BACKGROUND:U937 cells can be used as a cell model for studying the biological characteristics,signaling pathways,and therapeutic targets of acute myeloid leukemia.Although it has been reported that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia,its biological function in U937 cells remains unclear,and its mechanism of action in the occurrence and development of acute myeloid leukemia needs to be further clarified. OBJECTIVE:To investigate the expression level of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia and its effect on the proliferation and apoptosis of U937 cells. METHODS:RNA-sequencing was used to analyze the bone marrow monocyte samples from acute myeloid leukemia patients,and the differentially expressed gene long non-coding RNA KIAA0125 was screened.The expression of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia was detected by qRT-PCR.The relationship between long non-coding RNA KIAA0125 mRNA expression and prognosis in bone marrow cells of 173 acute myeloid leukemia patients and 70 healthy people was statistically analyzed by GEPIA database.Subsequently,recombinant lentivirus technology and CRISPR/Cas9-SAM technology were used to construct U937 cell lines with knockdown/overexpression of long non-coding RNA KIAA0125.qRT-PCR was used to detect the knockdown/overexpression efficiency of long non-coding RNA KIAA0125.Next,CCK-8 assay,flow cytometry,and western blot assay were used to detect the effects of knockdown/overexpression of long non-coding RNA KIAA0125 on the proliferation and apoptosis of U937 cells.Finally,western blot assay was used to detect the effect of knockdown/overexpressed long non-coding RNA KIAA0125 on Wnt/β-catenin signaling pathway-related proteins. RESULTS AND CONCLUSION:(1)The results of qRT-PCR showed that long non-coding RNA KIAA0125 was highly expressed in peripheral blood of acute myeloid leukemia patients.The results of GEPIA database showed that long non-coding RNA KIAA0125 was highly expressed in bone marrow cells of acute myeloid leukemia patients,and the high expression group had worse overall survival.(2)The knockdown efficiency of long non-coding RNA KIAA0125 in knockdown group was 70%,and the U937 cells that stably down-regulated long non-coding RNA KIAA0125 expression were successfully constructed.The expression of long non-coding RNA KIAA0125 in overexpression group was four times that of vector group,and stable U937 cells were successfully constructed.(3)Knockdown of long non-coding RNA KIAA0125 inhibited the proliferation of U937 cells and promoted their apoptosis.Overexpression of long non-coding RNA KIAA0125 promoted the proliferation of U937 cells but had no significant effect on the apoptosis of U937 cells.(4)Knockdown of long non-coding RNA KIAA0125 inhibited the activity of Wnt/β-catenin signaling pathway,while overexpression of long non-coding RNA KIAA0125 activated Wnt/β-catenin signaling pathway.These results confirm that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia peripheral blood.Long non-coding RNA KIAA0125 may affect the proliferation and apoptosis of U937 cells by regulating the Wnt/β-catenin signaling pathway,and may be a potential prognostic marker for acute myeloid leukemia.

OBJECTIVE To analyze the efficacy and safety of luspatercept in the treatment of myelodysplastic syndromes （MDS） anemia， and provide reference for clinical medication. METHODS The literature related to luspatercept for MDS anemia in PubMed， Cochrane Library， Embase and Web of Science were searched by computer， and the search time was from the establishment of the database to January 2024. The quality of literature was evaluated after they were screened according to inclusion and exclusion criteria， the single-group rate meta-analysis and sensitivity analysis were performed by using RevMan 5.4 software， and the subgroup analysis was conducted. RESULTS A total of 756 patients in 9 articles were included in this study. The results of meta-analysis showed that the proportion of MDS patients who reached ≥8 weeks of red blood cell transfusion independence （RBC-TI） was 46% after using luspatercept [95%CI （0.28， 0.64）， P＜0.000 01]. The proportion of MDS patients whose hematological improvement in erythrocyte （HI-E） was 59% [95%CI （0.43， 0.74）， P＜0.000 01]. Among them， 5 articles reported that the proportion of MDS patients with grade 3-4 adverse reactions was 14% [95%CI （0.07， 0.22）， P＝0.000 2]， and the poor general condition， infection， blood and lymphatic system disease were the common adverse reactions. Subgroup analysis showed that the source of heterogeneity was the blood transfusion burden in the proportion of MDS patients with RBC-TI≥8 weeks， and the source of heterogeneity was the 0931-8356251。revised international prognostic scoring system （IPSS-R） risk grade， SF3B1 mutation status and blood transfusion burden in the proportion of MDS patients with HI-E. Sensitivity analysis showed that the results of this study were stable. CONCLUSIONS Luspatercept can significantly improve blood transfusion dependence， reduce blood transfusion burden and promote hematology improvement in MDS patients. But attention should be paid to the occurrence of grade 3-4 adverse events； adverse events such as poor general condition， infection， blood and lymphatic system diseases are more common.

OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged

Objective:To investigate the association between cytokines and ocular chronic graft-versus-host disease (cGVHD) and identify specific biomarkers for ocular cGVHD to enhance clinical diagnosis, treatment, and evaluation.Methods:A mouse model of cGVHD was established to explore the correlation between cGVHD and serum cytokines. Based on the findings from the animal experiments and literature review, a panel of 16 cytokine combinations was identified. Enzyme-linked immunosorbent assay (ELISA) was used to compare the cytokine concentrations in the serum and tear samples from patients who underwent allogeneic hematopoietic stem cell transplantation from June 2017 to March 2022 at the Medical Center of Hematology, Xinqiao Hospital, Army Medical University.Results:① Compared with the control group, mice with cGVHD exhibited elevated serum IL-1β, IL-6, IL-8, IL-17, IFN-γ, CX3CL1, CXCL11, CXCL13, CCL11, and CCL19 concentrations (all P<0.05). ② Analysis of the cytokine profiles of the serum and tear samples revealed that compared with patients without ocular cGVHD, those with ocular cGVHD exhibited increased serum IL-8 [ P=0.032, area under the curve (AUC) =0.678]; decreased serum IL-10 ( P=0.030, AUC=0.701) ; elevated IL-8, IFN-γ, CXCL9, and CCL17 in tear samples; and lower IL-10 and CCL19 in tear samples (all P<0.05, all AUC>0.7). Moreover, cytokines in tear samples showed correlations with ocular surface parameters related to ocular cGVHD. Conclusions:Tear fluid demonstrates greater specificity and sensitivity as a biomarker for diagnosing ocular cGVHD than serum biomarkers. Among the identified cytokines in tear samples, IL-8, IL-10, IFN-γ, CXCL9, CCL17, and CCL19 serve as diagnostic biomarkers for ocular cGVHD post-transplantation, offering practical reference value for diagnosis.

Objective This study used resting-state functional magnetic resonance imaging(rs-fMRI)to investigate the changes of local brain regional homogeneity in patients with depression and childhood maltreatment,and we calculated the relationship between altered ReHo values and the severity of childhood maltreatment.Methods 25 patients with depression and childhood maltreatment,25 patients with depression without childhood maltreatment,and 25 age,gender,and education-matched healthy controls were prospectively enrolled.All subjects underwent resting-state functional magnetic resonance imaging and ReHo analysis.One-way analysis of variance was used to compare the group differences,along with multiple comparison correction.Pearson correlation analysis was used to explore the relationship between region ReHo values with clinical scales.Results Compared with the group of depression without childhood maltreatment,the abnormal brain regions of depression with childhood maltreatment are mainly located in the dorsolateral prefrontal cortex,cerebellum,parietal gyrus,and precentral gyrus.The ReHo values of depression with childhood maltreatment in the left cerebellum and the left dorsolateral prefrontal cortex are correlated with the severity of childhood maltreatment.Conclusions Depression with childhood mal-treatment is associated with changes in local spontaneous brain activity,which are correlated with the severity of childhood maltreatment.The brain changes in the dorsolateral prefrontal cortex and cerebellum may explain the neurobiological mechanisms of depression with childhood maltreatment.

Objective:To compare the efficacy between Kirschner wire and clavicular hook plate in the fixation of distal clavicle fractures in older children.Methods:A retrospective analysis was conducted of the 28 pediatric patients with distal clavicle fracture who had undergone surgical treatment at Department of Pediatric Orthopedics, The Second General Hospital of Fuzhou from December 2014 to December 2023. There were 20 boys and 8 girls. Age: 10.0 (9.0, 12.8) years old; 22 left sides and 6 right sides; by the Craig modified Neer classification: 22 cases of type Ⅱ, 5 cases of type Ⅳ, and 1 case of type Ⅴ. The patients were divided into 2 groups based on their internal fixation methods. The Kirschner wire group of 12 cases were treated with open reduction and Kirschner wire fixation; the hook plate group of 16 cases were treated with open reduction and clavicular hook plate fixation. Operation time, hospital stay, fracture healing time, incidence of complications, and scores at the final follow-up (the Constant-Murley shoulder function score, quick disabilities of the arm, shoulder, and hand (quickDASH) score, and visual analog scale (VAS) for aesthetic satisfaction) were recorded and compared between the 2 groups.Results:There were no statistically significant differences in the baseline data between the 2 groups, indicating comparability ( P>0.05). The postoperative follow-up period for the 28 patients was (14.8±6.5) months. The operation time in the Kirschner wire group [(34.3±12.1) min] was significantly shorter than that in the hook plate group [(49.4±16.8) min] ( P<0.05), and the VAS score for aesthetic satisfaction at the final follow-up in the Kirschner wire group [(8.2±1.1) points] was significantly higher than that in the hook plate group [(6.2±2.6) points] ( P<0.05). There were no statistically significant differences between the 2 groups in terms of fracture healing time, hospital stay, incidence of complications, or Constant-Murley score and quickDASH score at the final follow-up ( P>0.05). Conclusions:For pediatric patients with distal clavicle fracture, both Kirschner wire fixation and clavicular hook plate fixation can achieve good functional outcomes. However, Kirschner wire fixation has advantages of shorter operation time, higher postoperative aesthetic satisfaction, and no need of a secondary surgery for implant removal.

