Efficacy and safety of peginterferon-α2b for treatment of myeloproliterative neoplasms / 南方医科大学学报

OBJECTIVE@#To evaluate the clinical efficacy and adverse reactions of peginterferon-α2b for treatment of chronic myeloproliferative neoplasms (MPN).@*METHODS@#We retrospectively analyzed the data of 107 patients with MPN, including 95 with essential thrombocythemia (ET) and 12 with polycythemia vera (PV), who all received peginterferon-α2b treatment for at least 12 months. The clnical and follow-up data of the patients were analyzed to evaluate the efficacy and adverse reactions of the treatment.@*RESULTS@#After receiving peginterferon- α2b treatment, both ET and PV patients achieved high hematological remission rates, and the total remission rates did not differ significantly between the two groups (86% vs 78%, P>0.05). In the overall patients, the spleen index decreased by 13.5% (95%CI: 8.5%-18.5%) after the treatment. The patients with hematological remission showed a significantly greater reduction of the total symptom score than those without hematological remission (P < 0.01). The median percentage of JAK2V617F allele load of PV patients decreased from 67.23% (49.6%-84.86%) at baseline to 19.7% (0.57%-74.6%) after the treatment, and that of JAK2V617F-positive ET patients decreased from 48.97% (0.45%-74.24%) at baseline to 22.1% (0.33%-65.42%) after the treatment. Mild adverse reactions (grade 1-2) were observed in both ET and PV groups without significant differences between them. The overall incidence of thrombotic events during the treatment was 2.8% in these patients, and no serious adverse reactions were observed.@*CONCLUSION@#For patients with chronic myelodysplasia, peginterferon-α2b treatment can achieve a high peripheral blood cell remission rate and maintain a long-term stable state with good effect in relieving symptoms such as splenomegaly. Peginterferon- α2b treatment caused only mild adverse reactions, which can be tolerated by most of the patients.

Cell-loaded hydrogel microspheres based on droplet microfluidics: a review / 生物工程学报

Droplet microfluidics technology offers refined control over the flows of multiple fluids in micro/nano-scale, enabling fabrication of micro/nano-droplets with precisely adjustable structures and compositions in a high-throughput manner. With the combination of proper hydrogel materials and preparation methods, single or multiple cells can be efficiently encapsulated into hydrogels to produce cell-loaded hydrogel microspheres. The cell-loaded hydrogel microspheres can provide a three-dimensional, relatively independent and controllable microenvironment for cell proliferation and differentiation, which is of great value for three-dimensional cell culture, tissue engineering and regenerative medicine, stem cell research, single cell study and many other biological science fields. In this review, the preparation methods of cell-loaded hydrogel microspheres based on droplet microfluidics and its applications in biomedical field are summarized and future prospects are proposed.

Five-year outcomes of biodegradable versus second-generation durable polymer drug-eluting stents used in complex percutaneous coronary intervention / 中华医学杂志(英文版)

BACKGROUND@#There are few data comparing clinical outcomes of complex percutaneous coronary intervention (CPCI) when using biodegradable polymer drug-eluting stents (BP-DES) or second-generation durable polymer drug-eluting stents (DP-DES). The purpose of this study was to investigate the safety and efficacy of BP-DES and compare that with DP-DES in patients with and without CPCI during a 5-year follow-up.@*METHODS@#Patients who exclusively underwent BP-DES or DP-DES implantation in 2013 at Fuwai Hospital were consecutively enrolled and stratified into two categories based on CPCI presence or absence. CPCI included at least one of the following features: unprotected left main lesion, ≥2 lesions treated, ≥2 stents implanted, total stent length >40 mm, moderate-to-severe calcified lesion, chronic total occlusion, or bifurcated target lesion. The primary endpoint was major adverse cardiac events (MACE) including all-cause death, recurrent myocardial infarction, and total coronary revascularization (target lesion revascularization, target vessel revascularization [TVR], and non-TVR) during the 5-year follow-up. The secondary endpoint was total coronary revascularization.@*RESULTS@#Among the 7712 patients included, 4882 (63.3%) underwent CPCI. Compared with non-CPCI patients, CPCI patients had higher 2- and 5-year incidences of MACE and total coronary revascularization. Following multivariable adjustment including stent type, CPCI was an independent predictor of MACE (adjusted hazard ratio [aHR]: 1.151; 95% confidence interval [CI]: 1.017-1.303, P  = 0.026) and total coronary revascularization (aHR: 1.199; 95% CI: 1.037-1.388, P  = 0.014) at 5 years. The results were consistent at the 2-year endpoints. In patients with CPCI, BP-DES use was associated with significantly higher MACE rates at 5 years (aHR: 1.256; 95% CI: 1.078-1.462, P  = 0.003) and total coronary revascularization (aHR: 1.257; 95% CI: 1.052-1.502, P  = 0.012) compared with that of DP-DES, but there was a similar risk at 2 years. However, BP-DES had comparable safety and efficacy profiles including MACE and total coronary revascularization compared with DP-DES in patients with non-CPCI at 2 and 5 years.@*CONCLUSIONS@#Patients underwent CPCI remained at a higher risk of mid- to long-term adverse events regardless of the stent type. The effect of BP-DES compared with DP-DES on outcomes was similar in CPCI and non-CPCI patients at 2 years but had inconsistent effects at the 5-year clinical endpoints.

