Human T cell leukemia virus type 1 (HTLV-1), an etiological factor that causes adult T cell leukemia and lymphoma (ATL), infects over 20 million people worldwide. About 1 million of HTLV-1-infected patients develop ATL, a highly aggressive non-Hodgkin's lymphoma without an effective therapy. The pX region of the HTLV-1 viral genome encodes an oncogenic protein, Tax, which plays a central role in transforming CD4+ T lymphocytes by deregulating oncogenic signaling pathways and promoting cell cycle progression. Expression of Tax following viral entry is critical for promoting survival and proliferation of human T cells and is required for initiation of oncogenesis. Tax exhibits diverse functions in host cells, and this oncoprotein primarily targets IκB kinase complex in the cytoplasm, resulting in persistent activation of NF-κB and upregulation of its responsive gene expressions that are crucial for T cell survival and cell cycle progression. We here review recent advances for the pathological roles of Tax in modulating IκB kinase activity. We also discuss our recent observation that Tax connects the IκB kinase complex to autophagy pathways. Understanding Tax-mediated pathogenesis will provide insights into development of new therapeutics in controlling HTLV-1-associated diseases.
Autophagy ; CD4-Positive T-Lymphocytes ; metabolism ; virology ; Cell Cycle ; Cell Transformation, Neoplastic ; genetics ; Gene Expression Regulation, Neoplastic ; Gene Products, tax ; genetics ; metabolism ; Human T-lymphotropic virus 1 ; physiology ; Humans ; I-kappa B Kinase ; genetics ; metabolism ; Leukemia-Lymphoma, Adult T-Cell ; genetics ; metabolism ; virology ; Membrane Microdomains ; metabolism ; virology ; NF-kappa B ; genetics ; metabolism ; Protein Binding ; Signal Transduction ; genetics

Objective To evaluate the early diagnostic value of circulating microRNA-1 (miR-1) on acute myocardial infarction (AMI). Methods A prospective cohort study was conducted. The patients with chest pain admitted to the Second People's Hospital of Wuxi from November 2012 to June 2015 were enrolled. According to AMI diagnostic criteria, the patients were divided into AMI group and non-AMI group, and healthy individuals during the same period were served as heath controls. The venous samples of the onset patients were collected within 3 hours after admission. The plasma miR-1 was determined by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR), and the levels of plasma cardiac troponin I (cTnI) and MB isoenzyme of creatine kinase (CK-MB) were measured by electrochemiluminescence. The correlation between plasma miR-1 and cTnI as well as CK-MB was performed by Spearman analysis. The early diagnostic performance of plasma miR-1, cTnI, and CK-MB for AMI was estimated by receiver operating characteristic (ROC) curve analysis. Results There were 127 patients in AMI group, and 107 in non-AMI group, including 82 patients with angina pectoris, 2 with pulmonary embolism, 3 with aortic dissection, 2 with acute pericarditis, 3 with myocarditis, 13 with acute heart failure, and 2 with peptic ulcer. Ninety volunteers were served as healthy controls. There was no difference in clinical characteristics including gender and hyperlipidemia between AMI group and non-AMI group. The expressions of plasma miR-1, cTnI and CK-MB were significantly increased in AMI patients as compared with those of the healthy controls [miR-1 (2-ΔΔCt): 4.32±2.60 vs. 1.44±0.75 and 0.98±0.18, cTnI (μg/L): 3.23 (0.63, 10.70) vs. 0.02 (0.00, 0.17) and 0.00 (0.00, 0.00), CK-MB (U/L): 32.40 (14.20, 95.40) vs. 14.40 (11.20, 17.10) and 8.90 (8.28, 9.50), all P < 0.01]. The expression of plasma miR-1 had a significantly positive correlation with cTnI and CK-MB in AMI patients (r1 = 0.395, r2 = 0.490, both P < 0.000). It was demonstrated by ROC curve analysis that the area under ROC curve (AUC) for the diagnostic value of miR-1 on AMI was 0.905 [95% confidence interval (95%CI) = 0.860-0.950, P = 0.000], the sensitivity was 86.6%, and the specificity was 95.4%; the AUC for cTnI was 0.908 (95%CI = 0.870-0.946, P = 0.000), the sensitivity was 81.9%, and the specificity was 95.9%; the AUC for CK-MB was 0.795 (95%CI = 0.736-0.854, P = 0.000), the sensitivity was 63.0%, and the specificity was 92.9%. Conclusions Plasma miR-1 has the capacity in early diagnosis of AMI, superior to CK-MB, and equal to cTnI. It can provide additional diagnostic information beyond cTnI. The diagnostic accuracy for early AMI can be improved with the combination of plasma miR-1 and cTnI.

