Renal interstitial fibrotic assessment using non-Gaussian diffusion kurtosis imaging in a rat model of hyperuricemia.

BACKGROUND: To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia. METHODS: A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment. RESULTS: The HUA, AP, and AP + EM group MKOS and MKIS values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOS and MKIS values were positively correlated with Masson's trichrome staining results (r = 0.687, P < 0.001 and r = 0.604, P = 0.001, respectively). The MDOS and FAIS were negatively correlated with Masson's trichrome staining (r = -626, P < 0.0014 and r = -0.468, P = 0.01, respectively). CONCLUSION: DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.

[Spatiotemporal Change and Source Apportionment of Non-point Source Nitrogen and Phosphorus Pollution Loads in the Three Gorges Reservoir Area].

The Three Gorges Reservoir area (TGRA) is a critical water source protection area in China and one of the regions with rapid economic development in the Yangtze River basin. Non-point source pollution is the leading cause of the deterioration of the water environment in the TGRA; therefore, studying the non-point source pollution status in the TGRA is of great significance to the regional ecological security and sustainable development. The improved export coefficient model was used to estimate the total non-point source nitrogen and phosphorus pollution loads in the TGRA from 1990 to 2015, the spatial and temporal characteristics of the non-point source nitrogen and phosphorus pollution were analyzed, and the primary sources of pollution were determined by calculating the contribution rate of each pollution source. The results concluded that the nitrogen and phosphorus pollution loads were highest in the hinterland of the reservoir, followed by the end of the reservoir, with the lowest in the head of the reservoir, showing significant spatial heterogeneity in the TGRA. The total loads of nitrogen and phosphorus pollution increased firstly and then decreased, which reached the highest value in 2000 and the lowest value in 2015. The contribution rate of each pollution source to the nitrogen and phosphorus pollution loads, from highest to lowest, were land use, rural life, livestock, and poultry farming. Among them, the land use type of dry land was the predominant source of non-point source nitrogen and phosphorus pollution.

A three serum miRNA panel as diagnostic biomarkers of radiotherapy-related metastasis in non-small cell lung cancer.

Serum microRNAs (miRNAs) have been implicated as noninvasive biomarkers for lung cancer diagnosis. However, there are no sensitive and specific biomarkers for the detection of radiotherapy-related non-small cell lung cancer (NSCLC) metastasis. The present study aimed to investigate the role of three serum miRNAs, namely miRNA (miR)-130a, miR-25 and miR-191*, in diagnosing NSCLC, and their biological functions in radiation-mediated development of metastatic properties in A549 cells. To determine this, serum samples were collected from 84 patients with NSCLC and 42 age- and sex-matched healthy controls. Differential expression of serum miRNAs was analyzed by quantitative PCR. Significant associations between miRNA expression and overall survival of patients with NSCLC were identified using the Cox proportional regression model. A receiver operating characteristic curve was generated to evaluate diagnostic accuracy. The functions of miR-130a, miR-25 and miR-191* in lung cancer cells were studied by transfecting A549 cells with miRNA mimics and inhibitors. The results of the present study demonstrated that the expression levels of miR-130a, miR-25 and miR-191* in the serum of patients with NSCLC were increased compared with those in healthy controls, and these increases were associated with advanced age (≥60 years), radiotherapy, histological type (squamous carcinoma), low survival rate and low median survival time. Additionally, irradiation induced the upregulation of miR-130a, miR-25 and miR-191* expression in A549 cells in vitro and in a xenograft mouse model. Irradiation also promoted the invasiveness of A549 cells in vitro and metastasis in vivo. In conclusion, miR-130a, miR-25 and miR-191* may be potential biomarkers for the diagnosis of patients with NSCLC and may serve oncogenic roles in radiation-mediated metastasis of NSCLC.

Development and validation of a Chinese-language instrument measuring empowerment needs of patients after a percutaneous coronary intervention.

