Background:The Charlson Comorbidity Index (CCI) is widely used to assess comorbidity burden, its prognostic role in patients undergoing percutaneous coronary intervention (PCI) remains underexplored. This study aimed to investigate the impact of CCI on in-hospital adverse events and long-term major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with coronary artery disease (CAD) treated with PCI. Methods:A total of 572 consecutive CAD patients who underwent PCI between October 2016 and October 2020 were included. Patients were divided into low (CCI ≤ 4, n = 453) and high (CCI > 4, n = 119) comorbidity burden groups. Clinical characteristics, in-hospital adverse events, and long-term MACCEs were compared. Multivariate logistic regression and Cox proportional hazards models were used to identify independent predictors of outcomes. Results:Compared to the low-CCI group, patients in the high-CCI group were older, more frequently male, and had higher rates of diabetes, left main CAD, and multivessel disease (all p < 0.05). In-hospital adverse events were significantly more common in the high-CCI group (13.4% vs 2.0%, p < 0.01). CCI was an independent predictor of in-hospital events (OR = 3.13; 95% CI: 1.40-7.02). During a median follow-up of five years, the high-CCI group had a significantly higher incidence of MACCEs (51.3% vs 6.2%; HR = 2.72; 95% CI: 2.25-3.30, p < 0.01). Conclusion:CCI is a significant and independent predictor of both in-hospital and long-term adverse outcomes in CAD patients undergoing PCI.

Postoperative gastrointestinal function is one of the important factors influencing the prognosis of off-pump coronary artery bypass grafting (OPCAB) patients. Remote ischemic preconditioning (RIPC) is a noninvasive intervention that may offer multiorgan protection. This study aimed to evaluate the impact of preoperative RIPC on postoperative gastrointestinal function and clinical outcomes in OPCAB patients. This prospective, assessor- and statistician-blinded, sham-controlled, randomized clinical trial included 106 patients scheduled to undergo elective OPCAB. They were randomly assigned to the RIPC (n = 53) or sham-RIPC (n = 53) group. The RIPC group received bilateral upper limb ischemia/reperfusion cycles (200 mmHg, 5-min ischemia/5-min reperfusion, repeated for 5 cycles) twice daily for 3 consecutive preoperative days. The primary outcome was the incidence of postoperative gastrointestinal intolerance (POGI), defined as an I-FEED score of 3–5 within 7 days postoperatively. The secondary outcomes included markers of intestinal injury (intestinal fatty acid-binding protein (I-FABP)), systemic inflammation (interleukin-6 (IL-6), C-reactive protein (CRP)), and S-100 protein beta subunit (S-100β). The exploratory outcomes comprised gut microbiota analysis and other clinical parameters. The incidence of POGI was lower in the RIPC than in the sham-RIPC group (35.4

OBJECTIVE:Effective methods for establishing an aged animal model of diabetes and glycemic fluctuation have rarely been investigated. The aim of the study was to explore the feasibility of inducing glycemic fluctuation in aged Sprague-Dawley rats and to evaluate the corresponding changes in cognitive function. METHODS:Male rats aged 48 weeks were fed a high-fat and high-glucose diet and given streptozotocin intraperitoneally to establish a rat model of type 2 diabetes mellitus (T2DM). Then, glycemic fluctuation was induced via three different protocols: (1) intraperitoneal injection of glucose; (2) sequential fasting, insulin injection, and normal diet; and (3) intermittent intraperitoneal injections of glucose and insulin. RESULTS:All three protocols were effective at inducing glycemic fluctuation in aged rats with T2DM, with successful modeling rates of 60 %, 90 %, and 70 %, respectively. Aged T2DM rats with glycemic fluctuation showed significant increases in glycemic variability compared with controls, including in the mean blood glucose, postprandial glycemic excursion, largest amplitude of glycemic excursion, and standard deviation of blood glucose values (all P < 0.05). Additionally, rats with glycemic fluctuation had more severe insulin resistance and dyslipidemia (P < 0.05). Morris water maze testing showed a trend of longer escape latency in the navigation test for rats in the glycemic fluctuation groups, suggesting impaired cognitive function. Pathological analysis showed degenerative changes in the CA1 hippocampal region of rats in the glycemic fluctuation groups. Finally, differential gene expression analysis revealed 1323 significantly altered genes in the GV group, with 691 upregulated and 632 downregulated. The dysregulated genes were predominantly associated with the axon guidance pathway and potassium channel regulation. CONCLUSIONS:The proposed protocols were effective at establishing an aged T2DM rat model with glycemic fluctuation, and rats with glycemic fluctuation exhibited diminished cognitive function.

