Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.
Child ; Female ; Male ; Humans ; High-Throughput Nucleotide Sequencing ; Neoplasm, Residual/genetics* ; Retrospective Studies ; Genomics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Objective: This article aims to observe the changes in long noncoding RNA (lncRNA) expression profiles in rat hearts after ozone sub-chronic exposure. To provide scientific data to explore the role and mechanism of differentially expressed lncRNA in damaged hearts caused by ozone sub-chronic exposure. Methods: Eighteen Wistar rats were randomly divided into filtered air and ozone exposure groups, with nine rats in each group. The rats in filtered air group were exposed to filtered air, while the rats in ozone exposure group were exposed to ozone at 0.5 ppm(0.980 mg/m³)for 90 days at a frequency of 6 hours per day. After ozone exposure, cardiac tissues were collected and the total RNA was extracted. The expression level of lncRNA in the hearts of two groups was detected by microarray and qRT-PCR method and the potential functions of the differentially expressed lncRNA were analyzed by bioinformatics. Results: Compared with the filtered air group, lncRNA's expression profile was significantly altered in the rat hearts of ozone exposure group. A total of 167 lncRNA were up-regulated significantly and 64 lncRNA were down-regulated significantly. GO analysis indicated that the up-regulated lncRNA might involve in the process of regulating growth and development, and the down-regulated lncRNA might participate in nutrient catabolic. KEGG results showed that the up-regulated lncRNA might be involved in regulating the PI3K-Akt signaling pathway. The down-regulated lncRNA might regulate the metabolic processes of various vitamins and main energy-supplying substances. Conclusion: Ozone sub-chronic exposure can cause changes in the expression profile of lncRNA in rat hearts, which may regulate the effects of ozone sub-chronic exposure on the heart through the metabolism of energy and nutrients.
Animals ; Computational Biology ; Ozone/adverse effects* ; Phosphatidylinositol 3-Kinases ; RNA, Long Noncoding/genetics* ; Rats ; Rats, Wistar

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

To investigate the inflammatory mechanism of nasal instillation of fine particulate matter (PM)on hippocampal tissue injury in mice. Thirty C57BL/6J mice were randomly divided into 3 groups(n=10):control group, low-dose group, high-dose group. The nasal instillation doses of PM in the low-dose group and the high-dose group were 1.5 mg/kg BW and 7.5 mg/kg BW, respectively, and the control group was given saline with an equal volume. Saline was sprayed once every other time for 12 times. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were determined by ELISA method. HE staining and electron microscopy were used to observe the pathological changes and ultrastructure of lung tissue and hippocampus. The inflammatory cytokine levels in hippocampus were detected by antibody chip technique. There was no significant effect of PM nasal instillation on serum TNF-α, IL-1β and IL-6 levels (P＞0.05), and there was no obvious pathological changes in lung tissue structure. In hippocampus, low-dose and high-dose PM exposure could lead to disordered neuronal arrangement in the hippocampal CA3 region, and there were neurological changes around the neuron cells and ultrastructural changes such as edema around small blood vessels. Compared with the control group, the levels of inflammatory cytokines such as CX3CL1, CSF2 and TECK in the low-dose group were increased significantly (P ＜0.05), while sTNFR1 was decreased significantly (P＜0.05); the inflammatory factors CX3CL1, CSF2, and TCA-3 were significantly increased in the high-dose group (P＜0.05), while leptin, MIG, and FASLG were significantly decreased (P＜0.05). Nasal instillation of PM can induce tissue damage in the hippocampus of mice, and its mechanism of action may be the olfactory brain pathway. The increasing of TNF-α and IL-6 and the decreasing of sTNFR1 and FASLG may be involved in inflammatory mechanisms.

OBJECTIVE: To study the Polymorphism of the human platelet antigen(HPA) gene 1-17 and human leukocyte antigen(HLA) gene-A and B locus in Shandong Han population. METHODS: A total of 962 samples from routine voluntary platelet donors were genotyped for HPA1-17 system and HLA-A site, B by PCR-SSP and PCR-SSOP respectively．Gene frequencies were calculated by counting. HPA1-17 and HLA genotype combinations were analyzed by Arelequin 3.5. RESULTS: The gene frequencies of HPA-la, -1b, HPA-2a, -2b, HPA-3a, -3b, HPA-4a, -4b, HPA-5a, -5b, HPA-6a, -6b, HPA-15a, -15b were 0.9918, 0.0082, 0.9419, 0.0592, 0.5841, 0.4174, 0.9969, 0.0031, 0.9892, 0.0108, 0.9835, 0.0175,0.5488 and 0.4512, respectively． The most common HPA genotype combination was HPA-(1, 2, 4, 5, 6, 7-14, 16, 17) aa-3ab-15ab (0.2048). Moreover, HLA-A*2(0.3094) and HLA-B*13(0.1513) showed the highest frequency in their respective locus. The most common HLA genotype combination was HLA-A*2-B*13(0.1397) . CONCLUSION Distributions of HPA and HLA show high polymorphism in Shandong Han population. The ethnic and territorial difference of HPA distribution is also confirmed. It is imperative to establish local genetic database of volunteer platelet donors.
Alleles ; Antigens, Human Platelet/genetics* ; Gene Frequency ; Genotype ; Humans ; Polymorphism, Genetic

Background and Objectives: The effective use of MSCs for the treatment of some B cell-mediated immune diseases is quite limited. The main reason is that the immunomodulatory effects of mesenchymal stem cells (MSCs) on B cells are unclear, and their underlying mechanisms have not been fully explored. Methods: and Results: By co-culturing B cells with MSCs without (MSC/CTLsh) or with suppressor of cytokine signaling 1 (SOCS1) knockdown (MSC/SOCS1sh), we found that MSCs inhibited B cell proliferation, activation and terminal differentiation. Remarkably, the highest inhibition of B cell proliferation was observed in MSC/SOCS1sh co-culture. Besides, MSC/SOCS1sh reversed the inhibitory effect of MSCs in the last stage of B cell differentiation. However, MSC/SOCS1sh had no effect on inhibiting B cell activation by MSCs. We also showed that IgA+ B cell production was significantly higher in MSC/SOCS1sh than in MSC/CTLsh, although no difference was observed when both MSCs co-cultures were compared to isolated B cells. In addition, MSCs increased PGE2 production after TNF-α/IFN-γ stimulation, with the highest increase observed in MSC/SOCS1sh co-culture. Conclusions Our results highlighted the role of SOCS1 as an important new mediator in the regulation of B cell function by MSCs. Therefore, these data may help to develop new treatments for B cell-mediated immune diseases.

