Research progress on phenotype and function of microglia / 中国药理学通报

Microglia are the central nervous system's resident myeloid-derived immune cells, which play a major role in the innate and acquired immunological responses of brain. In the maintenance of brain tissue function under both healthy and pathological conditions, microglia take a protective or damaging role, depending on cell phenotypes and functions. The traditional microglia classification of pro- or anti-inflammatory phenotypes refers to the profile of macrophages, hence the term “brain macrophages:has been drawn. More microglia phenotypes are being discovered as new technologies and research methods are developed, and the newly discovered microglia phenotypes are often disease-, brain region-, and function-specific, providing an important foundation for studying the pathological processes underlying the development of specific diseases and developing appropriate interventions. Here, we provide a retrospective review of recent advances in the study of phenotype and function of microglia, and analyze the microglial cell lineage composition and its heterogeneous function.

Biomarkers for early screening and diagnosis of breast cancer: a review / 生物工程学报

The estimated new cases of breast cancer (BC) patients were 2.26 million in 2020, which accounted for 11.7% of all cancer patients, making it the most prevalent cancer worldwide. Early detection, diagnosis and treatment are crucial to reduce the mortality, and improve the prognosis of BC patients. Despite the widespread use of mammography screening as a tool for BC screening, the false positive, radiation, and overdiagnosis are still pressing issues that need to be addressed. Therefore, it is urgent to develop accessible, stable, and reliable biomarkers for non-invasive screening and diagnosis of BC. Recent studies indicated that the circulating tumor cell DNA (ctDNA), carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), extracellular vesicles (EV), circulating miRNAs and BRCA gene from blood, and the phospholipid, miRNAs, hypnone and hexadecane from urine, nipple aspirate fluid (NAF) and volatile organic compounds (VOCs) in exhaled gas were closely related to the early screening and diagnosis of BC. This review summarizes the advances of the above biomarkers in the early screening and diagnosis of BC.

Advances in predictive biomarkers associated with immune checkpoint inhibitors for tumor therapy / 生物工程学报

Malignant tumors are diseases that seriously threaten human health and social development. Traditional tumor therapies such as surgery, radiotherapy, chemotherapy and targeted therapy cannot fully meet the needs of clinical treatment, and emerging immunotherapy has become a research hotspot in the field of tumor treatment. Immune checkpoint inhibitors (ICIs) have been approved as a tumor immunotherapy method for the treatment of various tumors, such as lung cancer, liver cancer, stomach cancer and colorectal cancer, etc. However, during the clinical use of ICIs, only a small number of patients experienced durable responses, which also led to drug resistance and adverse reactions. Therefore, the identification and development of predictive biomarkers is crucial to improve the therapeutic efficacy of ICIs. The predictive biomarkers of tumor ICIs mainly include tumor biomarkers, tumor microenvironment biomarkers, circulation-related biomarkers, host environmental biomarkers and combinatorial biomarkers. They are of great significance for screening, individualized treatment and prognosis evaluation of tumor patients. This article reviews the advances of predictive markers for tumor ICIs therapy.

Comprehensive Diagnosis of Mantle Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the value of multiple detection methods based on histopathology and supplemented by bone marrow or peripheral blood sample detections in the comprehensive diagnosis of mantle cell lymphoma (MCL).@*METHODS@#The clinical, immunophenotypic, pathologic, cytogenetic and molecular features of 153 newly diagnosed MCL patients admitted to the hematology department of our hospital from May 2009 to September 2022 were analyzed.@*RESULTS@#144 (96.6%) of the 149 MCL patients who underwent marrow or peripheral blood IGH/CCND1 FISH detection at initial diagnosis were positive, of which 36 cases (24.2%) had a low proportion positive. The immunophenotypes in 115 patients were analyzed by flow cytometry (FCM), 89 cases (77.4%) conformed to MCL while 23 cases (20.0%) were initially diagnosed as B-cell lymphoproliferative disorders (B-LPD). Of the 75 cases who performed bone marrow biopsy, 50 cases (66.7%) had morphological and immunophenotypic characteristics consistent with MCL, 15 cases (20.0%) were classified as B-LPD, and 10 cases with no obvious abnormality. 77 patients underwent histopathology examination, of which 73 cases (94.8%) had typical clinicopathological features of MCL, including 2 CCND1 negative MCL, 2 pleomorphic variants, 5 pleomorphic variants and 4 cases diagnosed as other leukemia or lymphoma. Among 153 cases of MCL, 128 cases were classic MCL(cMCL), and another 25 cases (16.3%) were diagnosed as leukemic non-lymph node MCL (lnnMCL). The incidence of IGHV mutation, TP53 mutation and CD23 expression positive were significantly different between cMCL and lnnMCL.@*CONCLUSION@#Histopathology is still the main standard for the diagnosis of cMCL, and detection based on bone marrow or peripheral blood samples is an important means for the diagnosis of lnnMCL. Single marker or examination can cause a certain proportion of misdiagnosis. The accurate diagnosis of MCL depends on a combination of multiple detection methods.

