Objective: There is controversy about the prognostic factors for early stage Hodgkin's lymphoma (HL). The aim of this study is to investigate the prognostic factors for HL at early stage. Methods: The clinical data from 188 patients were analyzed retrospectively. One hundred patients (53.2%) received radiotherapy (RT) alone and 88 cases (46.8%) received combined chemotherapy and radiotherapy. The 5-year and 10-year overall survival (OS) and disease-free survival (DFS) rates were estimated by Kaplan-Meier survival analysis with log-rank test. The prognostic factors were determined by COX proportional hazards model. Results: The 5-year and 10-year OS rates were 84.5% and 76.3% for patients who received radiotherapy alone, respectively; they were 96.2% and 96.2% for those patients who received combined chemotherapy and radiotherapy, respectively (P = 0.340). The 5-year and 10-year DFS rates were 84.7% and 76.9% for patients who received radiotherapy alone, respectively; they were 93.4% and 71.8% for patients who received combined therapy, respectively (P = 0.015). Univariate analysis indicated that tumor size and patients' age (with the cut-off of 40 years old) were the prognostic factors for predicting OS (P = 0.002 and 0.001) and DFS rate (P = 0.033 and 0.019). The pathological type had marginal significance in predicting OS rate (P = 0.072) and B symptoms had marginal significance in predicting DFS rate (P = 0.072). Multivariate analysis indicated that five factors including age (P =0.022), gender (P = 0.036), tumor size (P = 0.024), the drainage areas of involved lymph nodes (with the cut-off of 3 areas) (P = 0.060), and clinical stage (P = 0.028) had significance or marginal significance for predicting HL. Conclusion: Being more than 40 years old, male, clinical stage II, bulky disease, and the number of involved mediastinum and lymph node regions ≥3 are the independent prognostic factors for patients with early HL.

Objective To investigate the role of the 5-hydroxymethylcytosine (5-hmC) DNA modification in the onset of systemic lupus erythemosus (SLE),we compared tihe levels 5-hmC between SLE patients and normal controls.Methods With informed consent,whole blood was obtained from patients,and genomic DNA was extracted.Using hMeDIP-seq analysis and validation by quantitative real-time quantitative polymerase chain reaction (RT-PCR),we identified the differentially hydroxymethylated regions that were associated with SLE.Results There were 1 701 genes with significantly different 5-hmC levels at the promoter region in the SLE patients compared with the normal controls.The CpG islands of 3 826 genes showed significant difference at 5-hmC levels in SLE patients compared with the normal controls.Out of the differentially hydroxymethylated genes,three were selected for validation,including TREX1,CDKN1A,and CDKN1B.The hydroxymethylation levels of these three genes were confirmed by quantitative RT-PCR.Conclusion Our studies indicate that there are significant alterations of 5-hmC in SLE patients;these differentially hydroxymethylated genes may contribute to the pathogenesis of SLE.Such novel findings show the significance of 5-hmC as a potential biomarker or promising target for epigenetic-based SLE therapies.