Patient empowerment has been shown to have some positive impacts on self-efficacy, self-esteem, and recovery. However, information about the empowerment needs of patients after a percutaneous coronary intervention is scarce. The aim of this study was to develop a Chinese-language instrument to measure empowerment needs of such patients. The initial instrument was generated based on a literature review and interviews with patients after a percutaneous coronary intervention procedure. Content validity was tested with a panel of experts using the Delphi method. In total, 226 patients were recruited for psychometric tests using the revised instrument. Expert authority coefficient was 0.92, and content validity index was 0.95. The internal consistency reliability was demonstrated by Cronbach's α coefficients (0.86 for the total score, 0.66-0.74 for the dimensions). The newly developed 19-item, five-dimension instrument has shown satisfactory validity (face/content validity and construct validity) and internal consistency reliability. The instrument could help clinical nurses who have close contact with patients after a percutaneous coronary intervention to gain a better understanding of their empowerment needs and could help develop appropriate health education to address such needs.

Patient with severe fever with thrombocytopenia syndrome virus infection and central nervous system disturbance in Dongyang, Zhejiang Province, China, 2017.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever that was first described in China in 2011. We report a patient who died of Severe fever with thrombocytopenia syndrome virus (SFTSV) infection, with a rapidly progressive central nervous system (CNS) disturbance, in Dongyang, Zhejiang Province, China, in 2017. CASE PRESENTATION: A 64-year-old man was admitted to hospital after 4 days of fever. SFTSV was detected 1 day after the patient was admitted to hospital. The patient presented with CNS disturbance and died 4 days after admission. Detailed clinical and epidemiological investigations and laboratory tests were conducted. Reduced platelet, white blood cell, lymphocyte, and neutrophil counts, elevated lactate dehydrogenase, creatine kinase, aspartate aminotransferaseand alanine aminotransferase concentrations, and an increased activated partial thromboplastin time were observed. In a phylogenetic analysis, the isolate clustered close to a strain derived from South Korea. CONCLUSIONS: This is the first case of SFTSV infection with CNS disturbance in Dongyang, Zhejiang Province, China. The surveillance of suspected cases of SFTS is important in SFTSV endemic regions.

Multifunctional neuron-specific enolase: its role in lung diseases.

Neuron-specific enolase (NSE), also known as gamma (γ) enolase or enolase-2 (Eno2), is a form of glycolytic enolase isozyme and is considered a multifunctional protein. NSE is mainly expressed in the cytoplasm of neurons and neuroendocrine cells, especially in those of the amine precursor uptake and decarboxylation (APUD) lineage such as pituitary, thyroid, pancreas, intestine and lung. In addition to its well-established glycolysis function in the cytoplasm, changes in cell localization and differential expression of NSE are also associated with several pathologies such as infection, inflammation, autoimmune diseases and cancer. This article mainly discusses the role and diagnostic potential of NSE in some lung diseases.

A novel calreticulin-related molecule that interacts with bacteria and enhances host resistance against bacterial infection in black rockfish, Sebastes schlegeli.

Calreticulin (CRT) is a highly conserved and multi-functional protein with diverse localizations. CRT has lectin-like properties and possesses important immunological activities in mammalian. In teleost, very limited studies on CRT immunologic function have been documented. In the present study, a CRT homologue (SsCRT) was cloned, identified and characterized from black rockfish, Sebastes schlegeli, an important aquaculture species in East Asia. The full length of SsCRT cDNA is 2180 bp and encoded a polypeptide of 425 amino acids. SsCRT contains a signal peptide, three distinct structural and functional domains (N-, P- and C-domains), and an endoplasmic reticulum (ER) retrieval signal sequence (KDEL). The deduced amino acid sequence of SsCRT shares 89-92% overall sequence identities with the CRT proteins of several fish species. SsCRT was distributed ubiquitously in all the detected tissues and was highly expressed in the spleen, muscle and liver. After the infection of fish extracellular bacterial pathogen Vibrio anguillarum and intracellular bacterial pathogen Edwardsiella tarda, the mRNA transcripts of SsCRT in spleen, liver, and head kidney were significantly up-regulated. The expression patterns were time-dependent and tissue-dependent. Recombinant SsCRT (rSsCRT) exhibited apparent binding activities against different bacteria and PAMPs. In vivo studies showed that the expressions of multiple immune-related genes such as TNF13B, IL-1ß, IL-8, SAA, Hsp70, and ISG15 in head kidney were significantly enhanced when black rockfish were treated with rSsCRT. Furthermore, rSsCRT reduced pathogen dissemination and replication in fish kidney and spleen. These results indicated that SsCRT served as an immune receptor to recognize and eliminate the invading pathogens, which played a vital role in the immune response of Sebastes schlegeli. These findings provide new insights into understanding the roles of CRT proteins in immune response and pathogen infection in teleost.