Comparison of chemical constituents in Artemisiae Argyi Folium from different Dao-di producing areas based on UPLC and HS-GC-MS / 中国中药杂志

This study aims to compare the chemical constituents in 24 batches of Artemisiae Argyi Folium samples collected from three different Dao-di producing areas(Anguo in Hebei, Nanyang in Henan, and Qichun in Hubei). An ultra-performance liquid chromatography(UPLC) method was established to determine the content of 13 nonvolatile components, and headspace-gas chromatography-mass spectrometry(HS-GC-MS) was employed for qualitative analysis and comparison of the volatile components. The content of phenolic acids in Artemisiae Argyi Folium was higher than that of flavonoids, and the content of nonvolatile components showed no significant differences among the samples from the three Dao-di producing areas. A total of 40 volatile components were identified, and the relative content of volatile components in Artemisiae Argyi Folium was significantly different among the samples from different Dao-di producing areas. The principal component analysis and partial least squares discriminant analysis identified 8 volatile components as the potential markers for discrimination of Artemisiae Argyi Folium samples from different Dao-di producing areas. This study revealed the differences in the chemical composition of Artemisiae Argyi Folium samples from three different Dao-di producing areas, providing analytical methods and a scientific basis for the discrimination and quality evaluation of Artemisia Argyi Folium in different Dao-di producing areas.

Added value of T 1-weighted StarVIBE sequence for PET/MR image quality / 中华核医学与分子影像杂志

Objective:To explore the added value of T 1-weighted stack-of-stars volumetric interpolated body examination (StarVIBE) sequence on PET/MR image quality. Methods:A retrospective analysis was performed on 60 patients (42 males, 18 females; age 11-86 (58±12) years) who underwent 18F-FDG PET/MR examination and with positive PET results in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from April 2020 to April 2021. All patients completed StarVIBE sequence collection, and volumetric interpolated body examination (VIBE) sequence was used as control. StarVIBE and VIBE sequence images were evaluated independently using five-point method by two physicians. The evaluation was carried out from six aspects: lesion display, lesion boundary display, vascular around lesions display, fusion level with PET image, image artifact and overall image quality. Wilcoxon signed rank test was used to compare the image quality of the two sequences, and Kappa test was performed to assess the consistency of the image quality scores between the two physicians. Results:There were 26 cases with cervical lesions, 14 cases with chest lesions, 7 cases with abdomen lesions and 13 cases with pelvic lesions. The scores of lesion display (4.0(3.8, 4.5) vs 3.5(3.0, 4.0)), lesion boundary display (4.0(4.0, 4.0) vs 3.0(3.0, 3.5)), vascular around lesions display (5.0(4.0, 5.0) vs 4.0(3.5, 4.5)), fusion level with PET image (5.0(5.0, 5.0) vs 4.5(4.0, 5.0)), image artifact (4.5(4.0, 5.0) vs 4.5(4.0, 5.0)) and overall image quality (5.0(4.0, 5.0) vs 4.0(4.0, 4.0)) of StarVIBE sequences were better than those of VIBE sequences ( z values: 3.77-6.54, all P<0.001). On the vascular around the lesions display, the scores of StarVIBE were significantly better than those of VIBE sequence in the neck (5.0(4.5, 5.0) vs 3.0(2.7, 3.5); z=4.49, P<0.001) and chest (4.5(4.3, 4.7) vs 4.0(3.6, 4.3); z=3.10, P=0.002). As for image quality, the scores of StarVIBE were also significantly better than those of VIBE in neck (5.0(4.5, 5.0) vs 4.0(3.7, 4.5); z=4.36, P<0.001) and chest (5.0(5.0, 5.0) vs 4.0(4.0, 4.5); z=3.02, P=0.003). In abdominal lesions, the score of StarVIBE was higher than that of VIBE in blood vessels (4.5(3.5, 5.0) vs 4.0(3.5, 4.5); z=2.07, P=0.038), and there was no difference between score of overall image quality (4.0(3.7, 4.5) vs 4.0(3.5, 4.5); z=0.27, P=0.785). The score of overall image quality of pelvic StarVIBE sequence was better than that of VIBE sequence (5.0(4.5, 5.0) vs 4.0(4.0, 4.5); z=2.12, P=0.034). Kappa value of image quality score between two physicians was 0.554, indicating moderate consistency. Conclusion:In whole-body PET/MR imaging, StarVIBE sequence can significantly improve the image quality of cervical, thoracic and pelvic lesions when comparing with VIBE sequence.