Background:Surgery is pivotal in the management of neuroblastoma (NB), particularly in patients with image-defined risk factors. The International Neuroblastoma Surgical Report Form (INSRF) was introduced to enhance surgical reporting quality and analyze the defining role of extensive surgery in NB. This study reports our experience with INSRF and explores new criteria for evaluating the extent of surgical resection. Methods:INSRF was deployed to critically analyze 166 patients with abdominal or pelvic NB who underwent surgery at our department between October 2021 and June 2023. Patient demographics, clinical characteristics, surgical data sets, and postoperative complications were described in detail. Receiver operating characteristic curves were used to explore a new method to evaluate the extent of resection. A questionnaire was formulated to obtain attitudes/feedback and commentary from surgical oncologists with INSRF. Results:One hundred sixty-six NB patients with a median disease age of 36.50 months. This study collated 320 INSRF reports. Among the 166 index cases, 137 were documented by 2 surgeons, with a concordance rate of 16.78%. Items with high inconsistency were (1) the extent of tumor resection (29.20%), (2) renal vein involvement (25.55%), (3) abdominal aorta encasement (16.79%), and (4) mesenteric infiltration (17.52%). According to INSRF, the extent of resection was complete excision in 86 (51.81%) patients, minimal residual tumor < 5 cm(3) in 67 (40.36%) patients, and incomplete excision > 5 cm(3) in 13 (7.83%) patients. In receiver operating characteristic curve analysis, the number of vessels encased by tumors >3 had a high predictive value in determining that a tumor could not be completely resected (area under the curve 0.916, sensitivity 0.838, specificity 0.826) using INSRF as the gold standard reference. The questionnaires showed that surgeons agreed that the extent of resection and tumor involvement of organ/vascular structures were important, while the definition and intervention(s) of intraoperative complications were less operational and understandable. Conclusions:INSRF has significant clinical applications in NB surgery. The extent of resection can be predicted based on the number of tumor-encased blood vessels. Supplementary information should be considered with the INSRF to aid practitioner reporting. Multicenter studies are needed to explore the defining role of INSRF in NB surgical management.

BACKGROUND:The relationship between low physical activity and cognitive impairment in type 2 diabetes mellitus (T2DM) patients remains unclear. AIM:To explore this association and identify risk factors for cognitive impairment in elderly T2DM patients. METHODS:A retrospective analysis was conducted on 245 elderly T2DM patients treated at Xuanwu Hospital, Beijing, in 2023. Patients were categorized into low physical activity (n = 126) and non-low physical activity (n = 119) groups. After propensity score matching (PSM) of 100 pairs, univariate and binary logistic regression analyses identified risk factors for cognitive impairment. A predictive model was constructed and evaluated using receiver operating characteristic curve analysis. RESULTS:Before PSM, the percentage of cognitive impairment was higher in the low physical activity group (P < 0.05), but after PSM, this difference was not significant (P > 0.05). Additionally, on regression analyses after PSM, age, occupation type, history of stroke, malnutrition, and frailty remained independent factors associated with cognitive impairment, while low physical activity did not. The constructed risk prediction model for cognitive impairment in elderly T2DM patients exhibited an area under the curve of 0.77. CONCLUSION:Low physical activity was not associated with cognitive impairment in our study population. Some results differed before and after PSM analysis, indicating that PSM supports objective assessment of risk factors by controlling for selection bias and confounding factors related to population characteristics. The constructed cognitive risk model provides insight for the development of a clinical tool for early prevention of cognitive impairment in elderly T2DM patients.

