Objective To investigate the effect of early use of ivabradine on cardiac function in patients with acute myocardial infarction(AMI)after percutaneous coronary intervention(PCI).Methods Eighty patients with AMI who were hospitalized in our hospital from Feb.2020 to May 2021 were enrolled,and were randomly assigned to ivabradine group or control group(1∶1).All patients were successfully treated with emergency PCI,and the ivabradine group was treated with ivabradine combined with metoprolol after PCI,while the control group was treated with metoprolol only.Both groups were followed up for 1 year.Echocardiography-derived parameters,heart rate and myocardial markers were analyzed.Results The left ventricular ejection fraction was significantly higher in the ivabradine group than in the control group at 1 week,3 months,and 1 year after PCI(all P＜0.05).The heart rate of the ivabradine group was significantly lower than that of the control group at 1 week after PCI(P＜0.05),while there was no significant difference in heart rates between the 2 groups at 3 months or 1 year after PCI(both P＞0.05).The brain natriuretic peptide of the ivabradine group was significantly lower than that of the control group on day 2 and day 3 after PCI(both P＜0.05).The troponin Ⅰ level of the ivabradine group was significantly lower than that of the control group on day 5 after PCI(P＜0.05).Conclusion Early use of ivabradine in patients with AMI after PCI can achieve effective heart rate control,reduce myocardial injury and improve cardiac function.

Objective:To study the distribution of drug resistance genes and virulence genes in multidrug-resistant Salmonella typhimurium strains.Methods:A total of 96 strains of Salmonella typhimurium were collected，and drug sensitivity tests were performed to evaluate the drug resistance and multidrug-resistance of Salmonella typhimurium.Multidrug-resistant Salmonella typhimurium strains were selected to conducted whole genome sequencing，and the distribution of drug resistance genes and virulence genes in the strain were analyzed.Results:Salmonella typhimurium strains had the highest resistance rates to ampicillin and ampicillin/sulbactam，with 89.58% and 76.04%，respectively.Followed by trimethoprim/sulfamethoxazole，ceftriaxone，and aztreonam，with 47.92%，38.54% and 33.33%，respectively，and low resistance rates to ciprofloxacin and levofloxacin，with 8.33% and 4.17%，respectively.Ninety-six strains were all sensitive to carbapenem antibiotics and piperacillin/tazobactam.Fifty-seven strains（59.38%）of Salmonella typhimurium showed multidrug-resistance.Resistance genes were detected in all 57 multidrug-resistant Salmonella typhimurium strains,with higher carrier rates of 98.25%,77.19%,and 59.65% for aac(6')-Iaa,aadA22,and blaTEM-1B,respectively.The multidrug-resistant Salmonella typhimurium strains had the highest carrier rates for invA，sipA，sseL，and sopB.Conclusion:Multidrug-resistant Salmonella typhimurium strains have a high incidence and a high carrier rate for multiple drug resistance genes and virulence genes.The monitoring and prevention of Salmonella typhimurium should be strengthened in the clinic in order to reduce the spreading epidemic of multidrug-resistant strains.

Aging-elevated DNMT3A R882H-driven clonal hematopoiesis (CH) is a risk factor for myeloid malignancies remission and overall survival. Although some studies were conducted to investigate this phenomenon, the exact mechanism is still under debate. In this study, we observed that DNMT3A R878H bone marrow cells (human allele: DNMT3A R882H) displayed enhanced reconstitution capacity in aged bone marrow milieu and upon inflammatory insult. DNMT3A R878H protects hematopoietic stem and progenitor cells from the damage induced by chronic inflammation, especially TNFα insults. Mechanistically, we identified that RIPK1-RIPK3-MLKL-mediated necroptosis signaling was compromised in R878H cells in response to proliferation stress and TNFα insults. Briefly, we elucidated the molecular mechanism driving DNMT3A R878H-based clonal hematopoiesis, which raises clinical value for treating DNMT3A R882H-driven clonal hematopoiesis and myeloid malignancies with aging.

