Evaluation of anticholinergic burden in elderly outpatients and the risk factors / 中南大学学报(医学版)

OBJECTIVES@#The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs.@*METHODS@#A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia.@*RESULTS@#A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine).@*CONCLUSIONS@#There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.

Progress on Prevention and Treatment of Cerebral Small Vascular Disease Using Integrative Medicine / 中国结合医学杂志

Cerebral small vessel disease (CSVD) is a senile brain lesion caused by the abnormal structure and function of arterioles, venules and capillaries in the aging brain. The etiology of CSVD is complex, and disease is often asymptomatic in its early stages. However, as CSVD develops, brain disorders may occur, such as stroke, cognitive dysfunction, dyskinesia and mood disorders, and heart, kidney, eye and systemic disorders. As the population continues to age, the burden of CSVD is increasing. Moreover, there is an urgent need for better screening methods and diagnostic markers for CSVD, in addition to preventive and asymptomatic- and mild-stage treatments. Integrative medicine (IM), which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives, has unique advantages for the prevention and treatment of CSVD. In this review, we summarize the biological markers, ultrasound and imaging features, disease-related genes and risk factors relevant to CSVD diagnosis and screening. Furthermore, we discuss IM-based CSVD prevention and treatment strategies to stimulate further research in this field.

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.

Clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm accelerated/blast phase / 中华血液学杂志

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.

Clinical and laboratory features compared between JAK2 exon12 and JAK2 V617F mutated polycythemia vera / 中华血液学杂志

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.

Clinical manifestations and gene analysis of 18 cases of hereditary protein S deficiency / 中华血液学杂志

Objective: To analyze the clinical manifestations and molecular pathogenesis of 18 patients with inherited protein S (PS) deficiency. Methods: Eighteen patients with inherited PS deficiency who were admitted to the Institute of Hematology & Blood Diseases Hospital from June 2016 to February 2019 were analyzed: activity of protein C (PC) and antithrombin (AT) , PS activity were measured for phenotype diagnosis; high throughput sequencing (HTS) was used for screening of coagulation disease-related genes; Sanger sequencing was used to confirm candidate variants; Swiss-model was used for three-dimensional structure analysis. Results: The PS:C of 18 patients ranged from 12.5 to 48.2 U/dL. Among them, 16 cases developed deep vein thrombosis, including 2 cases each with mesenteric vein thrombosis and cerebral infarction, and 1 case each with pulmonary embolism and deep vein thrombosis during pregnancy. A total of 16 PROS1 gene mutations were detected, and 5 nonsense mutations (c.134_162del/p.Leu45*, c.847G>T/p.Glu283*, c.995_996delAT/p.Tyr332*, c.1359G> A/p.Trp453*, c.1474C>T/p.Gln492*) , 2 frameshift mutations (c.1460delG/p.Gla487Valfs*9 and c.1747_1750delAATC/p.Asn583Wfs*9) and 1 large fragment deletion (exon9 deletion) were reported for the first time. In addition, the PS:C of the deep vein thrombosis during pregnancy case was 55.2 U/dL carrying PROC gene c.565C>T/p.Arg189Trp mutation. Conclusion: The newly discovered gene mutations enriched the PROS1 gene mutation spectrum which associated with inherited PS deficiency.

Progress and thoughts on the regulation of wound repair by growth factors / 中华烧伤杂志

Growth factors play an important role in wound healing, and they mainly accelerate wound healing by activating the related signal pathways. Chinese scientists have been conducting basic and clinical researches on growth factors for 30 years, with a series of growth factor drugs being developed and widely used in the treatment of burns and trauma and chronic refractory ulcers. This paper expounds the frontier progress of growth factors on wound healing from the perspectives of immunity, nerve, fat, and so on, and puts forward the further thoughts of the research team on the regulation of wound healing by growth factors.