Sarcopenic obesity (SO) is a syndrome characterized by a gradual reduction in skeletal muscle mass, strength, and function coupled with excessive fat accumulation, which considerably increases the risk of metabolic disorders and atherosclerotic cardiovascular disease. Owing to its extensive influence on the health of elderly individuals and distinct pathophysiological mechanisms, SO should be considered an independent clinical condition. Atherosclerosis, the fundamental pathophysiological underpinning of atherosclerotic cardiovascular disease, has garnered increased interest because of its association with SO. Existing research indicates that SO may synergistically promote atherosclerosis development through multiple pathways, including hormonal dysregulation, adipo-myokine imbalance, insulin resistance, chronic low-grade inflammation, and lipid metabolic abnormalities. The current literature gaps predominantly encompass the absence of standardized diagnostic criteria for SO, inconsistent results in studies investigating the relationship between SO and atherosclerosis, and inadequate causal validation. Studies indicate associations between SO and carotid atherosclerosis, coronary atherosclerosis, arterial stiffness, and 10-year atherosclerotic cardiovascular disease risk; however, conclusions remain inconsistent, and most studies are cross-sectional. Additionally, this field has insufficient focus on peripheral atherosclerosis, such as in the lower extremities. Moreover, the pathophysiological mechanisms remain unclear. A complex vicious cycle potentially exists among decreased muscle mass and function, fat accumulation, and atherosclerosis, a relationship that has not received sufficient attention. Therefore, this review aims to integrate existing evidence, summarize advances in diagnostic criteria for SO, review the epidemiological association between sarcopenic obesity and atherosclerosis, and analyze the reasons for heterogeneity in conclusions. It further explores potential pathophysiological mechanisms, delving into the vicious cycle among declining muscle mass and function, fat accumulation, and atherosclerosis. Finally, this review proposes future research directions, including diagnostic standardization, in-depth mechanism exploration, conducting prospective cohort studies to validate causal relationships, and developing intervention targets for SO-Atherosclerosis comorbidity.

BACKGROUND:In lung adenocarcinoma (LUAD), there remains a dearth of efficacious diagnostic studies including some inflammation-related genes to identify the LUAD subgroups with different clinical outcomes. METHODS:First, two molecular subgroups were identified with mRNA expression profiling from The Cancer Genome Atlas (TCGA) by K-means algorithm. Gene set enrichment analysis (GSEA), immune infiltration, and Gene set variation analysis (GSVA) were applied to explore the biological functions between these two subtypes. Then, univariate and multivariate Cox regression analyses were selected to evaluate the independence of these subtypes in LUAD. Next, lasso regression was applied to identify the high-precision mRNAs to predict the subtype with favorable prognosis. Finally, a two-mRNA model was constructed using the method of multivariate Cox regression, and the effectiveness of the model was validated in a training set (n = 310) and three independent validation sets (n = 1. RESULTS:Comprehensive genomic analysis was conducted of 310 LUAD samples and identified two subtypes associated with molecular classification and clinical prognosis: immune-enriched and non-immune-enriched subgroup. Then, a new model was developed based on two mRNAs (MS4A1 and MS4A2) in TCGA dataset and divided these LUAD patients into high-risk and low-risk subgroup with significantly different prognosis (HR = 1.644 (95% CI 1.153-2.342); p < 0.01), which was independence of the other clinical factors (p < 0.05). In addition, this new model had similar predictive effects in another three independent validation sets (HR > 1.445, p < 0.01). CONCLUSIONS:We constructed a robust model for predicting the risk of LUAD patients and evaluated the clinical outcomes independently with strong predictive power. This model stands as a reliable guide for implementing personalized treatment strategy.

Diabetes is highly prevalent among the elderly worldwide, with the highest number of diabetes cases in China. Yet, the management of diabetes remains unsatisfactory. Recent advances in digital health technologies have facilitated the establishment of smart wards for diabetes patients. There is a lack of smart wards tailored specifically for older diabetes patients who encounter unique challenges in glycemic control and diabetes management, including an increased vulnerability to hypoglycemia, the presence of multiple chronic diseases, and cognitive decline. In this review, studies on digital health technologies for diabetes in China and beyond were summarized to elucidate how the adoption of digital health technologies, such as real-time continuous glucose monitoring, sensor-augmented pump technology, and their integration with 5th generation networks, big data cloud storage, and hospital information systems, can address issues specifically related to elderly diabetes patients in hospital wards. Furthermore, the challenges and future directions for establishing and implementing smart wards for elderly diabetes patients are discussed, and these challenges may also be applicable to other countries worldwide, not just in China. Taken together, the smart wards may enhance clinical outcomes, address specific issues, and eventually improve patient-centered hospital care for elderly patients with diabetes.

