Reliability and validity of the Chinese version of the Information Security Attitude Questionnaire for nurses.

AIM: Nurses play a crucial role within medical institutions, maintaining direct interaction with patient data. Despite this, there is a scarcity of tools for evaluating nurses' perspectives on patient information security. This study aimed to translate the Information Security Attitude Questionnaire into Chinese and validate its reliability and validity among clinical nurses. DESIGN: A cross-sectional design. METHODS: A total of 728 clinical nurses from three hospitals in China participated in this study. The Information Security Attitude Questionnaire (ISA-Q) was translated into Chinese utilizing the Brislin two-way translation method. The reliability was assessed through internal consistency coefficient and test-retest reliability. The validity was determined through the Delphi expert consultation method and factor analysis. RESULTS: The Chinese version of ISA-Q consists of 30 items. Cronbach's α coefficient of the questionnaire was 0.930, and Cronbach's α coefficient of the six dimensions ranged from 0.781 to 0.938. The split-half reliability and test-retest reliability were 0.797 and 0.848, respectively. The content validity index (S-CVI) was 0.962. Exploratory factor analysis revealed a 6-factor structure supported by eigenvalues, total variance interpretation, and scree plots, accounting for a cumulative variance contribution rate of 69.436%. Confirmatory factor analysis further validated the 6-factor structure, demonstrating an appropriate model fit. CONCLUSION: The robust reliability and validity exhibited by the Chinese version of ISA-Q establish it as a dependable tool for evaluating the information security attitudes of clinical nurses. IMPLICATIONS FOR NURSING PRACTICE: The Chinese iteration of the ISA-Q questionnaire offers a profound insight into the information security attitudes held by clinical nurses. This understanding serves as a foundation for nursing managers to develop targeted intervention strategies aimed at fortifying nurses' information security attitudes, thereby enhancing patient safety.

Psychometric evaluation of the Chinese version of the burnout syndrome assessment scale in nurses.

Objective: This study aimed to translate the Burnout Syndrome Assessment Scale (BOSAS) into Chinese and validate its reliability and validity among Chinese emergency department and ICU nurses. Methods: The scale was translated into Chinese using Brislin's translation principle. A total of 626 nurses from Jiangxi, Zhejiang, and Fujian provinces in China participated in an online questionnaire survey. The survey included the general information questionnaire for nurses developed by the research team and the Chinese version of the Burnout Syndrome Assessment Scale. Reliability and validity of the Chinese version of the scale were analyzed using SPSS.25 and AMOS.24 software. Results: The Chinese version of the Burnout Syndrome Assessment Scale consists of a total of 20 items, encompassing two dimensions: personal burnout and job burnout. This structure is consistent with the original English version of the scale. The Chinese version of BOSAS demonstrated high internal consistency, with a Cronbach's α coefficient of 0.941. Additionally, the scale exhibited good split-half reliability (0.765) and test-retest reliability (0.871). The content validity index (S-CVI) was 0.971, indicating strong content validity. Exploratory factor analysis confirmed the same 2-factor structure as the original scale, and confirmatory factor analysis further validated this structure, with all fit indices indicating appropriateness. Conclusion: The Burnout Syndrome Assessment Scale has been successfully introduced and its reliability and validity have been verified in Chinese emergency department and ICU nurses.

Relationship Between Gout And Constitution Of Traditional Chinese Medicine.

Objective: The objective of this study was to explore common TCM constitutions among gout patients and investigate the potential relationship between traditional Chinese medicine's (TCM) constitution and clinical parameters. Methods: A total of 219 gout patients with 195 participants were included in this study. All participants completed a baseline questionnaire on demographic characteristics, including age, weight, and family history. The biased constitution of TCM was identified by questionnaires surveyed with a TCM constitution table. Results: Of 195 patients with gout, phlegm-damp accounted for the majority of TCM constitution classifications, followed by Qi-deficiency, damp-heat, and Yang-deficiency constitutions. Besides, patients with these four constitutions have a higher BMI, blood sugar, and homocysteine. Conclusion: The major types of constitution among these gout patients were phlegm-damp, Yang-deficiency, Qi-deficiency, and damp-heat. Gout symptoms with TCM constitutional theory may contribute to provide new insights into more rapid diagnosis and treatment for the effective prevention or therapy of gout. It is necessary to design more case-control studies and high-quality cohort in the future researches to provide a more helpful evidence-based basis for evaluating the relationship between TCM constitution and gout patients.

Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation.

Heterologous organ transplantation is an effective way of replacing organ function but is limited by severe organ shortage. Although generating human organs in other large mammals through embryo complementation would be a groundbreaking solution, it faces many challenges, especially the poor integration of human cells into the recipient tissues. To produce human cells with superior intra-niche competitiveness, we combined optimized pluripotent stem cell culture conditions with the inducible overexpression of two pro-survival genes (MYCN and BCL2). The resulting cells had substantially enhanced viability in the xeno-environment of interspecies chimeric blastocyst and successfully formed organized human-pig chimeric middle-stage kidney (mesonephros) structures up to embryonic day 28 inside nephric-defective pig embryos lacking SIX1 and SALL1. Our findings demonstrate proof of principle of the possibility of generating a humanized primordial organ in organogenesis-disabled pigs, opening an exciting avenue for regenerative medicine and an artificial window for studying human kidney development.

The gene spectrum of thalassemia in Yangjiang of western Guangdong Province.

Background: Thalassemia presents a higher incidence in southern China. The objective of this study is to analyze the genotype distribution of thalassemia in Yangjiang, a western city of Guangdong Province in China. Methods: The genotypes of suspected cases with thalassemia were tested by PCR and reverse dot blot (RDB). Unidentified rare thalassemia genotypes of the samples were further ascertained by PCR and direct DNA sequencing. Results: Among 22467 suspected cases with thalassemia, 7658 cases were found with thalassemia genotypes using our PCR-RDB kit. Among these 7658 cases, 5313 cases were found with α-thalassemia (α-thal) alone, --SEA/αα was the most common genotype, accounting for 61.75% of α-thal genotypes, and the following mutations were found: α3.7/αα, -α4.2/αα, αCSα/αα, αWSα/αα, and αQSα/αα. A total of 2032 cases were found with ß-thalassemia (ß-thal) alone. ßCD41-42/ßN, ßIVS-II-654/ßN, and ß-28/ßN accounted for 80.9% of all ß-thal genotypes, and the following genotypes were found: ßCD17/ßN, ßCD71-72/ßN, and ßE/ßN. Compound heterozygotes of ß-thal and ß-thalassemia homozygotes were identified in 11 and five cases, respectively, in this study. α-thal combined with ß-thal was identified in 313 cases, showing 57 genotype combinations of the coincidence of both Hb disorders; one extreme patient had a genotype of --SEA/αWSα and ßCD41-42/ß-28. In addition, four rare α-mutations (--THAI, HKαα, Hb Q-Thailand, and CD31 AGG>AAG) and six rare ß-mutations (CD39 CAG>TAG, IVS-Ⅱ-2 (-T), -90(C>T), Chinese Gγ+(Aγδß)0, CD104 (-G), and CD19 A>G) were also found in this study population. Conclusion: This study provided detailed genotypes of thalassemia in Yangjiang of western Guangdong Province in China and reflected the complexity of genotypes in this high-prevalence region, and this would be valuable for diagnosis and counseling for thalassemia in this area.

Depletion of iNOS-positive inflammatory cells decelerates neuronal degeneration and alleviates cerebral ischemic damage by suppressing the inflammatory response.

Ischemic stroke leads to neuronal damage and severe inflammation that activate iNOS expression in different cell types, especially inflammatory cells in the brain. It is shown that NO released from iNOS contributes to the pathological development of cerebral ischemia. However, the role of these iNOS-expressing inflammatory cells in ischemic stroke has not been fully elucidated. Our purpose is to test if ischemia-induced iNOS+ inflammatory cells may exaggerate cerebral inflammation to exacerbate neuronal deficit. We studied the dynamics of iNOS+ cells after stroke and found an early and sustained iNOS expression at lesion site. Since iNOS is highly expressed in inflammatory cells after injury, we depleted the iNOS + inflammatory cells via the selective scavenger GdCl3, and investigated its effect on stroke outcome, neuronal and vascular deficit, and inflammatory response. After GdCl3 treatment, half of iNOS+ inflammatory cells were depleted, including mainly activated microglia/macrophages and some astrocytes. Selective depletion of iNOS+ inflammatory cells resulted in a pronounced reduction in brain damage, resulting in improvement of motor ability. Histologic studies and in vivo two-photon imaging data revealed a slowdown of neuronal degeneration after the depletion of iNOS+ inflammatory cells. In contrast to iNOS inhibition alone, depletion of iNOS+ inflammatory cells profoundly altered the immune microenvironment profile, in addition to reducing NO production. qRT-PCR analysis showed that depletion of iNOS+ inflammatory cells significantly restrained the production of pro-inflammatory cytokines, which moderated the immune microenvironment at the lesion site. Taken together, our data demonstrate that depleting iNOS+ inflammatory cells prevents neuronal damage not only by inhibiting NO, but also importantly by suppressing the inflammatory response, which is beneficial to ischemic injury. These results provide evidence that iNOS+ inflammatory cells, as a vital source of pro-inflammatory cytokines, contribute to the development of ischemic damage and could be a potential therapeutic target for the treatment of ischemia.

