Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-alpha-producing antigen-presenting cells

OBJECTIVE: To explore whether there are extrinsic factors that impair the suppressive function of CD4+,CD25+ regulatory T cells in patients with untreated active systemic lupus erythematosus (SLE). METHODS: We studied 15 patients with untreated active SLE, 10 patients with SLE in remission, and 15 healthy control subjects. Percentages of CD4+,CD25+,FoxP3+ Treg cells and levels of forkhead box P3 (FoxP3) protein were analyzed by flow cytometry. Expression of messenger RNA (mRNA) for FoxP3 in purified Treg cell populations was assessed by real-time polymerase chain reaction analysis. Experiments examining Treg cell function in SLE were designed to distinguish primary from secondary T cell dysfunction. Levels of interferon-alpha (IFNalpha) in supernatants from the function assays were determined with an IFN-stimulated response element-luciferase reporter assay. RESULTS: The percentage of CD4+,CD25+, FoxP3+ cells in peripheral blood was significantly increased in SLE patients as compared with controls (mean +/- SEM 9.11 +/- 0.73% versus 4.78 +/- 0.43%; P < 0.0001). We found no difference in FoxP3 expression at either the mRNA or protein level in any CD4+,CD25+ T cell subset from SLE patients as compared with controls. Antigen-presenting cells (APCs) from SLE patients were responsible for decreased Treg cell activity and could also render dysfunctional Treg cells from healthy control subjects. CD4+,CD25+ Treg cells from SLE patients exhibited normal suppressive activity when cultured with APCs from healthy controls. A partial Treg cell blockade effect was induced by the high levels of IFNalpha derived from SLE patient APCs. CONCLUSION: We suggest that blockade of Treg cell-mediated suppression by IFNalpha-producing APCs in SLE patients may contribute to a pathogenic loss of peripheral tolerance in this disease.     

Comparative analysis of Behcet's disease in the APLAR region

Aims: Behcet's disease (BD) was originally a disease of the Silk Road. Some authors think that BD from the Silk Road is different from those seen in other countries. The aim of this study was to analyze the clinical manifestations of BD in APLAR countries, where some of them are in the Silk Road (SR) and some others not (NSR). Methods: Data from Australia (NSR), Hong Kong (NSR), India (SR), Iran (SR), and Singapore (SR) were selected and analyzed under the same protocol. Prior published data from China (SR) Japan (SR) and Korea (SR) were included in the analysis. Results: The mean age at the onset of the disease was under 30 for all countries except Japan and Singapore. The male gender was more frequent except in Australia and Korea. Oral aphthosis was the most frequent manifestation (90–100%). Genital aphthosis was less frequent (57–82%). Skin manifestations were also frequent (61–87%). Ocular manifestations were reported from 21–69% of patients. The difference was mainly due to patients’ selection bias and the low number of patients in some reports. The same was true for joint (30–87%), gastrointestinal (6–38%), neurological (2.5–29%) and vascular manifestations (5–28%). Conclusion: Despite the percentage difference among some countries, the general pattern of the disease was the same, suggesting that the minor differences seen in different parts of the world were not enough to call the disease a syndrome, or to differentiate Behcet's disease of the Silk Road from those seen in Western countries.     

Solvent-assisted thermal reduction of microcrystalline graphene oxide with excellent microwave absorption performance

To prepare a new kind of electromagnetic wave absorber, and improve the processing technology and accessional value of natural microcrystalline graphite minerals (NMGMs), reduced microcrystalline graphene oxide (rGO-M), a novel absorber with high absorption, low reflection and a wide absorption band, was prepared from NMGMs using a solvent-assisted thermal reduction method. Moreover, the as-produced rGO-M with adjustable electrical resistivity can be easily transferred into well distributed bulk materials by freeze-drying technology. These unique structures and compositions make a great contribution to the impedance match, and cause strong conductive loss and various dipole polarization effects which greatly enhance the absorption. Meanwhile, the effective bandwidths below −5 dB and −10 dB are 11.7 GHz and 3.32 GHz respectively, and the reflection loss can reach −42.68 dB. The study will be beneficial to the development of carbon resources and carbon materials research. Besides, it can provide a scientific basis for the further improvement of the comprehensive utilization and the level of deep processing technology of NMGM resources.

Reduced microcrystalline graphene oxide (rGO-M), a novel absorber with high absorption, low reflection and a wide absorption band, was prepared from NMGMs using a solvent-assisted thermal reduction method.     

Design,synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity,cell cycle arrest and apoptotic response

A series of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives (3a₁−3d₆) were designed and synthesized as antitumor agents. In vitro antitumor assay results showed that some compounds exhibited moderate to high inhibitory activities against HepG2, SK-OV-3, NCI-H460 and BEL-7404 tumor cell lines, and most compounds exhibited much lower cytotoxicities against HL-7702 normal cell line compared to 5-FU and cisplatin. In vivo antitumor assay results showed that the representative compound 3a₁ exhibited effective inhibition on tumor growth in the HepG2 xenograft mouse model. Mechanistic studies suggested that 3a₁ may exert antitumor activity by the up-regulation of Bax, intracellular Ca²⁺ release, ROS generation, p21, p27 and p53, downregulation of Bcl-2, activation of caspase-9 and caspase-3 and subsequent cleavage of PARP, and inhibition of CDK activity.

A series of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives were designed and synthesized as antitumor agents under the combination principle. The antitumor activity and mechanisms were then evaluated.     