Background:Neuroblastoma is the predominant extracranial solid tumor occurring in children, and genetic factors like genetic polymorphism play a crucial role in its etiology. In this study, we investigated the associations between three NEFL polymorphisms (rs11994014 G>A, rs2979704 T>C, and rs1059111 A>T) and neuroblastoma susceptibility in a cohort of 402 neuroblastoma patients and 473 controls from Jiangsu Province. Methods:Genotyping was determined using the TaqMan method. Genotype distributions between cases and controls were assessed via both univariate and multivariate logistic regression models to assess the associations between NEFL polymorphisms and neuroblastoma risk. Stratified analyses were performed based on age, sex, clinical stage, and site of origin to explore potential effect modifications and subgroup-specific associations. Results:In the overall analysis, no significant associations were found between any of the three NEFL polymorphisms and neuroblastoma risk. When subjects were grouped on the basis of the number of risk genotypes, no significant alteration in susceptibility was observed in children carrying three risk genotypes compared with controls carrying fewer risk genotypes. Stratified analyses based on age, sex, clinical stage, and site of origin also revealed no significant results. Conclusions:Our findings suggest that NEFL polymorphisms do not significantly modify neuroblastoma susceptibility in this population, suggesting that the previously reported neuroblastoma susceptibility loci in NEFL in Caucasians may not be consistent across different populations. Further research, including larger, more diverse cohorts, is necessary to clarify the potential role of NEFL and other genetic factors in neuroblastoma etiology.

Background: Depression exhibits bidirectional links with metabolic dysregulation, yet prior studies conflate depression-specific alterations with comorbidities. This case-control study rigorously excludes metabolic disorders and chronic medications to delineate intrinsic depression- associated metabolic signatures and their clinical implications. Methods: A case-control study included 1,243 moderate-to-severe depressive patients and 1,350 healthy controls, balanced via propensity score matching (caliper = 0.15). Continuous variables were compared using Mann-Whitney U tests, multivariate logistic regression adjusted confounders, and subgroup analyses employed 1:1 propensity matching (caliper = 0.2). Metabolic risks were quantified via adjusted odds ratios (ORs) and 95% confidence intervals (CIs), targeting the triglyceride-glucose (TyG) index, direct bilirubin (DBIL), and blood urea nitrogen (BUN). Results: Before adjustment, the moderate-to-severe depressive episode group showed significantly lower white blood cell count (4.7 vs. 5.5), hemoglobin (131.0 vs. 138.0), total protein (65.1 vs. 72.7), and high-density lipoprotein cholesterol (1.1 vs. 1.4) compared to controls (all P < 0.001), while the TyG index showed no difference (P = 0.979). After adjustment, TyG index was an independent risk factor for depressive episode (adjusted OR = 1.88, 95% CI: 1.09-2.95). In severe depressive episode subgroups, onset age (adjusted OR = 0.99, P = 0.043) and BUN (adjusted OR = 0.89, P = 0.037) were protective, while elevated DBIL was associated with psychotic symptoms (adjusted OR = 1.09, P = 0.041). Conclusions: This case-control study demonstrates significant associations between depressive episodes and systemic metabolic dysregulation, including inflammation, hepatic function, and lipid metabolism. The TyG index was independently associated with depressive episode status after adjustment, while elevated DBIL was associated with psychotic symptoms in severe depressive episode. Depression severity was associated with onset age and BUN levels. These findings suggest TyG index and DBIL as potential biomarkers meriting further investigation. However, the retrospective, case-control design limits causal inference and assessment of predictive utility; prospective studies are required to evaluate their clinical significance.