Objective Light acts as an important zeitgeber and regulates the body's circadian rhythm.Excessive lighting at night leads to light pollution,which interferes with the circadian rhythm and thus adversely affects the body.To observe the adverse effect of continuous light on female reproductive endocrinology and explore effective treatment,the animal experiment was carried out.Methods 185 sexual maturity female SD rats in the age of 2 months with normal estrous cycle were enrolled.60 rats were selected randomly and enrolled into control group.Normal illumination conditions were given.The remaining rats were given 300±20lux light intensity for 24h/d last for 50 days to get reproductive rhythm disorder model.The model rats (100) were randomly divided into models group (n =50) and Traditional Chinese Medicine (TCM) group (n =50).Traditional Chinese Medicine group was treated with sequential TCM.At last we get 50 rats enrolled into model group and herbal group respectively.The TCM group rats were given therapy of nourishing yin and tonifying yang sequential TCM,while the two other groups were gavaged the same volume of physiological saline.The estrous cycle was observed in all groups.20 days later,blood were collected dynamically and E2 (estradiol),P (progesterone),LH (Luteinizing Hormone),FSH (Follicle-Stimulating Hormone)and melatonin were compared to evaluate the therapeutic effect of TCM.Finally,try to explain the mechanism of TCM's effect from the perspective of melatonin.Results At the first day,E2 was lower in TCM group and models group than control group (P＜ 0.05).At the second day,E2 was higher in traditional Chinese Medicine group than control group (9＜0.05).At the third day,E2 was higher in TCM group and models group than that in control group (P＜ 0.05).Progesterone in control group showed low level in pre-estrous and estrous period and elevated in the late stage of estrous.Progesterone showed no obvious change during the estrous cycle in TCM group and models group.At the third and fourth day,Progesterone was significantly lower in models group than TCM group and control group.At the first day,LH in models group [(249.8±50.2)mIU/mL] and TCM group [(83.4±37.3)mIU/mL] were significantly lower than control group [(430.0± 100.4)mIU/mL] (P＜0.05).At the first day,FSH in models group and TCM group were significantly lower than control group (P＜0.05).At the fourth day,FSH in TCM group was significantly lower than control group and models group (P＜0.05).Compared the melatonin among three groups,the circadian rhythm was high at night but low in the day in control group.The highest level was nearly 5 times higher than the lowest level.Neither the models group nor the TCM group had obvious recent rhythm changes.Conclusion Continuous light can induce disordered estrous cycle and loss of rhythm.Traditional Chinese Medicine can somehow induce circulation reconstruction.Continuous light can induce disordered endocrine,E2,FSH,LH surge abnormal,ovulation failure,luteal phase defect.TCM can induce ovulation and luteal support.Continuous light can destroy melatonin circadian rhythm and TCM can increase melatonin,which could be the mechanism of TCM's effect.

This study aims to construct inactivated coxsackievirus A16 (CVA16) vaccine and to investigate its protective effect in ICR mice. A clinical isolate of CVA16, 521-01T, was cultured in VERO cells, inactivated by formaldehyde, and purified by ultracentrifugation for vaccine preparation. Purity and other characteristics of the vaccine were determined by SDS-PAGE and Western blot. Female ICR mice were subcutaneously inoculated with inactivated CVA16 or Al(OH)3-absorbed CVA16, followed by booster immunization at the end of 2 and 4 weeks. CVA16-specific IgG titers in serum were determined by ELISA, and titers of neutralizing antibodies were determined by viral neutralization assay. The immunity of T lymphocytes was evaluated by IFN-gamma ELISPOT assay. The protective effect was evaluated by challenging the neonatal offspring (< 48 hours) of vaccinated female mice with 1 000 LD50 of CVA16 521-01T. The mortality rates of different groups were compared. The results showed that Al(OH)3 +CVA16 could induce high titers of specific IgG antibodies in ICR mice. After being boosted two times, the serum IgG antibody titer could reach up to 1 : 1 x 10(5) (P = 0.000), and neutralizing antibody titer was higher than 1 : 256. Additionally, more spot forming cells were induced in the immunized groups than in the negative controls. The maternal antibodies showed protective effect in 100% of the neonatal mice challenged with 1 000 LD50 of CVA16 521-01T. The inactivated CVA16 vaccine has ideal immunogenicity and immunoprotective effect. This research lays a foundation for the development and evaluation of CVA16 vaccines.
Animals ; Antibodies, Neutralizing ; immunology ; Antibodies, Viral ; immunology ; Enterovirus ; immunology ; Enterovirus Infections ; immunology ; prevention & control ; virology ; Female ; Humans ; Immunization ; Mice ; Mice, Inbred ICR ; T-Lymphocytes ; immunology ; virology ; Vaccines, Inactivated ; administration & dosage ; immunology ; Viral Vaccines ; administration & dosage ; immunology