Evaluation of the chemical composition of nephrolithiasis using dual-energy CT in Southern Chinese gout patients.

BACKGROUND: A study to evaluate the prevalence of uric acid (UA) nephrolithiasis with dual-energy CT (DECT) and explore the risk factors for kidney stones in primary gout patients. METHODS: Eighty-four consecutive gout patients underwent urinary tract ultrasonography or DECT to confirm the existence of kidney stones. Urine and blood samples were also taken for laboratory analysis. RESULTS: Forty-one subjects (48.8%) had nephrolithiasis diagnosed; 38 had a kidney stone. Thirty-two of the 38 patients underwent a DECT scan, and 27 patients had nephrolithiasis in DECT. Among them, 63.0% (17/27) and 14.8% (4/21) of the patients had pure UA and UA-based mixed stone, respectively, and 22.2% (6/27) had a non-UA stone. Those with nephrolithiasis suffered from more frequent acute attacks and had longer disease durations of gout. At least one urine biochemical abnormality was found in 81% of patients. Forty-four (55.0%) patients presented hypomagnesuria. Forty-three (51.8%) patients had low urine volume. Unduly acidic urine (UAU) was present in 36 patients (44.4%). Hyperuricosuria was only found in ten (12.2%) patients. In comparison to the non-lithiasic group, the lithiasic group was more likely to have a UAU. Binary logistic regression showed that female gender was a protective factor, while disease duration of gout and low urine pH were risk factors for nephrolithiasis. CONCLUSION: Our results indicated that nephrolithiasis, especially UA stones, were more common than previous reports in gout patients indicated, and that disease duration of gout, and low urine pH, were risk factors for nephrolithiasis.

The risk of systemic lupus erythematosus associated with Epstein-Barr virus infection: a systematic review and meta-analysis.

Previous systematic reviews have found a higher sero-prevalence of EBV antibodies in SLE patients compared with controls. Because many studies have been published, there is a need to apply more precise systematic review methods. We examined the association between EBV and SLE patients by conducting a systematic review and meta-analysis of case-control studies that examined the prevalence of EBV antibodies and the DNA-positive rate. We searched the MEDLINE and EMBASE databases from 1966 to 2018 with no language restrictions. The Mantel-Haenszel odds ratios (OR) for EBV antibody sero-positivity were calculated, and meta-analyses were conducted. Quality assessment was performed using a modified version of the Newcastle-Ottawa scale, and 33 studies were included. Most studies found a higher sero-prevalence of VCA IgG and EA IgG in SLE patients compared with controls. Meta-analysis demonstrated a significantly higher OR for sero-positivity to VCA IgG and EA IgG for SLE cases (2.06 [95% confidence interval (CI) 1.30-3.26, p = 0.002] and 7.70, [95% CI 4.64-12.76, p < 0.001], respectively). The overall OR for the DNA-positive rate for SLE patients compared with controls was 3.86 (95% CI 1.52-9.83, p = 0.005). Other antibodies, i.e., VCA IgA/IgM, EBNA IgA, and EA IgA/IgM, also demonstrated a significant difference between SLE patients and controls. These findings support previous systematic reviews; however, publication bias cannot be excluded. The methodological conduct of studies could be improved, particularly when selecting controls and analyses of laboratory conduct.

Spatial-temporal evolution and prediction of urban landscape pattern and habitat quality based on CA-Markov and InVEST model.

The change of urban landscape caused by human activities is one of the most important factors affecting terrestrial ecosystem. The distribution of urban landscape pattern has great impacts on the service function of regional biodiversity. To reveal the variation of landscape pattern and habi-tat quality in cities and its driving factors, we extracted landscape type information of Wuhan in 2005, 2010, 2015, and analyzed spatial-temporal evolution of landscape pattern using Markov transition model. The CA-Markov model was used to simulate the landscape pattern in 2020 under the natural growth scenario. The driving factor for landscape variation was analyzed using Logistic regression model. Combined with InVEST model, spatial pattern of habitat quality and its variation in three phases were calculated and evaluated. The simulated habitat quality in 2020 was obtained and its distribution characteristics were analyzed. The relationship between variation of landscape pattern and human activities was explored. The results showed that cultivated land and manufactured surface were the landscape types with highest variations between 2005 and 2015. The area of cultivated land continued to decline, with most of the area being transferred into manufactured surface. The area of manufactured surface continued to increase, most of which was transferred from paddy field and dry land. From 2005 to 2015, the habitat quality declined, with a large number of landscapes with high habitat quality level being changed to low habitat quality level. The overall index of habitat quality decreased and the biodiversity service function declined, indicating the degeneration of habitat quality. In 2015-2020, the evolutionary trend of landscape pattern and habitat quality would keep consistent with the past decade, with an increasing area of artificial surface, decreasing index of habitat quality, weakening biodiversity service function, and degenerating habitat quality. The most important factor accounted for the landscape pattern change in the study area was the changes in Gross Domestic Product (GPD) and regional fiscal revenue. Human socio-economic activities were the key driving force for the spatial variation of landscape and degeneration of habitat quality. Urbanization and land reclamation by filling lakes were the main reasons for landscape pattern variation in Wuhan.

Insecticidal Activities of Chloramphenicol Derivatives Isolated from a Marine Alga-Derived Endophytic Fungus, Acremonium vitellinum, against the Cotton Bollworm, Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae).

A great deal of attention has been focused on the secondary metabolites produced by marine endophytic fungi, which can be better alternatives to chemicals, such as biopesticides, for control of polyphagous pests. On the basis of its novel biocontrol attributes, chemical investigation of a marine alga-derived endophytic fungus, Acremonium vitellinum, resulted in the isolation of three chloramphenicol derivatives (compounds 1⁻3). Their chemical structures were elucidated by detailed analysis of their nuclear magnetic resonance spectra, high-resolution electrospray ionization mass spectrometry, and by comparison with the data available in the literature. In this paper, compound 2 was firstly reported as the natural origin of these fungal secondary metabolites. The insecticidal activities of compounds 1⁻3 against the cotton bollworm, Helicoverpa armigera, were evaluated. The natural compound 2 presented considerable activity against H. armigera, with an LC50 value of 0.56 ± 0.03 mg/mL (compared to matrine with an LC50 value of 0.24 ± 0.01 mg/mL). Transcriptome sequencing was used to evaluate the molecular mechanism of the insecticidal activities. The results presented in this study should be useful for developing compound 2 as a novel, ecofriendly and safe biopesticide.

Prenylated Diphenyl Ethers from the Marine Algal-Derived Endophytic Fungus Aspergillus tennesseensis.

Considerable attention has been paid to marine derived endophytic fungi, owing to their capacity to produce novel secondary metabolites with potent bioactivities. In this study, two new compounds with a prenylated diphenyl ether structure-diorcinol L (1) and (R)-diorcinol B (2)-were isolated from the marine algal-derived endophytic fungus Aspergillus tennesseensis, along with seven known compounds: (S)-diorcinol B (3), 9-acetyldiorcinol B (4), diorcinol C (5), diorcinol D (6), diorcinol E (7), diorcinol J (8), and a dihydrobenzofuran derivative 9. Their structures were elucidated by extensive NMR spectroscopy studies. Compound 2 represents the first example of an R-configuration in the prenylated moiety. All these isolated compounds were examined for antimicrobial and cytotoxic activities. Compounds 1⁻9 exhibited antimicrobial activities against some human- and plant-pathogenic microbes with MIC values ranging from 2 to 64 µg/mL. Moreover, compound 9 displayed considerable inhibitory activity against the THP-1 cell line in vitro, with an IC50 value of 7.0 µg/mL.