Glycemic variability (GV) markedly exacerbates cognitive impairment in elderly patients with type 2 diabetes mellitus (T2DM), in part through chronic inflammation. This study investigated the therapeutic efficacy of the NLRP3 inflammasome inhibitor MCC950 in mitigating GV-induced cognitive impairment in an aged rat model of T2DM. Aged Sprague-Dawley rats with induced T2DM were subjected to GV conditions, and the effects of MCC950 were evaluated through measurement of body weight, blood glucose, lipid profiles, insulin level, inflammatory markers, and cognitive function. Transcriptomic analysis was performed on the hippocampus and prefrontal cortex. Treatment with MCC950 significantly alleviated weight loss and hyperglycemia in the GV group compared with the control group. MCC950 also reduced the levels of cholesterol, triglycerides, and pro-inflammatory markers (interleukin-1β (IL-1β) and interleukin-18 (IL-18)). Most notably, MCC950 improved spatial learning and memory retention in the GV group. Immunohistochemical analysis indicated a reduction in inflammasome activation and an increase in the expression level of the neuronal marker NeuN in the hippocampus. Transcriptomic analysis revealed that MCC950 altered neuroactive ligand-receptor interaction pathways in the hippocampus and influenced receptor binding and cell adhesion processes in the prefrontal cortex. These findings validated the efficacy of NLRP3 inhibitor in mitigating GV-induced cognitive impairment in elderly rats with T2DM and provided the basis for subsequent clinical studies exploring the broader potential of NLRP3-targeted interventions in addressing diabetes-associated cognitive impairment.

Dengue virus (DENV) infection remains a critical global health threat, with DENV-2 being the most virulent serotype capable of causing lethal dengue hemorrhagic fever (DHF), a severe complication characterized by plasma leakage and hemorrhagic manifestations. While the search for viral receptors and immunocompetent animal models has persisted since the first recorded outbreak in 1779, significant gaps remain. Here, we establish the first immunocompetent murine model of DHF with intact innate/adaptive immunity by generating hTim4-transgenic C57BL/6J mice. This model recapitulates fatal DHF complications seen in humans, including systemic hemorrhage, dengue encephalitis and intestinal ischemia/gangrene. Integrated single-cell RNA sequencing and spatial transcriptomics analysis of hemorrhagic gut lesions demonstrated that DENV-2 infection induces Syk protein overexpression, leading to enhanced Th2 cytokine secretion and impaired hemostatic regulation. This cascade enhances vascular permeability, promotes plasma leakage, and drives multiorgan hemorrhage, a mechanism corroborated by parallel analyses of human DHF tissues. Critically, Th2-biased cytokine storm mirrors clinical findings in severe human dengue cases. Our work not only identifies hTim4 as a functional DENV-2 receptor but also provides a mechanistically grounded platform for DHF pathogenesis studies, bridging critical gaps between preclinical models and human immunopathology.

Abstract Background Lymphatic leakage is one of the postoperative complications of neuroblastoma. The purpose of this study is to summarize the clinical characteristics and risk factors of lymphatic leakage and try to find effective prevention and treatment measures. Methods A retrospective study included 186 children with abdominal neuroblastoma, including 32 children of lymphatic leakage and 154 children of non-lymphatic leakage. The clinical information, surgical data, postoperative abdominal drainage, treatment of lymphatic leakage and prognosis of the two groups were collected and analyzed. Results The incidence of lymphatic leakage in this cohort was 14% (32 children). Through univariate analysis of lymphatic leakage group and non-lymphatic leakage group, we found that lymphatic leakage increased the complications, prolonged the time of abdominal drainage and hospitalization, and delayed postoperative chemotherapy (p < 0.05). In this cohort, the median follow-up time was 46 (95% CI: 44–48) months. The follow-up data of 7 children were partially missing. 147 children survived, of which 23 had tumor recurrence (5 children recurred in the surgical area). 37 children died, of which 32 had tumor recurrence (9 children recurred in the operation area). In univariate analysis, there was no statistical difference in overall survival (p = 0.21) and event-free survival (p = 0.057) between lymphatic leakage group and non-lymphatic leakage group, while 3-year cumulative incidence of local progression was higher in lymphatic leakage group (p = 0.015). However, through multivariate analysis, we found that lymphatic leakage did not affect event-free survival, overall survival and cumulative incidence of local progression in children with neuroblastoma. Resection of 5 or more lymphatic regions was an independent risk factor for lymphatic leakage after neuroblastoma surgery. All 32 children with lymphatic leakage were cured by conservative treatment without surgery. Of these, 75% (24/32) children were cured by fat-free diet or observation, 25% (8/32) children were cured by total parenteral nutrition. The median drain output at diagnosis in total parenteral nutrition group was higher than that in non-total parenteral nutrition group (p < 0.001). The cut-off value was 17.2 ml/kg/day. Conclusions Lymphatic leakage does not affect the prognosis of children with neuroblastoma, but long-term drain output caused by lymphatic leakage will still adversely affect postoperative complications and follow-up treatment, which requires attention and active treatment measures. More attention should be paid to the children with 5 or more lymphatic regions resection, and the injured lymphatic vessels should be actively found and ligated after tumor resection to reduce the postoperative lymphatic leakage. Early application of total parenteral nutrition is recommended for those who have drain output at diagnosis of greater than 17.2 ml/kg/day. Level of evidence Level III, Treatment study (Retrospective comparative study).