AIM:To compare the changes of surgically induced corneal higher order aberrations after phacoemulsification with 2.8mm clear corneal incisions at different sites.METHODS:The clinical data of 100 cases (100 eyes) of patients with cataract treated by phacoemulsification with 2.8mm clear corneal incision in our hospital from March 2015 to April 2016 were analyzed retrospectively.According to the site of incision,they were divided into Group A (temporal clear corneal incision,n =55) and Group B (upper clear corneal incision,n=45).Changes of the best corrected visual acuity (BCVA),surgically induced astigmatism (SIA) and corneal topography were compared between the two groups before surgery,at 1d,1wk,1 and 3mo after surgery.The corneal wavefront aberrations were measured by wavefront aberration analyzer,and the changes of higher-order aberrations in corneal 6mm range were recorded.RESULTS:The BCVA of two groups decreased at 1d,1wk,1 and 3mo after surgery (P＜0.05),and the BCVA of Group A at 1d,1wk,and 1mo after surgery was lower than that of Group B (P＜0.05).SIA of the two groups decreased at 1wk,1 and 3mo after surgery (P＜0.05),and the SIA of Group A at different time points after surgery were lower than those of Group B (P＜0.05).The surface asymmetry index (SAI) and the surface rule index (SRI) of the two groups increased at 1 d after surgery,and were gradually decreased at 1wk,1 and 3mo after surgery.The SRI and SAI in Group A were lower than those in Group B at 1d and 1wk after surgery (P＜ 0.05).The total corneal higher-order aberrations (tHOAs) and four-order spherical aberration (SA)showed significant differences between the two groups at 3mo after surgery (P＜0.05).CONCLUSION:The application of 2.8mm temporal clear corneal incision in phacoemulsification can promote the recovery of visual acuity,reduce the effect of surgery on corneal shape,and reduce corneal higher-order aberrations.

Objective To investigate the clinical efficacy of gentle moxibustion plus oral Gushen Dingchuan pills in treating the clinical remission stage of bronchial asthma.Methods Ninety patients with bronchial asthma in the clinical remission stage were randomized to groups A,B and C,30 cases each.group A received moxa-stick gentle moxibustion;group B,oral administration of Gushen Dingchuan pills;group C,moxa-stick gentle moxibustion plus oral administration of Gushen Dingchuan pills.The course of treatment was three months in all the three groups.The TCM symptom score and the Asthma Control Test (ACT) score were recorded and serum immunoglobulin E (IgE) content was measured in the two groups before and after treatment.The clinical therapeutic effects were compared between the groups.Results The total efficacy rate was 76.7％ in group A,80.0％ in group B and 93.3％ in group C.there was a statistically significant difference in the total efficacy rate between group C and group A or B (P＜0.05).There were statistically significant pre-/post-treatment differences in the TCM symptom score,the ACT score and serum IgE content in all the three groups (P＜0.01).There were statistically significant post-treatment differences in the TCM symptom score,the ACT score and serum IgE content between between group C and group A or B (P＜0.01,P＜0.05).Conclusion Gentle moxibustion plus oral Gushen Dingchuan pills can improve immunologic function in patients with bronchial asthma in the clinical remission stage.

Objective:To study the influencing factors of serum high-sensitivity cardiac troponin T(hs-cTnT)levels in chronic kidney disease(CKD)patients.Methods:The clinical data of CKD patients treated at a hospital were collected.Fasting blood samples were collected to measure the level of hs-cTnT.Single factor analysis,univariate linear regression analysis and multiple linear regression analysis were carried out to screen the influencing factors of hs-cTnT.Objective:The level of hs-cTnT was detected in 324 CKD patients,and the median level was 0.012 μg/L.In early-stage CKD patients,Cys C,UACR and left ventricular mass index(LVMI)were positively correlated with hs-cTnT level(P<0.05),and the hs-cTnT level increased significantly in CKD patients with hypertension or diabetes.The estimated glomerular filtration rate(eGFR)was negatively correlated with the hs-cTnT level(P=0.003).Conclusions:The elevated levels of hs-cTnT in CKD patients are associated with a variety of factors,so clinicians should make a comprehensive assessment of the causes of elevated hs-cTnT level.

A 44-year old male patient was admitted to the First Affiliated Hospital, Zhejiang University School of Medicine with left ptosis and pain on the left head and neck for 20 days.Brain MRI showed subacute cerebral infarction on left parietal lobe and intramural hematoma on left internal carotid artery. CT angiography showed stenosis line on the C1 segment of left internal carotid artery. Digital subtraction angiography showed dissection on the C1 segment of left internal carotid artery.The condition of patients was improved after anticoagulant therapy.
Adult ; Aneurysm, Dissecting ; complications ; diagnosis ; Carotid Artery, Internal ; pathology ; Cerebral Infarction ; pathology ; Horner Syndrome ; complications ; diagnosis ; Humans ; Magnetic Resonance Imaging ; Male