INTRODUCTION: Non-vitamin K oral anticoagulants (NOACs) were shown to have better outcomes than warfarin for non-valvular atrial fibrillation (NVAF). Given limited local real-world data, this study aims to evaluate the safety and efficacy of NOACs versus warfarin for NVAF in Singapore. METHODS: This single-centre retrospective cohort study included 439 patients ≥ 21 years old that were newly prescribed with oral anticoagulants (OACs) for NVAF in 2015. Follow-ups for patients upon OAC initiation lasted either for 2 years or until the occurrence of bleeding or thromboembolism event or death (whichever was earlier). Primary endpoints included major bleeding and stroke, while secondary endpoints included overall bleeding and thromboembolic events. Time-to-events was evaluated via Kaplan-Meier survival analysis. Data on time in therapeutic range (TTR) and compliance were analysed. RESULTS: Patients were assigned to 4 groups: warfarin (157, 35.8%), rivaroxaban (154, 35.1%), apixaban (98, 22.3%) and dabigatran (30, 6.8%). With a mean age of 70.8 (±10.8) years old, the population were predominantly males (56.5%) and comprised Chinese (73.8%), Malays (18.7%) and others (7.5%). The rates of stroke per year were 0.7%, 1.7%, 2.2% and 0% for warfarin, rivaroxaban, apixaban and dabigatran, respectively ( CONCLUSION NOACs were associated with similar stroke and major bleeding rates as warfarin for NVAF.

The 1H-NMR fingerprints of three different species tibetan medicine sea buckthorn were established by 1H-HMR metabolomics to find out different motablism which could provide a new method for the quality evaluation of sea buckthorn. The obtained free induction decay (FID) signal will be imported into MestReNova software and into divide segments. The data will be normalized and processed by principal component analysis and.partial least squares discriminant analysis to perform pattern recognition. The results showed that 25 metabolites belonging to different chemical types were detected from sea buckthorn,including flavonoids, triterpenoids, amino acids, carbohydrates, fatty acids, etc. PCA and PLS-DA analysis showed three different varietiest of sea buckthorn that can be clearly separated by the content of L-quebrachitol, malic acid and some unidentified sugars, which can be used as the differences metabolites of three species of sea buckthorn. 1H-NMR-based metabonomies method had a holistic characteristic with sample preparation and handling. The results of this study can offer an important reference for the species identification and quality control of sea buckthorn.
Hippophae ; metabolism ; Magnetic Resonance Spectroscopy ; methods ; Medicine, Tibetan Traditional ; Metabolomics

Purpose: Emerging evidence from animal models suggests that intermittent hypoxia due to obstructive sleep apnea (OSA) is a risk factor for breast cancer. Despite their biological plausibility, human epidemiological studies have reported conflicting results. Therefore, we conducted a meta-analysis to delineate this relationship. Methods: We searched the PubMed, Embase, Scopus, and Cochrane Library databases for eligible studies from inception until June 6, 2021. Two reviewers selected randomized trials or observational studies reporting the association between OSA and breast cancer incidence compared with those without OSA. Two reviewers extracted relevant data and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and Newcastle-Ottawa Scale (NOS). We pooled the maximally covariate-adjusted hazard ratios (HRs) using a random-effects inverse varianceweighted meta-analysis and performed pre-specified subgroup analyses. Results: We included six studies out of 1,707 records, comprising a combined cohort of 5,165,200 patients. All studies used the International Classification of Diseases codes to classify OSA and breast cancer. OSA patients had a 36% increased breast cancer risk (HR, 1.36; 95% confidence interval [CI], 1.03–1.80; N = 6, I 2 = 96%) compared to those without OSA. Most studies adjusted for confounders, such as age, sex, obesity, diabetes mellitus, alcohol use, and hypertension. Subgroup analyses for studies with (1) multivariate adjustment and (2) at least five years of follow-up yielded HRs of 1.35 (95% CI, 0.98–1.87; N = 5, I 2 = 96%) and 1.57 (95% CI, 1.14–2.18; N = 4; I 2 = 90%), respectively. One Mendelian randomization study suggested a causal relationship, with a two-fold increase in the odds of breast cancer in patients with OSA. Conclusion This meta-analysis suggested that OSA is a risk factor for breast cancer. Future studies should explore the dose-response relationship between OSA and breast cancer, and whether treatment may mitigate breast cancer risk or progression.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide ; toxicity ; Carcinogens ; toxicity ; Cell Line, Tumor ; DNA Damage ; drug effects ; Dose-Response Relationship, Drug ; HSP70 Heat-Shock Proteins ; biosynthesis ; Humans