Viral encephalitis continues to be a significant public health concern. In our previous study, we discovered a lower expression of antiviral factors, such as IFN-β, STING and IFI16, in the brain tissues of patients with Rasmussen’s encephalitis (RE), a rare chronic neurological disorder often occurred in children, characterized by unihemispheric brain atrophy. Furthermore, a higher cumulative viral score of human herpes viruses (HHVs) was also found to have a significantly positively correlated with the unihemispheric atrophy in RE. Type I IFNs (IFN-I) signaling is essential for innate anti-infection response by binding to IFN-α/β receptor (IFNAR). In this study, we infected WT mice and IFNAR-deficient A6 mice with herpes simplex virus 1 (HSV-1) via periocular injection to investigate the relationship between IFN-I signaling and HHVs-induced brain lesions. While all mice exhibited typical viral encephalitis lesions in their brains, HSV-induced epilepsy was only observed in A6 mice. The gene expression matrix, functional enrichment analysis and protein-protein interaction network revealed four gene models that were positively related with HSV-induced epilepsy. Additionally, ten key genes with the highest scores were identified. Taken together, these findings indicate that intact IFN-I signaling can effectively limit HHVs induced neural symptoms and brain lesions, thereby confirming the positive correlation between IFN-I signaling repression and brain atrophy in RE and other HHVs encephalitis.

INTRODUCTION AND IMPORTANCE:Congenital hepatoblastoma is an exceedingly rare neoplasm, predominantly documented as isolated instances, with contentious aspects surrounding its therapeutic approaches and prognostic implications. This study aims to comprehensively summarize and evaluate the management experience of congenital hepatoblastoma (CHB).CASE PRESENTATION:This cohort comprised five infants diagnosed with hepatoblastoma, confirmed through pathological examination, and with an onset of symptoms before 28 days of age. They were enrolled between November 2019 and May 2022. The treatment course they underwent has been summarized, and their prognosis has been subject to analysis.CLINICAL DISCUSSION:Distinguishing congenital hepatoblastoma from other medical conditions is typically necessary. Given the patient's tender age, the approach to treatment demands comprehensive assessment, particularly in cases involving unique tumor locations or substantial tumor sizes. The selection of treatment modalities, encompassing preoperative neoadjuvant chemotherapy and surgical techniques, becomes of paramount importance. Furthermore, determining the treatment's endpoint poses a notable challenge and often necessitates a comprehensive evaluation.CONCLUSION:For pediatric patients afflicted with CHB, the application of preoperative neoadjuvant chemotherapy mitigates surgical risks, while the incorporation of surgical procedures followed by postoperative chemotherapy significantly enhances the overall prognosis. Additionally, AFP-L3% levels may serve as a valuable adjunctive marker signifying the conclusion of treatment.