Clinical Characteristics of Chronic Myeloid Leukemia Patients with Deletion and Non-deletion of ASS Gene on Derivative Chromosome 9 / 肿瘤防治研究

Objective To investigate the clinical characteristics of patients with chronic myeloid leukemia (CML) in chronic phase with deletion and non-deletion of the argininosuccinate synthesis gene (ASS gene) on the derivative chromosome 9. Methods The clinical data of patients with CML initially treated with imatinib and BCR/ABL1/ASS1 3-color fusion probe to detect ASS gene deletion were analyzed. The patients were divided into deletion group (n=27) and non-deletion group (n=92). Clinical characteristics, treatment effects, and prognosis were analyzed. Results The average age of 119 patients was 37.22±12.72 years old. The sokal score differed between the deletion and non-deletion groups (χ2=4.304, P=0.038). No statistically significant difference in other general characteristics was found (P > 0.05). The 3-month CCyR rate, 6-month CCyR rate, and BCR-ABLIS≤ 1% rate in the deletion group were lower than those in the non-deletion group (P < 0.05). The median follow-up of 119 patients was 35.0 (3.0-60.0) months. The PFS in the deletion group was lower than that in the non-deletion group (χ2=4.293, P=0.038). Overall survival was not significantly different between the two groups (χ2=0.008, P=0.931). Conclusion The deletion of the ASS gene in patients with chronic CML is related to the poor efficacy of imatinib treatment, poor prognosis, and high risk of disease progression.

A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies / 中华血液学杂志

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

Genetic analysis and prenatal diagnosis of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 due to variants of PIGT gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic etiology of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 (MCAHS3) and provide prenatal diagnosis for her parents.@*METHODS@#A female child who had presented at Linyi People's Hospital on 27 July 2022 for recurrent convulsions for over 4 years was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were taken from the child and her parents and subjected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out on amniotic fluid sample at 18 weeks' gestation. Bioinformatic software was used to analyze the pathogenicity of the protein model for the variant loci.@*RESULTS@#The child was a 4-year-old female with frequent seizures, peculiar facial appearance, hypotonia and severe developmental delay. Genetic analysis revealed that she has harbored compound heterozygous variants of the PIGT gene, namely c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q), which were respectively inherited from her mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1126del (p.H376Tfs*56) variant was predicted to be pathogenic (PVS1+PM2_Supporting+PM4), and c.1285G>C (p.E429Q) variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PM4). Prenatal diagnosis suggested that the fetus also harbored the same compound heterozygous variants, and the pregnancy was terminated with induced labor.@*CONCLUSION@#The c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q) compound heterozygous variants of the PIGT gene probably underlay the MCAHS3 in this patient, and prenatal diagnosis has prevented birth of further affected child in this family.

