Background With economic development and globalization, shift work has become prevalent across industries. Its relationship with type 2 diabetes mellitus (T2DM) attracts increasing attention. Objective To thoroughly explore the relationship between shift work and T2DM, and analyze the impacts of specific shift patterns on T2DM, so as to provide a basis for formulating reasonable shift schedules. Methods We conducted a 1:2 matched case-control study among adults (20-60 years) who ordered occupational health examinations at the Wuxi No.8 People's Hospital from November to December 2023. The case group comprised 200 T2DM patients, while the controls were 400 age-stratified matched non-diabetic individuals. General demographic characteristics, behavioral habits, medical history, and shift work exposure data (including shift patterns, frequency, and length of service) 5 years prior to diagnosis were collected through standardized questionnaires. Logistic regression adjusted for selected confounders was employed to evaluate the association between shift work and T2DM. Results The logistic regression analysis demonstrated that shift work was associated with an increased risk of T2DM. After adjusting for confounding factors, shift workers had a 3.55 times higher risk of being diagnosed T2DM compared to non-shift workers (OR=3.55, 95%CI: 1.026, 12.263). The risk varied across different shift patterns, and the three-shift two-rotation system showed the highest risk (OR=4.17, 95%CI: 1.921, 9.035), followed by the two-shift system (OR=2.94, 95%CI: 2.016, 4.281) and four-shift three-rotation system (OR=2.66, 95%CI: 1.611, 6.093). Workers with more than 3 monthly shift days had a 2.74-fold increased risk (95%CI: 1.658, 4.512) compared to non-shift workers. Additionally, working more than 8 h daily (OR=1.74, 95%CI: 1.185, 2.562) and having more than 20 years of service (OR=2.51, 95%CI: 1.581, 3.976) were both significantly associated with a higher T2DM risk. The trend tests revealed that each incremental increase in monthly shift days and length of service elevated T2DM risk by 2.61 times (95%CI: 1.813, 3.765) and 1.49 times (95%CI: 1.147, 1.931), respectively (P<0.05). Conclusion Shift work is an independent risk factor for T2DM, with three-shift two-rotation system posing the highest risk. Shift frequency, daily working hours, and length of service are all significant factors affecting the risk of T2DM. These findings support industry-specific shift policy reform and targeted glucose monitoring and health interventions are recommended for workers engaged in high-risk shift patterns (e.g., three-shift two-rotation system, frequent shifts) and those with prolonged shift work history (>20 years).

OBJECTIVES: To investigate the clinical features and prognosis of children with non-Down-syndrome-related acute megakaryoblastic leukemia (non-DS-AMKL). METHODS: A retrospective analysis was conducted on the medical data of 17 children with non-DS-AMKL who were admitted to Children's Hospital of The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023, and their clinical features, treatment, and prognosis were summarized. RESULTS: Among the 17 children with non-DS-AMKL, there were 8 boys and 9 girls. Fourteen patients had an onset age of less than 36 months, with a median age of 21 months (range:13-145 months). Immunophenotyping results showed that 16 children were positive for CD61 and 13 were positive for CD41. The karyotype analysis was performed on 16 children, with normal karyotype in 6 children and abnormal karyotype in 9 children, among whom 5 had complex karyotype and 1 had no mitotic figure. Detected fusion genes included EVI1, NUP98-KDM5A, KDM5A-MIS18BP1, C22orf34-BRD1, WT1, and MLL-AF9. Genetic alterations included TET2, D7S486 deletion (suggesting 7q-), CSF1R deletion, and PIM1. All 17 children received chemotherapy, among whom 16 (94%) achieved complete remission after one course of induction therapy, and 1 child underwent hematopoietic stem cell transplantation (HSCT) and remained alive and disease-free. Of all children, 7 experienced recurrence, among whom 1 child received HSCT and died of graft-versus-host disease. At the last follow-up, six patients remained alive and disease-free. CONCLUSIONS Non-DS-AMKL primarily occurs in children between 1 and 3 years of age. The patients with this disorder have a high incidence rate of chromosomal abnormalities, with complex karyotypes in most patients. Some patients harbor fusion genes or gene mutations. Although the initial remission rate is high, the long-term survival rate remains low.
Humans ; Male ; Female ; Leukemia, Megakaryoblastic, Acute/etiology* ; Child, Preschool ; Infant ; Child ; Retrospective Studies ; Prognosis ; Down Syndrome/complications*