内皮素对妊娠与分娩的影响

用放射免疫法测定81例妇女血浆及羊水内反素-1(ET-1)和前列腺素E_2(PGF_2)的含量,其中第二产程妇女20例、潜伏期14例、正常晚孕15例、期妊娠10例、产后期12例.正常非孕10例为对照组.结果第二产程、潜伏期、正常晓孕期、中期妊娠组血浆ET-1含量均显著高于非孕及产后期妇女,且随妊娠及产程的进展而逐渐增高,至第二产程达高峰,产后迅速降至非孕时水平.各孕产期羊水ET-1及PGE_2的含量显著高于血浆ET-1及PGE_2的含量.血浆及羊水PGE_2浓度随ET-1含量的增减而变化,两者呈显著正相关.提示血浆及羊水ET-1水平随妊娠的进展而增加,促使足月妊娠子宫产生收缩,ET-1还可通过刺激前列腺素E_2的生成而在分娩的发动与分娩的维持中起重要作用.     

Proton pump inhibitors versus histamine-2 receptor blockers for stress ulcer prophylaxis in patients with sepsis: a retrospective cohort study

ObjectiveWe aimed to compare the efficacy and risks of proton pump inhibitor (PPI) versus histamine-2 receptor blocker (H2B) use for stress ulcer prophylaxis (SUP) in critically ill patients with sepsis and risk factors for gastrointestinal bleeding (GIB).MethodsIn this retrospective cohort study, we used the Medical Information Mart for Intensive Care III Clinical Database to identify critically ill adult patients with sepsis who had at least one risk factor for GIB and received either an H2B or PPI for ≥48 hours. Propensity score matching (PSM) was conducted to balance baseline characteristics. The primary outcome was in-hospital mortality.ResultsAfter 1:1 PSM, 1056 patients were included in the H2B and PPI groups. The PPI group had higher in-hospital mortality (23.8% vs. 17.5%), GIB (8.9% vs. 1.6%), and pneumonia (49.6% vs. 41.6%) rates than the H2B group. After adjusting for risk factors of GIB and pneumonia, PPI use was associated with a 1.28-times increased risk of in-hospital mortality, 5.89-times increased risk of GIB, and 1.32-times increased risk of pneumonia.ConclusionsAmong critically ill adult patients with sepsis at risk for GIB, SUP with PPIs was associated with higher in-hospital mortality and higher risk of GIB and pneumonia than H2Bs.     

The change of insulin levels after six weeks antidepressant use in drug-naïve major depressive patients

Background

A reciprocal relationship between diabetes risk and depression has been reported. There are few studies investigating glucose–insulin homeostasis before and after short-term antidepressant treatment in drug-naïve major depressive disorder (MDD) patients.

Methods

This study included 104 healthy controls and 50 drug-naïve MDD patients diagnosed according to the DSM-IV criteria. These MDD patients were randomly assigned to receive fluoxetine or venlafaxine for six weeks. Depressive symptoms, body mass index, fasting plasma levels of glucose and insulin were measured.

Results

Compared to the healthy controls, the fasting plasma insulin and the homeostasis model of assessment for pancreatic β-cell secretory function (HOMA-β) was significantly lower in the MDD patients before antidepressant treatment (7.7±4.8 μIU/mL vs. 5.1±4.2 μIU/mL, p=0.006; 114.2±72.3% vs. 74.8±52.0%, p=0.005, respectively). However, these indices were not correlated with depression severity. After 6 weeks of fluoxetine or venlafaxine treatment, the level of HOMA-β borderline significantly increased (108.1±75.5%, p=0.059).

Limitations

The study was limited by the follow-up duration and lack of a placebo group.

Conclusions

Antidepressants might affect insulin secretion independently of the therapeutic effects on MDD. Further studies are needed to investigate the long-term effects of antidepressants on insulin regulation in MDD patients.     

Mental Health Multimorbidity among Caregivers of Older Adults During the COVID-19 Epidemic

ObjectiveTo investigate mental health status and associated factors among caregivers of older adults during the COVID-19 epidemic in China.MethodsFrom March 1 to 31, 2020, 916 caregivers of older adults participated in an online cross-sectional survey on the prevalence of anxiety, depression, and sleep problems. The seven-item Generalized Anxiety Disorder Scale (GAD-7) was administered to measure anxiety symptoms, the two-item Patient Health Questionnaire (PHQ-2) was used to assess depressive symptoms, and a self-developed questionnaire was used to assess sleep quality and duration. Six questions about COVID-19-related experiences were used to assess community-level infection contact and the level of exposure to media information. The prevalence rates of anxiety, depression and sleep problems were computed. The Wald χ² were applied to compare the differences between subgroups. Multiple logistic regression analyses were performed to investigate factors associated with anxiety, depression, sleep problems, and multimorbidity.ResultsThe prevalence rates of anxiety, depression, and sleep problems were 46.8%, 29.8%, and 10.8%, respectively. Approximately 263 participants (28.7%) presented with two or more mental health problems. Being female (OR, 2.254; 95% CI, 1.510–3.363), having community-level COVID-19 contact (OR, 1.856; 95% CI, 1.189–2.898), and having a mental disorder (OR, 3.610; 95% CI, 1.644–7.930) were associated with increased risk of multimorbidity among caregivers. Caregivers who preferred positive information (OR, 0.652; 95% CI, 0.472–0.899) had reduced risk of multimorbidity.ConclusionAnxiety and depression were common among caregivers of older adults during the COVID-19 epidemic. Being female and having community-level COVID-19 contact were independent risk factors for experiencing multiple mental health problems. Preexisting mental disorders increased the risk of multimorbidity among caregivers, while enhanced access to positive media information decreased the risk of multimorbidity.     

Clinical and genetic analysis of six Chinese children with Poirier-Bienvenu neurodevelopmental syndrome caused by CSNK2B mutation

neurogenetics - Mutations in CSNK2B lead to Poirier-Bienvenu neurodevelopmental syndrome (POBINDS), a rare neurodevelopmental disorder. Only 14 cases of POBINDS have been reported worldwide. The...