Objective To investigate the response of multiple myeloma (MM) cells to 8-chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) and the impact of arsenic trioxide (As2O3) on the above reaction.Methods MM-derived cell lines RPMI8226 and U266 were used as in vitro models.Cell apoptosis was evaluated according to cellular morphology and DNA content measured by flow cytometry.Meanwhile,rhodamine 123 (Rh123) staining and flow cytometry assay were used to detect the changes of mitochondrial transmembrane potentials (△ψm) in MM cells before and after the treatment.The synergic effects of 8-Cl-cAMP and As2O3 were evaluated by King' s formula.Results The 8-Cl-cAMP could induce growth inhibition of RPMI8226 and U266 cells in dose and time-related manners.The 8-Cl-cAMP could trigger apoptosis and △ψm collapse in MM cells through cellular morphology and flow cytometry analysis.As2O3 accelerated 8-Cl-cAMP-mediated apoptosis of RPMI8226 cells,but there were few synergic effects observed.Conclusion 8-Cl-cAMP could induce cell proliferation inhibition and apoptosis in MM cells.Mitochondria may be one of targets in 8-Cl-cAMP-mediated apoptosis.Furthermore,As2O3 catalyzes 8-Cl-cAMP-induced apoptosis.

This paper is to explore changes of intestinal mucosal barrier, intestinal flora, and bacterial translocation in rats with severe acute pancreatitis (SAP). Twenty four male SD rats were randomly divided into the control group (n = 10) and the experimental group (n = 14). The model of severe acute pancreatitis of rats was induced by the method of injecting adversely 5% sodium taurocholate into the common biliary-pancreatic duct. All of the rats were killed after 24 hours and the level of the serum amylase and the plasma endotoxin was determined after that. The pathological changes of pancreas and small intestine were observed through hematoxylin-eosin staining (HE staining) and the abdominal viscera bacterial translocation rates were tested. With the method of real-time polymerase chain reaction (RT-PCR) the quantity of the intestinal flora was analyzed. In the control group, the level of Escherichia coli, Lactobacillus and Bifidobacterium were 2.08 ± 1.29, 11.04 ± 7.55 and 12.21 ± 4.95, respectively. On the contrast, the level of Escherichia coli in the cecum contents was much higher (9.72 ± 3.58, P < 0.01), while the Lactobacillus number was decreased significantly (0.67 ± 0.34, P < 0.01), and the Bifidobacterium number was also decreased (4.59 ± 3.42, P < 0.05) in the experimental group, so the ratio of Bifidobacterium/Escherichia coli was reversed. Besides, in the experimental group, the plasma endotoxin positive rates and the bacterial translocation rates were much higher (P < 0.01 or P < 0.05) and the pathology scores of pancreas and small intestines were also significantly higher (P < 0.01) than those in the control group. These results indicated that in severe acute pancreatitis rats, the intestinal mucosal barrier was severely damaged and the dysbacteriosis occurs in the intestinal canal. And these might relate to the occurrence and development of multiple organ infection.
Animals ; Bacterial Translocation ; Endotoxins ; Intestinal Mucosa ; pathology ; Intestines ; microbiology ; Male ; Pancreas ; pathology ; Pancreatitis ; microbiology ; pathology ; Rats ; Rats, Sprague-Dawley

Objective To investigate the effects of arsenic trioxide (AS2O3)on SOCS-1 gene methylation and expression of P-STAT3 in multiple myeloma (MM) cells.Methods MM cell lines U266 and CZ-1 were used as in vitro models.Methylation status of SOCS-1 gene was detected by the methylation specific PCR (MSP)while P-STAT3 protein expression was determined by Western blotting assay before and after AS2O3 treatment.Meanwhile growth inhibition and apoptosis of MM cells were determined by flow cytometry.Results Hypermethylation of SOCS-1 gene was observed in each MM cell line compared with wide type.After exposure to AS2O3,it was shown that SOCS-1 gene was demethylated obviously,meanwhile the expression level of P-STAT3 protein and cell proliferation was inhibited significantly in each cell line.The apoptosis rate was increased.When U266 and CZ-1 were treated with AS2O3 of 0,0.5,1.0,2.0 μmol/L respectively,the total cell apoptosisis ratio of U266 was 0.06％,0.56％,48.96％,61.07％ (X2 =9.19,P ＜ 0.05); and the total cell apoptosisis ratio of CZ-1 was 4.2％,,40.3％,,47.72％,,68.49％ (X2 =8.96,P ＜0.05 ).Conclusion AS2O3 could inhibit JAK/STAT signal transduction pathway by inducing SOCS-1 gene demethylation in MM cells which might be related to cell apoptosis.

