Objective: To explore the association between sleep quality, sleep duration with blood pressure in primary and secondary school students with different nutritional status, so as to provide a reference for targeted intervention measures. Methods: By using stratified cluster random sampling method, a total of 10 871 students aged 7 to 18 years were selected from 36 primary and secondary schools in 6 counties of Yangzhou from October to November 2023. Physical examination and questionnaire survey were conducted respectively. Student Health Status and Influencing Factors Questionnaire was used to collected basic information. The overweight/obesity and sleep quality of primary and secondary school students were determined according to the Screening for Overweight and Obesity among School age Children and Adolescents and the Pittsburgh Sleep Quality Index scale. The χ 2 test was used to compare the prevalence of elevated blood pressure in different groups of primary and secondary school students. Multivariate Logistic regression model was used to explore the association between sleep and blood pressure in primary and secondary school students. Results: The prevalence of elevated blood pressure among primary and secondary school students in Yangzhou was 13.86 %, higher among boys (15.13%) than girls (12.62%) ( χ 2=14.30, P <0.01). The elevated blood pressure rate of obese and overweight primary and secondary school students were 26.98% and 14.90%, respectively, higher than 8.71% of non overweight and obese children ( χ 2=482.58, P <0.01). There were statistically significant differences in elevated blood pressure rate among primary and secondary school students in different sleep quality and sleep duration ( χ 2= 8.45, 71.58, P <0.05). After controlling for gender, residence, educational stage, parental education, sedentary time, the results of multiple Logistic regression analysis showed that no correlation between sleep quality and elevated blood pressure under different nutritional status was found among primary and secondary school students. In primary and secondary school students with obesity, prevalence of elevated blood pressure was higher among those with sleep duration <8 and 8 to <9 h/d ( OR=1.54, 1.72, P <0.05). However, there was no significant association found in the other groups ( OR=1.04-1.28, P >0.05). In gender stratification, sleep duration < 8, 8 to <9 and 9 to <10 h/d of obese boys were positively correlated with elevated blood pressure ( OR=1.97, 2.09, 1.86, P <0.05). Conclusion Among obese primary and secondary school students, sleep duration <9 h/d is associated with an increased risk of elevated blood pressure, especially among obese boys.

Objective: To analyze the prevalence and determinants of comorbid overweight/obesity and elevated blood pressure among primary and secondary school students in Yangzhou City, and to explore the association between sleep patterns, eating behavior and the comorbidity of overweight/obesity and elevated blood pressure, so as to provide reference for developing prevention strategies targeting common comorbidities in students. Methods: By using stratified cluster random sampling, a total of 8 735 primary and secondary school students were selected from 36 schools in six counties of Yangzhou from October to November 2023. Students underwent physical examinations and a questionnaire survey was conducted using the questionnaire on students health status and influencing factors. The Chi square test was used to compare the detection rate of comorbid overweight/obesity and elevated blood pressure in different groups of primary and secondary school students. The Logistic regression model was used to explore the association between sleep and dietary behaviors and their combined effects and coexistence. Results: The detection rate of comorbid overweight/obesity and elevated blood pressure among primary and secondary school students in Yangzhou was 9.85%, which was higher among boys (12.14%) than girls (7.59%)( χ 2=50.86, P <0.01). After controlling for gender, residence, educational stage, parental education, smoking, drinking, and moderate to vigorous exercise, multivariate Logistic regression analysis showed that irregular breakfast consumption and inadequate daily sleep were associated with a higher risk of comorbidities compared with regular breakfast consumption and adequate daily sleep among overall and primary school students (overall: OR =1.52, 95% CI =1.18- 1.96 , primary school students: OR =2.79, 95% CI =1.61-4.82)(both P <0.05). From the perspective of primary school students of different genders, the risk of comorbidities in girls who consumed breakfast irregularly and had inadequate daily sleep was 3.59 times higher than that in girls who consumed breakfast irregularly and had inadequate daily sleep (95% CI =1.65-7.82, P <0.01). Conclusion The sleep patterns and breakfast behaviors of primary and secondary school students are found to be associated with comorbid overweight/obesity and elevated blood pressure, especially in primary school girls.

BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Objective:To investigate the changes in retinal structure and microcirculation in the patients with high myopia(HM)and the non-HM individuals,and to elucidate the correlations between axial length(AL)and the related parameters.Methods:A total of 80 eyes from 40 patients with simple HM(non-pathological myopia)were enrolled as case group,while 80 eyes from 40 age-and sex-matched non-HM subjects were selected as control group.The best-corrected visual acuity(BCVA),AL,spherical equivalent(SE),and optical coherence tomography angiography(OCT A)examination were performed in all the subjects.OCTA examination was used to measure the vascular density of the superficial retinal capillary plexus(SCP),deep retinal capillary plexus(DCP),and radial peripapillary capillary(RPC),as well as central macular thickness(CMT),and the area and volume of the foveal avascular zone(FAZ)of the subjects in two groups.The differences in these parameters of the subjects between two groups were analyzed.The AL of the subjects in two groups was measured using a biometer,and its correlations with the parameters mentioned above were evaluated.Results:No statistically significant differences were observed in age or sex distribution between two groups(P＞0.05).Compared with control group,both SCP and DCP vessel densities acrossing the whole(excluding the foveal),parafoveal,and perifoveal regions of the macular retina of the patients in case group were significantly decreased(P＜0.05).Compared with control group,the RPC vessel densities in the optic disc region of the patients in case group were significantly decreased in the whole,peripapillary,peripapillary superior,and peripapillary inferior sectors(P＜0.001),while the RPC vessel density was increased inside the disc(P＜0.01).Compared with control group,the whole FAZ volume of the patients in case group was increased(P＜0.01),while the parafoveal and perifoveal CMT were decreased(P＜0.001).In case group,AL was negatively correlated with SCP vessel density(r=-0.642,P＜0.001),DCP vessel density(r=-0.388,P＜0.001),RPC vessel density(r=-0.639,P＜0.001),and CMT(r=-0.495,P＜0.001),but positively correlated with FAZ volume(r=0.580,P＜0.001);no significant correlation was found between AL and FAZ area(r=-0.062,P=0.587).Conclusion:The patients with HM may exhibit early reductions in SCP,DCP,and RPC vessel densities,thinning of the central retina,and increased FAZ volume.Furthermore,as AL increases,SCP,DCP,and RPC vessel densitiesas as well as CMT decreases,while FAZ volume increases,suggesting significant associations between AL and the parameters mentioned above.

Objective:To investigate the efficacy and safety of daratumumab-based regimens for the treatment of relapsed/refractory multiple myeloma (RRMM).Methods:A retrospective case series study was conducted. Thirty-seven RRMM patients treated with daratumumab-based regimens at Shanxi Bethune Hospital from January 2017 to November 2023 were selected, and their efficacy and adverse reactions were analyzed.Results:The median age [ M ( Q1, Q3)] of 37 RRMM patients was 62 (56, 68) years, the median number of previous treatment lines was 2 (1, 3.5) lines, 12 cases (32.4%) had extramedullary lesions, 12 cases (32.4%) had lactate dehydrogenase (LDH) ≥ 245 U/L, and 11 cases (29.7%) had previously received the third-line or more treatment. Among 27 patients who completed fluorescence in situ hybridization testing, 8 cases (29.6%) had high-risk cytogenetical changes. The median time from diagnosis to use of daratumumab was 23.1 (5.9, 52.0) months. The overall response rate (ORR) of 37 RRMM patients after treatment was 75.7% (28/37), with ORR of 88.0% (22/25) and 50.0% (6/12) for patients without and with extramedullary lesions, respectively, and the difference was statistically significant ( P = 0.036). The median follow-up time was 12.3 (4.6, 22.7) months, the median progression-free survival (PFS) time was 7.8 months (95% CI: 2.0- 13.7 months), and the median overall survival (OS) time was 22.4 months (95% CI: 17.5-29.5 months). The median PFS time for patients without and with extramedullary lesions was 11.8 and 4.2 months, and the median OS time was 23.5 and 8.3 months, respectively, and the differences in PFS and OS between the two were statistically significant (both P < 0.05); the median PFS time for patients with LDH ≥ 245 U/L and < 245 U/L was 6.5 and 11.9 months, and the median OS time was 30.2 and 12.1 months, respectively, and the differences in PFS and OS between the two were statistically significant (both P < 0.05). The incidence of non-hematological adverse reactions was 32.4% (12/37), with the most common being infusion-related adverse reactions (29.7%, 11/37), all of which were grade 1-2; the incidence of ≥ grade 3 hematological adverse reactions was 13.5% (5/37), with thrombocytopenia being the most common (8.1%, 3/37). Conclusions:The ORR of RRMM patients treated with daratumumab-based regimens is high, and the adverse reactions are tolerable.

Objective To investigate the correlation between serum galectin-3(Gal-3),fibroblast growth factor-21(FGF-21)and the lung function and and the Modified British Medical Research Council dyspnea in-dex(mMRC)score in invalids with chronic obstructive pulmonary disease(COPD).Methods A total of 79 patients with COPD who received treatment in the hospital from April 2021 to April 2023 were selected as the observation group,and 60 healthy individuals in the hospital during the same period were selected as control group.The expressions of Gal-3 and FGF-21 in serum were detected and compared.The first second forced ex-piratory volume(FEV1),FEV1/forced vital capacity(FVC)and mMRC score in two groups were compared,and the correlation between the expression levels of Gal-3 and FGF-21 and FEV1,FEV1/FVC and mMRC score in COPD patients was analyzed.Results The expression levels of serum Gal-3 and FGF-21 in the obser-vation group were higher than those in the control group(P＜0.05).The pulmonary function indexes in ser-um of observation group were higher than those in the control group,while the mMRC score was lower than that in the control group(P＜0.05).The expression levels of Gal-3 and FGF-21 were positively correlated with FEV1 and FEV1/FVC(P＜0.05),was negatively correlated with mMRC score(P＜0.05).Conclusion The expression of serum Gal-3 and FGF-21 in COPD invalids is abnormal,and the expression levels of serum Gal-3 and FGF-21 in COPD patients were correlated with FEV1,FEV1/FVC and mMRC score,which could be used as important reference indicators for diagnosis and disease evaluation of COPD.