OBJECTIVETo test the dissolution rate of silymarin dropping pill as well as to be compared with other three commercial products of the silymarin.

METHODBy UV spectrophotometry, we studied the dissolution conditions of silymarin dropping pill and compared its dissolution rate with Yiganling tablets (film-coating, sugar-coating) and Legalon capsule which are available in the market.

RESULTThe dissolution parameters T50 and Td of silymarin dropping pill, Yiganling tablet (film-coating), Yiganling tablet (sugar-coating) and Legalon capsule are 6.78, 9.85 min, 51.01, 73.78 min, 74.35, 86.97 min and 53.10, 72.65 min.

CONCLUSIONThe dissolution rate of silymarin dropping pill is superior to that of two kinds of Yiganling tablets and Legalon capsule.

Capsules ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Silymarin ; administration & dosage ; chemistry ; Solubility ; Spectrophotometry, Ultraviolet ; Tablets

OBJECTIVETo investigate the effect of curcumin (Cur) on radiosensitivity of nasopharyngeal carcinoma cell CNE-2 and its mechanism.

METHODThe effect of curcumin on radiosensitivity was determined by the clone formation assay. The cell survival curve was fitted by Graph prism 6. 0. The changes in cell cycle were analyzed by flow cytometry (FCM). The differential expression of long non-coding RNA was detected by gene chip technology. Part of differentially expressed genes was verified by Real-time PCR.

RESULTAfter 10 micro mol L-1 Cur had worked for 24 h, its sensitization enhancement ratio was 1. 03, indicating that low concentration of curcumin could increase the radiosensitivity of nasopharyngeal carcinoma cells; FCM displayed a significant increase of G2 phase cells and significant decrease of S phase cells in the Cur combined radiation group. In the Cur group, the GUCY2GP, H2BFXP, LINC00623 IncRNA were significantly up-regulated and ZRANB2-AS2 LOC100506835, FLJ36000 IncRNA were significantly down-regulated.

CONCLUSIONCur has radiosensitizing effect on human nasopharyngeal carcinoma CNE-2 cells. Its mechanism may be related to the changes in the cell cycle distribution and the expression of long non-coding IncRNA.

Cell Cycle ; drug effects ; radiation effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; radiation effects ; Curcumin ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; radiation effects ; Humans ; RNA, Long Noncoding ; genetics ; Radiation Tolerance ; drug effects

OBJECTIVE: To investigate the different kinds of controversial cases of mental disability after brain damage, to analysis the problems in the first appraisal, and to explore solutions of the problems. METHODS: The reappraisals of mental disorders after traumatic brain damage were collected from 2007-2011 in Shanghai forensic center, and the first appraisal and reappraisal cases were analyzed and compared. RESULTS: The changes of conclusion in reappraisal cases showed the following major reasons: inappropriate appraisal time, not comprehensive and object investigation of mental state of patients in first appraisal, misunderstanding the standards, etc. CONCLUSION The quality improvement of appraisal should adopt the following measures: regulating the practice, improvement of the professional skills of experts, choosing appropriate appraisal time, improvement of appraisal standards, etc.
Accidents, Traffic ; Activities of Daily Living ; Adolescent ; Adult ; Aged ; Brain Concussion/diagnosis* ; Brain Injuries/complications* ; Child ; Disability Evaluation ; Female ; Forensic Psychiatry ; Humans ; Intellectual Disability/psychology* ; Male ; Mental Disorders/psychology* ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Time Factors ; Young Adult

Objective To evaluate the short-term clinical efficacy of unilateral biportal endoscopic(UBE)technique in the treatment of adjacent segment disease after lumbar interbody fusion.Methods The clinical data of 21 patients with adjacent segment disease after lumbar interbody fusion who treated with UBE technique and followed up for more than 3 months in our hospital from March 2020 to January 2023 were retrospectively analyzed.The operation time,decrease value of hemoglobin 1 day before and after operation,drainage volume of the operation area,time of bed rest and complications were recorded.The Japanese Orthopaedic Association(JOA)score was used to evaluate lumbar function 1 day before operation,3 days and 3 months after operation to determine the improvement.The visual analogue scale(VAS)score was used to evaluate the pain 1 day before operation,3 days and 3 months after operation.Results The operation time was 60～175 minutes,with an average of(95.38±18.64)minutes;the decrease value of hemoglobin was 2～6 g/L,with an average of(1.42±0.18)g/L;the time of bed rest was 27～88 hours,with an average of(36.42±15.33)hours;the drainage volume of the operation area was 50～315 mL,with an average of(85.56±15.65)mL;and one case of dural tear occurred during the operation,who was converted to open surgery for repairing dural sac.There was statistically significant difference in VAS score before operation compared with that 3 days and 3 months after operation(P<0.05).There was statistically significant difference in the JOA score before operation compared with that 3 days and 3 months after surgery(P<0.05).Conclusion UBE technique is effective in the treatment of adjacent segment disease after lumbar interbody fusion,with the advantages of small trauma,little bleeding and short time of bed rest.However,patients with the serious adjacent segment degeneration and severe spinal stenosis may have dural tear during operation.Once it occurs,active repair should be performed to avoid cauda equina herniation and necrosis,or switch to open surgery,if necessary.