Microplastics exposure causes oxidative stress and microbiota dysbiosis in planarian Dugesia japonica.

Planarians are widely used as water quality indicator species to provide early warning of harmful pollution in aquatic ecosystems. However, the impact of microplastics on freshwater planarians remains poorly investigated. Here we simulated waterborne microplastic exposure in the natural environments to examine the effect on the antioxidant defense system and microbiota in Dugesia japonica. The results showed that exposure to microplastics significantly changed the levels of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione S-transferase, indicating that microplastic exposure induces oxidative stress in planarians. High-throughput 16S rRNA gene sequencing results revealed that exposure to microplastics altered the diversity, abundance, and composition of planarian microbiota community. At phylum level, the relative abundance of the dominant phyla Proteobacteria and Bacteroidetes changed significantly after microplastic exposure. At genus level, the abundance of dominant genera also changed significantly, including Curvibacter and unclassified Chitinophagales. Predictive functional analysis showed that the microbiota of microplastic-exposed planarians exhibited an enrichment in genes related to fatty acid metabolism. Overall, these results showed that microplastics can cause oxidative stress and microbiota dysbiosis in planarians, indicating that planarians can serve as an indicator species for microplastic pollution in freshwater systems.

Specific depletion of resident microglia in the early stage of stroke reduces cerebral ischemic damage.

BACKGROUND: Ischemia can induce rapid activation of microglia in the brain. As key immunocompetent cells, reactive microglia play an important role in pathological development of ischemic stroke. However, the role of activated microglia during the development of ischemia remains controversial. Thus, we aimed to investigate the function of reactive microglia in the early stage of ischemic stroke. METHODS: A Rose Bengal photothrombosis model was applied to induce targeted ischemic stroke in mice. CX3CR1CreER:R26iDTR mice were used to specifically deplete resident microglia through intragastric administration of tamoxifen (Ta) and intraperitoneal injection of diphtheria toxin (DT). At day 3 after ischemic stroke, behavioral tests were performed. After that, mouse brains were collected for further histological analysis and detection of mRNA expression of inflammatory factors. RESULTS: The results showed that specific depletion of microglia resulted in a significant decrease in ischemic infarct volume and improved performance in motor ability 3 days after stroke. Microglial depletion caused a remarkable reduction in the densities of degenerating neurons and inducible nitric oxide synthase positive (iNOS+) cells. Importantly, depleting microglia induced a significant increase in the mRNA expression level of anti-inflammatory factors TGF-ß1, Arg1, IL-10, IL-4, and Ym1 as well as a significant decline of pro-inflammatory factors TNF-α, iNOS, and IL-1ß 3 days after stroke. CONCLUSIONS: These results suggest that activated microglia is an important modulator of the brain's inflammatory response in stroke, contributing to neurological deficit and infarct expansion. Modulation of the inflammatory response through the elimination of microglia at a precise time point may be a promising therapeutic approach for the treatment of cerebral ischemia.

LIMPID: a versatile method for visualization of brain vascular networks.