Clinical and genetic analysis of a child with hyperekplexia / 中华神经科杂志

Objective:To analyze the clinical phenotype and gene sequencing results of a child with hyperekplexia, and to clarify her genetic etiology.Methods:The clinical information of the child was collected, and the whole exome sequencing of the child and her parents was performed. The suspected pathogenic variants were verified by Sanger sequencing and bioinformatics analysis.Results:There was a 12 years old girl, who was hospitalized in the Department of Pediatric Neurology of Linyi People′s Hospital because of "paroxysmal limb stiffness for more than 11 years and aggravated for half a month" on July 4, 2022. The girl showed exaggerated startle reflexes and generalized siffness in response to external sudden, unexpected stimuli, occasionally accompanied by apnea and cyanosis, frequent attacks occurred several times a day, lasting for 1-30 minutes, and early head and abdomen flexion can be relieved. She showed normal growth and development, no abnormality in brain magnetic resonance imaging and video electroencephalogram during seizure. The whole exome sequencing showed that there was a missense heterozygous mutation c.643T>C(p.W215R) in the SLC6A5 gene of the child. Neither of the parents carried this mutation, which was a novel and de novo variant. According to the guidelines of American College of Medical Genetics and Genomics, this variant was a likely pathogenic variant [PS2: de novo (both maternity and paternity confirmed) in the patient with the disease and no family history; PM2: undetected variants in the normal population; PP3: multiple softwares predicted that this mutation would have harmful effects on genes or gene products], and highly conserved. Swiss modeling found that the hydrogen bond of the modified amino acid also changed. Conclusions:Hyperekplexia is relatively rare and prone to misdiagnosis. The main clinical features are excessive startle reflexes (limb shaking, or jumping) to unexpected external stimuli, resulting in overall stiffness, normal growth and development, and normal video electroencephalogram during the seizure. The likely pathogenic heterozygous missense variant c.643T>C (p.W215R) of SLC6A5 gene is the genetic cause of this case.

Research advances of lncRNAs in nonalcoholic fatty liver disease / 中国药理学通报

Long non-coding RNAs (lncRNAs), a class of noncoding RNAs, are commonly defined as RNA molecules more than 200 nucleotides in length. LncRNA has been shown to get involved in various biological processes, such as chromatin modification, transcriptional activation and intranuclear transport. Emerging research have also indicated that lncRNA plays a vital role in the pathological processes of many diseases. Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases with an increasing incidence. Recent studies have confirmed that lncRNAs are key contributors to pathological processes that are underpinning the initiation and progression of NAFLD, including insulin resistance, lipid metabolism disorders and inflammation. This review summarizes the findings of the role of lncRNAs in the pathological processes of NAFLD that have obtained to date, in order to provide a theoretical basis for the prevention, treatment, clinical detection of NAFLD, and the development of innovative anti-NAFLD drugs.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Clinical and prognostic analysis of rhabdomyosarcoma in infants: a single-center report / 中华实用儿科临床杂志

Objective:To analyze the clinical characteristics and prognosis of infants with rhabdomyosarcoma (RMS), thus enhancing the understanding of this disease.Methods:Clinical data of all RMS patients younger than 12 months treated in the Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University from May 2006 to June 2019 were retrospectively analyzed, including the age, gender, histological type, tumor primary site, tumor size, and the prognosis.Patients were followed up until December 31, 2019.The 3-year event free survival (EFS) rate of children was performed by plotting the Kaplan-Meier survival curves.Results:A total of 15 RMS children younger than 12 months were enrolled, accounting for 4.9% of all RMS cases in the same period, including 6 males and 9 females.The median age at diagnosis was 7.0 months (3.0-11.5 months). Classified by the primary site, 40.0% (6 cases) located in the head and neck, followed by 26.7% (4 cases) located in the limbs, 26.7% (4 cases) located in other parts, and 6.7% (1 case) located in the urogenital system.Embryonal RMS, alveolar RMS and spindle cell RMS accounted for 46.6% (7 cases), 26.7% (4 cases), and 26.7% (4 cases), respectively.Ten cases (66.7%) were stage Intergroup Rhabdomyosarcoma Study (IRS)-Ⅲ and 1 case (6.7%) was in stage Ⅳ.There were 10 cases (66.6%) in the middle-risk group, 4 cases (26.7%) in the low-risk group, and 1 case (6.7%) in the high-risk group.Two cases had a larger than 5 cm primary tumor; lymph node involvement was confirmed in 3 cases, and pulmonary metastasis occurred in 1 case at the time of diagnosis.All children were treated with chemotherapy, and 13 cases received postoperative chemotherapy and 1 case received preoperative chemotherapy.One case were not operated.Only 3 children underwent radiotherapy, including 1 case underwent particle implantation and 2 cases received external radiotherapy.Among the 15 children with RMS, 5 cases had relapse and disease progression with the 3-year EFS rate of (59.1±14.5)%, and 2 died with the 3-year overall survival rate of (80.8±12.6)%.Conclusions:The median age of diagnosis of RMS in single-center infants is 7 months.Head and neck are the most common primary sites of RMS.Nearly 50% of the children have the primary site of RMS with poor prognosis.More than a quarter of the pathological subtypes are the spindle cell type.Local treatment significantly influences the local progression or recurrence of RMS.