Objective:To summarize the clinical characteristics, causes of misdiagnosis and preventive measures of infectious mononucleosis (IM) in children, and to improve the ability of clinicians in early diagnosis of IM in children.Methods:The clinical data of 468 children with IM in Xi′an Children′s Hospital from January 2018 to December 2021 were retrospectively analyzed, including general situation, disease onset, diagnosis and misdiagnosis.Results:Among the 468 children, 33 cases were clinically diagnosed and 435 cases were a definitely diagnosed; 281 males (60.04%) and 187 females (39.96%); the incidence rate was highest in preschool children (43.80%, 205/468) and in autumn (33.12%, 155/468). The first symptoms were fever (52.99%, 248/468), eyelid edema (15.38%,72/468) and neck mass (14.96%, 70/468). The fever rate was 90.38% (423/468), and the median time of first fever appearance was on the first (first, second) day of disease course, and the median duration of fever was 6 (4, 8) d. The median time of first visit was on the third (first, fifth) day of disease course, and the time of diagnosis was on the seventh (fifth, ninth) day of disease course. Blood routine examination showed that the proportion of white blood cell count increased was 51.92% (243/468), the proportion of lymphocytes increased was 61.75% (289/468), and the proportion of abnormal lymphocytes increased (≥10%) in peripheral blood was 58.97% (276/468). The lymphocyte subsets of 364 children were detected, the rate of helper T lymphocytes (Th cells) decreased was 80.22% (292/364), the rate of suppressor T lymphocytes (Ts cells) increased was 99.45% (362/364), the value and decreased rate of Th cells/Ts cells were 0.24 (0.16, 0.40) and 100.00% (364/364), rate of B lymphocytes decreased was 93.96% (342/364), rates of natural killer cells decreased and increased were 35.16% (128/364) and 0.55% (2/364). The misdiagnosis rate was 55.13% (258/468), and the misdiagnosis time was on the fifth (fourth, seventh) day of disease course. Among the 258 misdiagnosed children, 105 cases (40.70%) were misdiagnosed as upper respiratory tract infection, 65 cases (25.19%) as acute suppurative tonsillitis, 27 cases (10.47%) as acute cervical lymphadenitis or neck mass.Conclusions:Due to the complex and diverse clinical manifestations of IM in children, it is easy to be misdiagnosed in the early stage of the disease. So, it is necessary for clinicians to master the clinical characteristics of IM in children, constantly improve the level of diagnosis and treatment, and reduce the misdiagnosis rate.

Objective:To examine the survival rates and clinical characteristics of people with newly discovered non-M 3 acute myeloid leukemia (AML) who carry the ASXL1 gene mutation. Methods:From January 2016 to April 2021, the clinical information of patients with newly diagnosed non-M 3 AML at Shandong University's Qilu Hospital was retrospectively examined, and their clinical characteristics and survival were compared and analyzed. Gene mutation was detected by next-generation sequencing. Results:① The study included 256 AML patients who were initially diagnosed and had complete data, including 47 cases of ASXL1 gene mutation-positive (ASXL1 +) patients and 209 cases of ASXL1 gene mutation-negative (ASXL1 -) patients. All patients were divided into three groups: elderly (≥60 years old, n=92) , middle-aged (45-59 years old, n=92) , and young (≤44 years old, n=72) . ②WBC, and age were higher in patients with ASXL1 mutations compared to ASXL1 - patients, while complete response after the first round of treatment (CR 1) was lower ( P<0.05) . In the elderly group, WBC and the proportion of aberrant cells in nuclear cells in ASXL1 + patients were higher than those in ASXL1 - patients ( P<0.05) . In the young group, the WBC of ASXL1 + patients was higher than that of ASXL1 - patients ( z=-2.314, P=0.021) . ③IDH2 mutation and ASXL1 mutation was related ( P=0.018, r=0.34) . In ASXL1 + patients, the proportion of peripheral blasts in the high VAF group (VAF>40% ) was higher than that in the low VAF group (VAF<20% ) , and the proportion of aberrant nuclear cells was higher in the duplication and replacement mutation patients than in the deletion mutation patients ( P<0.05) . ④The overall survival (OS) and progression-free survival (PFS) of ASXL1 + patients were shorter than those of ASXL1 - patients (median, 10 months vs 20 months, 10 months vs 17 months; P<0.05) . The proportion number of aberrant cells in nuclear cells (≥20% ) , complex karyotypes, and TET2 mutation were all independent risk variables that had an impact on the prognosis of ASXL1 + patients, according to multivariate analysis ( P<0.05) . Conclusion:ASXL1-mutated non-M 3 AML patients have higher WBC in peripheral blood, a higher proportion of aberrant cells in nuclear cells, lower CR 1 rate, and shorter OS and PFS. Additionally, a poor prognosis is linked to higher VAF, duplication, and substitution mutations in the ASXL1 gene, as well as the high proportion of aberrant cells in nuclear cells, complex karyotype, and TET2 mutation.

