Establishment and behavioral evaluation of a mouse model of long-term free-choice alcohol drinking / 北京大学学报(医学版)

OBJECTIVE@#To establish a model of long-term free drinking mouse by feeding mice with alcohol to simulate the state of human voluntary long-term drinking, and on this basis, to further discuss the evaluation criteria of long-term free drinking mice model in sports, anxiety and cognitive behavior.@*METHODS@#Forty six-week-old SPF C57BL/6 male mouse were randomly divided into two groups: Long-term free drinking group (n=20) and normal control group (n=20). The two groups were given solid feed normally. The long-term free drinking group was free to take 10% alcohol and water every day, while the normal drinking group only took water every day. The mice were fed for 7 months, and were evaluated by a series of behavioral methods, including Rota-rod test, balance beam test, open filed test, the elevated plus maze, two-box social behavior, new object recognition, Y maze and water maze.@*RESULTS@#With the increase of drinking days, the mice showed significant alcohol addiction in the alcohol preference test. With the increase of alcohol intake, the mice in the long-term free choice drinking group had slightly shiny fur and reduced diet. Compared with the control group, the weight gain began to slow down from the third month, and the weight decreased significantly by the sixth and seventh months (P=0.006, P < 0.001). The mice showed reduced balance locomotion ability (P=0.003, P=0.001) in the rotary bar and balance beam test. In the open field and elevated cross test, the mice had obvious anxiety-like behavior (P < 0.001). The mice showed decreased social ability in the two boxes of social behavior (P < 0.016). In the experiment of new object recognition and Y maze, the exploration of new object decreased (P=0.018, P=0.040). In the water maze, cognitive functions, such as learning and spatial memory were reduced (P < 0.001).@*CONCLUSION@#The successful establishment of the long-term free drinking mouse model is more convenient for us to carry out further research on the neural mechanism of alcohol addiction, and lays an experimental foundation for exploring the neural mechanism of alcohol addiction and related new targets.

Risk of Hepatitis B Virus (HBV) Reactivation in HBsAg-Negative, Anti-HBc-Negative Patients Receiving Rituximab for Autoimmune Diseases in HBV Endemic Areas

Background/Aims@# Rituximab is known to be associated with high hepatitis B virus (HBV) reactivation rate in patients with resolved HBV infection and hematologic malignancy. However, data regarding HBV reactivation (HBVr) in rheumatic patients receiving rituximab is limited. To assess the HBVr rate in hepatitis B surface antigen (HBsAg)-negative patients receiving rituximab for autoimmune diseases in a large real-world cohort. @*Methods@# From March 2006 to December 2019, 900 patients with negative HBsAg receiving at least one cycle of rituximab for autoimmune diseases in a tertiary medical center in Taiwan were retrospectively reviewed. Clinical outcome and factors associated with HBVr were analyzed. @*Results@#After a median follow-up period of 3.3 years, 21 patients developed HBVr, among whom 17 patients were positive for hepatitis B core antibody (anti-HBc) and four were negative. Thirteen patients had clinical hepatitis flare, while eight patients had HBsAg seroreversion without hepatitis. Old age, anti-HBc positivity, undetectable serum hepatitis B surface antibody level at rituximab initiation and a higher average rituximab dose were associated with a higher HBVr rate. There was no significant difference in the HBVr risk between rheumatoid arthritis and other autoimmune diseases. Among anti-HBc-negative patients, subjects without HBV vaccination at birth had an increased risk of HBVr (4/368, 1.1%) compared with those who received vaccination (0/126, 0%). @*Conclusions@#In HBV endemic areas where occult HBV is prevalent, anti-HBc-negative patients, may still be at risk for HBVr after rituximab exposure. HBVr may still be considered in HBsAgnegative patients developing abnormal liver function after rituximab exposure, even in patients with negative anti-HBc.

