Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Adult ; Aged ; Betacoronavirus ; genetics ; isolation & purification ; Coronavirus Infections ; diagnostic imaging ; therapy ; virology ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnostic imaging ; therapy ; virology ; Tomography, X-Ray ; Treatment Outcome

Objective To retrospectively analyze the relationship between the atherosclerosis plaques in abdominal aorta and superial mesenterial artery (SMA) and the development of ischemia bowel disease (IBD) in elderly patients. Methods Elderly patients diagnosed as IBD (n=20) and non-IBD elderly patients with coronary heart disease (n=20) were selected in our hospital from January 2010 to December 2015. Data of CT imaging of abdominal aorta and SMA were evaluated by Syngo.Via software in two groups. Results The calcified plaques were dominated by dots in control group, while they were the annular lesions in IBD group, according to the CT imaging data. The mean sum of calcification in SMA was significantly increased in IBD group than that in control group (χ2=5.010,P=0.025). The stenosis of SMA was more significant in IBD group compared to that of control group (Z=3.370,P=0.001). The degree of SMA lesion was positively correlated with its opening stenosis in the IBD group (rs=0.650,P=0.002). Conclusion The basic vascular lesion is dot calcification in elderly patients with coronary heart disease, and the opening stenosis in SMA induced by mass calcification is the main cause of atherosclerosis-induced ischemic intestinal disease in elderly people.

OBJECTIVETo investigate the effectiveness of psychosocial services provided by social workers in reducing dropout rate and increasing treatment dosage in methadone maintenance treatment (MMT) users.

METHODSFrom May in 2009 to April in 2010, 300 MMT users were recruited from three MMT clinics in Guangzhou, and were randomly allocated into the intervention group and the control groups. The control group (152 cases) received standard MMT services while the intervention group (148 cases) received additional services provided by social workers. Methadone dosage, dropout rate, perceptions toward MMT etc. were compared between the two groups.

RESULTSThe 1-month dropout rate of the control and intervention groups were 19.7% (30/152) and 6.8% (10/148) (P < 0.05) respectively; the 6-month dropout rate of the control and intervention groups were 75.5% (115/152) and 50.7% (75/148) (P < 0.05) respectively. The intervention group had higher average treatment dosage than the control group ((56.0 ± 21.2) vs (64.4 ± 23.1) ml/d, (58.0 ± 24.0) vs (66.1 ± 26.6) ml/d, P < 0.05). At 1-month and 6-month, the intervention group had higher scores of MMT-related perception ((1.26 ± 0.68) vs (1.84 ± 0.95), (1.55 ± 0.83) vs (2.44 ± 1.23), P < 0.05), self-efficacy of maintenance ((3.68 ± 1.33) vs (4.20 ± 1.05), (3.80 ± 1.38) vs (4.43 ± 0.79), P < 0.05) and satisfaction toward MMT((4.08 ± 0.54) vs (4.15 ± 0.60), (4.01 ± 0.67) vs (4.31 ± 0.64), P < 0.05) as compared to the control group. The reverse was true for the score of negative experiences ((1.05 ± 0.86) vs (0.96 ± 0.92), (1.46 ± 0.87) vs (1.11 ± 1.07), P < 0.05).

CONCLUSIONThe psychosocial interventions provided by social workers were effective in reducing dropout rate, increasing treatment dosage and improving cognitions of MMT users.

Adult ; Female ; Heroin Dependence ; drug therapy ; Humans ; Male ; Methadone ; administration & dosage ; therapeutic use ; Opiate Substitution Treatment ; Patient Compliance ; Social Work ; Substance Abuse Treatment Centers ; Treatment Outcome