Objective:To explore the influence of storage and delivery conditions of the peripheral blood samples from patients with chronic myeloid leukemia (CML) on the real-time quantitative PCR (RQ-PCR) detection of the BCR-ABL (P210) transcript levels.Methods:The peripheral blood samples of 84 CML patients were collected. The same sample was divided into different groups according to storage time (0, 6, 12, 24, 48, and 72 h) , temperature (room temperature, 18-24 ℃; low temperature, 2-8 ℃) , and vibration conditions (3, 6, and 12 h) . RQ-PCR was used to detect BCR-ABL (P210) transcript levels of the different groups. This study logarithmically transformed (log 10N) the original data [BCR-ABL copy number, ABL copy number, and BCR-ABL (P210) transcript levels]. Results:①Agarose gel electrophoresis showed significant RNA degradation of samples after storage for 48 and 72 h at room temperature. ②Among the overall samples, the BCR-ABL copy number of the samples stored at room temperature for 48 and 72 h was significantly lower than that of the samples stored at low temperature ( P<0.05) . However, the BCR-ABL (P210) transcript levels had no significant difference between samples stored at low temperature and room temperature. ③No significant changes were noted in the BCR-ABL (P210) transcript levels at different storage times (6, 12, 24, 48, and 72 h) regardless of storage temperature ( P>0.05) compared with that at baseline (0 h, -0.56±1.51) . ④ The BCR-ABL copy number of the overall sample only decreased significantly ( P<0.05) at 48 h (2.93±1.59) and 72 h (2.79±1.42) compared with that at baseline (0 h, 3.35±1.60) when stored at room temperature. The ABL copy number in the overall sample decreased significantly at 48 and 72 h (whether low and room temperature; P<0.05) . However, no significant changes were noted in the BCR-ABL (P210) transcript levels after vibration for 3 h (-1.29±1.81) , 6 h (-1.24±1.72) , and 12 h (-1.18±1.68; P>0.05) compared with that at baseline (0 h, -0.60±1.37) . Conclusion:Sample storage time, storage temperature, and vibration can interfere with the results of BCR-ABL and ABL copy number but have no significant effect on the quantitative determination of BCR-ABL (P210) transcript levels. This study provides strong support for the feasibility of transregional transportation of peripheral blood samples from patients with CML.

Objective: To investigate the clinical value of plasma brain natriuretic peptide (BNP) levels in predicting the severity of hand, foot and mouth disease (HFMD) in children with coxsackie virus A6 (CV-A6) infection. Methods: A total of 305 children with CV-A6 type HFMD admitted to Xi′an Children′s Hospital from January 2017 to December 2018 were divided into general group (200 cases) and severe group (105 cases) according to the severity of the disease.The receiver operating characteristic curve was used to calculate the value of plasma BNP levels to predict the severe CV-A6 HFMD.Multivariate logistic regression analysis was used to analyze the correlation between the related factors and the severity of CV-A6 HFMD. Results: Compared with the normal group, children in the severe group had statistically significant differences in WBC level, BNP level, neurological symptoms, circulatory disorders, and blood glucose levels(all P<0.05). The optimal cut-off value of the receiver operating characteristic curve for BNP level to predict severe HFMD was 294.85 ng/L.Multivariate logistic regression analysis found that WBC>15×10⁹/L, blood glucose> 8.3 mmol/L, and BNP>294.85 ng/L were related to the severity of CV-A6 HFMD(OR=2.275, P=0.013; OR=6.057, P=0.028; OR=1.008, P<0.001). Conclusion BNP>294.85 ng/L is closely related to the severity of CV-A6 HFMD and has predictive value.It is an early warning factor for the severity of CV-A6 HFMD.