POST1/C12ORF49 regulates the SREBP pathway by promoting site-1 protease maturation

Sterol-regulatory element binding proteins (SREBPs) are the key transcriptional regulators of lipid metabolism. The activation of SREBP requires translocation of the SREBP precursor from the endoplasmic reticulum to the Golgi, where it is sequentially cleaved by site-1 protease (S1P) and site-2 protease and releases a nuclear form to modulate gene expression. To search for new genes regulating cholesterol metabolism, we perform a genome-wide CRISPR/Cas9 knockout screen and find that partner of site-1 protease (POST1), encoded by C12ORF49, is critically involved in the SREBP signaling. Ablation of POST1 decreases the generation of nuclear SREBP and reduces the expression of SREBP target genes. POST1 binds S1P, which is synthesized as an inactive protease (form A) and becomes fully mature via a two-step autocatalytic process involving forms B'/B and C'/C. POST1 promotes the generation of the functional S1P-C'/C from S1P-B'/B (canonical cleavage) and, notably, from S1P-A directly (non-canonical cleavage) as well. This POST1-mediated S1P activation is also essential for the cleavages of other S1P substrates including ATF6, CREB3 family members and the α/β-subunit precursor of N-acetylglucosamine-1-phosphotransferase. Together, we demonstrate that POST1 is a cofactor controlling S1P maturation and plays important roles in lipid homeostasis, unfolded protein response, lipoprotein metabolism and lysosome biogenesis.

Impact of Herbal Preparations on Outcomes of Highly Active Antiretroviral Therapy: A One-Year Prospective Cohort Study / 中国结合医学杂志

OBJECTIVE@#To investigate the impacts of two herbal preparations for human immunodeficiency virus/aquired immune deficiency syndrome (HIV/AIDS) patients, Shenling Fuzheng Capsule (, SLFZC) and Qingdu Capsule (, QDC), on the efficacy of highly active antiretroviral therapy (HAART).@*METHODS@#HIV/AIDS patients met the criteria were all enrolled in a 1-year cohort study, in which patients receiving HAART alone were designated as Group A, those receiving HAART in combination with SLFZC were designated as Group B, and those receiving HAART in combination with QDC were designated as Group C, 100 cases in each group. The dose of SLFZC was 1.48 g (4 capsules), 3 times daily, and QDC 1.56 g (4 capsules), 3 times daily. T cell subsets, HIV RNA and HIV-1 drug resistance were detected at enrollment and 1 year after treatment. Patients were followed up every 3 months, during which side-effects and other clinical data were recorded.@*RESULTS@#After 1-year treatment, the median increment in CD counts was 165.0, 178.0 and 145.0 cells/μL for Group A, B and C, respectively. HIV RNA was undetectable in 94% of patients in Group A, 96% in Group B and 92% in Group C. There were no differences regarding the increment in CD counts, HIV RNA and frequency of HIV-1 drug resistance mutations. Two of the 14 suspected side-effect symptoms, i.e. fatigue and dizziness, were lower in Groups B and C than in Group A (P<0.05, respectively) CONCLUSIONS: SLFZC and QDC do not have a negative impact on immunological and virological response to HAART; however, these preparations are not as potent in reducing HAART-associated side-effects as anticipated.

Clinical Efficacy and Transcriptomic Analysis of Congrong Shujing Granules () in Patients with Parkinson's Disease and Syndrome of Shen (Kidney) Essence Deficiency / 中国结合医学杂志

OBJECTIVE@#To evaluate the clinical efficacy and safety of Congrong Shujing Granules ( , CSGs) in treating patients with Parkinson's disease (PD) and Chinese medicine (CM) syndrome of Shen (Kidney) essence deficiency, and to investigate the potential mechanism involving efficacy through a transcriptome sequencing approach.@*METHODS@#Eligible PD patients with syndrome of Shen essence defificiency were randomly assigned to a treatment group or a control group by a random number table, and were treated with CSGs combined with Western medicine (WM), or placebo combined with WM, respectively. Both courses of treatment lasted for 12 weeks. The Unifified Parkinson's Disease Rating Scale (UPDRS) score, the PD Question-39 (PDQ-39) score, CM Syndrome Scale score, and drug usage of all patients were evaluated before and after treatment. Safety was evaluated by clinical laboratory tests and electrocardiographs. Blood samples from 6 patients in each group were collected before and after the trial and used for transcriptomic analysis by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Differentially expressed genes were validated using reverse transcription-polymerase chain reaction.@*RESULTS@#A total of 86 PD patients were selected from the Third Affifiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2017 and December 2017. Finally, 72 patients completed the trial, including 35 in the treatment group and 37 in the control group. When compared with the control group after treatment, patients in the treatment group showed signifificant decreases in UPDRS sub-II score, PDQ-39 score, CM syndrome score, and Levodopa equivalent dose (P0.05). A possible mechanism of clinical effificacy was proposed that involved regulating cell metabolism-related processes and ribosome-related pathways. Treatment with CSGs had shown to affect relevant gene loci for PD, including AIDA, ANKRD36BP2, BCL2A1, BCL2L11, FTH1P2, GCH1, HPRT1, NFE2L2, RMRP, RPS7, TGFBR1, WIPF2, and COX7B.@*CONCLUSIONS@#CSGs combined with WM can be used to treat PD patients with CM syndrome of Shen essence defificiency with a good safety. The possible mechanism of action and relevant gene loci were proposed. (Registration No. ChiCTR-IOR-16008394).

