risks.

Radiotherapy plays a pivotal role in the treatment of malignant tumors. The emergence of radiation resistance in malignant tumors, contributing to tumor recurrence, progression, or distant metastasis, remains a significant treatment challenge. Exploring the mechanisms underlying radiation resistance and overcoming the radio-resistance of tumors have become urgent problems in oncological practice. Cuproptosis, a copper-dependent form of regulated cell death, is driven by the aggregation of lipoylated proteins and the reduction of Fe-S cluster proteins, etc. Copper and cuproptosis are not only intricately related to the incidence and development of tumors, but also participate in radiation resistance of tumor cells. Strategic interventions targeting copper and inducing cuproptosis will present promising avenues for overcoming radiation resistance and further improving the prognosis of tumor patients. This review comprehensively delineates established and potential mechanisms governing the intricate crosstalk between radiation resistance and cuproptosis, aiming to provide reference for overcoming radiation resistance in malignant tumor cells.

Objective:To establish and evaluate a confirmation method for hepatitis B surface antigen(HBsAg)based on chemiluminescent immunoassay and neutralization test.Methods:①Detection procedure of the confirmation method:Initially,optimal concentration of neutralizing antibody was determined through a preliminary trial.During the confirmation of HBsAg,in the detection cups and control cups already containing test serum,neutralizing antibody and pre-test four items(hepatitis B serological markers,HCV antibody,syphilis spiral body antibody,HIV antibody)negative serum were added in a 1∶1 ratio(100 μl∶100 μl),respectively.After thorough mixing,the mixture was incubated at 37℃for 30 min,and the pre-treated serum was tested using the Siemens Atellica IM HBsAg detection program.②Reliability evaluation of the confirmation method:Coincidence rate of the confirmation method results and the Siemens confirmation reagent test results for 64 serum samples with different concentrations of HBsAg reactivity was compared and analyzed.③Determination of the diagnostic value and positive judgment value of the confirmation method:Taking the Siemens confirmation reagent test results for 64 HBsAg reactive serum samples as"the gold standard",neutralization rate of the confirmation method test results was statistically analyzed using ROC curve.Results:①In the preliminary trial,when the concentration of HBsAb was≥1 285.12 mU/ml,neutralization rate of the test results was>50%,and the neutralization rate was increased with the concentra-tion of HBsAb.After the same concentration of HBsAb neutralized different concentrations of HBsAg,trend of the neutralization rate change was not significant.②Coincidence rate of the two methods was 100.00%.③Area under the curve(AUC)was 0.993 4,the pos-itive judgment value was neutralization rate≥47.93%,with a sensitivity of 98.15%and specificity of 100.00%.Conclusion:This de-tection method is simple,easy-to-use,cost-effective,and has high diagnostic value,suitable for confirming HBsAg at different con-centrations.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To analyze the safety of reduced clinical target volume (CTV) irradiation of suspicious positive lymph nodes in IIa region in patients with N 0-N 1 nasopharyngeal carcinoma (NPC) and the protective effect of submandibular gland and long-term resting dry mouth, and to explore the diagnostic value of multimodal imaging for suspicious cervical lymph nodes. Methods:Clinical data of T 0-4N 0-1M 0 stage NPC patients admitted to Jiangsu Cancer Hospital from July 2015 to April 2017 were retrospectively analyzed. Clinical, radiation therapy planning, multimodal imaging and other relevant data were collected. All patients were treated with an optimized regimen of IMRT with a prophylactic radiation dose of 50.4 Gy (named as CTV50) for IIa region. Imaging characteristics and treatment response of suspicious lymph nodes were monitored by MRI, MRI-DWI, PET-CT and repeated enhanced positioning CT, etc. The dosimetry of the submandibular gland between optimized and standard dose plans (CTV50 vs. CTV60) was compared by paired t-test. The long-term dry mouth degree of the patients was evaluated using advanced radiation injury from Radiation Therapy Oncology Group (RTOG), Jiangsu Cancer Hospital Multi-dimensional Dry Mouth Evaluation Scale and summated xerostomia inventory (SXI). The difference of dry mouth degree was analyzed by rank-sum test. Results:A total of 106 patients were included in this study, including 149 cervical lymph node negative sides, 73 sides of which had ≤3 recognizable lymph nodes, and 76 of which were>3 in Ⅱa region. Among patients with N 1 stage, 63 patients underwent contralateral single neck area optimization, and 43 patients (N 0 stage and N 1 stage patients with retropharyngeal lymph node metastasis) underwent double-neck area optimization. A total of 109 suspicious lymph nodes with a short diameter of >5 mm were found on the largest cross section, of which 105 had clear portal structure. The ratio of long to short diameter was ≥1.5 in 93 cases, and the maximum standardized uptake value (SUV max) in PET-CT was ≥2.5 in 76 cases. No lymph node recurrence was found in the CTV optimized area. There was no significant difference in the average dose of GTV in tumor target area after optimization ( P>0.05), and the D mean and V 39 Gy in submandibular gland were significantly lower than those in unoptimized plan (both P<0.01). There was no significant difference in long-term dry mouth and resting dry mouth between patients with unilateral and bilateral optimization of submandibular gland (both P>0.05). Conclusions:The optimal program of CTV50 reduction irradiation in Ⅱa area of N 0-N 1 NPC patients is safe and effective. The submandibular gland has obvious dosimetric advantages, and patients have a good subjective response to resting dry mouth. The multimodal imaging tools such as enhanced CT, MRI-DWI and PET-CT should be performed to deliver individual evaluation and treatment for suspicious lymph nodes.