During its global epidemic, Zika virus (ZIKV) attracted widespread attention due to its link with various severe neurological symptoms and potential harm to male fertility. However, the understanding of how ZIKV invades and persists in the male reproductive system is limited due to the lack of immunocompetent small animal models. In this study, immunocompetent murine models were generated by using anti-IFNAR antibody blocked C57BL/6 male mice and human STAT2 (hSTAT2) knock in (KI) male mice. After infection, viral RNA could persist in the testes even after the disappearance of viremia. We also found a population of ZIKV-susceptible S100A4+ monocytes/macrophages that were recruited into testes from peripheral blood and played a crucial role for ZIKV infection in the testis. By using single-cell RNA sequencing, we also proved that S100A4+ monocytes/macrophages had a great impact on the microenvironment of ZIKV-infected testes, thus promoting ZIKV-induced testicular lesions. In conclusion, this study proposed a novel mechanism of long-term ZIKV infection in the male reproductive system.

Abstract Objective To summarize the clinical characteristics of children with adrenocortical carcinoma (ACC) and preliminarily explore the indications for and efficacy of neoadjuvant chemotherapy in certain patients. Methods The data of 49 children with adrenocortical tumors (ACT) in the past 15 years were retrospectively analyzed, and after pathology assessment using Weiss system grading, 40 children diagnosed with ACC were included. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and three-dimensional (3D) reconstruction of contrast-enhanced computed tomography data were used to evaluate the response to neoadjuvant chemotherapy. Results Forty patients (17 males, 23 females) with ACC were enrolled. Abnormal hormone levels were common in children with ACC (n = 31), and in terms of clinical presentation, sexual precocity was the most common (n = 14, 35.0%), followed by Cushing’s syndrome (n = 12, 30.0%). Seven of 40 children received neoadjuvant chemotherapy due to a maximum lesion diameter greater than 10 cm (n = 4), invasion of surrounding tissues (n = 2), intravenous tumor thrombus (n = 2), and/or distant metastasis (n = 2); 2 patients achieved partial response, and 5 had stable disease according to the RECIST 1.1 standard. Furthermore, 3D tumor volume reconstruction was performed in 5 children before and after neoadjuvant chemotherapy. Tumor volumes were significantly reduced in all 5 children, with a median volume reduction of 270 (interquartile range, IQR 83, 293) (range: 49–413) ml. After surgery with/without chemotherapy, the 5-year overall survival rate for all children was 90.0% (95% CI-confidence interval 80.0–100.0%), and the 5-year event-free survival rate was 81.5% (95% CI 68.0–97.7%). Conclusion In the diagnosis and treatment of pediatric ACC, a comprehensive endocrine evaluation is necessary to facilitate early diagnosis. Surgery and chemotherapy are important components of ACC treatment, and neoadjuvant chemotherapy should be considered for children with ACC who meet certain criteria, such as a large tumor, distant metastases, or poor general condition.

目的 探讨老年 2 型糖尿病患者认知功能与糖化白蛋白(GA)及糖化血红蛋白(HbA1c )比值(GA/HbA1c )的相关性.方法 选择2019 年 1～12 月于首都医科大学宣武医院老年综合科就诊的 161 例老年2 型糖尿病患者作为研究对象,运用简易精神状态评价量表(MMSE)评估认知功能情况,根据MMSE 得分将患者分为认知功能障碍组(41 例)及认知功能正常组(120 例).比较两组一般资料及实验室检查结果的差异,计算年龄、HbA1c 、GA、GA/HbA1c 与 MMSE 的相关性,logistic 回归分析认知功能的独立影响因素,ROC 曲线对 GA/HbA1c 在老年 2 型糖尿病认知功能障碍中的诊断价值进行评估.结果 认知功能障碍组的年龄与 GA/HbA1c 均高于认知功能正常组(P＜0.05).MMSE 得分与年龄及GA/HbA1c 均呈负相关(P＜0.05).logistic 回归分析显示,年龄与 GA/HbA1c 均为影响老年 2 型糖尿病患者认知功能障碍的独立危险因素(P＜0.05).GA/HbA1c 诊断老年 2 型糖尿病患者认知功能障碍的ROC 曲线下面积为0.669(95％CI:0.575～0.763,P＜0.05).结论 GA/HbA1c 与老年 2 型糖尿病患者认知功能障碍相关且易于获得,对认知功能障碍具有一定的预测能力.

