Epigenetics recording varied environment and complex cell events represents the origin of cellular aging / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Although a relationship between epigenetics and aging phenotypic changes has been established, a theoretical explanation of the intrinsic connection between the epigenetics and aging is lacking. In this essay, we propose that epigenetic recording of varied cell environment and complex history could be an origin of cellular aging. Through epigenetic modifications, the environment and historical events can induce the chromatin template into an activated or repressive accessible structure, thereby shaping the DNA template into a spectrum of chromatin states. The inner nature of diversity and conflicts born by the cell environment and its historical events are hence recorded into the chromatin template. This could result in a dissipated spectrum of the chromatin state and chaos in overall gene expression. An unavoidable degradation of epigenome entropy, similar to Shannon entropy, would be consequently induced. The resultant disorder in epigenome, characterized by corrosion of epigenome entropy as reflected in chromatin template, can be stably memorized and propagated through cell division. Furthermore, the hysteretic nature of epigenetics responding to the emerging environment could exacerbate the degradation of epigenome entropy. As well as stochastic errors, we propose that outside entropy (or chaos) derived from the varied environment and complex cell history, gradually input and imprinted into the chromatin via epigenetic modifications, would lead inevitably to cellular aging, the extent of which could be aggravated by hysteresis of epigenetics without error erasing and correction.

Analysis of Risk Factors Affecting the Chemotherapy-related Infections in Patients with ALL / 中国实验血液学杂志

OBJECTIVE@#To analyze the risk factors affecting the chemotherapy-related infections in patients with acute lympho-blastic leukemia (ALL).@*METHODS@#The clinical data of 102 patients with ALL from January 2014 to December 2018 were collected and retrospectively studies. The risk factors of chemotherapy-related infections were analyzed by univa-riate and multivariate logistic regression.@*RESULTS@#A total of 386 courses of chemotherapy were completed, out of which the infection occurred in 201 course, with the infection rate of 52.07%, identified infection number was 215 case-times, including perianal infection of 13.95% (30/215), oral infection of 13.49% (29/215), blood flow infection of 1721% (37/215), lower respiratory tract infection of 37.21% (80/215), urinary infection of 3.26% (7/215), skin infection of 3.72% (8/215), digestive and intra abdominal infection of 9.30% (20/215), and other infections of 1.86 (4/215). Totally 88 strains of pathogenic bacteria were detected, including 29 Gram-positive bacteria (32.95%), 52 Gram-negative bacteria (59.09%) and 7 fungi (7.95%). Gram-positive bacteria mainly were Staphylococcus haemolyticus and Enterococcus faecium, susceptible to tegacycline, vancomycin and linezolid; Gram-negative bacteria mainly were Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae, susceptible to tegacycline, amikacin, piperacillin/tazobactam and imipenem; Candida was the dominant fungus. Living in an ordinart ward, neutrophil defi-ciency for more than 7 days after chemotherapy and incomplete remission were independent risk factors of related infections during the induction chemotherapy in ALL inpatients, and hospitalization time also closely related with chemo-therapy-related infections in ALL inpatients (P<0.05). Neutrophil deficiency for more than 7 days after chemotherapy was an independent risk factor of chemotherapy-related infections in ALL inpatients in the consolidation chemotherapy (P<0.05).@*CONCLUSION@#Patients with ALL are prone to chemotherapeutic-related infections, and those who lack neutrophils for more than 7 days after chemotherapy and who do not reach complete remission are more prone to infection. Living in laminar flow ward and reducing hospitalization stay can help reduce the incidence of infection.