Prevalence and associated factors of campus bullying of primary and secondary school students in Haidian District of Beijing / 中国学校卫生

Objective@#To understand the prevalence and associated factors of school bullying among primary and secondary school students in Haidian District, and to provide scientific basis for intervention plan.@*Methods@#From September to October 2021, 1 906 primary and secondary school students in Haidian District were selected by stratified cluster random sampling for electronic questionnaire survey,an electronic questionnaire survey was conducted on students by using the questionnaire of the Student Health Status and Influencing Factors Questionnaire.@*Results@#The prevalence of campus bullying among primary and secondary school students in Haidian District was 4.3%, of which primary school (7.6%) > junior middle school (4.1%) > vocational high school (2.5%) > senior high school (1.9%) ( χ 2=23.49, P ＜0.01), boys (5.5%) were more than girls (3.0%) ( χ 2=7.44, P ＜ 0.01 ), students from abnormal families (6.9%) were higher than students from normal families (3.9%) ( χ 2=4.24, P =0.04). Multivariate Logistic regression analysis showed that students in primary school had a higher risk of being bullied in school ( OR =2.13). Abnormal family ( OR = 1.07 ), smoking experience ( OR =2.28), experience of being beaten and scolded by parents( OR =2.49) and fighting behavior ( OR =1.84) were positively correlated with school bullying ( P <0.05).@*Conclusion@#Campus bullying is prevalent in primary and secondary schools in Haidian District, which warrents further attention of schools and education departments. Family school partnership and targeted prevention and intervention measures for key populations are expected.

Expression of lncRNA TGFB2-AS1 in the placenta of preeclampsia and its relationship with placental spiral artery recasting / 中华内分泌外科杂志

Objective:To investigate the relationship between the expression level of long non-coding RNA transforming growth factor β2-antisense RNA1 (lncRNA TGFB2-AS1) and placental spiral artery recasting in the placenta of preeclampsia.Methods:A total of 108 pregnant women with severe preeclampsia who were hospitalized in Zaozhuang Maternal and Child Health Hospital and delivered by cesarean section from Oct. 2019 to Jun. 2021 were selected as the research objects, and they were divided into the late-onset preeclampsia group (late-onset severe preeclampsia pregnant women, 56 cases) and early-onset preeclampsia group (early-onset severe preeclampsia pregnant women, 52 cases) ; at the same time, 58 normal pregnant women were selected as the normal pregnancy group. The general data of pregnant women were collected, such as age, systolic blood pressure and diastolic blood pressure. Real-time fluorescent quantitative PCR (qRT-PCR) method was used to detect the expression level of lncRNA TGFB2-AS1 in placental tissues, a scanning electron microscope was used to measure the lumen area and wall thickness of spiral arteries. Pearson correlation analysis method was used to analyze the correlation between the level of lncRNA TGFB2-AS1 in the placenta tissue and the thickness of the spiral artery wall and the area of the lumen of pregnant women with early-onset and late-onset severe preeclampsia.Results:The tube wall thickness [ (119.69±8.31) μm], systolic blood pressure [ (162.86±4.94) mmHg], diastolic blood pressure [ (103.09±2.35) mmHg], and 24-hour urine protein [ (2.17±0.31) g/24 h] in the early preeclampsia group were higher than those in the late preeclampsia group [ (101.04±5.78) μm, (146.95±6.43) mmHg, (92.13±4.74) mmHg, (1.62±0.23) g/24 h] and the normal pregnancy group [ (99.82±5.56) μm, (116.42±9.31) mmHg, (74.25±6.74) mmHg, (0.06±0.02) g/24 h], the placental tissue lncRNA TGFB2-AS1 level (0.62±0.16), lumen area [ (133.74±20.16) μm 2], gestational week of delivery [ (32.15±1.74) weeks], weight of the newborns [ (2.25±0.26) g] were lower than those in the late-onset preeclampsia group [ (0.99±0.21), (185.49±22.75) μm 2, (36.14±1.59) weeks, (3.37±0.32) g] and the normal pregnancy group [ (1.02±0.23), (186.42±23.71) μm 2, (38.19±1.56) weeks, (3.42±0.37) g] ( P<0.05). The systolic blood pressure, diastolic blood pressure, and 24-hour urine protein in the late preeclampsia group were higher than those in the normal pregnancy group, gestational week of delivery was lower than the normal pregnancy group ( P<0.05). Placental tissue lncRNA TGFB2-AS1 of pregnant women with early-onset severe preeclampsia was positively correlated with the lumen area, and negatively correlated with the thickness of the tube wall ( P<0.05). There was no correlation between lncRNA TGFB2-AS1 and the lumen area and wall thickness in the placental tissue of pregnant women with late-onset severe preeclampsia ( P>0.05) . Conclusion:The lncRNA TGFB2-AS1 expression in the placenta tissue of pregnant women with early-onset severe preeclampsia is abnormally low, which may be related to the insufficient recasting of the placental spiral artery.