OBJECTIVETo understand the epidemic condition, distribution and biological characteristics of non-O1/non-O139 Vibrio cholerae from 2001 to 2009 in Haizhu District, to provide a scientific basis for the prevention and control of acute diarrhea.

METHODSReferring to the detecting method written in "Cholera control handbook" in the fifth edition, 764 specimens from outside environment (including the water in the Pearl River, drinking water, water for breeding fish, aquatic products and delicatessen foods), 189 specimens of healthy population and 3398 intestinal samples of patients with diarrhea, summing up to 4351 specimens for non-O1/non-O139 Vibrio cholerae test.

RESULTS4,351 specimens were detected of 101 strains of non O1/non O139 Vibrio cholerae, the total detection rate was 2.32%; 66 strains were identified by serotyping and grouped into 26 different serotypes, the typing rate was 65.3%. The strains VBO9, VBO38 and VBO76 were the dominant bacteria.Nine strains of the same type of non-O1/non-O139 Vibrio cholerae were found from external environments also from patients with diarrhea, suggesting that there might be a correlation between the two.

CONCLUSIONNon-O1/non-O139 Vibrio cholerae have diversified serotypes, causing certain infection rate among the population in this region. These bacteria exist extensively in external environment and they are the potential hazard to the citizens.

China ; epidemiology ; Cholera ; epidemiology ; microbiology ; Humans ; Serotyping ; Vibrio cholerae ; classification ; isolation & purification

OBJECTIVETo study the clinicopathologic features of various types of mature T-cell and natural killer (NK)/T-cell lymphoma in Guangdong, China, with respect to the 2008 WHO classification of lymphoid neoplasms.

METHODSEleven hundred and thirty-seven (1137) cases of mature T-cell or NK/T-cell lymphoma diagnosed during the period from 2002 to 2006 in Guangzhou area were retrieved. The clinical data, histologic features and immunohistochemical findings were reviewed by a panel of experienced hematopathologists. Additional immunostaining was performed if indicated. The cases were re-classified according to the 2008 WHO classification of lymphoid neoplasms.

RESULTSNine hundred and sixty-three (963) cases fulfilled the diagnostic criteria of mature T-cell or NK/T-cell lymphoma and accounted for 20.1% of all cases of lymphoma encountered during the same period (963/4801). A predominance of extranodal involvement was noted in 644 cases (66.9%), while 319 cases (33.1%) showed mainly nodal disease. The prevalence of various lymphoma subtypes was as follows: peripheral T-cell lymphoma, unspecified (PTCL, NOS) 293 cases (30.4%), extranodal NK/T-cell lymphoma, nasal type 281 cases (29.2%), anaplastic large cell lymphoma (ALCL) 198 cases (20.6%), and angioimmunoblastic T-cell lymphoma (AILT) 46 cases (4.8%). The male-to-female ratio was 1.99. The median age of the patients was 44 years, with the peak age of PTCL, NOS, extranodal NK/T-cell lymphoma, nasal type and AILT being 55 to 64 years, 25 to 54 years and 65 to 74 years, respectively. ALK-positive ALCL occurred more frequently in young age, while the ALK-negative ALCL cases occurred mainly in the elderly.

CONCLUSIONSExtranodal lesions predominate in mature T-cell and NK/T-cell lymphomas occurring in Guangzhou area. There is a male predominance and the overall incidence shows no increasing trend with age of the patient. The peak age of various subtypes however varies. The most common subtype was PTCL, NOS, followed by extranodal NK/T-cell lymphoma, nasal type, ALCL and AILT. The relatively frequent occurrence of extranodal NK/T-cell lymphoma, nasal type in Guangdong area is likely associated with the high incidence of Epstein-Barr virus infection there.

Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; Epstein-Barr Virus Infections ; Female ; Humans ; Immunoblastic Lymphadenopathy ; metabolism ; pathology ; virology ; Infant ; Lymphoma, Extranodal NK-T-Cell ; metabolism ; pathology ; virology ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; virology ; Lymphoma, T-Cell ; classification ; metabolism ; pathology ; virology ; Lymphoma, T-Cell, Peripheral ; metabolism ; pathology ; virology ; Male ; Middle Aged ; Protein-Tyrosine Kinases ; metabolism ; Receptor Protein-Tyrosine Kinases ; Retrospective Studies ; Sex Factors ; World Health Organization ; Young Adult

BACKGROUNDSome single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha gene have been reported to be associated with type 2 diabetes in different populations, and studies on Chinese patients yielded controversial results. The objective of this case-control study was to explore the relationship between SNPs of PGC-1alpha and type 2 diabetes in the southern Chinese population and to determine whether the common variants: Gly482Ser and Thr394Thr, in the PGC-1alpha gene have any impacts on interaction with myocyte enhancer factor (MEF) 2C.

METHODSThe SNPs in all exons of the PGC-1alpha gene was investigated in 50 type 2 diabetic patients using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and direct sequencing. Thereafter, 263 type 2 diabetic patients and 282 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A bacterial two-hybrid system and site-directed mutagenesis were used to investigate whether Gly482Ser and Thr394Thr variants in the PGC-1alpha gene alter the interaction with MEF2C.

RESULTSThree frequent SNPs (Thr394Thr, Gly482Ser and Thr528Thr) were found in exons of the PGC-1alpha gene. Only the Gly482Ser variant had a different distribution between diabetic patients and healthy subjects, with the 482Ser allele more frequent in patients than in controls (40.1% vs 29.3%, P < 0.01). Even in controls, the 482Ser (A) carriers were more likely to have higher levels of total cholesterol and low-density lipoprotein cholesterol than the 482Gly (G) carriers. The 394A-482G-528A haplotype was associated with protection from diabetes, while the 394A-482A-528A was associated with the susceptibility to diabetes. The bacterial two-hybrid system and site-directed mutagenesis revealed that the 482Ser variant was less efficient than the 482Gly variant to interact with MEF2C, whereas the 394Thr (A) had a synergic effect on the interaction between 482Ser variant and MEF2C.

CONCLUSIONSThe results suggested that the 482Ser variant of PGC-1alpha conferred the susceptibility to type 2 diabetes in the southern Chinese population. The underlying mechanism may be attributable, at least in part, to the altered interaction between the different variants (Gly482Ser, Thr394Thr) in the PGC-1alpha gene and MEF2C.

Aged ; Asian Continental Ancestry Group ; genetics ; China ; Diabetes Mellitus, Type 2 ; ethnology ; genetics ; Female ; Genotype ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; MEF2 Transcription Factors ; Male ; Middle Aged ; Myogenic Regulatory Factors ; metabolism ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Polymorphism, Single-Stranded Conformational ; Protein Binding ; Transcription Factors ; genetics ; metabolism

OBJECTIVETo study the differential expression of four TRAIL receptors on bone marrow mononuclear cells (BMMNC) from multiple myeloma (MM) patients and myeloma cell line KM3 cells, to compare their altered expressions after chemotherapy and to explore the mechanisms by which TRAIL selectively kills tumor cells.

METHODSSemi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry were used to investigate the expression of four TRAIL receptors on BMMNCs in 23 MM patients, KM3 cells and 15 controls, and the changes of their expression pattern after chemotherapy and after incubation of KM3 cells with sub-clinical concentration of doxorubicin.

RESULTSDR4 and DR5 were highly expressed on KM3 cells with no expression of DcR1 and DcR2. Expressions of DR4 and DR5 on BMMNCs from MM patients were higher and expression of DcR1 and DcR2 were lower than that of controls (P < 0.05). The expression of DR5 on MM and KM3 cells was up-regulated after chemotherapy and exposure to doxorubicin (P < 0. 05).

CONCLUSIONSThe expressions of four TRAIL receptors on myeloma cells and normal controls were different, which might account for the selective killing effect of TRAIL on MM cells. Up-regulated DR5 on KM3 cells after incubating with doxorubicin and after chemotherapy suggests the cytotoxic agents might enhance the apoptosis of MM cells.

Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cells, Cultured ; Doxorubicin ; pharmacology ; Female ; Flow Cytometry ; Gene Expression ; drug effects ; Humans ; Leukocytes, Mononuclear ; cytology ; drug effects ; metabolism ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; genetics ; pathology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction