Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center / 中华血液学杂志

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.

Diagnosis of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology / 中华神经科杂志

Endometrial carcinoma is one of common malignant tumors in female reproductive system, but it is extremely rare in leptomeningeal metastasis. The clinical manifestations and signs of meningeal carcinomatosis are complex and not specific. It is difficult to get a precise diagnosis early, and it has high rate of misdiagnosis and missed diagnosis. Accurate diagnosis and treatment of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology are reported. The patient is an elderly female with a history of endometrial cancer. The main manifestations were fever, headache and dizziness; cerebrospinal fluid cytology showed tumor cells; AKT1 gene and TP53 gene were detected in endometrial carcinoma tissue, plasma and cerebrospinal fluid by next-generation sequencing. After treatment with intrathecal chemotherapy, immunotherapy combined with anti angiogenesis, the patient′s condition still progressed gradually and died finally. The purpose of this case report is to raise clinical awareness of recognition and treatment in early meningeal metastasis of endometrial carcinoma.

Venetoclax combined with azacitidine in treatment of myelodysplastic syndromes complicated with monoclonal globulinemia of unknown significance: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the therapeutic effect of venetoclax combined with azacitidine in treatment of myelodysplastic syndromes (MDS) complicated with monoclonal globulinemia of unknown significance (MGUS).Methods:The clinical data of a patient with MDS complicated with MGUS in the Second People's Hospital of Shenzhen in December 2020 were retrospectively analyzed, and the literatures were reviewed.Results:According to results of bone marrow smear, cytogenetics, and next-generation sequencing, the patient was diagnosed as MDS and MGUS complicated with ASXL1, RUNX1, EZH2, STAG2 mutations as well as t(11;14). No response was observed after 2 courses of azacitidine and 1 course of azacitidine plus HAG. Later the patient achieved complete remission and negative RUNX1 and STAG2 mutations after a course of venetoclax combined with azacitidine. Meanwhile, M protein exhibited a decrease more than 50%. To date, the patient was still in complete remission.Conclusions:The regimen of venetoclax combined with azacitidine shows a significant efficacy and good tolerance to patient with co-occurrence of MDS and MGUS with t(11; 14).

Geritinib in the targeted therapy of acute myeloid leukemia with FLT3 mutation: report of 5 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the efficacy and safety of geritinib in the treatment of acute myeloid leukemia (AML) with FLT3 mutation.Methods:The clinical data of 5 AML patients with FLT3 mutation who were diagnosed in the University of Hong Kong-Shenzhen Hospital, Shenzhen People's Hospital, Shenzhen Second People's Hospital, Shenzhen University General Hospital from March 2020 to April 2021 were retrospectively analyzed. Relapsed patients concurrently received two- or three-drug chemotherapy combined with geritinib. Blood routine was checked once a week; liver function and renal function were checked once every 2 weeks during treatment. Bone marrow puncture was performed once every 1 to 3 months to monitor the bone marrow morphology, minimal residual disease (MRD) and FLT3 mutation expression levels. The efficacy, side effects, overall survival of these patients were analyzed after treatment with geritinib.Results:The white blood cell was increased in all the 5 patients at the initial diagnosis. FLT3 mutations analysis showed FLT3-internal tandem duplication (ITD) (3 cases) and FLT-3 tyrosine-kinase domain (TKD) (2 cases). Among 5 patients, 1 patient was relapse-free with maintenance therapy of oral geritinib after hematological stem cell transplantation (HSCT) for 60 days; among other 4 relapsed and refractory patients, 1 female patient after pregnancy relapsed after transplantation and then achieved complete remission followed by the maintenance therapy with geritinib after oral geritinib, 1 16-year-old patient achieved treatment outcome close to the complete remission after treatment with geritinib, 1 patient achieved complete remission after treatment with geritinib, and then underwent haplo-HSCT followed by the maintenance therapy with geritinib and the other 1 relapsed patient achieved complete remission after treatment with geritinib. After transplantation, 3 patients receiving maintenance treatment of geritinib did not relapse. The main side effects included anemia, decreased neutrophil count, rash, and increased aminotransferase. The median follow-up time of 5 patients was 15 months (6-20 months). All 5 cases survived until the last follow-up in November 2021 and 4 patients were disease-free.Conclusions:Relapsed and refractory AML patients with FLT3 mutation can achieve complete remission after treatment with geritinib and get a chance for transplantation. Geritinib may reduce the risk of recurrence after transplantation and improve survival rate. No serious side effects occur in geritinib treatment.