Objective To explore the mechanisms of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in improvement of renal injury in rats with diabetic nephropathy (DN) by regulating mammalian target of rapamycin (mTOR)/p70 ribosome protein S6 kinase (S6K1)/coiled-coil myosin-like Bcl-2-interacting protein (Beclin 1) pathway. Methods The model of SD rats with DN was established by a method of high-fat diet combined with intraperitoneal injection of streptozotocin, and they were randomly divided into model group, MSC-EVs group, and MSC-EVs+MHY1485 (mTOR activator) group, with 12 rats in each group. Another 12 SD rats were normally fed for 6 weeks and then intraperitoneally injected with an equal dose of sodium citrate solution as controls. After grouping with MSC-EVs and MHY1485, blood glucose and levels of renal function indicators [blood urea nitrogen (BUN), serum creatinine (Scr), and urinary microalbumin (UmALB)] in rats were detected. HE staining was used to detect the pathological morphology of renal tissue in rats of each group; immunohistochemistry was used to detect the expression of mTOR/S6K1/Beclin 1 pathway related proteins in the renal tissues of rats in each group; the Western blot was used to detect the mTOR/S6K1/Beclin 1 pathway and autophagy-related protein expression in the renal tissues of rats in each group. Results Compared with the control group, the renal tissue morphology of rats in the model group were impaired, and the blood glucose, BUN, Scr, UmALB, relative positive expressions of p-mTOR and p-S6K1, p-mTOR/mTOR, p-S6K1/S6K1 increased significantly (P < 0.05), while microtubule associated protein 1A/1B light chain 3 (LC3) Ⅱ/LC3Ⅰ, expression of Beclin 1 protein, and relative positive expression of Beclin 1 significantly reduced (P < 0.05); compared with the model group, the MSC-EVs group had less impairment in the renal tissue morphology, and the blood glucose, BUN, Scr, UmALB, relative positive expressions of p-mTOR and p-S6K1, p-mTOR/mTOR, and p-S6K1/S6K1 decreased significantly (P < 0.05), while expression of LC3Ⅱ/LC3Ⅰ, Beclin 1 protein, and relative positive expression of Beclin 1 increased significantly (P < 0.05); compared with the MSC-EVs group, the impairment of the renal tissue morphology was worse in the MSC-EVs+MHY1485 group, and the blood glucose, BUN, Scr, UmALB, relative positive expressions of p-mTOR and p-S6K1, expression of p-mTOR/mTOR, and p-S6K1/S6K1 increased significantly (P < 0.05), while the expression of LC3Ⅱ/LC3Ⅰ, Beclin 1 protein, and relative positive expression of Beclin 1 decreased significantly (P < 0.05). Conclusion MSC-EVs can enhance autophagy, reduce levels of blood glucose, Scr, BUN and urinary protein in rats with DN, alleviate renal tissue damage, and the mechanism may be achieved by inhibiting the activation of the mTOR/S6K1/Beclin 1 pathway.

Novel coronavirus Omicron variant infection can cause severe illness and even death in certain populations. Omicron variant infection may lead to systemic inflammatory response, coagulation disorder, multi-organ dysfunction and other pathophysiological changes, which are different from other Novel coronavirus variants to a certain extent, so therapeutic strategies should not be the same. The National Medical Center for Major Public Health Events invited experts in fields of infectious diseases, respiratory medicine, intensive care, pediatrics and fever clinic to develop this quick guideline based on the current best evidence and extensive clinical practices. This quick guideline aims to standardize the diagnosis and treatment of novel coronavirus Omicron infection, and to improve the disease management abilities of clinicians.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Abstract With the development of society, the health and well being of children and adolescents are receiving increasing attention from the government and scholars. The implementation of the health (promoting) school construction plan has a significant effect on promoting students health and well being, which is especially important in the normalized stage of COVID-19 epidemic prevention and control. The study summarizes the importance of health (promoting) schools for students health and well being, reviews the development of health (promoting) school construction in China, and proposes countermeasures and recommendations to further promote health (promoting) school construction in China in the light of the new era.