Analysis of incidence and influencing factors of stroke in Philadelphia chromosome-negative myeloproliferative neoplasms / 白血病·淋巴瘤

Objective:To investigate the occurrence of stroke and its associated risk factors in patients with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPN).Methods:The data of patients diagnosed as Ph-negative MPN in the Affiliated Yuebei People's Hospital of Shantou University Medical College from January 2016 to December 2019 were retrospectively analyzed. The occurrence of stroke in these patients and the clinical characteristics were summarized. Logistic regression was used to analyze the risk factors of stroke in MPN patients.Results:A total of 193 Ph-negative MPN patients were collected, including 103 males and 90 females. The median age of onset was 62 years old (24-93 years old). There were 129 patients (66.84%) with essential thrombocythemia, 46 patients (23.83%) with polycythemia vera, and 18 patients (9.33%) with primary myelofibrosis. In 193 patients with MPN, there were 31 patients (16.06%) with stroke, including 30 cases (15.54%) of ischemic stroke and 1 case (0.52%) of hemorrhagic stroke, and the incidence of ischemic stroke was higher than that of hemorrhagic stroke, the difference was statistically significant (χ 2 = 54.258, P < 0.01). Among the patients with stroke, JAK2V617F mutation was observed to be the most common driver mutation (80.65%, 25/31). The small-artery occlusive cerebral infarction was the most common in ischemic stroke (63.33%, 19/30). Compared with MPN patients without stroke, those with stroke displayed higher hemoglobin level [(156±35) g/L vs. (138±40) g/L] and concurrent JAK2V617F and CALR mutations rate [3.23% (1/31) vs. 0.62% (1/162)], and lower CALR mutation rate [3.23% (1/31) vs. 19.14% (31/162)], the differences were statistically significant (all P < 0.05). Logistic regression analysis revealed that hemoglobin ≥ median level (140 g/L) was a risk factor for stroke in MPN patients ( OR = 2.903, 95% CI 1.163-7.244, P = 0.022), and CALR mutation acted as a protective factor for stroke ( OR = 0.090, 95% CI 0.009-0.932, P = 0.044). Conclusions:Ischemic stroke is more common than hemorrhagic stroke in Ph-negative MPN patients, and the small-artery occlusive cerebral infarction is also more frequently found in these patients. Hemoglobin ≥140 g/L is a risk factor for stroke in MPN patients, and CALR mutation is a protective factor.

Clinical analysis of driver mutations in classical myeloproliferative neoplasms / 白血病·淋巴瘤

Objective:To explore the driver mutations in patients with classical myeloproliferative neoplasms (MPN) and their relationships with clinical characteristics.Methods:The clinical data of 186 patients with classical MPN in the Affiliated Yuebei People's Hospital of Shantou University Medical College from January 2013 to October 2019 who met the World Health Organization 2016 MPN diagnostic criteria were retrospectively analyzed. The mutations of diver genes JAK2, CALR and MPL and clinical characteristics, such as white blood cell count, hemoglobin, and platelet count in patients with essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) were analyzed.Results:Among the 186 MPN patients, 100 were male and 86 were female, with a median age of onset of 62.0 years old (24.0-93.0 years old). There were 125 patients (67.20%) with ET, 44 patients (23.66%) with PV, and 17 patients (9.14%) with PMF. The JAK2V617F mutation was found in 133 patients (71.51%, 133/186). The JAK2V617F mutation rates in patients with ET, PV and PMF were 66.40% (83/125), 88.64% (39/44) and 64.71% (11/17), respectively. Two patients (1.08%, 2/186) with PV were found with JAK2 exon 12 mutation. The CALR exon 9 mutation was found in 32 patients (17.20%, 32/186), with the CALR mutation rates of 24.00% (30/125), 0 and 11.76% (2/17) in patients with ET, PV and PMF, respectively. The MPL exon 10 mutation was found in one ET patient (0.54%, 1/186). CALR mutated ET patients showed higher platelet count [(1 155±537)×10 9/L vs. (997±330)×10 9/L, t = -2.095, P = 0.038], and lower leukocyte count ( t = 2.434, P = 0.017) and hemoglobin ( t = 3.087, P = 0.003) than JAK2V617F mutated ET patients. Two cases of MPN had rare concurrent driver mutations, of which one ET patient with JAK2V617F and CALR mutations and one PMF patient with JAK2V617F and MPLW515L mutations. Conclusions:The detection result of driver mutations is an important basis for precision health care for MPN. Different types of MPN have different detection rates of driver mutations, which are of great significances for judging the clinical characteristics of patients.

Bioinformatics analysis of screening of differentially expressed genes and related biological characteristics in esophageal squamous cell carcinoma / 中华消化杂志

Objective:To analyze the differentially expressed genes in esophageal squamous cell carcinoma (ESCC) by bioinformatics method, to screen the key genes related to the carcinogenesis and development of ESCC and to find out biomarkers for early diagnosis and prognosis of ESCC.Methods:The ESCC microarray datasets GSE26886, GSE77861, GSE100942, GSE20347, GSE23400, GSE38129 and GSE17351 from gene expression omnibus datasets were downloaded. The differentially expressed genes in ESCC and normal esophageal mucosa tissues of each dataset were screened out, and then the common differentially expressed key genes of seven dataset were selected out. After that, the key differentially expressed genes were analyzed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway. Cytoscape software and molecular complex detection were used for protein-protein interaction network (PPI), and the critical hub genes were screened out. The expression of hub genes was divided into high-expression group and low-expression group. The relationship between hub genes and the prognosis of patients with ESCC was analyzed by Kaplan-Meier database.Results:A total of 626 differentially expressed key genes of ESCC were screened out from the seven datasets, including 302 up-regulated genes and 324 down-regulated genes. The results of GO analysis showed that the key differentially expressed genes were mainly involved in collagen binding, regulation of cell cycle and epithelial cell differentiation.The results of KEGG analysis indicated that the differentially expressed genes were focused on extracellular matrix-receptor interaction, p53 signaling pathway and arachidonic acid metabolism signaling pathway. Five hub genes were screened out from PPI, which were collagen type Ⅲ α1 chain ( COL3 A1), collagen type Ⅹ α1 chain ( COL10 A1), collagen type Ⅵ α3 chain ( COL6 A3), collagen type Ⅴ α2 chain ( COL5 A2) and collagen type Ⅰ α1 chain ( COL1 A1). The expression levels of COL3 A1, COL10 A1, COL6 A3, COL5 A2 and COL1 A1 in ESCC tissues were higher than those of normal esophageal mucosa tissues. The prognosis of high-expression group was worse than that of low-expression group. Conclusions:There are differentially expressed genes profiles between ESCC tissues and normal mucosa tissues. COL3 A1, COL10 A1, COL6 A3, COL5 A2 and COL1 A1 are key genes in the genesis and development of ESCC and also related to the prognosis of the patients, which may be new molecular markers for the diagnosis and treatment of ESCC.

EPAC Negatively Regulates Myelination via Controlling Proliferation of Oligodendrocyte Precursor Cells / 神经科学通报·英文版

Increasing evidence suggests that a cyclic adenosine monophosphate (cAMP)-dependent intracellular signal drives the process of myelination. Yet, the signal transduction underlying the action of cAMP on central nervous system myelination remains undefined. In the present work, we sought to determine the role of EPAC (exchange protein activated by cAMP), a downstream effector of cAMP, in the development of the myelin sheath using EPAC1 and EPAC2 double-knockout (EPAC) mice. The results showed an age-dependent regulatory effect of EPAC1 and EPAC2 on myelin development, as their deficiency caused more myelin sheaths in postnatal early but not late adult mice. Knockout of EPAC promoted the proliferation of oligodendrocyte precursor cells and had diverse effects on myelin-related transcription factors, which in turn increased the expression of myelin-related proteins. These results indicate that EPAC proteins are negative regulators of myelination and may be promising targets for the treatment of myelin-related diseases.