Efficacy and safety of azacytidine combined with low-dose HAG regimen in treatment of newly diagnosed elderly acute myeloid leukemia patients ineligible for intensive chemotherapy / 白血病·淋巴瘤

Objective:To evaluate the efficacy and safety of azacitidine combined with HAG regimen in the treatment of newly diagnosed elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy.Methods:Eighteen newly diagnosed elderly AML patients ineligible for intensive chemotherapy from July 2019 to September 2021 in the Second People's Hospital of Shenzhen were prospectively enrolled in this study. They were non-randomly divided into azacitidine combined with HAG regimen (AZA-HAG) group (9 cases) and decitabine combined with HAG regimen (DEC-HAG) group (9 cases). The primary endpoint of the study was overall response [complete remission (CR)+partial remission], and the secondary endpoints included CR + complete remission with incomplete count recovery (CRi), overall survival (OS) and drug safety. Kaplan-Meier method was used to analyze the OS.Results:The median age of 18 patients was 67 years old (60-77 years old) , and 8 of them were in high-risk group. After one course of treatment, the overall response and CR+CRi were observed in 7 of 9 patients in AZA-HAG group, and they were observed in 8 of 9 patients in DEC-HAG group, and there was no significant difference between the two groups (both P = 1.000). The median duration of CR+CRi was 7 months in both groups, and the median OS time was 12 months in both groups; there was no significant difference in OS between the two groups ( χ2 = 0.02, P = 0.895). In AZA-HAG group, 1 patient with TP53 mutation and 1 patient with ASXL1+RUNX1 mutation acquired CR, and 1 patient with NPM1 wild-type combined with FLT3-ITD and ASXL1 mutation did not respond. There was no significant difference in the incidence of grade 3-4 hematological adverse reactions between the two groups (all P < 0.05). Conclusions:Azacitidine combined with low-dose HAG regimen in the treatment of newly diagnosed elderly AML patients ineligible for intensive chemotherapy has satisfactory efficacy and long-term survival, and the adverse reactions can be tolerated.

Observation on the efficacy of liposomal doxorubicin intensive preconditioning regimen and allogeneic hematopoietic stem cell transplantation for treatment of leukemia / 白血病·淋巴瘤

Objective:To investigate the efficacy of liposomal doxorubicin intensive preconditioning regimen and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treatment of leukemia.Methods:The data of 20 patients with intensive preconditioning regimen allo-HSCT who were admitted to Shenzhen Second People's Hospital from January 2016 to June 2017 were retrospectively analyzed. The transplantation effect, occurrence of complications and prognosis of patients were analyzed.Results:The median time of granulocyte engraftment was 17 d (13-23 d); the median time of platelet engraftment was 22.5 d (minimum 13 d, maximum >90 d). The acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 2 cases and 1 case, respectively. Eight cases occurred hemorrhagic cystitis, 15 cases occurred Epstein-Barr viremia, 8 cases occurred cytomegaloviremia, 1 case occurred sepsis, 1 case occurred acute liver injury, and 2 cases occurred fungal pneumonia. The median follow-up time was 31.7 months (0.8-53.8 months). One patient died of intracranial infection on the 25th day after transplantation; 3 patients relapsed during the follow-up period, and 2 of them died; the other 16 patients carried 100% donor genes during the follow-up period.Conclusions:The liposomal doxorubicin intensive preconditioning regimen and allo-HSCT have a good effect on leukemia. Increasing the intensity of pretreatment does not increase the treatment-related adverse reactions. The incidence rates of Epstein-Barr viremia and cytomegaloviremia are high, but they are improved after active treatment.

