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.

Objective:To analyze the current status of Alzheimer's disease(AD)treatment costs under different co-morbid states in Sichuan,and to provide references and basis for prioritizing the formulation of related health policies.Methods:Based on the System of Health Accounting 2011(SHA 2011).Results:The total treatment cost of Alzheimer's disease patients in Sichuan Province in 2019 was 277 280 400 yuan,accounting for 0.13%of the province's disease treatment cost in 2019.There were significant differences in treatment costs among different co-morbidity groups,with family health expenditure being the main financing option(54.44%).The higher the co-morbidity index,the greater the share of family health expenditure.Treatment costs mainly flowed to hospitals,with the proportion of treatment costs going to general hospitals gradually increasing as the co-morbidity index increased.The treatment cost of women is higher than that of men,and the treatment cost of low,middle and high co-morbidity groups were mainly concentrated in the age groups of 55～69,70～89 and 80 years old and above respectively.Conclusion:It is recommended to optimize the financing scheme and build a multi-level medical insurance system.Continuously improve the protection mechanism to narrow the difference in treatment between outpatient and inpatient;improve the service capacity of primary health care institutions;pay attention to key populations and do a good job of preventing AD,so as to alleviate the overall burden of Alzheimer's disease in China,and promote the realization of healthy aging.

Objective:To analyze the current status of Alzheimer's disease(AD)treatment costs under different co-morbid states in Sichuan,and to provide references and basis for prioritizing the formulation of related health policies.Methods:Based on the System of Health Accounting 2011(SHA 2011).Results:The total treatment cost of Alzheimer's disease patients in Sichuan Province in 2019 was 277 280 400 yuan,accounting for 0.13%of the province's disease treatment cost in 2019.There were significant differences in treatment costs among different co-morbidity groups,with family health expenditure being the main financing option(54.44%).The higher the co-morbidity index,the greater the share of family health expenditure.Treatment costs mainly flowed to hospitals,with the proportion of treatment costs going to general hospitals gradually increasing as the co-morbidity index increased.The treatment cost of women is higher than that of men,and the treatment cost of low,middle and high co-morbidity groups were mainly concentrated in the age groups of 55～69,70～89 and 80 years old and above respectively.Conclusion:It is recommended to optimize the financing scheme and build a multi-level medical insurance system.Continuously improve the protection mechanism to narrow the difference in treatment between outpatient and inpatient;improve the service capacity of primary health care institutions;pay attention to key populations and do a good job of preventing AD,so as to alleviate the overall burden of Alzheimer's disease in China,and promote the realization of healthy aging.

Objective To explore the safety and efficacy of laparoscopic left renal vein stent implantation combined with microsurgical varicocelectomy in the treatment of nutcracker syndrome complicated with varicocele.Methods A retrospective analysis was conducted on the data of 50 patients with nutcracker syndrome complicated with varicocele admitted to our hospital during Nov.2018 and Jul.2023.All patients underwent laparoscopic left renal vein stent implantation combined with microsurgical varicocelectomy.Results Altogether 47 patients were followed up after operation,with a mean age of(21.45±3.84)years.All operations were successful,and gross hematuria,proteinuria,abdominal pain and other symptoms relieved within 3-7 days after surgery.Postoperative follow-up showed that no patients had serious complications or recurrence of clinical symptoms.Left renal vein ultrasound and CT showed that the blood flow of the left renal vein was restored,and the stent position was stable.Compared with those before surgery,the angle between the abdominal aorta and the superior mesenteric artery[(44.91±6.59)° vs.(22.58±6.61)°]and the diameter of the left renal vein at the angle[(6.03±0.99)mm vs.(1.87±0.46)mm]were significantly increased,and the blood flow velocity of the left renal vein at the angle[(48.77±14.79)cm/s vs.(102.53±41.15)cm/s]was significantly decreased,with statistically significant differences(P＜0.001).Scrotal ultrasound confirmed that there was no recurrence of varicocele 6 months after surgery,and the diameter of the spermatic vein was significantly reduced,with statistically significant differences(P＜0.001).Semen analysis showed that the sperm concentration[(60.27±48.45)×106/mL vs.(36.57±36.67)×106/mL,P=0.032]and percentage of rapid forward movement of sperm were significantly increased[(22.54±10.70)vs.(15.01±10.77),P=0.005],with statistically significant differences.The increase value of semen concentration[(23.7±41.48)×106/mL vs.(6.12±4.97)×106/mL,P=0.016)]increased after combined operation compared with left renal venous stenting alone,and there was no significant difference in the diameter of spermatic vein,inner diameter of renal vein and flow rate between the two surgical methods(P＞0.05).Conclusion Laparoscopic left renal vein stent implantation combined with microsurgical varicocelectomy is a minimally invasive,safe and effective method for the treatment of nutcracker syndrome complicated with varicocele.

Objective To clarify and analyze the reasons for failure in screening healthy menopausal female in a bioequivalence trial.Methods To summarize and clarify the data of 185 healthy menopausal female subjects participating in a bioequivalence trial of estradiol valerate conducted,and summarize the reasons for screening failure.Results The main reasons for screening failure include laboratory tests(32.04％),gynecological transvaginal color Doppler ultrasound(16.57％),vital signs(14.36％),chest computed tomography(CT,11.60％),and medical history/medication history(7.73％).Conclusion Screening failures in healthy menopausal female subjects were characterized mainly by abnormal gynecological transvaginal color Doppler ultrasound and non-compliance with basal hormone levels compared to generally healthy subjects.