Background With growing concerns about global population aging, comorbidity, and disability have emerged as key variables that influence the health of the older adults in terms of disease and function. This study sought to examine the impact of comorbidity and impairment using disease and functional status indicators of all-cause mortality in the older adults. Hypertension, which was chosen as the indicator chosen for disease, has the greatest prevalence in the older population. A total of 15 self-reported chronic conditions were added as indicators of comorbidity, and grip strength was chosen as a measure of functional status. The study also evaluated the association between grip strength and comorbidity, as well as its consequences on all-cause death and survival in a hypertensive senior population. Methods We chose a total of 2,990 hypertensive participants aged ≥60 years whose data for grip strength were collected in the National Health and Nutrition Examination Survey conducted between 2011 and 2014. The association of all-cause death with grip strength and comorbidity was examined using a Cox proportional hazard regression model. The interaction between comorbidity and all-cause mortality, as well as its association with grip strength, was also examined. Results The hazard ratio [95% confidence intervals (CIs)] for all-cause mortality in the highest grip strength tertile was 0.266 (0.168–0.419), compared to the lowest grip strength tertile. The all-cause mortality decreased with an increase in the number of co-morbidities [2.677 (1.557–4.603) in the group with ≥3 chronic diseases]. The weighted generalized model revealed a negative correlation between grip strength and comorbidities in more than three groups after accounting for all possible variables (β = −2.219, −3.178 ~ −1.260, p < 0.001). The risk of mortality reduced with increasing grip strength in patients with ≥3 comorbidities ( p -value for trend <0.05), but no meaningful difference was found in the interaction between comorbidities and grip strength ( p -value for interaction >0.05). Conclusion In older hypertension patients, grip strength and comorbidities were correlated with all-cause death, and there was a negative correlation between grip strength and comorbidities. Higher grip strength was associated with fewer fatalities in patients with ≥3 comorbidities, suggesting that functional exercise can improve the prognosis of comorbidities.

Background: Melanoma is a highly malignant tumor. Currently, immune-checkpoint blockade (ICB) therapy has a good effect on melanoma; however, the efficiency of this therapy is still low. Thus, the combination of new therapeutic targets and ICB may be essential in the treatment of melanoma.Methods: In this study, the RNA-seq and single-cell data of melanoma were retrieved from the Gene Expression Omnibus (GEO) database. The protein expression quantitative trait loci (eQTL) were found from the eQTLGen and Genotype-Tissue Expression (GTEx) databases, and SMR analysis was performed using data of melanoma and 15 other common cancers in the genome-wide association study (GWAS) database as outcome data. New melanoma characteristic genes were screened using the model of support vector machines (SVM) and analyzed using SMR in melanoma and pan-cancer to explore the role of the genes in melanoma and to determine whether the genes were a specific target of melanoma. The cells that the target acted on were determined using the cell grouping method and verified by protein levels.Findings: The melanoma characteristic genes MYOF and NFKBIE were selected using the SVM model. The SMR analysis showed that only the expression of MYOF was significantly negatively correlated with melanoma (blood: OR = 0.82, 95%CI = 0.68-0.98, P = 0.027; skin: OR = 0.80, 95%CI = 0.66-0.98, P = 0.03). However, NFKBIE was not associated with melanoma, and MYOF was associated with melanoma but not pan-cancer. Single-cell RNA sequencing showed that the expression of MYOF was significantly decreased during ICB treatment, which was consistent with the results from peripheral blood mononuclear cells. Single-cell RNA sequencing also indicated that MYOF might affect the therapeutic effect by acting on monocytes.Interpretation: The expression of MYOF was down-regulated after ICB treatment, as compared with that at the early stage of treatment, indicating that MYOF might be used as a predictor of ICB efficacy. Concerning the Mendelian randomization results, MYOF has the potential to be a specific target of therapies for melanoma.Funding: This work was supported by the National Natural Science Foundation of China (Grant No. 81974478, 82173009).Declaration of Interest: The authors have no conflicts of interest to disclose.Ethical Approval: This study involves human participants and was approved by the Medical Ethics Committee of Xiangya Hospital of Central South University (License No. 202308636).