Epigenetics recording varied environment and complex cell events represents the origin of cellular aging / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Although a relationship between epigenetics and aging phenotypic changes has been established, a theoretical explanation of the intrinsic connection between the epigenetics and aging is lacking. In this essay, we propose that epigenetic recording of varied cell environment and complex history could be an origin of cellular aging. Through epigenetic modifications, the environment and historical events can induce the chromatin template into an activated or repressive accessible structure, thereby shaping the DNA template into a spectrum of chromatin states. The inner nature of diversity and conflicts born by the cell environment and its historical events are hence recorded into the chromatin template. This could result in a dissipated spectrum of the chromatin state and chaos in overall gene expression. An unavoidable degradation of epigenome entropy, similar to Shannon entropy, would be consequently induced. The resultant disorder in epigenome, characterized by corrosion of epigenome entropy as reflected in chromatin template, can be stably memorized and propagated through cell division. Furthermore, the hysteretic nature of epigenetics responding to the emerging environment could exacerbate the degradation of epigenome entropy. As well as stochastic errors, we propose that outside entropy (or chaos) derived from the varied environment and complex cell history, gradually input and imprinted into the chromatin via epigenetic modifications, would lead inevitably to cellular aging, the extent of which could be aggravated by hysteresis of epigenetics without error erasing and correction.

Clinical and pathological features and imaging manifestations of bronchial anthracofibrosis: the findings in 15 patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bronchial anthracofibrosis (BAF) has been defined as a luminal narrowing associated with anthracotic pigmentation on bronchoscopy without a relevant history of pneumoconiosis or smoking. The aim of the study is to study the clinical features and imaging manifestations of BAF, and to promote the awareness of this disease.</p><p><b>METHOD</b>Between October 2006 and January 2012, 15 patients were diagnosed at our department as BAF that showed a narrowing or obliteration of lobar or segmental bronchi with anthracotic pigmentation in the overlying mucosa on bronchoscopy. The medical records including clinical features, imaging manifestations, electronic bronchoscopic findings, and pathological features were analysed, and the literature was reviewed.</p><p><b>RESULTS</b>A total of 15 patients were analyzed; 13 were female (86.7%) and two were male (13.3%) and the age range was from 62 to 86 years with a mean age of 74.5 years. Three cases (20.0%) had a history of tuberculosis. The most common clinical symptoms of BAF were cough (100%), expectoration (73.3%), dyspnea (60.0%), and fever (46.7%). Twelve cases displayed mild to moderate obstructive ventilatory dysfunction. In the electronic bronchoscopic evaluation, the most common findings were black bronchial mucosal pigmentation, bronchial stenosis, bronchial occlusion, and bronchial mucosal folds. Pathological evaluation revealed chronic inflammation of the bronchial mucosa, submucosal carbon particle deposition, and mucosal or submucosal fibrosis. Chest CT scans showed that 15 patients had bronchial stenosis or obstruction (direct signs) with the right middle lobe being the most common site (11 cases, 73.3%). The indirect sign was mainly the presence of bronchial obstructive diseases (including secondary infection), represented by 11 cases of pulmonary consolidation (73.3%), seven cases of atelectasis (46.7%), and five cases of nodules (33.3%). The CT mediastinal window showed bronchial lymph node lesions, mediastinal lymph node calcification (12 cases, 80.0%), and enlargement of multiple mediastinal lymph nodes.</p><p><b>CONCLUSIONS</b>The diagnosis of BAF was mainly based on bronchoscopic evaluation. Its pathogenesis is currently unclear, although it may be related to tuberculosis or bio-fuel inhalation. The diagnosis of BAF has important clinical significance, and improved awareness of this disease will contribute to prevention of unnecessary thoracotomies.</p>

Efficacy observation on acupuncture prescription of regulating yin-yang and five viscera for intractable insomnia / 中国针灸

<p><b>OBJECTIVE</b>To explore a more optimal therapy for intractable insomnia.</p><p><b>METHODS</b>Seven hundred cases of intractable insomnia that were in accordance with the criteria were randomly divided into an observation group (368 cases) and a control group (332 cases). The acupuncture prescription of regulating yin-yang and five viscera was applied in the observation group, where Dazhui (GV 14), Shenmai (BL 62), Guanyuan (CV 4), Zhaohai (KI 6), Geshu (BL 17), etc. were selected. The acupuncture prescription of tranquilizing mind was applied in the control group, where Baihui (GV 20), Sishencong (EX-HN 1), Anmian (Extra), Shenmen (HT 7), Sanyin jiao (SP 6) were selected. The treatment was given once a day, ten times of which made a session. After the treatment for 4 sessions, the clinical efficacy and Pittsburgh sleep quality index (PSQI) were compared between two groups.</p><p><b>RESULTS</b>The total effective rate was 92.6% (338/365) in the observation group, which was superior to 73.1% (242/331) in the control group (P < 0.05). The PSQI score was obviously decreased in two groups after the treatment (both P < 0.05), in which the decreasing in the observation group was superior to that in the control group (P < 0.05).</p><p><b>CONCLUSION</b>The acupuncture prescription of regulating yin-yang and five viscera has better effect for intractable insomnia, which could be considered as a more optimal therapy.</p>

Linker for activation of T cells contributes to airway inflammation in an asthmatic mouse model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Allergic asthma is associated with airway inflammation and hyperresponsiveness caused by dysregulated production of cytokines secreted by allergen-specific helper T-type 2 (Th2) cells. The linker for activation of T cells (LAT) is a membrane-associated adaptor protein, which has been shown to take part in regulating T cell receptor (TCR) signaling and T cell homeostasis. In this study, we established an asthmatic mouse model to examine the changes in LAT levels during allergic airway disease and the effects of LAT transgenic expression on airway inflammation.</p><p><b>METHODS</b>T cells from mouse lung tissues were isolated from allergen challenged (ovalbumin (OVA)) and control mice, and the purity of these isolated T cells was examined by fluorescence-activated cell sorter (FACS). Semi-quantitative RT-PCR and Western blotting were used to detect the expression of the LAT gene and LAT protein, respectively. After an intranasally administered mixture of pCMV-HA-LAT plasmid and Lipofectamine 2000, 24 hours before and 72 hours after allergen challenge, the BALF cell count and the differential cytologies were studied. In addition, IL-4 and IFN-γ levels in the BALF were determined by ELISA, and pathological changes in lung tissues were observed.</p><p><b>RESULTS</b>LAT protein and mRNA expression were decreased in lung T cells in a mouse model of allergen-induced airway disease. After intranasal administration of pCMV-HA-LAT, histopathological examination of the lungs showed that intervention with LAT overexpression prevented mice from developing airway inflammation, and the number of total cells, eosinophils, neutrophils, and lymphocytes in the BALF was reduced significantly compared with the OVA sensitized and challenged group. In addition, the Th2 cytokine IL-4 decreased, while the Th1 cytokine IFN-γ increased compared to the OVA sensitized and challenged group or the OVA sensitized group plus pCMV-HA treatment.</p><p><b>CONCLUSION</b>This study demonstrates that LAT might effectively diminish Th2 cytokine responses, lung histopathological changes and lung inflammation to allergen challenge in a model of experimentally induced asthma.</p>

Small interfering RNA-mediated knockdown of Notch1 in lung / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The immunologic response to allergens mediated by T lymphocytes is an incipient key element in the pathogenesis of asthma, and Th1/Th2 balance is regarded as the core of asthma pathogenesis. Notch is a single-pass transmembrane receptor protein that regulates differentiation, proliferation and apoptosis in a broad range of cells. It is considered that the Notch signal pathway works in every stage of T cell development and differentiation. Whether the pathway of asthma pathogenesis is related to Notch1 remains unknown. This study is aimed to investigate whether the pathway of asthma pathogenesis is related to Notch1 by examining the effect of knockdown of the Notch1 gene by small interfering RNA on T cell differentiation.</p><p><b>METHODS</b>An OVA-induced asthma mouse model was established. The expression of Notch1 in the tissue and T cells of the lung from asthmatic mice was detected by RT-PCR and Western blotting. The expression of Notch1 and cytokine interleukin (IL)-4 and interferon (IFN)-gamma in activated lung T cells was detected by RT-PCR and enzyme-linked immunosorbent assay after blocking Notch1 by small interfering RNA.</p><p><b>RESULTS</b>The mRNA and protein expression of Notch1 increased significantly both in the lung tissue and lung T cells of asthmatic mice (both P < 0.05). IL-4 decreased and IFN-gamma increased significantly in active lung T cells after Notch1 was blocked by Notch1-specific small interfering RNA (IL-4: (2.51 +/- 0.51) pg/ml vs 0.64 +/- 0.27) pg/ml protein; IFN-gamma: (21.72 +/- 4.24) pg/ml vs (39.79 +/- 4.09) pg/ml protein, P < 0.05).</p><p><b>CONCLUSION</b>This study demonstrated that the Notch1 signal might play a role in the pathogenesis of asthma by its involvement in Th1/Th2 differentiation.</p>

Construction of linker for activation of T cells gene eukaryotic expression vector in mouse / 上海第二医科大学学报

Objective To construct the eukaryotic expression vector of linker for activation of T cells(LAT) gene in mouse. MethodsLAT cDNA of mouse mononuclear cells was amplified with polymerase chain reaction.The fragment was inserted into the eukaryotic expression vector of pCMV-HA plasmid.The recombinant plasmid was verified by DNA sequencing and used to transfect lymphocytes of the asthmatic model. Results The length of amplified fragment was 729 bp.The sequence of LAT gene was confirmed by Genbank.The LAT protein could be detected in the lymphocytes of asthmatic model.Conclusion The recombinant eukaryotic expression vector pCMV-HA-LAT can be successfully constructed.

Cloning and sequence analysis of recombinant fusion gene of Escherichia coli heat-liable enterotoxin B subunit and Actinobacillus actinomycetemcomitans fimbria associative protein / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To clone the recombinant fusion gene of Escherichia coli heat-liable enterotoxin B subunit (Ltb) and Actinobacillus actinomycetemcomitans fimbria associative protein (Fap).</p><p><b>METHODS</b>Two couples of primers were designed for PCR according to the known sequence of ltb and fap. The ltb and fap gene were obtained by amplification PCR technique from plasmid EWD299 of Escherichia coli and Actinobacillus actinomycetemcomitans 310 DNA respectively, and fused them by PCR. The fusion gene ltb-fap were cloning into plasmid pET28a(+). The recombined plasmid pET28a ltb-fap was transformed into Escherichia coli DH5alpha. The recombinant was screened and identified by restriction enzyme and PCR. The cloned gene was sequenced.</p><p><b>RESULTS</b>The ltb-fap about 531bp in size was obtained successfully, and identified by PCR, restrictive enzyme and sequence analysis.</p><p><b>CONCLUSION</b>The vector of pET28a ltb-fap was obtained.</p>

Abnormal expression of hMSH2 mRNA and mutation P53 protein in acute lymphoblastic leukemia / 中国实验血液学杂志

In order to investigate the mechanism of acute lymphoblastic leukemic cell malignant proliferation, the expressions of hMSH2 mRNA and mutation P53 (mtP53) protein in bone marrow cells of de novo acute lymphoblastic leukemia (ALL) were determined by in situ hybridization and immunocytochemical methods. The results showed the that percentage of positive cell with hMSH2 mRNA expression was (32.88 +/- 11.46)% in the de novo ALL group and (64.22 +/- 8.51)% in the control group. The percentage of positive cell with mtP53 protein expression was (29.25 +/- 9.45)% in the de novo ALL group, and (12.63 +/- 6.66)% in the control group. There was a significant negative correlation between the positive percentages of hMSH2 mRNA expression and mtP53 protein expression (r = -0.45, P < 0.05). It is concluded that defective MSH2 mRNA expression plays an important role in the pathogenesis of acute lymphoblastic leukemia, mtP53 protein mutation plays an important role in the development of acute lymphoblastic leukemia, the hMSH2 mRNA defect can lead to accumulation of the mutant P53 protein in acute lymphoblastic leukemia, and both jointly promote the pathogenesis of ALL.