OBJECTIVE: By analyzing the correlation between genotypes and phenotypes, we explored the impact of the variant c.917T>C (p.L306P) in the ABO*B.01 allele on the expression and function of B-glycosyltransferase (GTB). This study aims to elucidate the molecular mechanisms underlying the occurrence of this subtype. METHODS: The study subjects included a blood donor specimen with incompatible forward and reverse ABO typing results. ABO phenotyping was determined using ABO blood group serology and GTB activity testing. Subsequently, Sanger sequencing and third-generation sequencing based on the PacBio platform were employed to sequence the ABO gene, resulting in the determination of haplotype sequences. Mutations were identified through sequence alignment. An in vitro cell expression system was established to assess the impact of the mutation site on antigen expression. RESULTS: The index case in this study was identified as B subtype with the allelic genotype c.917T>C in ABO*B.01/ABO*O.01.01 , which has not been previously reported. in vitro expression results revealed decreased levels of GTB expression and overall GTB activity in the mutant cells. Furthermore, the expression of the B antigen on the cell membrane was weaker in the mutant cells compared to the wild-type cells. CONCLUSION The p.L306P variation caused by the c.917T>C mutation in the ABO*B.01 allele may be a genetic factor contributing to the reduced expression of B antigens on the surface of red blood cells.
Humans ; ABO Blood-Group System/genetics* ; Alleles ; Genotype ; Mutation ; Glycosyltransferases/genetics* ; Haplotypes ; Phenotype

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

OBJECTIVE: Astragali Radix (AR, Huangqi in Chinese) has been utilized generally as a bulk drug for the treatment of chronic atrophic gastritis (CAG) in China. The efficacy of wild-simulated AR (WAR) and transplanted AR (TAR) commercially available is unclear. This study aimed to further clarify the therapeutic action of WAR and TAR to treat CAG rats based on endogenous-xenobiotics metabolism. METHODS: Ultra-high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometer (UHPLC-Q-TOF/MS) based metabolomics had been used to analyze the cecal contents metabolic features and metabolic process differences of two ARs in the treatment of CAG. RESULTS: Apparent pharmacodynamic indicator examination revealed that the WAR group had a more substantial curative effect. Metabolomics studies revealed that seven endogenous metabolites were significant differences in two ARs. Furthermore, following treatment, 77 and 65 xenobiotics metabolites were identified in the WAR and TAR groups, respectively. Finally, the most critical riboflavin metabolic route in the formation of CAG was chosen for molecular docking with the relevant exogenous components, and WAR scored higher than TAR. CONCLUSION In this work, we analyzed the efficacy differences of AR from diverse cultivation forms by combining metabolomics and medicinal chemistry technologies, and it gave a fresh perspective for TCM efficacy evaluation and quality control research.

ObjectiveBody fluid stains left at crime scenes are frequently trace amounts, while the identification of body fluids through real time fluorogenic quantitative technique often necessitates the repeated detection within the limited sample, as multiple miRNA markers are the basis for the identification. Based on the goal of both the throughput and efficiency improvement of miRNA analysis in trace samples, a duplex real time fluorogenic quantitative PCR assay system was designed to accurately quantify two miRNAs simultaneously, and the system should be further verified by actual sample for the body fluid identification. MethodsThe duplex real time fluorogenic quantitative PCR system of miR-451a to miR-21-5p was established with specially designed primers and probes, and the concentrations of the primers and probes were both optimized. The specificity, sensitivity and reproducibility of the system were validated, while its capability for body fluid identification was assessed using the miR-451a to miR-21-5p ratio. ResultsThe optimized assay system exhibited excellent specificity and repeatability, with coefficients of variation consistently below 8% for both intra- and inter-batch variability. The amplification efficiency of miR-451a and miR-21-5p reached 71.77% and 74.81%, respectively, with high and relatively consistent results. By utilizing this duplex real time fluorogenic quantitative PCR assay system, a total of 58 body fluid samples were analyzed, exhibiting a discrimination rate of 100% between blood and non-blood samples, as well as between peripheral blood and menstrual blood samples. Moreover, the results, obtained from single real time fluorogenic quantitative PCR assay system and duplex real time fluorogenic quantitative PCR assay system, showed no statistically significant difference with randomly selected blood samples (n=20). Compared to previous single real time fluorogenic quantitative PCR assay system, the sensitivity of duplex real time fluorogenic quantitative PCR assay system exhibited remarkable improvement. A minimum input of only 0.1 ng total RNA was sufficient for accurate detection of peripheral blood and menstrual blood samples, while saliva, semen, and vaginal secretion required only 1 ng total RNA for precise identification purposes. Additionally, the duplex real time fluorogenic quantitative PCR assay system successfully differentiated between different types of body fluids in simulated samples under natural outdoor conditions. ConclusionThe duplex real time fluorogenic quantitative PCR assay system effectively reduced both the time and material costs by half compared to the single system, especially suitable for the examination of body fluid stains left at crime scenes, solving the contradiction between the trace amount and the multiple sample volumes demand of repeated real time fluorogenic quantitative PCR. The duplex real time fluorogenic quantitative PCR assay successfully distinguished blood and other body fluid, as well as peripheral blood and menstrual blood samples, which maintains an equivalent capability for body fluid identification with half sample, time and reagent consumption. This system provides an efficient tool for identifying suspicious body fluids, as well as a foundation for more multiplexed real time fluorogenic quantitative PCR assay system research.