Study of risk factors associated with prognosis in patients with aortic acute cerebral infarction / 中国综合临床

Objective:To explore the risk factors associated with a three-month prognosis in patients with aortic acute cerebral infarction.Methods:A prospective study was conducted on 191 patients with aorthropathic acute cerebral infarction included in the Department of Neurology from June 2018 to December 2019, and the patients were divided into good prognosis group (153 cases) and poor prognosis group (38 cases) according to the MRS score of the patient's 3-month prognosis, and the general data, past medical history and blood pressure variability evaluation index (BPV) between the two groups were correlated analysis. The t-test was used to compare the measurement data with normal distribution, the χ 2 test was used to compare the counting data, and the Logistic regression analysis was used to analyze the risk factors. Results:The proportion of patients with diabetes history in the poor prognosis group (20.3% (31/153)), admission NIHSS score ((3.03±2.01) points), standard deviation (SD) ((12.06±4.46) mmHg) and coefficient of variation (CV) ((8.61±3.08)%) of systolic blood pressure at 24 h were lower than those in the good prognosis group (47.4% (18/38), (5.61±3.84) points, (14.75±3.46) mmHg, (10.41±2.18)%), the differences were statistically significant (the statistical values were χ 2=11.73, t=4.01, t=3.46, t=3.38; P values were 0.001, <0.001, 0.001, and 0.001, respectively). Because 24 h systolic blood pressure SD and 24 h systolic blood pressure CV had obvious collinearity, they were respectively included in the Logistic regression model. Taking diabetes history, NIHSS score and 24 h systolic blood pressure SD into the variables, the multivariate Logistic regression results of adverse prognostic risk factors in patients with acute cerebral infarction showed that the history of diabetes mellitus ( OR=3.649, 95% CI: 1.545-8.648, P=0.003), NIHSS score ( OR=1.472, 95% CI: 1.247-1.725, P<0.001) and 24 h systolic blood pressure SD ( OR=1.201, 95% CI: 1.085-1.336, P<0.001). Taking diabetes history, NIHSS score and 24 h systolic blood pressure CV into consideration, multivariate Logistic regression results of adverse prognostic risk factors in patients with acute cerebral infarction showed that the history of diabetes mellitus ( OR=4.695, 95% CI: 1.873-11.766, P=0.001), admission NIHSS score ( OR=1.922, 95% CI: 1.513-2.441, P<0.001) and 24 h systolic blood pressure CV ( OR=1.220, 95% CI: 1.045-1.425, P=0.012). All are independent risk factors influencing the prognosis of patients. Conclusion:The effect of 24 h systolic blood pressure SD and 24 h systolic blood pressure CV on patient prognosis was more valuable in clinical prediction, and the prognosis value of controlling blood glucose levels in patients with diabetes was higher in patients with cerebral infarction.

Effect of high-intensity interval exercise on depression-related behavior in mice / 生理学报

This paper was aimed to clarify the effect of high-intensity interval training (HIIT) on depression. Animal running platforms were used to establish HIIT exercise models, depression models were prepared by chronic unpredictable mild stress (CUMS), and depression-related behaviors were detected by behavioral experiments. The results showed that HIIT exercise improved depression-related behavior in CUMS model mice. Western blot and ELISA results showed that in the hippocampus, medial prefrontal cortex (mPFC) and amygdala of the CUMS model mice, glucocorticoid receptor (GR) protein expression was down-regulated, and the content of tumor necrosis factor α (TNF-α) was increased, compared with those in the control group, whereas HIIT exercise could effectively reverse these changes in CUMS model mice. These results suggest that HIIT exercise can exert antidepressant effect, which brings new ideas and means for the clinical treatment of depressive diseases.

Whether the limitation of the phalangeal epiphysis "before the equal-diameter period" should be extended to "before the ultra-diameter period" in X-ray diagnosis of Kashin-Beck disease / 中华地方病学杂志