Objective To investigate the changes in function of liver and kidney of the rabbits bearing VX2 liver tumor after transarterial embolization and hyperthermia with magnetic nanoparticles suspended in lipiodol(MN-L) and its therapeutic effect Methods Thirty-two rabbits bearing VX2 liver tumor were randomly divided into four groups and each group contained 8 rabbits The four groups were MN-L embolization hyperthermia group (Group A), MN-L embolization group(Group B),Lipiodol embolization group(Group C), and Control group (Group D), Each rabbit in Group A and B was embolized with 0.5-0.8 ml MN-L through hepatic artery, while each rabbit in Group C was embolized with 0.5-0.8 ml lipiodol.Hyperthermia in alternating magnetic field was performed in Group A after embolization.The remaining groups did not undergo hyperthermia.The rabbits in control group were not treated.The function of liver and kidney of all the animals was measured 1d before embolization,and 1,7,and 14 d after embolization/hyperthermia respectively.Alanine aminotransferase (ALT) and aspartate aminotransaminase (AST) were used to reflect the function of liver,and blood urea nitrogen(BUN) and creatinine (Cr) were used to reflect the function of kidney.CT was performed on all of subjects before and after embolization to determine the embolization effect and the tumor size, and follow-up CT was performed weekly.All of subjects were sacrificed 14 days after embolization/hyperthermia, and their livers, spleens, kidneys and lungs were removed for histopathology examination.The data from every group were analyzed using analysis of variance of repeated measure data.Results On 1 day before embolization and 1,7, and 14 d after embolization/hyperthermia, the function of liver of the rabbits was as follows:Group A:ALT was (43.9±19.0),(795.1±327.1),(67.0±9.3), and(41.9±10.8) U/L respectively,and AST was (50.2±13.6),(1011.2±655.9),(62.4±24.1),and(51.6±7.9) U/L respectively; Group B: ALT was(45.0±19.1),(580.8±160.4),(67.2±31.0),and(47.6±7.8) U/L respectively, and AST was (52.9±20.3),(735.2±186.1),(57.9±24.8),and (50.9±9.8) U/L respectively; Group C: ALT was (47.4±14.6),(558.5±167.8),(63.5±21.9),and (48.0±9.3) U/L respectively, and AST was (51.8±9.5),(752.5±112.0),(56.5±20.6),and(51.4±8.6) U/L respectively.Both ALT and AST mean values of the rabbits were significantly elevated 1 d after embolization/hyperthermia in Group A, B and C, and the data showed statistically significant difference comparing with that before therapy and that of Group D 1 d after therapy (P<0.01).The function of liver showed no statistically significant difference between 7 or 14 days after embolization and 1 day before embolization in Group A,B and C. BUN and Cr mean values in pre-embolization and post-embolization rabbits revealed no statistically significant difference in group A, B, C and D.The MN-L /lipiodol were deposited in the tumor when it was injected, which was validated by CT.To compare with immediate CT after embolization, the MN-L deposited in tumors was not significantly different on CT 7 d after embolization .On the 14 th day after treatment,the MN-L deposited in tumors became concentrative and compact in Group A, while the MN-L/lipiodol deposited at the rim of tumors disappeared on CT in five rabbits of Group B and C.And the tumor size decreased by 21.7% compared to that before treatment in Group A [from (7.8±1.4)cm~3 to(6.1±0.6) cm~3,F=17.56, P<0.01], but tumor size increased by 16.2% and 18.9% in Group B and C respectively [from (7.9±1.1)and (7.8±0.9)cm~3 to (9.1±0.8) and (9.3±1.0)cm~3, F =25.23,55.50, P<0.01].Histopathologically, the tumor of Group A was necrotic for at least 80% 14 day after embolization, while the tumor of Group B and C was necrotic for 30% to 50% .Conclusion Transarterial embolization and hyperthermia with MN-L is safe, effective and feasible on the rabbits bearing VX2 liver tumor.

BACKGROUNDAtrial fibrillation is a common arrhythmia with multi-factorial pathogenesis. Recently, a single nucleotide polymorphism (G/T) at position 1057 in the KCNE4 gene, resulting in a glutamic acid (Glu, E)/aspartic acid (Asp, D) substitution at position 145 of the KCNE4 peptide, was found in our laboratory to be associated with idiopathic atrial fibrillation (atrial fibrillation more frequent with KCNE4 145D). However, the functional effect of the KCNE4 145E/D polymorphism is still unknown.

METHODSWe constructed KCNE4 (145E/D) expression plasmids and transiently co-transfected them with the KCNQ1 gene into Chinese hamster ovary-K1 cells and performed whole-cell patch-clamping recording to identify the possible functional consequences of the single nucleotide polymorphism. Quantitative data were analyzed by Student;s t test. Probability values less than 0.05 were considered statistically significant.

RESULTSA slowly activating, non-inactivating voltage-dependent current ((24.0 +/- 2.9) pA/pF, at +60 mV)) could be recorded in the cells transfected with KCNQ1 alone. Co-expression of wild type KCNE4 inhibited the KCNQ1 current ((7.3 +/- 1.1) pA/pF)). By contrast, co-expression of KCNE4 (145D) augment the KCNQ1 current ((42.9 +/- 7) pA/pF)). The V(1/2) of activation for the KCNQ1/KCNE4 (145D) current was shifted significantly towards the depolarizing potential compared to that for the KCNQ1 current ((-2.3 +/- 0.2) mv vs (-13.0 +/- 1.5) mv, P < 0.01)) without changing the slope factorkappa. Furthermore, KCNE4 (145D) also affected the activation and deactivation kinetics of KCNQ1 channels.

CONCLUSIONWe provide experimental evidence that the KCNE4 (145E/D) polymorphism exerts the effect of "gain of function" on the KCNQ1 channel. It may underlie the genetic mechanism of atrial fibrillation. Further studies on the functional association between I(Ks) and KCNE4 (145D) polymorphism in cardiac myocytes are suggested.

Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Humans ; KCNQ1 Potassium Channel ; physiology ; Polymorphism, Single Nucleotide ; Potassium Channels, Voltage-Gated ; analysis ; genetics ; physiology

OBJECTIVETo perform in vitro magnetic resonance imaging on magnetic iron oxide (Fe(2)O(3)-PLL) labeled rabbit peripheral blood endothelial progenitor cells (EPCs).

METHODSFe(2)O(3) was incubated with PLL for 2 hours to form Fe(2)O(3)-PLL. Rabbit peripheral blood mononuclear cells (MNCs) were isolated and EPCs were selected by adherence method, expanded and incubated with Fe(2)O(3)-PLL. Intracellular iron was detected by Prussian blue stain and under electron microscope. MTT assay was used to evaluate cell survival and proliferation of Fe(2)O(3)-PLL labeled EPCs. Flow cytometry was used to analysis cell cycle and apoptosis. The cells underwent in vitro MR imaging with various sequences.

RESULTSIron-containing intracytoplasmatic vesicles could be observed clearly with Prussian blue staining and electron microscope observation. Survival, life cycle and apoptosis values obtained by MTT and flow cytometry analysis were similar among unlabelled EPCs and EPCs labeled with various concentrations Fe(2)O(3)-PLL. The signal intensity on MRI was significantly decreased in labeled cells compared with that in unlabeled cells. The percentage change in signal intensity (DeltaSI) was most significant on T(2)*WI and DeltaSI was significantly lower in cells labeled for 7 days than that labeled for 1 day.

CONCLUSIONSThe rabbit peripheral blood EPCs can be labeled with Fe(2)O(3)-PLL without significant change in viability and proliferation. The labeled EPCs can be imaged with standard 1.5 T MR equipment. The degree of MR signal decreasing may indirectly reflect the cells count, growth state and division.

Animals ; Biomarkers ; Blood Cells ; Cells, Cultured ; Endothelial Cells ; cytology ; Ferric Compounds ; Magnetic Resonance Imaging ; methods ; Male ; Rabbits ; Stem Cells ; cytology

OBJECTIVETo investigate the effect of cigarette smoking on thyroid gland volume, thyroid function and thyroid autoantibodies in the areas with different iodine intakes.

METHODSA cross-sectional epidemiological study in Panshan (mild iodine-deficient area), Zhangwu (more than adequate iodine intake area) and Huanghua (iodine-excessive area) was conducted in 3761 subjects in 1999.80.2 % of them were followed up in 2004. Questionnaires, thyroid function, thyroid autoantibodies, urinary iodine concentration,and thyroid B ultrasound were performed.

RESULTSThe prevalence of goiter was higher in smokers than in non-smokers (15.1% vs. 11.5%, P< 0.05). The average thyroid volume was higher in smokers with phenomenon more obvious in Panshan and Huanghua areas. Data from logistic analysis showed that smoking cigarette was an independent risk factor of goiter. There was no difference in serum TSH and Tg level between smokers and non-smokers. The positive rate of TPOAb (>100 IU/ml) was higher in smokers than in non-smokers(10.8% vs. 9.0 % , P <0.05) and was especially obvious in Huanghua area. Smoking was a independent risk factor of increasing positive rate of TPOAb. During the prospective observation,it was found that the incidence of positive TPOAb(>,100 IU/ml) was 7.4% in the subjects that were from non-smokers turning to smokers and 2.9% in those whose smoking behavior did not change. Logistic analysis indicated that the shifting from non-smoking to smoking was independent risk factor for the increase on high incidence of positive TPOAb.

CONCLUSIONSmoking cigarette was a independent risk factor of goiter. Smoking was also a risk factor of increasing TPOAb positive rate. Shifting from not smoking to smoking was an independent risk factor of increasing high incidence of positive TPOAb.

Autoantibodies ; blood ; Cross-Sectional Studies ; Female ; Goiter ; blood ; epidemiology ; immunology ; physiopathology ; Humans ; Incidence ; Male ; Smoking ; adverse effects ; Thyroid Function Tests ; Thyroid Gland ; physiopathology ; Thyroid Hormones ; blood