Correlation between single nucleotide polymorphism and protein expression of FcγRⅡb in Hashimoto′s thyroiditis / 中华内分泌代谢杂志

Objective:To investigate whether FcγRⅡb rs775 single nucleotide polymorphism confers susceptibility to Hashimoto′s thyroiditis and its impact on expression of FcγRⅡb protein on B cell surface.Methods:A total of 187 Hashimoto′s thyroiditis patients(HT group) were enrolled, including 46 males(24.60%) and 141 females(75.40%), with a median age of 43(32, 53) years, and 187 healthy controls(conrol group), including 62 males(33.16%) and 125 females(66.84%), with a median age of 41(31, 51) years. The peripheral blood of two groups were sequenced, genotype and allele frequencies distribution of FcγRⅡb rs775 T>C were compared with clinical parameters as strata between the two groups. At the same time, the expression of inhibitory receptor FcγRⅡb on B cell surface was detected using flow cytometry.Results:Compared with control group, the mutant homozygous CC genotype was obviously enrichment in HT group( OR=3.321, 95% CI 1.175-9.386, P=0.018), and the proportion of CC genotype increased in male of HT group( P=0.076). However, there is no significant difference in genotype and allele frequencies between control group and HT group after stratification by sex. In addition, the percentage of FcγRⅡb on B cell surface decreased significantly in HT group( P=0.029). Conclusion:There was no significant correlation between FcγRⅡb polymorphism and the down-regulation of FcγRⅡb protein on B cell surface in Hashimoto′s thyroiditis patients, and FcγRⅡb can be a predisposed factor for Hashimoto′s thyroiditis.

Study on effects of dioscin against depression and its mechanisms / 中国药理学通报

Aim To investigate the effects and possible molecular mechanisms of dioscin(DIO)against depression in mice.Methods Eighty mice were randomly divided into control group, DIO control group, model group, DIO groups(20, 40 and 80 mg·kg-1 DIO)and FLU group(20 mg·kg-1 fluoxetine).After establishing the depression model with chronic unpredictable moderate stress(CUMS)in mice, the corresponding drugs were administered by gavage continuously for four weeks in each group.The behavior of mice was tested, and the contents of corticosterone(CORT), brain-derived neurotrophic factor(BDNF), 5-hydroxytryptamine(5-HT), malondialdehyde(MDA), superoxide dismutase(SOD)and catalase(CAT)were evaluated by ELISA or enzyme labeling method.In addition, HE staining, Nissl staining and PET scanning were operated for the brain tissues.Western blot was used to detect the protein expressions.Results Compared with model group, DIO significantly improved the behaviors of depressed mice.And it reduced the contents of CORT in serum, increased BDNF and 5-HT in hippocampus.Meanwhile, DIO obviously reduced MDA in serum, increased SOD in serum and CAT in brain tissues.DIO improved the steatosis of brain tissues, disorder and looseness of neurons, and increased glucose metabolism in brain tissues of depressed mice.The molecular mechanism suggested that compared with model group, DIO significantly increased the protein level of UCP2 to adjust the levels of Nrf2, SOD2, GLUT1 and G6Pase.Conclusions DIO improves the depression symptoms of depressed mice, which should be through adjusting UCP2-mediated oxidative stress and glucose metabolism.

Impact of prolonging dual antiplatelet therapy on long-term prognosis of elderly patients with coronary heart disease complicated with diabetes mellitus undergoing drug-eluting stent implantation / 中华心血管病杂志

Objective: To explore and compare the effect of standard or prolonged dual antiplatelet therapy (DAPT) on the long-term prognosis of elderly patients with coronary heart disease complicated with diabetes mellitus after drug-eluting stent (DES) implantation. Methods: Consecutive patients with diabetes mellitus, ≥65 years old, underwent DES implantation, and had no adverse events within 1 year after operation underwent percutaneous coronary intervention (PCI) from January to December 2013 in Fuwai Hospital were enrolled in this prospective cohort study. These patients were divided into three groups according to DAPT duration: standard DAPT duration group (11 ≤ DAPT duration≤ 13 months) and prolonged DAPT duration group (13<DAPT duration≤ 24 months; DAPT duration>24 months). All the patients were followed up at 1, 6 months, 1, 2 and 5 years in order to collect the incidence of major adverse cardiovascular and cerebrovascular events (MACCE), and type 2 to 5 bleeding events defined by the Federation of Bleeding Academic Research (BARC). MACCE were consisted of all cause death, myocardial infarction, target vessel revascularization or stroke. The incidence of clinical adverse events were compared among 3 different DAPT duration groups, and Cox regression model were used to analyze the effect of different DAPT duration on 5-year long-term prognosis. Results: A total of 1 562 patients were enrolled, aged (70.8±4.5) years, with 398 female (25.5%). There were 467 cases in standard DAPT duration group, 684 cases in 13<DAPT duration≤ 24 months group and 411 cases in DAPT duration>24 months group. The patients in standard DAPT duration group and the prolonged DAPT duration groups accounted for 29.9% (467/1 562) and 70.1% (1 095/1 562), respectively. The 5-year follow-up results showed that the incidence of all-cause death in 13<DAPT duration≤ 24 months group (4.8%(33/684) vs. 8.6%(40/467),P=0.011) and DAPT duration>24 month group(4.1%(17/411) vs. 8.6%(40/467),P=0.008) were significantly lower than in standard DAPT group. The incidence of myocardial infarction in 13<DAPT duration≤ 24 months group was lower than in standard DAPT duration group (1.9%(13/684) vs. 5.1%(24/467),P=0.002). The incidence of MACCE in 13<DAPT duration≤ 24 months group was the lowest (standard DAPT duration group, 13<DAPT duration≤ 24 months group and DAPT duration>24 month group were 19.3% (90/467), 12.3% (84/684), 20.2% (83/411), respectively, P<0.001). There was no significant difference in the incidence of stroke and bleeding events among the three groups (all P>0.05). Multivariate Cox analysis showed that compared with the standard DAPT group, prolonged DAPT to 13-24 months was negatively correlated with MACCE (HR=0.601, 95%CI 0.446-0.811, P=0.001), all-cause death (HR=0.568, 95%CI 0.357-0.903, P=0.017) and myocardial infarction (HR=0.353, 95%CI 0.179-0.695, P=0.003). DAPT>24 months was negatively correlated with all-cause death (HR=0.687, 95%CI 0.516-0.913, P=0.010) and positively correlated with revascularization (HR=1.404, 95%CI 1.116-1.765, P=0.004). There was no correlation between prolonged DAPT and bleeding events. Conclusions: For elderly patients with coronary heart disease complicated with diabetes mellitus underwent DES implantation, and had no MACCE and bleeding events within 1 year after operation, appropriately prolonging of the DAPT duration is related to the reduction of the risk of cardiovascular adverse events. Patients may benefit the most from the DAPT between 13 to 24 months. In addition, prolonging DAPT duration does not increase the incidence of bleeding events in this patient cohort.

Analysis of the effect of gene mutations on the efficacy of ruxolitinib in patients with myelofibrosis based on second-generation sequencing technology / 中华血液学杂志

Objective: To assess the effect of gene mutations on the efficacy of ruxolitinib for treating myelofibrosis (MF) . Methods: We retrospectively analyzed the clinical data of 56 patients with MF treated with ruxolitinib from July 2017 to December 2020 and applied second-generation sequencing (NGS) technology to detect 127 hematologic tumor-related gene mutations. Additionally, we analyzed the relationship between mutated genes and the efficacy of ruxolitinib. Results: ①Among the 56 patients, there were 36 cases of primary bone marrow fibrosis (PMF) , 9 cases of bone marrow fibrosis (ppv-mf) after polycythemia vera, and 11 cases of bone marrow fibrosis (PET-MF) after primary thrombocytosis (ET) . ②Fifty-six patients with MF taking ruxolitinib underwent NGS, among whom, 50 (89.29%) carried driver mutations, 22 (39.29%) carried ≥3 mutations, and 29 (51.79%) carried high-risk mutations (HMR) . ③ For patients with MF carrying ≥ 3 mutations, ruxolitinib still had a better effect of improving somatic symptoms and shrinking the spleen (P=0.001, P<0.001) , but TTF and PFS were significantly shorter in patients carrying ≥ 3 mutations (P=0.007, P=0.042) . ④For patients carrying ≥ 2 HMR mutations, ruxolitinib was less effective in shrinking the spleen than in those who did not carry HMR (t= 10.471, P=0.034) , and the TTF and PFS were significantly shorter in patients carrying ≥2 HMR mutations (P<0.001, P=0.001) . ⑤Ruxolitinib had poorer effects on spleen reduction, symptom improvement, and stabilization of myelofibrosis in patients carrying additional mutations in ASXL1, EZH2, and SRSF2. Moreover, patients carrying ASXL1 and EZH2 mutations had significantly shorter TTF [ASXL1: 360 (55-1270) d vs 440 (55-1268) d, z=-3.115, P=0.002; EZH2: 327 (55-975) d vs 404 (50-1270) d, z=-3.219, P=0.001], and significantly shorter PFS compared to non-carriers [ASXL1: 457 (50-1331) d vs 574 (55-1437) d, z=-3.219, P=0.001) ; 428 (55-1331) d vs 505 (55-1437) d, z=-2.576, P=0.008]. Conclusion: The type and number of mutations carried by patients with myelofibrosis and HMR impact the efficacy of ruxolitinib.

Long-term prognosis effects of single and staged percutaneous coronary intervention in patients with multi-vessel coronary artery disease / 中国医师进修杂志

Objective:To compare the influence of single and staged percutaneous coronary intervention (PCI) on long-term prognosis in patients with multi-vessel coronary artery disease.Methods:Using prospective research methods, 1 832 patients with multi-vessel coronary artery disease from January to December 2013 in Fuwai Hospital, Chinese Academy of Medical Sciences were selected. According to the time of PCI, the patients were divided into single PCI group (1 218 cases) and staged PCI group (614 cases). The patients were followed up for 2 years, the primary endpoint was major cardiovascular and cerebrovascular event (MACCE), including target vessel-related myocardial infarction (TV-MI), target vessel-related revascularization (TVR), cardiogenic death and stroke, and the secondary endpoint was stent thrombosis. The propensity score matching (PSM) was applied to balance the discrepancies between 2 groups, and the baseline and follow-up data were compared. The Kaplan-Meier survival curves were drawn to evaluate the survival rates events; multifactor Cox proportional risk regression was used to analyze whether staged PCI was an independent risk factor for the endpoint events.Results:The in-hospital stay, duration of procedure and synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score in single PCI group were significantly lower than those in staged PCI group: (5.54±3.09) d vs. (9.50±4.06) d, (43.12±28.55) min vs. (79.54±44.35) min, (14.04±7.63) scores vs. (18.51±7.79) scores, and there were statistical differences ( P<0.01); there were no statistical difference in complete revascularization rate and SYNTAX score after PCI between 2 groups ( P>0.05). Based on 2-year follow-up, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.5% (6/1 218) and 2.0% (12/614) vs. 0.4% (5/1 218), and there were statistical differences ( P<0.01). Kaplan-Meier survival curves analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were better than those in staged PCI group (99.5% vs. 97.9% and 99.6% vs. 98.0%, P<0.01). Multifactor Cox proportional risk regression analysis results showed that staged PCI was an independent risk factor for stent thrombosis ( HR = 3.91, 95% CI 1.25 to 12.18, P = 0.019). After PSM, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.7% (4/614) and 2.0% (12/614) vs. 0.5% (3/614), and there were statistical differences ( P<0.05); Kaplan-Meier survival curve analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were significantly higher than those in staged PCI group: (99.3% vs. 97.9% and 99.5% vs. 98.0%, P<0.05); multifactor Cox proportional risk regression analysis results showed that staged PCI was not an independent risk factor of stent thrombosis ( HR = 2.29, 95% CI 0.58 to 9.00, P = 0.234). Both before and after PSM, there were no evidences for interaction between the type of angina pectoris and staged PCI ( P>0.05). Conclusions:Although a seemingly increase exists in the incidence of TV-MI and stent thrombosis in the staged PCI group, staged PCI is an independent risk factor neither for MACCE and its components, nor for stent thrombosis. In addition single PCI reduces the in-hospital days and duration of PCI procedure, which may be a relatively reasonable approach to clinical practice.