Circular RNA ame_circ_000115 regulates expression of genes in larval gusts of Apis mellifera ligustica stressed by Ascosphaera apis / 生物工程学报

Circular RNAs (circRNAs) are a new class of non-coding RNAs, which have been confirmed to regulate insect gene expression and immune response through multiple manners such as competing endogenous RNA (ceRNA) regulatory network. Currently, function of circRNA in honey bee immune response remains unclear. In this study, PCR and Sanger sequencing were performed to validate the back splicing (BS) site of ame_circ_000115 (in short ac115). RT-qPCR was used to detect the expression profile of ac115 in larval guts of Apis mellifera ligustica stressed by Ascosphaera apis. Dual-luciferase reporter gene assay was conducted to verify the binding relationship between ac115 and ame-miR-13b. Interference of ac115 in larval guts was carried out by feeding specific siRNA, followed by determination of the effect of ac115 interference on expression of six genes relevant to host immune response. The results confirmed the existence of BS site within ac115. Compared with the un-inoculated group, the expression of ac115 in 4-day-old larval gut of the A. apis-inoculated group was up-regulated with extreme significance (P < 0.000 1), while that in 5- and 6-day-old larval guts were significantly up-regulated (P < 0.05). The brightness of specific band for ac115 in 4-, 5- and 6-day-old larval guts of the siRNA-circ_000115-fed group gradually became weak, whereas that of the siRNA-scrambl-fed group was pretty high without obvious variation. Compared with that of the siRNA-scramble-fed group, the expression of ac115 in 4-day-old larval gut of the siRNA-circ_000115-fed group was significantly down-regulated (P < 0.05), whereas that of the 5- and 6-day-old larval guts were down-regulated with extreme significance (P < 0.001). Ame-miR-13b was truly existed and expressed in A. m. ligustica larval guts, and there was true binding relationship between ac115 and ame-miR-13b. Compared with that of the siRNA-scramble-fed group, the expression of antimicrobial peptide genes hymenoptaecin and abaecin in 6-day-old larval gut of the siRNA-circ_000115-fed group was significantly up-regulated (P < 0.05), while that of ecdysone receptor (Ecr) was down-regulated with extreme significance (P < 0.01). These results indicate that ac115 is truly expressed in A. m. ligustica larval guts, BS site truly exists within ac115, and effective interference of ac115 in A. m. ligustica larval guts can be achieved via feeding siRNA. Moreover, ac115 potentially regulates Ecr expression through adsorption of ame-miR-13b and expression of hymenoptaecin and abaecin using a non-ceRNA manner, further participating in host stress-response.

Exploration of O-PIRTAS Flipped Classroom Combined with TBL in Quality Education of Basic Medical Courses ———Taking the Molecular Mechanism of Cellular Signal Transduction as an Example / 中国生物化学与分子生物学报

Basic medicine is the starting point to contact medicine for students, and also the key period for the formation of professional ethics and core qualities. While imparting basic professional knowledge, it is necessary and effective to integrate ability training and value guidance into the whole person education and carry out the fundamental task of building moral principle and cultivating students. Based on the high-quality resources of national online first-class courses, the teaching team combined the advantages of O-PIRTAS flipped classroom and TBL teaching, and explored the molecular mechanism of cell signal transduction in practice. Through introducing rich and diversified materials and cases, such as Nobel Prize research process, major research achievements of Chinese scholars, frontier progress of disciplines, mechanism of action of targeted drugs, clinical diseases, etc, students were guided to gain knowledge, exercise ability and improve quality via discussion and cooperation. Through the interactive links of online and offline, in-class and out-of-class, individual and team, listening and speaking, learning and practice, basic theory and extension and exploration, students’ abilities in autonomous learning, team cooperation, communication and expression had been significantly improved and they had a deeper understanding of scientific spirit and humanistic spirit. At the same time, students have been trained with preliminary dialectical thinking and innovation consciousness, enhanced sense of mission and national confidence, and strong professional concept of serving people’ s health. The teaching team believes that the high-quality resources and the control of exploration activities are important steps to improve the teaching effect of O-PIRTAS flipped classroom combined with TBL.

bFGF and IGF-1 promotes differentiation of bone mesenchymal stem cells into cardiomyocyte-like cells and its related mechanisms / 中国药理学通报