Correction to: EPAC Negatively Regulates Myelination via Controlling Proliferation of Oligodendrocyte Precursor Cells / 神经科学通报·英文版

The original version of this article unfortunately contained a mistake.

Expression of activator of basal transcription 1 in gastric cancer tissue and its clinical significance / 吉林大学学报(医学版)

Objective:To investigate the expression of activator of basal transcription 1 (ABT1) protein in gastric cancer tissue and its relationships with the clinical parameters and prognosis of gastric cancer patients, and to clarify the role of ABT1in the occurrence and development of gastric cancer.Methods:A total of 100cases of cancer tissue of the gastric cancer patients and 80pairs of adjacent tissue were selected.The expressions of ABT1in cancer tissue and adjacent tissue were detected by immunohistochemistry and the proportion of stained cells and the degree of staining in the immunohistochemistry results were analyzed using semi-quantitative analysis.The relationships between the semi-quantitative analysis results and the clinical parameters of gastric cancer patients were statistically analyzed.Kaplan-Meier method was used to analyze the correlation between the ABT1 protein expression level and the survival of gastric cancer patients.Results:ABT1-positive staining was observed in the nucleus and cytoplasm of gastric cancer tissue and adjacent gastric tissue.The expression level of ABT1in gastric cancer tissue was lower than that in adjacent tissue (P=0.021) .The ABT1protein expression level in gastric cancer tissue was significantly negatively correlated with the pathological grade (r=-0.224, P=0.026) .The Kaplan-Meier analysis results of the survival curve showed that the high expression of ABT1was associated with good prognosis in the gastric cancer patients (HR=1.483, P＜0.01) .The survival rate of gastric cancer patients with high ABT1expression was significantly higher than that of the patients with low ABT1expression (HR=2.411, P=0.0272) .Conclusion:The expression of ABT1in gastric cancer tissue is lower, indicating that ABT1can be used one of the markers of good prognosis of gastric cancer.

bFGF promotes blood spinal cord barrier recovery in rats / 基础医学与临床

Objective To investigate the mechanisms of basic fibroblast growth factor(bFGF) promoting blood spi-nal cord barrier(BSCB) recovery in rats after spinal cord injury(SCI).Methods Rats were randomly divided into sham group,SCI model group, bFGF intervention group(80 μg/kg). The nerve function of hind limb motor was evaluated by Basso, Beattie, and Bresnahan (BBB) scores during postoperative 14 days. Neuron loss of injured spinal cords was observed by haematoxylin and eosin(HE) staining and NeuN staining.The integrity of BSCB was investigated with Evan's Blue staining and fluorescein isothiocyanate (FITC)-dextran extravasation. The expression protein of adhesive connection protein (p120-catenin,β-catenin) and tight junction protein expression(occludin, claudin-5) were analyzed by Western blot.Results Compared with SCI model group, bFGF intervention group neuron loss decreased significantly at 3 d after injury(P<0.05);the permeability of blood spinal cord barrier obvi-ously reduced at 1d after injury; the expressions of p120-catenin, beta-catenin, occludin, claudin-5 protein of bFGF intervention group were increased dramatically at 1 d after injury(P<0.05). Conclusions bFGF improves the recovery of BSCB in an SCI model by reducing the loss of neurons and increasing the expressions of adhesion junction proteins and tight juction proteins.

Exploration into quantitative MR diagnostic criteria of subacromial impingement syndrome / 实用放射学杂志