Heterogeneity of Outcomes Reporting in Trials Evaluating Traditional Chinese Medicine Breast Massage for Stasis Acute Mastitis: A Methodological Review / 中国医学科学杂志(英文版)

Objective To systematically analyze the current status of outcomes reporting in clinical trials on treating stasis acute mastitis with Traditional Chinese Medicine breast massage.Methods We searched CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Embase, Cochrane library, JBI, CINAHL, PsycINFO, Clinical Trials Registry Platform portal, Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, Center Watch Registry from inception to May 15, 2022 to find randomized controlled trials, non-randomized controlled trials, case series and cohort studies which reported the outcomes of stasis acute mastitis managed with Traditional Chinese Medicine breast massage, with search terms of mastitis, acute mastitis, lactation mastitis, puerperal mastitis, breast problem, breast engorgement, milk stasis, blocked ducked, breast pain, breast massage, and acupoint massage. Outcomes and the measurement schemes (measurement methods, timing of assessing outcome, frequency of assessing outcome, measurers) were extracted from the included studies. We used the Management of Otitis Media with Effusion in Children with Cleft Palate (MOMENT) to assess the quality of each study, then categorized outcomes derived from the included studies into different domains according to the Outcome Measures in Rheumatology Arthritis Clinic Trials (OMERACT) Filter 2.1 framework.Results We identified 85 clinical trials, in which 54 different outcomes were reported. A total of 81.2% (69/85) of studies were assessed as medium quality with a mean score of 2.6, and 18.8% (16/85) as low quality with a mean score of 0.9. These outcomes were organized in three core areas. Lump size (89.4%, 76/85) was the most frequently reported outcome, followed by breast pain (69.4%, 59/85) and milk excretion (68.2%, 58/85). Five methods were used to assess lump size and four methods to assess breast pain.Conclusions The outcomes reported in clinical trials regarding stasis acute mastitis treated by Traditional Chinese Medicine breast massage are heterogeneous. Developing a core outcome set to achieve consistent standards for reporting outcomes and modalities for validation of the outcomes is clearly warranted.

Effect of preoperative anemia on perioperative red blood cell transfusion and prognosis in children with septal defect / 中国输血杂志

【Objective】 To analyze the impact of preoperative anemia on perioperative red blood cell transfusion and prognosis of children undergoing septal defect repair. 【Methods】 The medical records of 208 patients under 18 years old with septal defect, i. e. ventricular septal, atrial septal, ventricular septal with atrial septal defect, in a hospital from December 2018 to March 2022 were collected. They were divided into anemic group (n=52) and non-anemic group (n=156) according to whether they were anemic before operation. The basic information, as well as preoperative, intraoperative and postoperative blood transfusion, postoperative ICU stay, postoperative infection rate and average length of stay were compared between the two groups. 【Results】 The incidence of preoperative anemia in the children with septal defect was 25.0% (52/208). The age, preoperative body weight(kg) and hemoglobin (g/L) of anemic group and non-anemic group was 0.67(0.33, 2) vs 2(1, 3), 6.5(5, 10) vs10.5(8, 14) and 102(91.5, 107) vs 127(121, 134) respectively, all P<0.05. Preoperative, intraoperative and postoperative blood transfusion rates in the anemic and non-anemic groups were 11.54% (6/52) vs 0% (0/156), 92.31% (48/52) vs 72.44% (113/156), 51.92% (27/52) vs 25.0% (39/156), all P<0.05. Postoperative ICU stay (d) and mean length of stay(d) of anemia group and non-anemia group was 3 (2, 6) vs 2 (2, 3) and 19(13, 25) vs14(11, 18) respectively, P<0.05. 【Conclusion】 Preoperative anemia is an important factor affecting perioperative red blood cell transfusion in children with septal defect repair, and also an important reason for prolonging postoperative ICU stay and hospital stay.

Clinical characteristics of liver injury caused by anti-tuberculosis drugs in newly treated pulmonary tuberculosis patients co-infected with hepatitis B virus / 公共卫生与预防医学

Objective To investigate the clinical characteristics of drug-induced liver injury caused by anti-tuberculosis drugs in newly treated pulmonary tuberculosis patients with hepatitis B virus (HBV). Methods A total of 133 patients with pulmonary tuberculosis and HBV who were treated in Zhuzhou Central Hospital from January 2018 to early January 2022 were selected, and all were treated with conventional anti-tuberculosis 2HRZE/4HR regimen. According to the liver injury, the patients were divided into liver injury group and no liver injury group. Univariate analysis was used to analyze the related factors of liver injury caused by anti-tuberculosis drugs, and multivariate logistic regression analysis was used to analyze the independent risk factors of liver injury caused by anti-tuberculosis drugs. Results Among 133 cases of newly treated pulmonary tuberculosis patients with HBV, 24 cases had liver injury caused by anti-tuberculosis drugs, accounting for 18.05%; 109 patients had no liver injury caused by anti-tuberculosis drugs, accounting for 81.95%. Univariate analysis showed that there were significant differences in smoking history, drinking history, diabetes history, hypertension history, anti-tuberculosis treatment plan, malnutrition, and use of hepatoprotective drugs between the liver injury group and the no liver injury group (P<0.05). Multivariate logistic regression analysis showed that smoking history, drinking history, diabetes history, hypertension history, PZA-containing regimen, malnutrition, and no use of hepatoprotective drugs were independent risk factors for liver injury caused by anti-tuberculosis drugs. Conclusion Smoking history, drinking history, diabetes history, hypertension history, PZA-containing regimen, malnutrition, and no use of hepatoprotective drugs are the risk factors for drug-induced liver injury caused by anti-tuberculosis drugs in newly treated pulmonary tuberculosis patients with HBV.

Expert consensus on platelet-rich plasma treatment for osteochondral lesion of talus (version 2023) / 中华创伤杂志

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

Pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma / 中华肿瘤杂志

Objective: To investigate the pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma (cHL-NS2) in our cancer center. Methods: A retrospective collection of 23 cases of cHL-NS2 admitted in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from July 2008 to April 2019 was performed. Fifty-five cases of nodular sclerosis grade 1 of classical Hodgkin's lymphoma (cHL-NS1) during the same period were selected as control group. Survival curves were plotted using the Kaplan-Meier method, and Cox regression model was used to analyze the influencing factors for survival. Results: The median age of 23 cases of cHL-NS2 was 30 years old. Five cases had extra nodal invasion, and 19 cases were Ⅰ-Ⅱ stage based on Ann Arbor system. The pathological morphology of cHL-NS2 showed that the lymph node structure was completely destroyed and was divided into nodules by thick collagen. The tumor cells in the nodules were abundant and proliferated in sheets. The boundaries between the tumor cells were not clear. The incidence of tumor necrosis in cHL-NS2 was 43.5% (10/23), which was significantly higher than 18.2% (10/55) in cHL-NS1 (P=0.040). The 3-year progression-free survival (PFS) rate of patients in the cHL-NS2 group was 58.1%, which was significantly lower than 89.7% in the cHL-NS1 group (P=0.002). In all of 78 cases, the 3-year PFS rate of patients who did not obtain complete response (CR) was 67.1%, which was significantly lower than 92.2% in patients who achieved CR (P=0.030). Multivariate Cox regression analysis demonstrated that both cHL-NS2 and failure to obtain CR by first-line treatment were independent indicators for short PFS time (P<0.05). Conclusions: In cHL-NS2, the morphology of tumor cells are diverse, and tumor necrosis can be easily found. Under the current first-line treatments of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), cHL-NS2 is an independent indicator for worse PFS.

Correlation of fetal cervical cystic hygroma with chromosomal and structural abnormalities: analysis of 70 cases / 中华围产医学杂志

Objective:To analyze the correlation of fetal cervical cystic hygroma (CCH) with chromosomal and structural abnormalities and to assess the prognosis of CCH.Methods:This study retrospectively enrolled 70 fetuses with CCH diagnosed by prenatal ultrasound in the First Affiliated Hospital of Xi'an Jiao Tong University from July 2015, to December 2021. According to whether complicated by structural malformations or other anomalies, all the subjects were divided into the non-isolated and isolated CCH groups. The correlation of CCH and the gestational age at detection with chromosomal and structural abnormalities were analyzed and the prognosis of the cases were summarized using Chi-square test. Results:There were 34 isolated CCH (34/70, 49%) and 36 non-isolated CCH (36/70, 51%) among the 70 cases. In the non-isolated CCH group, there were eight cases (22%, 8/36) with abnormal heart structure, ten (28%, 10/36) with abnormal anterior abdominal wall, 16 (44%,16/36) with systemic edema and/or pleural effusion, one (3%,1/36) with craniocerebral abnormalities and one with holoprosencephaly and cardiac structural abnormalities. Eighteen out of 44 cases undergoing chromosome testing had chromosomal abnormalities, which were trisomy-18 ( n=6), trisomy-21 ( n=3), trisomy-13 ( n=3), 45,XO ( n=3), and chromosome segment duplication or deletion ( n=3). The detection rate of chromosome abnormality was higher in non-isolated CCH group comparing with isolated CCH group [59%(13/22) vs 23%(5/22), χ2=6.02, P=0.014]. There was no significant difference in the gestational age at the detection of CCH or proportion of women of advanced maternal age between the isolated and non-isolated CCH groups (both P>0.05). The ratios of isolated CCH cases with normal chromosome detected at the gestational weeks of 14-27 +6 was higher than those detected at 11-13 +6 weeks [62%(13/21) vs 17%(4/23), χ2=7.39, P=0.001]. Out of the 17 cases with isolated CCH and normal chromosomes, 12 were live births. One of the 12 cases still had a cystic mass with a diameter of 3 cm in the neck nine months after birth, and the other 11 cases had no mass at birth but one case died at the age of five months (hospitalized one week for neonatal edema),one case was found with anal atresia three days after birth and underwent operation and the remaining nine cases were normal during five months to six years follow-up. Conclusions:Non-isolated CCH is at a higher risk of chromosomal abnormalities. Isolated CCH cases detected later had higher rate of normal chromosome and often have a higher survival rate.