Aim To elucidate the biological effects of insulin-like growth factor-1 ( IGF-1 ) and basic fibro-blast growth factor (bFGF) alone or in combination on the differentiation of bone mesenchymal stem cells (BMSCs) into cardiomyocytes (CMs), and to explore the mechanism in the differentiation process of BMSCs into CMs induced by IGF-1 or bFGF. Methods After four weeks of BMSCs induced by induction differentiation medium ( with or without LY294002) containing IGF-1 and/or bFGF, the expression levels of proteins associated with the cardiomyogenic phenotype in BMSCs were detected via immunocytochemistry, immuno-fluorescence staining, and Western blot. Meanwhile, the expression levels of pathway related proteins were detected by Western blot. The cell ultrastructure was observed by transmission electron microscopy (TEM) . The expression levels of myocardial specific genes were measured via RT-qPCR. Results Compared with the control group, the expression levels of myocardial specific proteins and genes significantly increased in the IGF-1, bFGF and combination groups and were the highest in the coinduction group. The TEM of the conduction group showed parallel myofilaments, mitochondria, endoplasmic reticulum and so on. The additon of LY294002 decreased the expression levels of myocardial specific proteins, genes and phosphorylation Akt. Conclusions The effect of IGF-1 combined with bFGF on the differentiation of BMSCs into CMs is markedly better than that induced by IGF-1 or bFGF a-lone, and the differentiation process may depend on the PI3K/Akt signaling pathway.

Phage antibody library technology in tumor therapy: a review / 生物工程学报

Tumor is a serious threat to human health. At present, surgical resection, chemoradiotherapy, targeted therapy and immunotherapy are the main therapeutic strategies. Monoclonal antibody has gradually become an indispensable drug type in the clinical treatment of cancer due to its high efficiency and low toxicity. Phage antibody library technology (PALT) is a novel monoclonal antibody preparation technique. The recombinant immunoglobulin variable region of heavy chain (VH)/variable region of light chain (VL) gene is integrated into the phage vector, and the antibody is expressed on the phage surface in the form of fusion protein to obtain a diverse antibody library. Through the process of adsorption-elution-amplification, the antibody library can be screened to obtain the antibody molecule with specific binding antigen as well as its gene sequence. PALT has the advantages of short antibody production cycle, strong plasticity of antibody structure, large antibody yield, high diversity and direct production of humanized antibodies. It has been used in screening tumor markers and preparation of antibody drugs for breast cancer, gastric cancer, lung cancer and liver cancer. This article reviews the recent progress and the application of PALT in tumor therapy.

Analysis of pathogenic microorganisms in 64 077 cases of umbilical cord blood / 中国输血杂志

【Objective】 To investigate the detection of pathogenic microorganisms in umbilical cord blood and maternal blood from 2012 to 2021, so as to improve the collection of umbilical cord blood and guarantee the safety of umbilical cord blood hematopoietic stem cells (HSC) . 【Methods】 Detection results of pathogenic microorganisms of umbilical cord blood and maternal blood among 64 077 cases from Tianjin Cord Blood Bank from 2012 to 2021 were retrospectively analyzed. 【Results】 A total of, 2 072 cases (3.23%) were detected positive, among which, 184 cases (0.29%) were positive for aerobic bacteria culture, 1 504 cases (2.34%) were positive for anaerobic bacteria culture, and 384 cases (0.60%) were positive for both aerobic and anaerobic bacteria culture. From 2012 to 2021,the overall positive rate showed a downward trend, with a difference in the positive rate between each year (P<0.05). The positive rate of anaerobic bacteria was higher than that of aerobic bacteria and that of anaerobic and aerobic bacteria (P<0.05). After Gram staining, the microscopic detection rate of bacterial positive samples was highest in G- bacilli, followed by G+ bacilli, G+ cocci, G- cocci and others. Among the 64 077 cases, 169 cases (0.26%) showed reactivity in cord blood tests and 1 231 cases (1.92%) showed reactivity in maternal blood tests. Umbilical cord blood and maternal blood HIV-Ag/Ab tests showed reactivity after initial screening. After confirmation by Western blotting, there was 1 case of uncertain maternal blood, while the rest were negative. The reactive rates of anti-TP (0.12%) and anti- HCV (0.11%) in umbilical cord blood were higher than those of HBsAg (0.03%) and CMV-IgM (1/64 077).There was a difference in the reactive rate of anti-TP detection in umbilical cord blood between different years (P<0.05),while there was no statistically significant difference in that of HBsAg, anti-HCV and CMV-IgM (P> 0.05).The reactive rate of HBsAg in maternal blood (1.38%) was higher than that of CMV-IgM(0.29%) , anti-TP(0.13%) and anti-HCV (0.12%) . There were differences in the reactive rates of HBsAg, anti-HCV ,and anti-TP in maternal blood among different years (P<0.05),and that of HBsAg showed a decreasing trend, while the reactive rate of CMV-IgM was not statistically significant (P>0.05). The reactive rates of HBsAg and CMV-IgM detected in maternal blood were significantly higher than those in umbilical cord blood (P<0.05) . The reactive rates of anti-HCV and anti-TP in maternal blood were consistent with those in umbilical cord blood (P>0.05). 【Conclusion】 The reactive rates of anti-HIV and CMV-IgM in cord blood, and that of anti-HIV in maternal blood are low, but those of anti-TP and anti-HCV in cord blood are relatively high. The reactive rate of HBsAg is high in maternal blood,but with a downward trend,but low in umbilical cord blood due to maternal-infantile transmission blocking. The detection of transfusion transmitted pathogens and bacteria plays a critical role on the safety of umbilical cord blood HSCs. Effective detection of transfusion transmitted pathogens and culture of bacteria are the key to ensure the quality of umbilical cord blood, which can improve the safety of umbilical cord blood HSCs transplantation.

Influence of the number of high-risk cytogenetic abnormalities on the clinical characteristics and prognosis in 360 patients with newly diagnosed multiple myeloma / 中华血液学杂志

Objective: To investigate the influence of the number of high-risk cytogenetic abnormalities (HRCA) on the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma (MM) . Methods: A total of 360 patients with newly diagnosed MM admitted to Jiangsu Province Hospital between November 2013 and September 2020 were included in this study. Cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH) was used to detect HRCA. Cytogenetic abnormalities were combined with clinical characteristics and outcomes for further analysis. Results: Among the 360 patients, 120 patients (33.3%) presented with no HRCAs, and 175 (48.6%) , 61 (16.9%) , and four (1.1%) patients had one, two, and three HRCA (s) , respectively. Patients were divided into three groups, including the no-HRCA group, one-HRCA group, and ≥two-HRCA group, according to the number of HRCAs. There were significant differences in the R-ISS stage, hemoglobin level, albumin level, and the proportion of bone marrow plasma cells among the three groups (P<0.05) . The COX proportional-hazards model identified extramedullary disease (P=0.018) , HRCA ≥ 2 (P=0.001) , and absence of autologous hematopoietic stem cell transplantation (P<0.001) as independent risk factors for progression free survival (PFS) and identified lactate dehydrogenase (LDH) level ≥ 220 U/L (P<0.001) , HRCA ≥2 (P=0.001) , and absence of autologous hematopoietic stem cell transplantation (P=0.005) as independent risk factors for overall survival (OS) . The median PFS was 28 months, 22 months, and 14 months (P=0.005) for the three cohorts, and their OS was not reached,60 months, and 30 months (P=0.001) , respectively. Conclusions: HRCA ≥ 2 is an independent risk factor for decreased survival in patients with newly diagnosed MM. More HRCAs result in heavier tumor burden, as well as a higher risk of disease progression and death.

Fancd2os Reduces Testosterone Production by Inhibiting Steroidogenic Enzymes and Promoting Cellular Apoptosis in Murine Testicular Leydig Cells

Background@#It is well-established that serum testosterone in men decreases with age, yet the underlying mechanism of this change remains elusive. @*Methods@#The expression patterns of Fancd2 opposite-strand (Fancd2os) in BALB/c male mice and testicular tissue derived cell lines (GC-1, GC-2, TM3, and TM4) were assessed using real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence. The Fancd2os-overexpressing or knockdown TM3 cells were constructed by infecting them with lentivirus particles and were used to evaluated the function of Fancd2os. The testosterone production was measured using enzyme linked immunosorbent assay (ELISA) and the steroidogenic enzymes such as steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) were analysed using RT-PCR. The apoptosis of TM3 cells induced by ultraviolet light or testicular tissues was detected using flow cytometry, Western blot or dUTP-biotin nick end labeling (TUNEL) assays. Pearson correlation analysis was used to assess the correlation between the Fancd2os expression and TUNEL-positive staining in mouse testicular Leydig cells. @*Results@#The Fancd2os protein was predominantly expressed in mouse testicular Leydig cells and its expression increased with age. Fancd2os overexpression inhibited testosterone levels in TM3 Leydig cells, whereas knockdown of Fancd2os elevated testosterone production. Fancd2os overexpression downregulated the levels of StAR, P450scc and 3β-HSD, while Fancd2os knockdown reversed this effect. Fancd2os overexpression promoted ultraviolet light-induced apoptosis of TM3 cells. In contrast, Fancd2os knockdown restrained apoptosis in TM3 cells. In vivo assays revealed that higher Fancd2os levels and mouse age were associated with increased apoptosis in Leydig cells and decreased serum testosterone levels. Pearson correlation analysis exhibited a strong positive correlation between the expression of Fancd2os and TUNEL-positive staining in mouse testicular Leydig cells. @*Conclusion@#Our findings suggest that Fancd2os regulates testosterone synthesis via both steroidogenic enzymes and the apoptotic pathway.