Visualization of cerebrovascular networks is crucial for understanding the pathogenesis of many neurological diseases. Recently developed optical clearing techniques offer opportunities in deep tissue imaging, and have been successfully applied in many research studies. The development of nanotechnology enables the labeling of brain vessels with functionalized micro/nanoparticles embedded with fluorescent dyes. We herein report an efficient method, named LIMPID (Labeled and Interlinked Micro/nanoparticles for Imaging and Delipidation), specific for the precise fluorescence imaging of vascular networks in clearing-treated tissues. This robust vessel labeling technique replaces conventional fluorescence dyes with functionalized polymer micro/nanoparticles that are able to cross-link with polyacrylamide to form dense hydrogels in vessels. LIMPID shows high-robustness during the clearing process without sacrificing fluorescence signals and clearing performance. LIMPID enables three dimension (3D) visualization of elaborate vascular networks in mouse brains and is compatible with other fluorescence-labeling techniques. We have successfully applied this method to acquire cortical vasculature images simultaneously with the neurons or microglia, as well as to evaluate vascular damage in a mouse model of stroke. The LIMPID method provides a novel tool for the precise analysis of vascular dysfunction and vascular diseases.

NIR-emitting semiconducting polymer nanoparticles for in vivo two-photon vascular imaging.

Two-photon fluorescence (TPF) imaging holds great promise for real-time monitoring of cerebral ischemia-reperfusion injury, which is important for the clinical diagnosis of stroke. However, biocompatible and photostable NIR-emitting probes for TPF imaging of ischemic stroke are lacking. Herein, we report the first NIR-emitting TPF probe (named NESPN) prepared using semiconducting polymers for TPF imaging of cerebral ischemia. By virtue of its excellent biocompatibility with the nervous system and bright fluorescence NIR emission, NESPN enables the real-time imaging of mouse brain vasculature with micrometer-scale spatial resolution, realizing clear visualization of ultrafine capillaries (∼3.16 µm). Moreover, NESPN can be utilized in the dynamic monitoring of cerebral blood flow velocity. Microangiography using NESPN was successfully used to indicate the openness of the penumbra area in the mouse brain stroke model. More importantly, this technique allows us to continuously monitor the whole process of ischemic stroke and subsequent reperfusion. This work provides a new and versatile tool for vascular research and diagnosis of vascular diseases.

Inhibition of Triggering Receptor Expressed on Myeloid Cell-1 Alleviates Acute Gouty Inflammation.

Gout is a prevalent form of aseptic inflammation caused by the deposition of monosodium urate (MSU) crystals in joints or tissues. Triggering receptor expressed on myeloid cell-1 (TREM-1) is a superimmunoglobulin receptor expressed on innate immune cells including granulocytes, monocytes, and macrophages. TREM-1 serves as a link between innate immunity and adaptive immunity, playing a crucial role in regulating inflammation and immune response. The purpose of this study was to investigate the potential role of TREM-1 in THP-1 cells and peripheral blood mononuclear cells (PBMCs) from patients with gouty arthritis (GA). In the current study, we found that the mRNA and protein levels of TREM-1 increased in PBMCs from GA patients and soluble TREM-1 in plasma as well. In addition, an increased level of TREM-1 was observed in THP-1 treated with monosodium urate (MSU) in vitro, along with upregulation of proinflammatory cytokines. Moreover, upon specific inhibition of TREM-1, Toll-like receptor 4 (TLR-4), and myeloid differentiation factor 88 (MyD88), the levels of MyD88 and proinflammatory cytokines were decreased after MSU challenge in THP-1 cells. Interestingly, inhibition of TLR-4 could enhance the effect of TREM-1 inhibitor in MSU-induced inflammation. Taken together, our findings suggested that TREM-1 could accelerate MSU-induced acute inflammation. Inhibition of TREM-1 may provide a new strategy for alleviating acute gouty inflammation.

Resveratrol ameliorates gouty inflammation via upregulation of sirtuin 1 to promote autophagy in gout patients.