Objective:To explore the relationship of Vitamin A and Vitamin D with the incidence and severity of hand, foot and mouth disease(HFMD) as well as with the anti-viral immune index interferon-α(INF-α), and to investigate the role of Vitamin A and Vitamin D in HFMD.Methods:A total of 305 children with Coxsackie virus A6(CA6) HFMD admitted at Xi′an Children′s Hospital from January 2017 to December 2018 were enrolled in the study.One hundred healthy children whose gender and age matched with those of children in the case group were selected as the healthy control group.Serum Vitamin A levels were detected by high performance liquid chromatography.Enzyme-linked immunosorbent assay was used to detect the levels of Vitamin D and IFN-α, and the correlation of the levels of Vitamin A and Vitamin D with the severity of HFMD was analyzed.Results:The levels of serum Vitamin A[(0.96±0.39) mg/mol] and Vitamin D [(42.14±15.13) μg/L] in patients with CA6 HFMD were lower than those of the healthy control group[(1.26±0.29) mg/mol, (49.63±8.86) μg/L], and the differences were statistically significant(all P<0.05). Logistic multivariate regression analysis showed that WBC>15×10 9/L, blood sugar>8.3 mmol/L, the deficiency of Vitamin A level and Vitamin D level were all risk factors for severe CA6 HFMD in children( OR=2.303, 4.622, 7.346, 5.211; all P<0.05). According to the receiver operating characteristic curve analysis, the Youden index was the largest at a Vitamin A level of 0.725 mg/mol, and the corresponding sensitivity and specificity were 82.0% and 64.8%, respectively.When Vitamin D level was 32.88 μg/L, the Youden index was the highest, and the sensitivity and specificity were 84.5% and 61.9%, respectively.The serum IFN-α concentration of patients with CA6 HFMD [(84.44±26.28) ng/L] was higher than that of the healthy control group [(36.58±14.39) ng/L], and the difference was statistically significant( P<0.05). In addition, the serum IFN-α concentration in severe HFMD children [(71.48±18.34) ng/L] was significantly lower than that in the common HFMD children [(91.25±27.27) ng/L], and the difference was statistically significant( P<0.05). The results of correlation analysis showed that serum IFN-α concentration is positively correlated with Vitamin A and Vitamin D levels ( r=0.783, 0.239; all P<0.001). Conclusions:The levels of serum Vitamin A and Vitamin D decreased in children with HFMD.WBC>15×10 9/L, blood sugar>8.3 mmol/L, the deficiency of Vitamin A level and Vitamin D level are related to severe HFMD.The se-rum IFN-α concentration is positively correlated with the levels of Vitamin A and Vitamin D. The deficiency of Vitamin A and Vitamin D is one of the early warning factors of severe HFMD.

Objective To investigate the clinical effect of anterior internal fixation plus vacuum sealing drainage in the treatment of ulnar and radial fractures of Gustilo type Ⅲ.Methods Twenty-eight patients with open ulnar and radial fracture of Gustilo type Ⅲ were managed from April 2007 to March 2014,and were divided into four groups(n =4).Group A were managed with external fixator and conventional changing dressings.Group B were managed with internal fixation and vacuum sealing drainage.Group C were managed with external fixator and vacuum sealing drainage.Group D were managed with internal fixation and conventional changing dressings.Result Twenty-eight cases were adopted telephone follow-up for 6 to 27 months.The soft tissue recovery time of each group respectively was (20.5 ± 2.37) days,(14.7 ±2.16) days,(15.6 ±2.17) days and(19.7 ±2.18) days.The hospital stay of each group respectively was (9.7 ± 2.54) weeks,(4.7 ± 1.46) weeks,(5.2 ± 2.34) weeks and 8.6 ± 2.16) weeks.The fracture healing time of each group respectively was (19.6 ± 2.74) weeks,(13.1±1.84) weeks,(18.1 ±2.54) weeks and (14.7 ± 1.74) weeks.There was significant difference of these data between the two groups(P ＜ 0.05).Conclusions Anterior internal fixation plus vacuum sealing drainage is a better way to treat ulnar and radial fractures of Gustilo type Ⅲ.The technique has short period,less complications,less painful and less expense.

OBJECTIVETo study the effect of glycolytic inhibitor 3-Bromopyruvate (3-BrPA) on the proliferation and apoptosis of mouse spleen lymphocytes and explore its mechanism.

METHODSAn one-way mixed lymphocyte culture (MLC) system was established, including BALB/c mouse spleen cells (H-2d) as stimulator and C57BL/6 mouse spleen cells (H-2b) as responder. With treatment of 3-BrPA at different concentrations (0-200 μmol/L), lymphocyte proliferation capacity was detected by the CCK-8 method, the expression of CD3, CD4, and CD8 by flow cytometry, and the concentrations of cytokine interleukin (IL)-4 and interferon (IFN)-γ in the supernatant by ELISA.

RESULTSAt a middle or high dose (over 20 μmol/L), 3-BrPA displayed a dose-dependent inhibitory effect on lymphocyte proliferation in the MLC system. The 50% inhibitory concentration (IC50) were 48.6, 41.2, and 41.9 μmol/L after 24, 36, and 48 h culture, respectively. With treatment of 50 μmol/L 3-BrPA, the IFN-γ level [(164.25 ± 20.14) ng/L] was significantly lower, compared with control [(277.61 ± 18.46) ng/L]. The IL-4 level [(31.06 ± 6.06) ng/L] was significantly higher, compared with control [(28.64 ± 3.97) ng/L]. Consequently, the IFN-γ/IL-4 ratio decreased significantly.

CONCLUSIONThese results indicate that 3-BrPA had a significant inhibitory effect on the proliferation of mouse spleen lymphocytes cultured in MLC system, accompanied with the Th2-biased secretion of cytokines.

Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Lymphocyte Culture Test, Mixed ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Pyruvates ; pharmacology ; Spleen ; cytology ; metabolism