Construction and analysis of the structural equation model for the influencing factors of endothelial function of the brachial artery / 中华健康管理学杂志

Objective:To examine the influencing factors of endothelial injury using the structural equation model (SEM).Methods:A total of 6 861 asymptomatic individuals free of cardiovascular disease underwent health examinations at the health management center of the third Xiangya hospital, Central South University from May 2015 to August 2020. And collected their questionnaire and checkup data. Spearman′s rank correlation coefficient was used to analyze metabolic factors and brachial artery flow-mediated dilatation (FMD). Exploratory factor analysis (3 430/6 861) and confirmatory factor analysis (3 431/6 861) were conducted on the diet items. An SEM was constructed using the diet pattern data, cardiovascular risk factors and FMD, and using multi-path regression analysis to determine the correlation between the indicators.Results:Based on the factor analysis, diet items were divided into three patterns: healthy food, meat, and supplementary food. The SEM indicated that age ( β=0.27) and blood pressure ( β=0.12) had obvious effects on low FMD. Triglyceride ( β=0.03), fasting blood glucose ( β=0.04), and body mass index ( β=0.08) were positively correlated with low FMD. On the upstream, healthy food was negatively correlated with blood pressure ( β=-0.04) and body mass index ( β=-0.04), meat was positively correlated with triglyceride ( β=0.33), blood pressure ( β=0.06), fasting blood glucose ( β=0.20), and body mass index ( β=0.16), and supplementary food was negatively correlated with fasting blood glucose ( β=-0.30). This was the only pattern that was directly correlated with FMD ( β=0.05). Conclusions:SEM is an effective method to analyze the influence of various risk factors on the population and the relationship between individual indicators. This study revealed direct and indirect correlations between age, diet pattern, cardiovascular-metabolic risk, and FMD impairment. Comprehensive control of dietary patterns and metabolic indicators could prevent and improve early cardiovascular injury.

Application of PD-L1, PD-L2, CD30, CD23 and BCL-6 in Diagnosis and Prognostic Evaluation of Primary Mediastinal Large B-cell Lymphoma / 肿瘤防治研究

Objective To explore the application value of treatment-related markers PD-L1, PD-L2, CD30, CD23, BCL-2, BCL-6, MUM1 and GATA3 in the diagnosis and prognostic evaluation of primary mediastinal B-cell lymphoma(PMBL). Methods A retrospective study was conducted on 34 patients diagnosed with PMBL, and 31 patients with DLBCL-NOS which was not primary in the mediastinum were taken as control group. The expressions of 8 proteins were detected by IHC staining. Results The median percentages of tumor cells with PD-L1, PD-L2 and CD30 expression in PMBL group were 70% (30%, 90%), 25% (0, 70%) and 17.5% (0, 60%) respectively, which were significantly higher than those in the DLBCL-NOS group (P < 0.05). The positive rates of CD30 and CD23 in PMBL group were 61.76% (21/34) and 76.47% (26/34) respectively, significantly different with those in the DLBCL-NOS group (P=0.000). The survival curve of PMBL patients with CD30 or BCL-6 expression showed a trend of poor prognosis, despite the P value was > 0.05. Conclusion The high expression levels of PD-L1, PD-L2 and CD30 in PMBL are helpful to accurately identify more patients who may respond to immune or targeted therapy. Immunohistochemical staining of PD-L1, PD-L2, CD30 and CD23 is helpful for the differential diagnosis of PMBL and DLBCL-NOS. As candidate prognostic indicators of PMBL, CD30 and BCL-6 should be further studied in a larger number of samples.