BACKGROUND: Resveratrol exerts an anti-inflammatory effect on collagen-induced arthritis and osteoarthritis in rats via activation of sirtuin 1 (SIRT1). Autophagy can be induced by resveratrol and leads to amelioration of interleukin-1 beta (IL-1ß) release in vitro. We aimed to determine the anti-inflammatory mechanisms of resveratrol in patients with gout. METHODS: Blood samples were obtained from patients with acute gout, intercritical gout (IG) and healthy controls (HC). The mRNA and protein levels of SIRT1 and nuclear factor-kappa B (NF-kB) p65 were determined in peripheral blood mononuclear cells (PBMCs) lysate from these patients. In the in vitro experiment, SIRT1, autophagy-related genes (beclin-1 and microtubule-associated protein 1 light-chain 3) and key genes involved in the gouty inflammatory pathway, including NF-κB p65, NLR family pyrin domain containing 3 (NLRP3), caspase-1 and IL-1ß, were determined in PBMCs lysate or plasma from IG patients exposed to monosodium urate (MSU) crystals with or without resveratrol. RESULTS: The mRNA and protein levels of SIRT1 were downregulated in PBMCs from gout patients in comparison with HC. In the in vitro experiment, the protein levels of SIRT1 were downregulated in PBMCs from IG patients exposed to MSU crystals and were restored by resveratrol in a dose-dependent manner. Furthermore, high doses of resveratrol ameliorated the release of the inflammatory cytokine IL-1ß. In addition, the mRNA levels of NLRP3 and NF-κB p65 were regulated by resveratrol, but caspase-1 and IL-1ß were not. Furthermore, resveratrol promoted MSU-induced autophagy in PBMCs from patients with gout. CONCLUSION: These findings suggest that resveratrol ameliorates gouty inflammation via upregulation of SIRT1 to promote autophagy in patients with gout.

Study on the expressions of NLRP3 gene transcript variants in peripheral blood monocytes of primary gout patients.

It is well-known that NLRP3 is closely related to the onset of primary gout (PG). However, the relation between NLRP3 gene transcript variants and the occurrence of PG remains unclear. This study was undertaken to evaluate whether NLRP3 gene transcript variants are involved in the occurrence of PG. A total of 44 acute phase PG (APPG), 52 non-acute phase PG (NAPPG) male patients, and 30 male health control (HC) were involved in this study. We measured NLRP3 and its transcript variants 2, 3, 4, 5, and 1 + 6 expressions in the PBMCs, together with the level of IL-1ß in the serum. Further, PBMCs of HC were stimulated with MSU crystals. The levels of NLRP3, NLRP3 gene transcript variants 2, 3, 4 mRNA, and protein expressions were significantly lower in the APPG and NAPPG groups than in the HC group (P < 0.05, respectively), and IL-1ß expression was significantly higher in the APPG group than in the HC and NAPPG groups (P < 0.05, respectively). Levels of IL-1ß and NLRP3-4 mRNA expressions were negatively correlated with APPG group (r = - 0.2828, P = 0.0252). After stimulating PBMCs of HC with MSU crystals, levels of NLRP3, NLRP3-4 mRNA, and NLRP3 protein expressions were reduced significantly (P < 0.05, respectively), and the level of IL-1ß in MSU group was increased significantly (P < 0.05). Here, we show that NLRP3-4 transcript variant may be closely related to the occurrence of PG. Thus, NLRP3-4 gene transcript variant may provide a novel target for the diagnosis and therapy of PG.

Expression of Reg IV and SOX9 and their correlation in human gastric cancer.

BACKGROUND: Reg IV is a member of the regenerating gene family and has been demonstrated to be overexpressed in gastric cancer. However, the functional mechanism of Reg IV in gastric cancer is still unclear. METHODS: Expression of Reg IV and SOX9 were investigated by immunohistochemistry (IHC) and real-time PCR, and the correlation between the expression of Reg IV and SOX9 was analyzed in gastric cancer tissues. Reg IV expression vectors and a siRNA of Reg IV and SOX9 were transfected into human gastric cancer cells and the protein and mRNA levels of Reg IV and SOX9 were investigated by western blot and real-time PCR. The invasion and migration ability of gastric cancer cells with overexpressed Reg IV and with gene silence of Reg IV and SOX9 were examined by transwell chambers and wound healing assay. RESULTS: The Reg IV and SOX9 protein expression levels were both significantly higher in gastric cancer tissues compared with adjacent tissues (p = 0.022, p = 0.003). Reg IV protein expression significantly correlated with tumor invasion depth (p <  0.001), but had no significant correlations with age, clinical stage or lymph node metastasis. SOX9 protein expression also had no significant correlations with age, clinical stage, tumor invasion depth or lymph node metastasis. Reg IV transcript expression demonstrated a significant correlation with invasion depth and lymph node metastasis (p = 0.005, p <  0.001) and no significant correlations with age, clinical stage, tumor tissue differentiation or tumor size. SOX9 transcript expression demonstrated a significant correlation with invasion depth and tumor tissue differentiation (p = 0.044, p = 0.007) and no significant correlations with age, clinical stage or tumor size. The Reg IV expression showed a positive correlation with the SOX9 expression (p <  0.000, p = 0.008). Overexpression of Reg IV could upregulate SOX9 expression and promote invasiveness and migration of tumor cells, and silencing of Reg IV could downregulate SOX9 and inhibit invasiveness and migration of tumor cells in MKN-45 and AGS cells. On the other hand, silencing of SOX9 could upregulate Reg IV protein expression. CONCLUSIONS: Our study demonstrated that Reg IV positively regulates the expression of SOX9 and is involved in tumor cell invasion and migration in gastric cancer.