Intensification of pegaspargase in pretransplant chemotherapy regimens reduced relapse of adult Philadelphia chromosome-negative acute lymphoblastic leukemia after transplantation / 中华器官移植杂志

Objective:To explore risk factors for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph-ALL).Methods:A retrospective analysis was performed for 65 adult Ph-ALL patients undergoing initial allo-HSCT from 2016 to 2018. The effect of baseline level and treatment pre-transplantation for relapse after allo-HSCT was analyzed.Results:There were 37 males and 28 females with a median age of 25(14-58) years during allo-HSCT. And the median follow-up period was 27 months post-HSCT. The 2-year overall survival (OS) was 78.8%(95%CI 67.8%-89.8%) and the 2-year relapse-free survival (RFS) 70.7% (95%CI 58.2%-83.2%). Pre-transplant chemotherapy was offered for 3 to 7 courses and the median dose of polyethylene glycol-conjugated asparaginase (PEG-ASP) was 3 doses (2 000 IU/m 2 per dose). Multiariate analysis revealed that the regimen included more than 4 doses of PEG-ASP pre-HSCT (HR=4.067, P=0.046) was a protective factor for post-transplant relapse (HR=0.193, P=0.009). High-risk chromosome karyotype was a risk factor for relapse (HR=0.193, P=0.009). The 2-year RFS rate was 90.0%(95%CI 79.2%-100.0%) for intensive PEG-ASP group and 56.9%(95%CI 39.1%-74.7%) for control group ( P=0.01). No significant inter-group difference existed in overall survival (OS)( P=0.079). The 2-year OS was 90.6% (95%CI 80.4%-100.0%) in intensive PEG-ASP group and 72.1% (95%CI 56.6%-87.6%) in control group. Conclusions:For adult ph-ALL patients, a higher dose of PEG-ASP in pretransplant chemotherapy regimens may improve post-transplant RFS and achieve a better outcome.

Application of lung ultrasound score inevaluating patients with primary graft dysfunction after lung transplantation / 中华器官移植杂志

Objective:To explore the application value of bedside lung ultrasound score(LUS)in evaluating patients with primary graft dysfunction(PGD)after lung transplantation.Methods:A total of 35 PGD patients after lung transplantation in surgical intensive care unit from June 2018 to May 2020 were selected as research objects. After lung transplantation, one physician collected the clinical data, including age, gender, preoperative 24 h APACHE II score, postoperative hemodynamic parameters, lactate and respiratory parameters; another physician was responsible for LUS examination and LUS at 12/24/48/72 h post-operation. The correlation between LUS and oxygenation index was analyzed by bivariate correlation analysis. Receiver operating characteristic curve(ROC)was utilized for calculating the predictive value, sensitivity and specificity of LUS score for severe PGD.Results:A negative correlation existed between LUS and oxygenation index in single lung transplant( r=-0.536, P<0.01)and a negative correlation between LUS and oxygenation index ( r=-0.518, P<0.01)in double lung transplant. The area under ROC curve of LUS showed that the predictive value of LUS of severe PGD patients with single lung transplant was 7.0 with a sensitivity of 86.7% and a specificity of 72.1%, the predicted value of LUS of severe PGD in double lung transplant was 13.0 with a sensitivity of 83.3% and a specificity of 60.0%. Conclusions:Lung ultrasound is simple and easy to operate and LUS can evaluate the severity of PGD patients after lung transplantation. It has a high potency of guiding clinical diagnosis and treatment.

The effectiveness and safety of ultrasound-guided hydrostatic reduction for pediatric acute intussusception / 中华超声影像学杂志

Objective:To evaluate the effectiveness and safety of ultrasound-guided hydrostatic reduction for pediatric acute intussusception.Methods:One thousand eight hundred and thirty patients with acute intussusception diagnosed by ultrasound in Shenzhen Children′s Hospital from September 2017 to July 2020 were treated with ultrasound-guided hydrostatic reduction method. The therapeutic effects, complications and ultrasonic features were observed.Results:Among 1 830 cases, 1 791 cases were diagnosed as primary intussusception, and 39 cases were secondary intussusception. The overall rate of successful ultrasound enema reduction were 1 780/1 830(93.7%) patients. All 50/1 830(2.7%) patients underwent surgery after unsuccessful enema reduction, including 42 cases of primary intussusception, and 8 cases of secondary intussusception. The complication of intestinal perforation occurred in 3 cases (0.16%), and there were no deaths.Conclusions:Ultrasound-guided enema reduction for pediatric acute intussusception is an effective and safe method without radiation exposure, and can be used as the preferred method for non-operative treatment of intussusception.