10.3969/j.issn.1007-3969.2013.04.010

Background and purpose:Herpes zoster is a common adverse event associated with the use of bortezomib. The objective of this study was to evaluate the efifcacy of different therapeutic regimens of valacyclovir prophylaxis: continuously administration and intermittent administration. Methods: We retrospectively analyzed the efficacy, side effects, expense of valacyclovir and emotional states of 31 patients with multiple myeloma who received bortezomib and valacyclovir prophylaxis. Among them, 14 patients underwent continuously administration of valacyclovir, the other 17 patients underwent intermittent administration. Continuously administration was deifned as daily oral valacyclovir 600 mg without cessation during entire period of bortezomib treatment. Intermittent administration was deifned as patients received valacyclovir at a dose of 600 mg daily during chemotherapy, while discontinue valacyclovir at the intermission time of bortezomib treatment. Results: There were no herpes zoster in patients of 2 arms. Adverse events over grade 3 associated with valacyclovir were not observed. Intermittent administration of valacyclovir showed a superiority of economic beneift. The emotional status were depended on the therapeutic effects of multiple myeloma. For those relapsed or refractory patients, continuously administration of valacyclovir might aggravate depression and anxiety. Conclusion:Intermittent administration of valacyclovir at a dose of 600 mg daily appears to be an effective prophylaxis for herpes zoster in patients receiving bortezomib.

Objective To evaluate the efficacy of pegaspargase (PEG-ASP) combined with GEMOX regimen for the treatment of extranodal natural killer (NK) / T-cell lymphoma (ENKL),and to observe the changes of coagulation function.Methods 35 patients with histologically confirmed ENKL were enrolled from January 2010 to December 2014.All patients received 180 cycles of PEG-ASP combined with GEMOX chemotherapy and the efficacies were observed.The coagulation items such as prothrombin time (PT),activated partial thromboplastin time (APTT),fibrinogen (Fbg) and international normalized ratio (INR) were tested respectively on day 1st,day 8th and day 14th of every treatment cycle.Results Among 35 patients,11 patients (31.43 ％) were in stage Ⅰ-Ⅱ,and 24 patients (68.57 ％) were in stage Ⅲ-Ⅳ.All patients were subjected to 180 cycles of PEG-ASP combined with GEMOX chemotherapy,and each case was estimated to receive 6 cycles.The overall response (CR+PR) rate (ORR) was 71.43 ％ (25/35),the ORR was 81.82 ％ (9/11) in stage Ⅰ-Ⅱ group,and 66.67 ％ (16/24) in stage Ⅲ-Ⅳ group.The increased PT and APTT and decreased Fbg were observed on day 8th of the chemotherapy.The increased APTT and decreased Fbg were still observed on day 14th of the chemotherapy.Compared the data of patients one day before chemotherapy with healthy persons,the changes had statistical significance (P ＜ 0.05).Conclusions PEG-ASP combined with GEMOX regimen in the treatment of ENKL is safer and more effective compared with traditional chemotherapy,but the abnormal alternations of coagulation might be common during therapy.Dealing with the bleeding risk and supplement with plasma,PPSB or Fbg in time should be necessary.

Thyroid hormone plays pivotal roles in growth, differentiation, development and metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the expression of TR target genes. The transcriptional activity of TRs is modulated by multiple factors including various TR isoforms, diverse thyroid hormone response elements, different heterodimeric partners, coregulators, and the cellular location of TRs. In the present review, we summarize recent advance in understanding the molecular mechanisms of thyroid hormone action obtained from human subject research, thyroid hormone mimetics application, TR isoform-specific knock-in mouse models, and mitochondrion study with highlights in metabolic regulations. Finally, as future perspectives, we share our thoughts about current challenges and possible approaches to promote our knowledge of thyroid hormone action in metabolism.
Animals ; Gene Knockout Techniques ; Humans ; Mice ; Mitochondria ; metabolism ; Protein Isoforms ; genetics ; metabolism ; physiology ; Receptors, Thyroid Hormone ; metabolism ; Thyroid Diseases ; metabolism ; pathology ; Thyroid Hormones ; genetics ; metabolism ; physiology