Study on the efficacy and safety of combination of sufficient argon plasma coagulation cauterization and clipping in the treatment of colonic diverticular bleeding / 中华消化杂志

Objective:To evaluate the efficacy and safety of combination of sufficient argon plasma coagulation(APC) cauterization and clipping in the treatment of colonic diverticular bleeding.Methods:From June 2018 to April 2022, the clinical data of patients were retrospectively analyzed, who visited Department of Gastroenterology of Air Force Medical Center due to overt gastrointestinal bleeding, and were confirmed or suspected to have colonic diverticular bleeding and received combination of sufficient APC cauterization and clipping treatment. The deadline for follow-up was September 30, 2022. During the follow-up after endoscopic treatment, the re-bleeding rate, hemoglobin level difference between the last follow-up and before treatment, wound healing under colonoscopy as well as the intraoperative and postoperative complications of patients were statistically analyzed. Descriptive analysis was used for statistical analysis.Results:A total of 15 patients were enrolled, including 13 males and 2 females, aged (60.8±14.8) years old. The course of the disease was 1 day to 13 years. A total of 145 colonic diverticula of 15 patients were treated under endoscopy. The median follow-up time was 14.5 months (5.3 to 49.5 months) months. Among the 15 patients, 12 patients received endoscopic therapy once and no bleeding occurred till the end of follow-up. Three patients suspected with diverticular bleeding received a second endoscopic treatment because of bleeding at the 12 days, 3 months and 8 months after the first treatment, respectively.No rebleeding occurred after the second endoscopic therapy till the end of follow-up. The re-bleeding rate of the first treatment was 3/15 and the re-bleeding rate of re-treatment was 0. At the end of follow-up, the hemoglobin concentration increased (35.9±26.3) g/L compared with that before the treatment. Two patients had perforation during operation and were closed with multiple titanium clips. There was no abdominal pain or other symptoms after operation. And the patients were discharged 3 and 4 days after treatment, respectively. Two patients suffered short-term postoperative wound bleeding and successful hemostasis was achieved after endoscopic treatment. One patient developed postoperative infection and the symptoms disappeared after anti-infection treatment.Conclusions:Combination of sufficient APC cauterization and titanium clipping is safe and effective in the treatment of colonic diverticular bleeding. For patients with dominant diverticular hemorrhage, or patients with recurrent gastrointestinal bleeding, if other etiology are excluded and colonic diverticular bleeding is highly suspected, the combination of sufficient APC cauterization and titanium clipping under endoscopy is feasible.

Data mining and analysis of febuxostat-induced cardiac ADR signals / 中国药房

OBJE CTIVE To mine and analyze t he cardiac adverse drug reaction （ADR）signals induced by febuxostat in post-marketing experience ，and to provide reference for rational drug use in clinic. METHODS Reporting odds ratio （ROR） method was used to mine the ADR signals induced by febuxostat from the FDA Adverse Event Reporting System during the first quarter of 2009 to the fourth quarter of 2020；the information of cardiac disease signals was counted and analyzed. RESULTS A total of 209 ADR signals were detected in 8 282 adverse drug event （ADE）reports with febuxostat as the primary suspected drug ， involving 27 cardiac signals and 754 ADE reports. The most reported signals were symptoms （262 reports），including dizziness ， oedema peripheral，chest pain ，palpitations and gravitational oedema and so on ，followed by coronary atherosclerotic heart disease signal，heart failure signal ，arrhythmia signal ，sudden cardiac death signal （233，157，90，12 reports，respectively）. More than half of the signals were mentioned in the drug instructions ，while the unmentioned signals were mainly kinds of cardiac failure ， arrhythmia and extrasystoles ，etc. The patients with cardiac ADEs who received febuxostat were more male than female ，and the age was 60 and over ；the drug dosage was mostly 40 mg/d or 80 mg/d as recommended in the drug instructions ，and cardiac ADEs mostly occurred within 1 month of medication. CONCLUSIONS Routine attention should be paid to the cardiac safety of febuxostat during medication ，further evaluation and validation of febuxostat-induced cardiac ADR signals are still needed.