Objective:To explore whether the limit of "before the equal-diameter period" is reasonable in the current criteria for "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010) in children, and to provide basic data and technical support for revision of the criteria for "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010).Methods:In 2018, the historical Kashin-Beck disease (KBD) areas in Heilongjiang Province were selected as the investigation sites. The right-hand X-ray films of all children aged 7-12 years old were taken. According to the different X-ray manifestations of the growth and development of the phalangeal epiphysis, they were divided into five periods: before the equal-diameter period, equal-diameter period, ultra-diameter period, pre-closure period and closure period. Firstly, after stratifying by basic data such as age and gender, the data were standardized and analyzed. Secondly, the detection rates of metaphysis-epiphysis (CRME) in each period were calculated and compared. Finally, based on the mean value of the detection rate of metaphyseal change in Linkou and Fuyu counties of Heilongjiang Province in 1990, the rates of expected detection and missed diagnosis of metaphyseal changes of KBD among investigated children were calculated and compared under the limitation of before the equal-diameter period, before the ultra-diameter period or age range reduction.Results:A total of 5 019 children were investigated. The proportion of children before the equal-diameter period was 53.94% (2 707/5 019), and that of before the ultra-diameter period was 77.92% (3 911/5 019). The results showed that the equal-diameter period mainly appeared in 7-10 years old, and showed a decreasing trend with the increase of age (χ 2trend = 390.10, P<0.05); the ultra-diameter period mainly occurred in 10-12 years old, showing a decreasing trend with the increase of age (χ 2trend = 65.39, P < 0.05); the pre-closure period mainly occurred in 10-12 years old, with an increasing trend with the increase of age (χ 2trend = 51.86, P<0.05); the closure period mainly occurred in 11-12 years old and increased with age (χ 2trend = 7.58, P<0.05). The CRME of children in ultra-diameter period was 14.78% (158/1 069), however CRME did not occur in children with equal-diameter period. Among children before equal-diameter period, before ultar-diameter period and aged 7-10 years old, the expected detection rates of metaphyseal changes of KBD were 5.90%, 8.53% and 7.42%, respectively. The expected missed diagnosis rates of metaphyseal changes of KBD were 5.06%, 2.45% and 3.52%, respectively. Conclusion:In order to improve the rate of expected detection and lower the rate of missed diagnosis of metaphyseal changes of KBD, children in "equal-diameter period" should be included in X-ray diagnosis and disease monitoring of KBD.

Projections from Infralimbic Cortex to Paraventricular Thalamus Mediate Fear Extinction Retrieval / 神经科学通报·英文版

The paraventricular nucleus of the thalamus (PVT), which serves as a hub, receives dense projections from the medial prefrontal cortex (mPFC) and projects to the lateral division of central amygdala (CeL). The infralimbic (IL) cortex plays a crucial role in encoding and recalling fear extinction memory. Here, we found that neurons in the PVT and IL were strongly activated during fear extinction retrieval. Silencing PVT neurons inhibited extinction retrieval at recent time point (24 h after extinction), while activating them promoted extinction retrieval at remote time point (7 d after extinction), suggesting a critical role of the PVT in extinction retrieval. In the mPFC-PVT circuit, projections from IL rather than prelimbic cortex to the PVT were dominant, and disrupting the IL-PVT projection suppressed extinction retrieval. Moreover, the axons of PVT neurons preferentially projected to the CeL. Silencing the PVT-CeL circuit also suppressed extinction retrieval. Together, our findings reveal a new neural circuit for fear extinction retrieval outside the classical IL-amygdala circuit.

Efficacy of Moxifloxacin against in Zebrafish Model / 生物医学与环境科学（英文）

Objective@#Moxifloxacin (MFX) shows good activity against and can be a possible antibiotic therapy to treat infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against using zebrafish (ZF) model .@*Methods@#A formulation of labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared.@*Results@#Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference.@*Conclusion@#MFX showed limited efficacy against using ZF model. Its activity needs to be confirmed.

Advances in the pathogenesis of articular cartilage injury in Kaschin-Beck disease / 中华地方病学杂志

Kaschin-Beck disease (KBD) is an endemic and deforming osteochondropathy, and its pathogen and pathogenesis remain unclear up to now. In recent years, the results in the research of pathogenesis of KBD showed that oxidative stress, excessive chondrocyte apoptosis, imbalance of chondrocyte extracellular matrix metabolism and pro-inflammatory factors were all involved in the occurrence and development of KBD. And this paper summarized the important progress in the pathogenesis of KBD.