Association of NLRP3 polymorphisms with susceptibility to primary gouty arthritis in a Chinese Han population.

The NLRP3-interleukin1ß (IL1ß) signaling pathway is involved in monosodium urate (MSU)-mediated inflammation. The aim of this present study was to determine whether single nucleotide polymorphisms (SNPs) in the NLRP3 gene are associated with susceptibility to gouty arthritis (GA) and whether these SNPs alter the expression of components of the NLRP3-IL1ß signaling pathway. The rs10754558, rs4612666, and rs1539019 SNPs were detected in 583 patients with GA and 459 healthy subjects. NLRP3 and IL1ß mRNA levels in peripheral blood mononuclear cells (PBMCs) and serum IL1ß levels were measured in different genotype carriers, and correlations between the NLRP3 SNPs and NLRP3 mRNA, IL1ß mRNA, and serum IL1ß levels were investigated. The GG genotype of NLRP3 rs10754558 was found to be significantly associated with patients with GA compared to the healthy control subjects via multivariate logistic regression analysis (adjusted OR = 2.68, P = 0.006). The CGA haplotypes were independently associated with patients with GA compared to the healthy control subjects (adjusted OR = 1.968, P = 0.02). The levels of NLRP3 mRNA, IL1ß mRNA, and serum IL1ß in the patients with GA were significantly different among the three genotypes of rs10754558 (all P < 0.01). The GG genotype of rs10754558 and the CGA haplotype of rs4612666-C, rs10754558-G, and rs1539019-A are both independent risk factors for primary GA development. The rs10754558 polymorphism might participate in regulating immune and inflammation responses in patients with GA by influencing the expression of components of the NLRP3 inflammasome. Future multicenter studies aimed at replicating these findings in an independent population as well as functional tests will aid in further defining the role of these SNPs in the development of GA.

Expression of PYCARD gene transcript variant mRNA in peripheral blood mononuclear cells of primary gout patients with different Chinese medicine syndromes.

OBJECTIVE: To study the expression level and role of apoptosis-associated speck-like protein containing a caspase recruitment domain (PYCARD) gene transcript variant mRNA in peripheral blood mononuclear cells (PBMCs) of primary gout (PG) patients with different Chinese medicine (CM) syndromes. METHODS: The expressions of PYCARD gene transcript variant mRNA and interleukin-1ß (IL-1ß) mRNA in PBMCs were investigated in 96 PG patients with acute phase (APPG, 44 cases) and non-acute phase (NAPPG, 52 cases) and 30 healthy controls (HCs) by reverse transcription-polymerase chain reaction (PCR) and/or realtime quantitative PCR. PYCARD and nuclear factor-κB (p50) [NF-κB (p50)] protein was detected by Western blot in PBMCs respectively. IL-1ß, IL-4 and IL-10 protein levels in plasma of HCs and PG patients were measured by enzyme-linked immuno sorbent assay. RESULTS: The main CM syndromes in APPG patients were obstruction of dampness and heat syndrome (ODHS, 36.36%) and intermingled phlegm-blood stasis syndrome (IPBSS, 27.27%), while in NAPPG patients were Pi (Spleen)-deficiency induced dampness syndrome (PDIDS, 40.38%) and qi-blood deficiency syndrome (QBDS, 26.92%). It showed statistical significances of the expressions of PYCARD gene and its transcript variant mRNA, the protein of PYCARD and NF-κB (p50) and the plasma IL-1ß, IL-4 and IL-10 in APPG, NAPPG, ODHS, IPBSS, PDIDS and QBDS groups, compared with the HC group respectively (P<0.05 or P<0.01). There were also significant differences of mRNA expressions of PYCARD-1 and PYCARD-2 as well as protein expressions of IL-1ß, IL-4 and IL-10 among the 4 CM syndromes groups (P<0.05 or P<0.01). Correlation analysis showed positive correlation between the mRNA expressions of PYCARD-1 gene transcript variant and IL-1ß in APPG patients (r=0.3088, P=0.0183). CONCLUSION: PYCARD gene and its transcript variant may play a critical and regulative role in the inflflammatory response of PG patients with different phases and CM syndromes.

Transcriptomic analysis reveals differential activation of microglial genes after ischemic stroke in mice.

Microglia are immune cells in the brain and play a pivotal role in the progression of ischemic injury, but the gene expression and signaling pathways related to the activation of microglia following ischemia remain unclear. In our experiment, we used digital gene expression (DGE) analysis to profile the transcriptome of ischemic tissue in a photothrombosis model. DGE analysis identified that a total of 749 genes were differentially regulated (643 up-regulated and 106 down-regulated) after 2days and 7days following stroke. We found 74.5% of these differentially expressed genes were microglial genes. Gene ontology (GO) analysis categorizes these differentially expressed genes at 2days and 7days to specific biological processes such as inflammatory response, cell activation, cell proliferation, and chemokine and cytokine production. Our data demonstrated that a large number of microglial genes were highly regulated at 2days after stroke, but the number of differentially expressed genes had reduced drastically by 7days. Importantly, some of the differentially expressed microglial genes at 7days did not show differential expression at 2days after stroke. DGE analysis indicated that specific genes related to microgliosis were regulated after ischemia. Consistent with the changes in transcriptome, the results from histological analysis of transgenic mice revealed that the microglia proliferated and aggregated surrounding the ischemic core during the period from 2days to 7days following photothrombosis. Together, these results suggested that transcriptomic changes in microglial genes after stroke may have a profound implication for pathophysiology and treatment of stroke.

In vivo two-photon imaging reveals a role of progesterone in reducing axonal dieback after spinal cord injury in mice.

Progesterone (PG) as a neuroprotective reagent has been used for the treatment of spinal cord injury (SCI) in experimental animal models. However, its effect and mechanism on axonal dieback at the early stage of SCI remain unclear. Here, we investigate the dynamics of injured axons and the effect of PG on the axonal dieback, glial response, and behavioral recovery in a mouse model of SCI. Two-photon intravital imaging combined with a simplified imaging window chamber were used to image axons in hemisected spinal cords over a period of 3 days. Repeated imaging showed that axonal dieback distance in mice treated with PG after SCI was significantly reduced than that in mice treated with vehicle after SCI (P < 0.05) at the time point of 24 h, 48 h, and 72 h after SCI. The densities of astrocytes and microglia in the SCI-vehicle treated group were significantly higher than those in mice treated with PG after SCI (P < 0.05). Real time polymerase chain reaction assay indicated that administration of PG after SCI down-regulated the expression of pro-inflammatory cytokines MCP-1, NOS2, and IL-1ß (P < 0.05). PG treatment also improved the behavioral performance post injury. These findings suggested that PG exerted a neuroprotective effect by attenuating axonal dieback, reducing the accumulation of astrocytes and microglia and inhibiting the release of pro-inflammatory cytokines.

Association of DNA methyltransferase polymorphisms with susceptibility to primary gouty arthritis.

Gouty arthritis is the most common type of inflammatory and immune disease, and the prevalence and incidence of gout increases annually. Genetic variations in the DNA methyltransferases (DNMTs) gene have not, to the best of our knowledge, been reported to influence gene expression and to participate in the pathogenesis of gout. The aim of the present study was to investigate whether the DNMT1, DNMT3A and DNMT3B polymorphisms contribute to gout susceptibility. These polymorphisms were screened for in 336 gout patients and 306 healthy control subjects (from a South China population) for association with gout. The distribution frequencies of DNMT1 rs2228611 AA genotype (P=0.007) and A allele (P=0.002; odds ratio=1.508, 95% confidence interval=1.158-1.964) were found to be significantly increased in the gout patients when compared with those in the healthy control subjects. The rs1550117 in DNMT3A and rs2424913 in DNMT3B exhibited no significant associations with gout susceptibility between the patients and control subjects. These results demonstrated that the DNMT1 rs2228611 polymorphism may be involved in the pathogenesis of gout, while DNMT3A rs1550117 and DNMT3B rs2424913 did not show any obvious significance in the current study; thus, may not be used as risk factors to predict the susceptibility to gout. However, further studies are required to investigate the functions and regulatory mechanism of the polymorphisms of DNMTs in gout.