Diagnosis and differential diagnosis value of immune marker CCR7 in chronic lymphocytic leukemia and other chronic B-cell lymphoproliferative disorders / 中华检验医学杂志

Objective:To investigate the clinical significance of cc-chemokine receptor 7 (CCR7) as a potential diagnostic or differential marker for chronic lymphocytic leukemia (CLL).Methods:A total number of 643 patients with B-cell chronic lymphoproliferative diseases (B-CLPD) admitted to the First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2018 were enrolled. The patients included 327 cases of CLL, 58 cases of mantle cell lymphoma (MCL), 34 cases of follicular lymphoma (FL), 36 cases of marginal zone lymphoma (MZL), 10 cases of hair-cell leukemia or its variants (HCL/HCLV-v), 40 cases of Waldorf′s macroglobulinemia (WM), 48 cases of CD5 +B-cell chronic lymphoproliferative disease unclassified (B-CLPD-U) and 90 cases of CD5 -B-CLPD-U. At the same time, 20 samples from healthy people from the medical examination center of our hospital were used as normal controls. Flow cytometry was used to detect the immune-phenotype and CCR7 expression level in B-CLPD patients, and Fluorescence in situ hybridization (FISH) was used to analyze the genomic alterations: the ataxia telangiectasia mutant gene (ATM) deletion, the 13q14 deletion, the P53 deletion and trisomy 12. Sanger sequencing was used to analyze gene mutations of splicing factor 3B subunit 1 (SF3B1), NOTCH1, tumor protein 53 (TP53) and immunoglobulin heavy chain variable region (IGHV). Measurement data were compared by Mann-Whitney test, and the positive rates were compared by chi-square test. The diagnostic value and optimal positive cutoff value of CCR7 were calculated using receiver operating characteristic (ROC) curve. Results:The positive rates of CCR7 expression in typical CLL and atypical CLL were 90.8% (257/283) and 84.1% (37/44), respectively, and there was no significant difference of the positive rates (χ 2=1.228, P=0.268) between groups. The positive expression rates of CCR7 in CLL, MCL, CD5 +B-CLPD-U, CD5 -B-CLPD-U, FL, WM, HCL/HCL-v and MZL were 89.9% (294/327), 10.3% (6/58), 6.3% (3/48), 8.9% (8/90), 0, 0, 0 and 13.9% (5/36) respectively, and the median mean fluorescence intensity (MFI) was 278 (246, 307), 114 (106, 128), 112 (106, 117), 110 (104, 121), 108 (105, 119), 111 (105, 124), 112 (108, 115) and 109 (105, 120) respectively. Compared with CLL, the positive expression rates of CCR7 in other types of B-CLPDs were lower significantly (χ 2=181.3, 177.8, 232, 164.7, 180.8, 62.6, 129, P<0.01). In addition, the sensitivity, specificity and accuracy of CCR7 for distinguishing CLL from other types of B-CLPD were 89.9%, 93.0% and 92.3%, respectively. The positive expression rate of CD49d in CCR7 +CLL patients was 13.9%, which was significantly lower than that in CCR7 -CLL patients (42.1%) (χ 2=7.6, P=0.01). The coincidence rate of 13q14 deletion was 50.3% in CCR7 +CLL patients, which was significantly higher than that in CCR7 -CLL patients (20%) (χ 2=6.56, P=0.01). Conclusions:The CC-chemokine receptor 7 (CCR7) antigen is an effective marker for the diagnosis and identification of chronic lymphocytic leukemia (CLL). The expression level of CCR7 in clinical specimens can distinguish CLL from other pathological subtypes of B-CLPDs.

Exploration of four dimensional training path of adversity quotient for nursing undergraduates in medical colleges / 中华医学教育探索杂志

How to improve the ability of nursing undergraduates in medical colleges to face more difficulties and reverse the dilemma in response to public health emergencies is a topic that needs to be further studied. It is an effective way to improve the level of students' adversity quotient by cultivating students' adversity quotient. This paper expounds the four dimensions of the composition of the four-dimensional adversity quotient, analyzes the factors influencing the formation of the four-dimensional adversity quotient, and puts forward the exploration of the path and method to cultivate the four-dimensional adversity quotient of undergraduate nursing students. In the practical teaching of nursing specialty, the adversity quotient can be cultivated through listening and communication.

Research on the relationship between occupational cognition, coping style and transition shock of nursing interns / 中华医学教育探索杂志

Objective:To analyze the relationship between transition shock of nursing interns and occupational cognition and coping styles, and explore the factors affecting the status quo of nursing interns transformation, so as to provide guidance for the development of nursing students to respond to clinical transition shock.Methods:A cross-sectional survey of nursing students in Hunan Province was conducted among nursing interns from 18 colleges and universities in Hunan Province by using the General Demographic Data Questionnaire and the Transition Shock of Newly Graduated Nurses Scale, the Nurses' Professional Cognitive Survey Scale, and the Simplified Coping Style Questionnaire. The collected data were processed by SPSS 18.0 software, and multivariate linear regression analysis was performed to analyze the influencing factors of the shock.Results:The overall scores of nursing students transition shock were (64.49±16.33) points, while the transition shock was negatively correlated with occupational cognition ( r=-0.433, P<0.01) and positive response ( r=-0.263, P<0.01). And the occupational cognition, proposed academic qualification, reason for choosing nursing profession and positive response were the main factors affecting the transition shock of nursing students ( P=0.00, R2=0.21). Conclusion:The transition shock of nursing students is at the middle level, and has a strong negative correlation with the nursing students' occupational cognition and positive response. School teachers and clinical instructors should pay attention to the confusion, suspicion and unclear feelings and experiences caused by the transition shock of nursing students, helping nursing students to improve their occupational cognition, and learning how to positively respond to the transition shock problem, thereby improving the quality of clinical internship teaching and training of nursing students.

Application of the ligation clip-assisted modified " expansion and collapse method" in thoracoscopic resection of the external posterior basal segment in children with congenital pulmonary airway malformation / 中华实用儿科临床杂志

Objective:To explore the feasibility of using ligation clip-assisted modified " expansion and co-llapse method" to determine the intersegment plane in thoracoscopic resection of the external posterior basal segment (S 9+ 10) in children with congenital pulmonary airway malformation (CPAM). Methods:Retrospective study.The clinical data of 12 CPAM children who underwent thoracoscopic S 9+ 10 resection in Children′s Hospital Affiliated to Shandong University from July 2019 to May 2021 were collected and analyzed.There were 7 males and 5 females.The age at operation ranged from 3.50 to 11.50 months.The body weight of patients ranged from 6.5 to 11.5 kg.In all the patients, the ligation clip-assisted modified " expansion and collapse method" was applied during the operation to determine the intersegment plane (S 9+ 10 was in the expansion state and the remaining lungs were in the collapse state) before thoracoscopic S 9+ 10 resection.After S 9+ 10 resection, the surgical treatment and postoperative recovery were summarized and analyzed. Results:All the operations were completed under thoracoscopy, and there was no conversion to thoracotomy.In 11 patients, the intersegment plane was accurately determined by the ligation clips-assisted improved " expansion and collapse method" , and the S 9+ 10 segment was successfully resected.Of these 11 cases, 8 cases had right S 9+ 10 resection and 3 cases had left S 9+ 10 resection.In the process of using the ligation clip-assisted improved " expansion and collapse method" to determine the intersegment plane, the operator needed to clamp the ligation clip after the anesthesiologist expanded the lung completely.Because the operation was not stable enough, the ligation clip fell off and did not clamp S 9+ 10, resulting in operation failure.The operation was changed to the traditional " expansion and collapse method" . Besides, the basal segment bronchus was cut off by mistake, so the right basal segment had to be resected.The operation time ranged from 85 to 205 min, with a median of 149 min.Intraoperative bleeding ranged from 5 to 15 mL, with a median of 10 mL.The indwelling time of drainage tubes ranged from 2 to 4 days, with a median of 3 days.The postoperative hospital stay ranged from 5 to 8 days, with a median of 6 days.Postoperative pathological examination results suggested 4 cases of type 1, 6 cases of type 2 and 2 cases of type 3.There were 2 cases of simple subcutaneous emphysema without postoperative complications such as bleeding, bronchopleural fistula and atelectasis.The follow-up time ranged from 6 to 28 months, with a median of 15 months.The chest CT of all children showed no residual lesions and no residual cavities in the involved hemithorax. Conclusions:Ligation clip-assisted improved " expansion and collapse method" for determining the intersegment plane is suitable for CPAM children with a narrow thoracic space, and the operation is simple and effective.It is relatively safe and feasible to use this method in S 9+ 10 resection.

From the Origins of SARS-CoV-2 to the Correct Application of BLAST / 中国生物化学与分子生物学报

Basic local alignment search tool (BLAST) is one of the popular sequence similarity analysis tools. However, some students and researchers just blindly use the default parameters. Moreover, some students are confused about how to choose the right program. In a word, it is prone to be misused and researchers often draw conclusions incorrectly. In view of this, we traced back the internet hot topic in early 2020 - "MORDERATELY STRONG CONFIRMATION OF A LABORATORY ORIGIN OF COVID-19", and took it as teaching materials to guide the student to use BLAST currently through reanalyzing and reproducing the source of errors. Then we arranged an interesting experiment about fabricating dinosaur genes through modifying a chicken gene. In the experimental design to make the students grasp the BLAST tools better, one group fabricated the dinosaur gene and the other group decrypted the added bases. This instructional design could be conducive to cultivate students ' ability about distinguishing different viewpoints correctly, and we hope it can be enlightening and helpful to the teaching of BLAST tools.