Correlation Analysis between Serum Complement C3，C4 Levels and LDL-C in Patients with Premature Coronary Artery Disease / 中山大学学报(医学科学版)

@#【Objective】The aim of this study was to investigate the associations between serum complement C3，C4 and low density lipoprotein cholesterol（LDL- C）levels and early- onset coronary heart disease.【Methods】We enrolled 255 cases of coronary angiography confirmed coronary artery disease from January 2018 to September 2018. All the patients were divided into early- onset coronary heart disease group（108 cases）and late- onset coronary heart disease group（147 cases）. Besides ，100 healthy subjects were enrolled and used as controls. Serum levels of C3 ，C4 and LDL-C were analyzed by automatic biochemical analyzer.【Results】Levels of serum C3，C4 and LDL-C in early-onset coronary heart disease group，late-onset coronary heart disease group and healthy control group were significantly different（P < 0.05）. In early-onset coronary heart disease group，C3 and C4 were positively correlated with LDL-C（P < 0.05）. However ，there was no significant correlation （P > 0.05） between C3 ，C4 and LDL- C in late- onset coronary heart disease group and healthy control group.【Conclusions】The levels of C3 and C4 were positively correlated with LDL-C only in the early-onset coronary heart disease patients.

Immune regulation by protein ubiquitination: roles of the E3 ligases VHL and Itch

Protein ubiquitination is an important means of post-translational modification which plays an essential role in the regulation of various aspects of leukocyte development and function. The specificity of ubiquitin tagging to a protein substrate is determined by E3 ubiquitin ligases via defined E3-substrate interactions. In this review, we will focus on two E3 ligases, VHL and Itch, to discuss the latest progress in understanding their roles in the differentiation and function of CD4 T helper cell subsets, the stability of regulatory T cells, effector function of CD8 T cells, as well as the development and maturation of innate lymphoid cells. The biological implications of these E3 ubiquitin ligases will be highlighted in the context of normal and dysregulated immune responses including the control of homeostasis, inflammation, auto-immune responses and anti-tumor immunity. Further elucidation of the ubiquitin system in immune cells will help in the design of new therapeutic interventions for human immunological diseases and cancer.

Effects of electroacupuncture on sympathetic nerve-related substance in myocardial tissue in mice with myocardial ischemia / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture (EA) on sympathetic nerve-related substance in myocardial tissue in mice with myocardial ischemia (MI), and to explore its possible mechanism.@*METHODS@#Thirty adult male C57BL/6 mice were randomly divided into a sham operation group, a model group and an EA group, 10 mice in each one. The model of MI was established in the model group and EA group by ligating the left anterior descending branch of coronary artery. The mice in the sham operation group were not treated with ligating at left anterior descending branch of coronary artery, but the remaining procedure was similar with the model group. The mice in the EA group were treated with EA at "Neiguan" (PC 6) with 2 Hz/100 Hz of frequency and 2 mA of intensity, 20 min per treatment, once a day for totally 5 days. No EA was given for model group and sham operation group. The electrocardiogram was recorded and △ST value was calculated to evaluate the model. TTC staining was applied to evaluate the infarct size. Immunohistochemical (IHC) method was applied to evaluate the positive nerve fiber density in myocardial tissue. Western blot method was applied to test the protein expression levels of neuregulin-1 (NRG-1), tyrosine hydroxylase (TH), growth associated protein-43 (GAP-43).@*RESULTS@#The electrocardiogram (lead II) results indicated compared with the sham operation group, the S-T segments in the model group and EA group were increased obviously (both <0.01), indicating the MI model was established successfully. The TTC staining results indicated compared with sham operation group, the infarction size was significantly increased in the model group (<0.01); compared with the model group, the infarction size in the EA group was significantly reduced (<0.01). The IHC results indicated compared with the sham operation group, the positive nerve fiber density in myocardial was increased in the model group (<0.01); compared with the model group, the positive nerve fiber density in myocardial was reduced in the EA group (<0.05). The Western blot results indicated compared with the sham operation group, the expression levels of TH, NRG-1 and GAP-43 were significantly increased in the model group (<0.01); compared with the model group, the expression level of TH and GAP-43 were significantly reduced (<0.01) and that of NRG-1 was increased in the EA group (<0.05).@*CONCLUSION@#EA could increase the expression of NRG-1 and reduce the expression of TH and GAP-43 in myocardial tissues in MI mice, which could suppress sympathetic nerve hyperexcitability after infarction to achieve myocardial protection effect.