Objective To investigate the relationships of MR indexes such as acromio humeral intervals (AHI),lateral extension of the acromion (LEA) and inclination angle of the acromion with the subacromial impingement syndrome (SIS).Methods 151 patients underwent MRI examination of shoulder joints,they were grouped according to age,gender and location of acromion.The differences in age,gender and MR indexes were compared between SIS group and non SIS group.The distribution statuses of SIS in different groups were compared at the same time,the relationships of various MR indexes with SIS were investigated and analyzed.Results There were no statistical differences in age,location distribution,the average shortest AHI value and the thickness of the subacromial bursal effusion between SIS group and non SIS group (P ＞ 0.05).There showed statistical difference in gender between the two groups (P =0.000),and there were more males than females in both groups.The acromion exactly covered the supraspinatus tendon in 79 patients,the average value of LEA in the SIS group was greater than that in the non SIS group,and there showed statistically significant difference between the two groups (P =0.002),the Youden index of LEA was 0.40,the sensitivity was 61％ and the specificity was 79％.The inclination angle of the acromion in the SIS group was smaller than that in the non SIS group,and there was a statistically significant difference between the two groups (P =0.019),the Youden index of the inclination angle of the acromion was 0.18,the sensitivity was 62％ and the specificity was 56％.47 patients in the SIS group had subacromial bursal effusion,51 patients in the non SIS group had subacromial bursal effusion.The thickness of the subacromial bursal effusion in the SIS group was greater than the non SIS group,and there showed statistically significant difference between the two groups (P =0.002),the Youden index of the thickness of the subacromial bursal effusion was 0.34,the sensitivity was 78 ％ and the specificity was 56 ％.Conclusion LEA,the inclination angle of the acromion and the thickness of the subacromial bursal effusion can be used as quantitative MR diagnostic criteria of SIS.The LEA measured by cardiothoracic ratio is simple and easy to use.

Analysis of Early-Death and Factors Affecting Prognosis of Patients with Acute Promyelocytic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the factors affecting the early-death, overall survival (OS) and relapse-free survival (RFS) of acute promyelocytic leukemia (APL) patients.</p><p><b>METHODS</b>The clinical and laboratorial charachteristics of 176 APL patients in our center were analyzed retrospectively during January 2002 to Mar 2016. The risk factors of early death and factors affecting OS and RFS of patients were analyzed.</p><p><b>RESULTS</b>Among total of 176 patients, early death occured in 10 patients. Multivariate analysis showed both age ≥60 years and fibrinogen<1.5 g/L (HR=6.4, 95%CI 1.4-28.2) (P=0.015), (HR=12.2, 95%CI 1.5-102.8) (P=0.021), respectively were the independent risk factors for the early death during the induction therapy. Among 154 patients with full follow-up data (median follow-up time was 101(2-262) months), the estimated 5-year OS and RFS rate were (98± 1)% and (77± 4)%, respectively. Cox regression analysis showed relapse during treatment as well as initial WBC count≥30× 10/L were independent prognostic indicators for OS. Accompanied psoriasis indicated higher relapse rate of APL(HR=4.8, 95%CI 1.8-12.5)(P=0.002), while the low-risk APL indicated lower relapse rate (HR=0.4, 95%CI 0.2-0.99)(P=0.048).</p><p><b>CONCLUSION</b>Importance should be attached to the early-death events in elder and low-fibrinogen APL patients. As for patients with psoriasis or non low-risk group, emphasizing the intensified dynamic supervision during the treatment helps to detect the early-relapse events. For relapsed patients and patients with ≥30× 10/L WBC count, seeking more optimized therapy strategy seems allow this cohorts to get better prognosis.</p>

Gene-gene interactions of suicidal behavior by multifactor dimensionality reduction analysis :Do both 5-HT and GAD1 work? / 西安交通大学学报(医学版)

Objective To investigate gene-gene interactions of suicidal behavior with single-nucleotide-polymorphism (SNP) in MAOA ,GAD1 and 5-HTR2C by multifactor dimensionality reduction .Methods For this case-control study ,six SNPs were captured in related genes and detected in blood samples obtained from 21 patients with suicidal behavior and 50 healthy individuals .The genotype frequency and allele frequency as well as the Hardy-Weinberg equilibrium (HWE) ,tests were performed and compared by plink software .The gene-gene interactions models were built by the MDR software .Results The HWE test for case group showed that rs3813928 rs518147 of 5-HTR2C gene was not in line with HWE ( P< 0 .05) .However ,the additive model analysis after adjustment by gender indicated that the polymorphism had a positive correlation with suicidal behavior in case group .The case and control groups differed significantly only in genotype frequencies of 5-HTR2C gene (χ2 =6 .18 , P=0 .04) .There was no significant difference in allele and genotype frequencies of the other genes ( P>0 .05) .The best combination model of MDR was rs5953210-rs769391 OR=20 .19 ,95% CI 4 .19-97 .38 , P<0 .01 ,with significant interaction . Conclusion The 5-HTR2C gene rs3813928 and rs518147 polymorphisms may play an important role in the susceptibility to suicidal behavior .The combination of MAOA with GAD1 has a significant interaction which may increase the risk of suicidal behavior .