Effect and Involved Mechanism of RSL3-induced Ferroptosis in Acute Leukemia Cells MOLM13 and Drug-resistant Cell Lines / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect and involved mechanism of RSL3 on ferroptosis action in acute leukemia cells MOLM13 and its drug-resistant cells.@*METHODS@#After MOLM13 treated with RSL3, CCK-8 assay was performed to detect cell viability, flow cytometry was used to detect the reactive oxygen species (ROS) level of the cells, RT-qPCR and Western blot were used to detect the expression of glutathione peroxidase 4 (GPX4). After MOLM13/IDA and MOLM13/Ara-C, the drug-resistant cell lines were constructed, the ferroptosis induced by RSL3 was observed. Bone marrow samples were collected from patients with acute monocytic leukemia. RT-qPCR and Western blot were performed to detect the expression of related genes and proteins involved in ferroptosis pathway.@*RESULTS@#RSL3 significantly inhibited the cell viability of MOLM13 and increased the intracellular ROS level, which were partially reversed by ferrostatin-1. The mRNA and protein expression of GPX4 decreased in MOLM13 treated with RSL3. RSL3 inhibited the viability of MOLM13/IDA and MOLM13/Ara-C cells more strongly than that of non-drug resistant cells, also increased the intracellular ROS level . The cytotoxic effects were partially reversed by ferrostatin-1. The mRNA and protein expressions of GPX4 in MOLM13/IDA and MOLM13/Ara-C cells were higher than those in non-drug resistant cells. The mRNA and protein levels of GPX4 in bone marrow of relapsed/refractory acute mononuclear leukemia patients were higher than those of ordinary acute mononuclear leukemia patients.@*CONCLUSION@#RSL3 can induce non-drug resistant cells MOLM13 ferroptosis by inhibiting GPX4 activity. MOLM13/IDA and MOLM13/Ara-C are more sensitive to RSL3 compared with non-drug resistant cells MOLM13, which may be caused by the differences in GPX4 expression. The expressions of GPX4 mRNA and protein in relapsed/refractory acute mononuclear leukemia are higher than those in ordinary acute mononuclear leukemia.

CT and MRI features of endolymphatic sac tumor / 中华放射学杂志

Objective:To explore CT and MRI features of the endolymphatic sac tumor (ELST).Methods:The CT and MRI morphology confirmed by surgical pathology for 19 patients with ELST were retrospectively analyzed from June 2011 to May 2019 in Eye & ENT Hospital of Fudan University. The features of CT and MRI included location, size, adjacent structures invasion, CT values, bone destruction, features of T 1WI and T 2WI, enhancement distribution characteristics, dynamic enhancement curve morphology, DWI signal characteristics. The ADC values of the lesions and ipsilateral medial pterygoid muscles were compared using a paired t test. Results:Nineteen ELST patients (one with bilateral diseases) were included. Totally 20 ears (right 9 and left 11) of 13 females and 6 males were studied. The masses with slightly high-density and obscure boundary were located around the vestibular aqueduct at the posterior edge of the petrosal bone. Bone destruction involved mastoid process of the middle ear (16 ears), jugular foramen (11 ears), semicircular canal (10 ears), facial nerve canal (7 ears) and internal auditory canal (9 ears). A large amount of residual bone could be found in the interior of nineteen masses. The CT value was (78.6±21.9) HU. The lesion showed central iso-intensity and peripheral hyperintensity on T 1WI and T 2WI in 16 ears, while no obvious hyperintensity on T 1WI in the other 4 ears. The hyperintensity on T 1WI was around the margin of the lesion in 10 ears, situated at lateral side in 5 ears and all over the lesion in 1 ear. Flow voids signals could be seen in 9 ears as well. Liquid-liquid plane was seen on T 2WI in 2 ears. The solid mass portion which showed iso-intensity on both T 1WI and T 2WI presented marked enhancement on contrast-enhanced T 1WI, while other part of the mass no enhancement. DWI of 14 ears illustrates no evidence of restricted diffusion, and the ADC value [(1.25±0.08)×10 -3 mm 2/s] was slightly higher than that of the medial pterygoid muscles ( t=4.437, P=0.001). The style of time-signal intensity curves of the dynamic contrast-enhanced MRI was rapidly ascending followed by descending curves in 2 ears. Conclusion:Imaging findings of ELST have some characteristics, including located around the vestibular aqueduct at the posterior edge of the petrosal bone, bone destruction, peripheral hyperintensity on T 1WI and no restricted diffusion, which is helpful for its diagnosis.