Research progress of histone 3 methyltransferase MLL4 / 生理学报

Mixed linked leukemia 4 (MLL4) is a specific methyltransferase of histone 3 position lysine 4 (H3K4). It is also one of the important members of COMPASS/Set1-like protein complex. Both MLL4 protein itself and its mediated H3K4 methylation modification can cause changes in chromatin structure and function, thus regulating gene transcription and expression. With the studies of MLL4 protein in recent years, the roles of MLL4 gene, MLL4 protein and protein complex in the development of tissues and organs, tumor diseases and other physiological and pathophysiological processes have been gradually revealed. In this paper, the research progress of MLL4 gene, MLL4 protein characteristics, biological function and its effect on disease were reviewed, in order to further understand the effect of histone methyltransferase on gene expression regulation, as well as its non-enzyme dependent function. This paper may provide new ideas for the prevention, diagnosis and treatment of related diseases.

Association of suicidal ideation with family environment and psychological resilience in adolescents / 中国当代儿科杂志

OBJECTIVE@#To study the association of suicidal ideation with family environment and psychological resilience in adolescents.@*METHODS@#Cluster sampling was used to perform an investigation among 3 230 junior and senior high school students in Xinxiang of Henan Province, China December 2014. A general social information questionnaire, 11-Item Kutcher Adolescent Depression Scale(KADS-11), Family Environment Scale-Chinese Version (FES-CV) and Connor-Davidson Resilience Scale (CD-RISC; Chinese version ) were used for evaluation. A multivariate logistic regression analysis and a case-control study were used to investigate the association of suicidal ideation with family environment and psychological resilience in adolescents.@*RESULTS@#A total of 2 960 usable questionnaires were received. Among the 2 960 adolescents, 247 (8.50%) had suicidal ideation (98 boys and 149 girls). The multivariate logistic regression analysis showed that after adjustment for age and sex, single-parent/remarried family was associated with an increased risk of suicidal ideation (OR=2.655). Suicidal ideation in boys was negatively correlated with family cohesion (OR=0.750, P<0.001) and organization (OR=0.855, P=0.036) and was positively correlated with family conflict (OR=1.159, P=0.017). Suicidal ideation in girls were negatively correlated with family cohesion (OR=0.771, P<0.001), emotional expression (OR=0.815, P=0.001) and intellectual-cultural orientation (OR=0.915, P=0.037). The adolescents with suicidal ideation had a significantly lower total score of psychological resilience than those without suicidal ideation (P<0.05). Compared with those without suicidal ideation, the adolescents with suicidal ideation had significantly lower scores on 4 factors of the CD-RISC (ability, tolerance of negative emotions, acceptance of changes and control) (P<0.05).@*CONCLUSIONS@#Family cohesion is a protective factor against suicidal ideation in adolescents. Family organization in boys and family emotional expression in girls are associated with a decreased risk of suicidal ideation. Enhanced psychological resilience may help to reduce the incidence of suicide ideation in adolescents.

Inhibition of C2CD3 regulates the proliferation, invasion and migration of epithelial ovarian cancer through inhibiting Hedgehog pathway / 上海交通大学学报（医学版）

Objective • To explore the relationship between the expression of C2 calcium dependent domain containing protein 3 (C2CD3) in ovarian cancer and clinicopathological parameters, and its effect on the proliferation and invasion of ovarian cancer SKOV3 cells and possible mechanisms. Methods • The expression of C2CD3 protein in ovarian tissue was detected by immunohistochemistry. The proliferation, migration and invasion abilities of SKOV3 cells were detected by EdU assay, wound healing assay and Transwell assay respectively. Western blotting was performed to investigate the expression of C2CD3, Shh, Ptch1, Smo and Gli1 proteins. Results • C2CD3 protein was located in cytoplasm in ovarian cancer. C2CD3 was highly expressed in ovarian cancer compared to normal ovarian tissue. C2CD3 immunostaining was significantly higher in tumor samples in advanced stages (stage III / ) than in early stages (stage / Ⅱ). The staining intensity was significantly correlated with the grade (grade3 vs. grade1+2). The association between C2CD3 expression and age (or tumor type) was not significant. Inhibition of C2CD3 gene significantly weakened the proliferation, invasion and migration abilities of SKOV3 cells, and the expression of Shh, Ptch1, Smo and Gli1 proteins was significantly decreased. Conclusion • The expression of C2CD3 protein is increased in ovarian cancer tissues. Inhibition of C2CD3 gene weakens the proliferation, invasion and migration capacities of ovarian cancer SKOV3 cells, which may be related to the inhibition of Shh, Ptch1, Smo and Gli1 proteins in Hedgehog pathway.

Genetic and epigenetic predispositions underlying cardiovascular outcomes among patients treated with clopidogrel and aspirin / 中国药理学与毒理学杂志

Coronary artery disease (CAD)is a major cause of death and disability worldwide, and consumes a considerable amount of medical resources every year.Clopidogrel is a first-line antiplate-let therapy for CHD, butit is associated with substantial variability in PK and pharmacodynamics re-sponse. To date, gene variants explain only a smallproportion of the variability.The study aimed to identify new genetic loci-modifying antiplatelet response to clopidogrel in Chinese patients with CAD by a systematic analysis combining antiplatelet effects and PK, and further to investigate the PON1 gene promoter DNA methylation and genetic variations possibly influencing clinical outcomes in pa-tients undergoing PCI. We identified novel variants in two transporter genes (SLC14A2rs12456693, ATP-binding cassette [ABC]A1 rs2487032) and in N6AMT1 (rs2254638) associated with P2Y12 reac-tion unit (PRU) and plasma active metabolite (H4) concentration. These new variants dramatically im-proved the predictability of PRU variability to 37.7％. The associations between these loci and PK pa-rameters of clopidogrel and H4 were observed in additional patients, and its function on the activation of clopidogrel was validated in liver S9 fractions (P<0.05). Rs2254638 was further identified to exert a marginal risk effect formajor adverse cardiac events in an independent cohort.Multivariate logistic regression analysis indicated that PON1methylation level at CpG site-161 (OR=0.95; 95％ CI=0.92–0.98;P<0.01)and the use of angiotensin converting enzyme inhibitors(OR=0.48;95％ CI=0.26–0.89;P<0.01) were associated with decreased risk of bleeding events. In conclusion, new genetic variants were systematically identified as risk factors for the reduced efficacy of clopidogrel treatment.The ab-normal expression of DNA methylation-regulating key genes in the pharmacokinetic and pharmacody-namics pathways of clopidogrel and aspirin may modify clinical outcomes in dual antiplatelet-treated pa-tients undergoing PCI.

Application of gastroscopy assistant nasal intestinal tube placement and jejunum nutrition in patients with severe internal diseases / 中国内镜杂志

Objective To investigate the value of endoscopic assisted nasal jejunal tube placement and jejunum nutrition in treatment of critically illed patients. Methods This study was a prospective study. 56 patients with severe cerebrovascular diseases in the department of NICU from May 2014 to May 2017 were enrolled in this study. All of the patients were found to have an increased gastric remnant within 72 hours after admission (>100 ml). In the nasal jejunal group, 28 patients received nasal endoscopy and nasal endoscopic feeding, and 28 cases were treated with routine nasogastric tube and enteral nutrition. Comparing the two groups of patients with gastrointestinal complications (including vomiting, gastroesophageal reflux, abdominal distension, diarrhea, stress ulcer incidence) and nutritional status parameters (including serum albumin, prealbumin, hemoglobin), incidence of hospital acquired pneumonia and inflammation indexes (including WBC, PCT and CRP), stay at NICU time, NICU expenses, GCS score and mortality rate. Results The success rate of nasal intestinal tube placement under nasal endoscopy guided wire was 100.0%. The nasal jejunal nutrition status parameters were better, NICU check-in time was shorter, NICU expenses were lower, and the inflammation index was lower than the control group. There were no significant differences in the incidence of gastrointestinal complications, the incidence of hospital acquired pneumonia, the GCS score and the fatality rate between the two groups. Conclusion For the patients with severe gastric remnant increase in NICU, it is worth recommending that naso jejunal tube be inserted into the jejunum by endoscopy and using jejunum nutrition.