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

Objective:To understand sexual needs and factors of risky sexual behaviors among elderly men at different ages in two communities of Qiandongnan Miao and Dong autonomous prefecture and provide basis for targeted HIV prevention and intervention.Methods:Two communities in the prefecture were selected as study sites. Questionnaire surveys were carried out among elderly men aged 50 and over who visited or consulted in the communities from June to December 2018, and they were tested for HIV and syphilis antibodies.Results:Among 400 elderly men, 209 (52.2%) were 50-64 years old, and 191(47.8%) were above 65 years old. They were mainly Miao people, accounting for 66.3% (265/400), and 235 (58.8%) had an education no more than 6 years. HIV awareness of the two age groups were only 25.8% (54/199) and 26.2% (50/191), respectively. Among those aged 50-64, 142 (68.0%) felt normal sexual desire, and 153 (73.6%) reported penile erections or erections in most cases whenever sex, and 52.9% (110) ejaculated most of the time. HIV prevalence was 1.0% (4/400). Compared with the over 65-year-old group, the proportion of having sex with spouse/stable partners (89.5%, 179/200), proportion of no condom use with their spouse/stable sexual partners during the most recent sex (93.8%, 168/179), proportion of having casual sex (11.0%, 23/209) and commercial sex (3.8%, 8/209) were all higher among 50-64 age group. In comparison to those aged over 65 years old, average monthly income>3 000, and use of sex helper, aged 50-64 ( OR=2.70, 95% CI: 1.22-5.95), average monthly income ≤1 000 yuan ( OR=2.79, 95% CI: 1.25-6.21), and no use of sex helper ( OR=3.78) (95% CI: 1.65-8.67) were related factors of HIV risky sexual behavior last time. Conclusion:Elderly men in the minority prefecture had low HIV awareness. Compared with those≥65 years old, the 50-64 age group had more active sexual behaviors and higher sexual needs. Those from 50-64 age group, with lower economic level and good sexual ability were more likely to have HIV risky sexual behaviors.

Objective:To understand sexual needs and factors of risky sexual behaviors among elderly men at different ages in two communities of Qiandongnan Miao and Dong autonomous prefecture and provide basis for targeted HIV prevention and intervention.Methods:Two communities in the prefecture were selected as study sites. Questionnaire surveys were carried out among elderly men aged 50 and over who visited or consulted in the communities from June to December 2018, and they were tested for HIV and syphilis antibodies.Results:Among 400 elderly men, 209 (52.2%) were 50-64 years old, and 191(47.8%) were above 65 years old. They were mainly Miao people, accounting for 66.3% (265/400), and 235 (58.8%) had an education no more than 6 years. HIV awareness of the two age groups were only 25.8% (54/199) and 26.2% (50/191), respectively. Among those aged 50-64, 142 (68.0%) felt normal sexual desire, and 153 (73.6%) reported penile erections or erections in most cases whenever sex, and 52.9% (110) ejaculated most of the time. HIV prevalence was 1.0% (4/400). Compared with the over 65-year-old group, the proportion of having sex with spouse/stable partners (89.5%, 179/200), proportion of no condom use with their spouse/stable sexual partners during the most recent sex (93.8%, 168/179), proportion of having casual sex (11.0%, 23/209) and commercial sex (3.8%, 8/209) were all higher among 50-64 age group. In comparison to those aged over 65 years old, average monthly income>3 000, and use of sex helper, aged 50-64 ( OR=2.70, 95% CI: 1.22-5.95), average monthly income ≤1 000 yuan ( OR=2.79, 95% CI: 1.25-6.21), and no use of sex helper ( OR=3.78) (95% CI: 1.65-8.67) were related factors of HIV risky sexual behavior last time. Conclusion:Elderly men in the minority prefecture had low HIV awareness. Compared with those≥65 years old, the 50-64 age group had more active sexual behaviors and higher sexual needs. Those from 50-64 age group, with lower economic level and good sexual ability were more likely to have HIV risky sexual behaviors.