To analyze the epidemiological and etiological characteristics of Hand-Foot-and-Mouth disease (HFMD) in Shanghai in 2009, epidemiological data was retrieved from the National Notifiable Disease Report System (NNDRS). Nucleic acid of enterovirus (EV) was detected by real-time RT-PCR from 799 HFMD cases from 15 districts/counties in Shanghai; the complete sequences of VP1 encoding region of several identified EV71 strains and sequences of VP4 encoding region of several untyped EV were determined and analyzed. Analysis and summary of the epidemiological data was conducted with Microsoft Excel, and sequence analyses were conducted with both BioEdit and MEGA software. Untyped EV was identified through comparing the VP4 sequence to sequence database using BLAST online service. It was showed that all the 18 districts/counties had reported HFMD cases; children less than 6 years old were the most susceptible population group; the peak of epidemics of HFMD was from April to July; EV71 and Coxsackievirus A16 (CA16) were the major pathogens for this epidemic, but the constituent ratio of EV71 and CA16 was different in different months and regions; CA16 infection was mainly responsible for the mild HFMD, but EV71 for most of the severe cases; EV71 strains of Shanghai were clustered with representatives of subgenotype C4a and showed the highest identity to them, based on the sequence analyses of VP1 encoding region; 2 of the untyped EV were identified as CA2 and CA10 respectively. All the results indicated that EV71 and CA16 were the major pathogens for the epidemic of HFMD in Shanghai, 2009; the circulating EV71 belonged to subgenotype C4a. Besides, other types of EV (for example: CA2 and CA10) were also responsible for a few of the HFMD cases.
Adolescent ; Child ; Child, Preschool ; China ; epidemiology ; Enterovirus A, Human ; classification ; genetics ; isolation & purification ; Epidemics ; Female ; Hand, Foot and Mouth Disease ; epidemiology ; virology ; Humans ; Infant ; Male ; Molecular Sequence Data ; Phylogeny

OBJECTIVETo investigate the effect of bicyclol on vascular oxidative stress injury induced by superoxide anion.

METHODSRat thoracic aortic rings were isolated for isometric tension recording using organ bath technique. Superoxide arterial injury was induced by pyrogallol exposure, and the effect of bicyclol on endothelium-dependent relaxation was evaluated.

RESULTSBicyclol (10(-8) - 10(-5) mol/L) relaxed endothelium-intact aortic rings precontracted by phenylephrine. This effect was abolished by L-NAME, an inhibitor of nitric oxide synthase and indomethacin, an inhibitor of cyclooxygenase. Exposure to pyrogallol (500 micromol/L) resulted in decrease of acetylcholine(ACh)-induced endothelium-dependent relaxation in aortic rings, and pre-incubation of bicyclol (10(-5) mol/L) for 45 min improved the relaxation attenuated by pyrogallol. In aortic rings pre-treated with indomethacin, bicyclol increased the ACh-induced relaxation that was inhibited by pyrogallol (500 micromol/L). This effect was not found in aortic rings pre-treated with L-NAME.

CONCLUSIONBicyclol has endothelium-dependent vasodilating effect on rat thoracic aorta and improves vascular function by attenuating oxidative stress. Nitric oxide from endothelium is involved in the anti-oxidative effect of bicyclol.

Animals ; Antioxidants ; pharmacology ; Aorta, Thoracic ; metabolism ; physiology ; Biphenyl Compounds ; pharmacology ; Endothelium, Vascular ; physiology ; In Vitro Techniques ; Male ; Oxidative Stress ; drug effects ; Pyrogallol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Superoxides ; pharmacology ; Vasodilation ; drug effects ; physiology