Effects of vitamin D levels on lung development in premature infants / 国际儿科学杂志

Lung development in premature infants includes alveolar cell differentiation,pulmonary vascular development,alveolar maturation.Vitamin D plays an important role in lung development in premature infants.Studies suggest that premature infants are often deficient or insufficiency in vitamin D.Low vitamin D levels,vitamin D binding protein polymorphisms,and vitamin D receptor gene polymorphisms increase the incidence of bronchopulmonary dysplasia and neonatal respiratory distress syndrome.Vitamin D regulates lung development in premature infants by promoting pulmonary vascular development,reducing inflammatory damage to alveolar epithelial cells,and promoting alveolar maturation,thereby reducing the risk of bronchopulmonary dysplasia,neonatal respiratory distress syndrome,and persistent pulmonary hypertension of newborn.This article reviews the relationship between vitamin D and lung development in premature infants.

Analysis of the efficacy and influencing factors of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia in the chronic phase and accelerated phase / 中华血液学杂志

Objective@#To explore the efficacy and prognosis of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia (CML) in the chronic phase (CP) and accelerated phase (AP) .@*Methods@#From January 2008 to November 2018, the data of CML patients who failed first- or second-line tyrosine kinase inhibitor (TKI) -therapy received nilotinib or dasatinib as second-line and third-line therapy were retrospectively reviewed.@*Results@#A total of 226 patients receiving nilotinib or dastinib as second-line (n=183) and third-line (n=43) therapy were included in this study. With a median follow-up of 21 (range, 1-135) months, the cumulative rates of complete hematological response (CHR) , complete cytogenetic response (CCyR) and major molecular response (MMR) were 80.4%, 56.3%and 38.3%, respectively in those receiving TKI as second-line TKI therapy. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 78.7%and 93.1%, respectively. Multivariate analyses showed that Sokal high risk, female gender, the best response achieved <CHR on the first-line TKI-therapy, the interval from diagnosis to switching to second-line TKI ≥18 months, AP or hematologic failure, or non-specific mutation of BCR-ABL kinase domain before second-line TKI therapy, developing severe hematologic toxicity during the second-line TKI therapy were variables associated with poor responses or outcomes on second-line TKI therapy. With a median follow-up of 6 (range, 3-129) months, the cumulative CHR, CCyR and MMR were 95.7%, 29.3%, and 18.6%, respectively in those receiving the third-line TKI therapy. The 2-year PFS and OS rates were 66.8% and 93.8%, respectively. The patients with an interval from diagnosis to starting TKI ≥6 months, achieving no cytogenetic response on the second-line TKI, the interval from diagnosis to starting second-line TKI ≥60 months, and progression to AP before the third-line TKI therapy had lower probabilities of responses and unfavorable outcomes.@*Conclusions@#The efficacy of dasatinib and nilotinib as second- or third-line TKI-therapy were active in the CML patients with TKI-resistance. The best response achieved on previous TKI-therapy, the disease phase before switching TKI, and the severe hematologic toxicity developing on the current TKI-therapy were associated with the responses and outcomes.

Reversal of Social Recognition Deficit in Adult Mice with MECP2 Duplication via Normalization of MeCP2 in the Medial Prefrontal Cortex / 神经科学通报·英文版

Methyl-CpG binding protein 2 (MeCP2) is a basic nuclear protein involved in the regulation of gene expression and microRNA processing. Duplication of MECP2-containing genomic segments causes MECP2 duplication syndrome, a severe neurodevelopmental disorder characterized by intellectual disability, motor dysfunction, heightened anxiety, epilepsy, autistic phenotypes, and early death. Reversal of the abnormal phenotypes in adult mice with MECP2 duplication (MECP2-TG) by normalizing the MeCP2 levels across the whole brain has been demonstrated. However, whether different brain areas or neural circuits contribute to different aspects of the behavioral deficits is still unknown. Here, we found that MECP2-TG mice showed a significant social recognition deficit, and were prone to display aversive-like behaviors, including heightened anxiety-like behaviors and a fear generalization phenotype. In addition, reduced locomotor activity was observed in MECP2-TG mice. However, appetitive behaviors and learning and memory were comparable in MECP2-TG and wild-type mice. Functional magnetic resonance imaging illustrated that the differences between MECP2-TG and wild-type mice were mainly concentrated in brain areas regulating emotion and social behaviors. We used the CRISPR-Cas9 method to restore normal MeCP2 levels in the medial prefrontal cortex (mPFC) and bed nuclei of the stria terminalis (BST) of adult MECP2-TG mice, and found that normalization of MeCP2 levels in the mPFC but not in the BST reversed the social recognition deficit. These data indicate that the mPFC is responsible for the social recognition deficit in the transgenic mice, and provide new insight into potential therapies for MECP2 duplication syndrome.

Reducing the consumption of personal protective equipment by setting up a multifunctional sampling station in the emergency department to screen for COVID-19 infection in Taiwan

In Taiwan, high-risk patients have been identified and tested for preventing community spread of COVID-19. Most sample collection was performed in emergency departments (EDs). Traditional sample collection requires substantial personal protective equipment (PPE), healthcare professionals, sanitation workers, and isolation space. To solve this problem, we established a multifunctional sample collection station (MSCS) for COVID-19 testing in front of our ED. The station is composed of a thick and clear acrylic board (2 cm), which completely separates the patient and medical personnel. Three pairs of gloves (length, 45 cm) are attached and fixed on the outside wall of the MSCS. The gloves are used to conduct sampling of throat/nasal swabs, sputum, and blood from patients. The gap between the board and the building is only 0.2 cm (sealed with silicone sealant). ED personnel communicate with patients using a small two-way broadcast system. Medical waste is put in specific trashcans installed in the table outside the MSCS. With full physical protection, the personnel conducting the sampling procedure need to wear only their N95 mask and gloves. After we activated the station, our PPE, sampling time, and sanitization resources were considerably conserved during the 4-week observation period. The MSCS obviously saved time and PPE. It elevated the efficiency and capacity of the ED for handling potential community infections of COVID-19.

Clinical Characteristics and Prognosis of U2AF1 Mutation in Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the incidence, clinical features of U2AF1 gene mutation in patients with acute myeloid leukemia(AML) and its effect of prognosis.@*METHODS@#A total of 161 patients with AML were enrolled. The second-generation sequencing method was used to detect U2AF1 gene mutation, and the relationship between U2AF1 mutation and clinical features, prognosis was analyzed.@*RESULTS@#The mutation rate of U2AF1 gene in 161 AML patients was 3.73%. The counts of peripheral blood leukocytes and platelets in the U2AF1 gene mutation group were lower than those in the wild type group. The complete response rate of U2AF1 gene mutation group was 66.67%, while that in wild type group was 55.48%, which shows no significant difference between the two groups (P=0.70). The median EFS of wild type group and the mutant group was not reached and reached to 133 days, respectively (P=0.03), while the medium OS in two groups was not reached and reached to 210 days (P=0.01).@*CONCLUSION@#The AML patients with U2AF1 mutation positive have a poor prognosis as compared with the wild type group, which may be a poor prognostic factor for acute myeloid leukemia.

Epidemiological characteristics of injury caused by fall in the elderly aged ≥60 years in Guang- zhou in 2014-2018 / 中华疾病控制杂志

@#Objective To explore the epidemiological characteristics and influencing factors of fall of elderly aged ≥ 60 years in Guangzhou from 2014 to 2018 ，so as to provide evidence for effective prevention and control measures． Methods Data on fall of the elderly was collected from the first diagno- sis in injury surveillance hospitals in Guangzhou from 2014 to 2018，and distribution description and epi- demiological analysis were adopted． Ｒesults 9 503 cases of fall of the elderly were reported in 5 injury surveillance hospitals，accounting for 49．41% of injuries in the elderly，and had occupied the first place in the cause of injury in 5 consecutive years． The sex ratio of men to women was 1 ∶ 1．67． Most of the patients had a primary or junior school degree，high rate in October-December，mainly occurred at home when doing leisure activities or life activities． The fall mainly led to injuries of head or lower extremities， contributed to contusion /bruise or fracture． And most of them were mild and moderate injury． Logistic re- gression showed that female，old age，high educational level，December to February，at home，walking， leisure activities and life activities were risk factors for falling among the elderly in Guangzhou ( all P ＜ 0．001) ． Conclusions Fall is the primary cause of injuries to the elderly in Guangzhou，especially the elderly female population． The targeted prevention and intervention measures should be developed ac- cording to their distribution characteristics．

Survey of Chinese orthopedists' cognition on the Chinese Osteoarthritis Guideline (2018 Edition) / 中华骨科杂志

Objective:To investigate the orthopedists' cognition on Chinese Osteoarthritis Guideline (2018 Edition).Methods:Questionnaire about Chinese Osteoarthritis Guideline (2018 Edition) was developed and sent to orthopedists via an invitation link to fill out after authorization from Chinese Osteoarthritis Association. The content of the questionnaire included the basic personal information of the physician, the awareness rate of the guidelines, the evaluation of the guidelines, and its application effects. The survey duration was from September 2019 to December 2019. Multivariate logistic regression and linear regression analysis were performed for the guideline awareness rate and comprehensive score, respectively.Results:A total of 628 physicians completed the questionnaire, of which 623 of 628 (99.2%) were available. About 72.4% of the orthopedists knew the guideline. The awareness rate was statistically related to the education of the physicians ( P<0.05). Respondents' overall score for the guideline was 8.39 with methodological score 8.28. A total of 41.2% of orthopedists thought that the guideline was very good compared with the European and American guidelines, and the clinical problem coverage rate was 78.6%. There is a statistically significant difference in the appraisal of the recommendations ( χ2=138.9, P<0.05) . More than 40% of orthopedists believed that the guidelines were of great help to orthopedists and patients, and that the guide could be promoted to the primary hospitals. Conclusion:After one year publication of Chinese Osteoarthritis Guideline (2018 Edition), most orthopedists have understood the present guideline and applied recommendations in clinical practice. However, the guideline need to be further promoted and disseminated in the future.

Clinical efficacy of computed tomography-guided iodine-125 seed implantation therapy for patients with metastatic epidural spinal cord compression: A retrospective study

Background: This study evaluated the clinical efficacy of computed tomography (CT)-guided radioactive iodine-125 (125 I) seed implantation in patients with metastatic epidural spinal cord compression (MESCC). Materials and Methods: A cohort of 22 patients with MESCC were retrospectively enrolled. All patients underwent CT-guided 125 I seed implantation therapy via standard procedures. Clinical indexes, including the University of Texas MD Anderson Cancer Center (MDA) criteria for tumor responses, numerical rating scale (NRS) for the degree of pain, Karnofsky Performance Status (KPS) for quality of life, American Spinal Injury Association (ASIA) impairment scale, grade of ESCC, and radiation dose, were evaluated and recorded pre- and post-operation. A follow-up evaluation was performed at least 3 months after the operation. Finally, pre- and post-operative differences in these clinical indexes were compared. Overall survival was recorded. Results: Operations were successfully performed on all patients. A median of 48 (range, 7–103) seeds were implanted in lesions, and the postoperative target verified dose D90 was 11,072.4 ± 1773.5 cGy. Patients were followed for a median of 6 months (range, 3–38 months). The median survival time was 10 months; the response rate was 18/22 (82%); the local control rates at 3, 6, and 12 months were 91.3%, 81.9%, and 81.9%, respectively; and the survival rates were 80%, 50.0%, and 21.9% at 6, 12, and 18 months, respectively. The ESCC grade was significantly lower (P < 0.05). Based on the ASIA impairment scale, the nerve functional reservation, recovery, and decline rates were 63.7% (14/22), 27.3% (6/22), and 9% (2/22), respectively. The NRS and KPS were both significantly improved in the 3rd month of follow-up (P < 0.05). Conclusion: CT-guided 125 I seed implantation represents an effective and safe palliative care for patients with MESCC, which can effectively relieve pain and spinal cord compression and improve nerve function and quality of life