Guided by the concept of "blood-pulse-heart-spirit"， it is believed that stable angina combined with insomnia is caused by disturbance of blood vessels， which leads to loss of nourishment for the heart body and heart spirit， so the core treatment principle is to regulate the blood vessels and calm the mind. At the beginning of the disease， it shows as the liver fails to govern the free flow of qi， and disorders qi and blood； during the progress of the disease， it shows as spleen deficiency and phlegm stagnation， phlegm and blood stasis obstructing the vessels； the central mechanism of the disease shows as disturbance of blood vessels and insufficient heart yin. For the pattern of liver depression and blood stasis， pattern of phlegm and blood stasis blocking the vessels， and pattern of heart yin deficiency， it is recommended to treat by Wuzang Shenning Formula （五脏神宁方） to dredge the liver and regulate the vessels， Banxia Houpo Decoction （半夏厚朴汤） plus Gualou Xiebai Banxia Decoction （瓜蒌薤白半夏汤） to dissolve phlegm and regulate the vessels， and Yunpi Tiaoxin Decoction （运脾调心汤） to nourish the yin and regulate the vessels. Throughout the treatment， pattern differentiation and treatment is accompanied by the method of calming the mind with heavy sedatives and nourishing the blood to calm the mind， so as to achieve the purpose of regulating mind and heart together and treating the body and spirit at the same time.

Objective To explore the feasibility and effectiveness of Commando procedure for mechanical valve dysfunction requiring reoperation. Methods The clinical data of patients who received Commando surgery (aortic/mitral curtain enlargement+valve replacement surgery) in the Department of Cardiovascular Surgery of Gaozhou People's Hospital from December 2021 to September 2022 were retrospectively analyzed. These patients who had undergone mechanical mitral or aortic valve replacement and then had mechanical valve dysfunction with mitral or aortic valve lesions requiring repeat combined valve replacement surgery were selected. Results Eleven patients were enrolled, including 2 males and 9 females, aged 63.63±11.64 years. All 11 patients successfully underwent the Commando operation, and were implanted with suitable artificial valves, among which the aortic valve size was 27.00±2.00 mm, and the mitral valve size was 27.72±3.13 mm. Cardiopulmonary bypass time was 195.81±39.29 min, aortic cross-clamping time was 121.81±28.60 min, mechanical ventilation time was 15.09±3.72 h, ICU stay time was 3.09±0.70 days, and total postoperative thoracic drainage volume was 417.18±68.65 mL. There was no perioperative death. Conclusion Commando procedure is a safe and effective method to perform combined valve operation for mechanical valve dysfunction. A larger artificial valve can be implanted during the procedure to obtain sound hemodynamic effects. In addition, for elderly patients, a suitable type of bioprosthetic valve can be implanted to improve the patient's quality of life. The early surgical effect is satisfactory, and the long-term impact needs further follow-up.

[摘 要] 目的：基于生物信息学方法探究几丁质酶-3样蛋白2（CHI3L2）在脑胶质瘤中的表达和生物学过程及其对患者临床预后的影响。方法：以中国脑胶质瘤基因组图谱（CGGA）为训练集（n = 325）、癌症基因组图谱（TCGA）为验证集（n = 702），对CHI3L2与脑胶质瘤患者临床病理特征的关系、预后价值和生物学过程进行交叉验证分析。用Kaplan-Meier法进行生存分析，采用Cox回归模型分析CHI3L2表达及相关临床病理特征与脑胶质瘤患者预后的关系，利用受试者工作特征（ROC）曲线分析CHI3L2在脑胶质瘤诊断中的价值，用GO、KEGG及GSVA途径分析CHI3L2在脑胶质瘤中的潜在生物学过程，构建CHI3L2的列线图以校准曲线及C-Index值来评估预测的准确性。WB法和qPCR 法检测CHI3L2在正常星形胶质细胞HA1800、胶质瘤U215和U87细胞中蛋白质与mRNA水平表达的影响。选取长沙市中心医院病理科保存的7例正常脑组织、5例低级别胶质瘤（LGG, WHOⅠ~Ⅱ级）和6例胶质母细胞瘤（GBM，WHO Ⅳ级）标本进行免疫组化染色分析，验证CHI3L2在正常脑组织和不同级别脑胶质瘤组织中的表达情况。结果：CHI3L2在GBM（P < 0.000 1）、非1p/19q编码（P < 0.000 1）、IDH-野生型（P < 0.000 1）、非MGMT甲基化（P<0.01）患者中显著表达，对GBM具有一定的预测价值，并且是脑胶质瘤患者总生存期（OS）的独立预后因素（P < 0.001）。构建的列线图对脑胶质瘤患者的生存预后预测性良好。CHI3L2与LGG和GBM的免疫细胞浸润水平、肿瘤免疫微环境和免疫细胞均有显著关系。脑胶质瘤中CHI3L2蛋白（P < 0.05）和mRNA（P < 0.000 1）的表达水平与更高的恶性程度相关，免疫组化的结果进一步验证了这个发现。结论：CHI3L2的表达与脑胶质瘤的恶性程度、临床病理特征及预后关系密切，并且参与脑胶质瘤的肿瘤微环境和免疫浸润，有望成为脑胶质瘤治疗策略中的一个新靶点。