Few individuals with Lennox-Gastaut syndrome have autism spectrum disorder: a comparison with Dravet syndrome.

BACKGROUND: Autism spectrum disorder (ASD) in epilepsy has been a topic of increasing interest, which in general occurs in 15-35% of the patients with epilepsy, more frequently in those with intellectual disability (ID). Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are two typical forms of intractable epileptic encephalopathy associated with ID. We previously reported that ASD was diagnosed in 24.3% of patients with DS, higher in those with profound ID. Given the severe epilepsy and high frequency of ID in LGS, it is necessary to know whether ASD is a common psychomotor co-morbidity of LGS. This study evaluated the autistic behaviors and intelligence in patients with LGS and further compared that between LGS and DS, aiming to understand the complex pathogenesis of epilepsy-ASD-ID triad. METHODS: A total of 50 patients with LGS and 45 patients with DS were enrolled and followed up for at least 3 years. The clinical characteristics were analyzed, and evaluations of ASD and ID were performed. RESULTS: No patients with LGS fully met the diagnostic criteria for ASD, but three of them exhibited more or less autistic behaviors. Majority (86%) of LGS patients presented ID, among which moderate to severe ID was the most common. Early onset age and symptomatic etiology were risk predictors for ID. The prevalence of ASD in LGS was significantly lower than that in DS (0/50 vs. 10/45, p < 0.001), while the prevalence and severity of ID showed no significant difference between the two forms of epileptic encephalopathy. CONCLUSIONS: This study demonstrated a significant difference in the co-morbidity of ASD between LGS and DS, although they had a similar prevalence and severity of ID, refuting the proposal that the prevalence of ASD in epilepsy is accounted for by ID. These findings suggest that the co-morbidity of ASD, ID, and epilepsy may result from multifaceted pathogenic mechanisms.

The effects of rainfall regimes and terracing on runoff and erosion in the Three Gorges area, China.

Changes in natural rainfall regimes have taken place and are expected to become more pronounced in future decades. These changes are also likely to be accompanied by changes in crop management practices. The main purpose of this study was to analyze runoff and soil loss in relation to rainfall regimes and terracing in the Three Gorges area, China. Based on 10 years of field observation and k-mean clusters, 101 rainfall events were grouped into three rainfall regimes. Rainfall regime I was the group of events with strong rainfall intensity, high frequency, and short duration. Rainfall regime III consisted of events with low intensity, long duration, and high rainfall amount. Rainfall regime II was the aggregation of events of high intensity and amount, and less frequent occurrence. The results showed that event runoff coefficients were not significantly different among rainfall regimes. However, the average soil erosion rates in rainfall regimes I and II were significantly higher than that in regime III. The average erosion rates under rainfall regimes I, II, and III were 21.6, 39.7, and 9.8 g m-2, respectively. The effect of rainfall regime on soil erosion also was changed by terracing. On unterraced cropland, soil erosion rate in rainfall regime I is significantly higher than that in regime III. However, the situation did not exist in unterraced orchard. Terracing significantly reduced runoff and soil erosion, and compensated the effects of rainfall regime on soil erosion, which indicated that runoff and erosion in terraced system may be little influenced by climate change. Based on these results, it was suggested more attention should be paid to the timing of rainfall events in relation to crop development and the high erosion on unterraced citrus orchard to control soil erosion in this area.

[Study on correlation between color and effective components contents of Glycyrrhiza uralensis].

To explore the correlation between color of Glycyrrhiza uralensis and its quality evaluation,the colors of root bark and transverse section were determined by Precision Color Reader and Visual Analyzer,and the contents of six flavonoids and two saponins in G.uralensis were determined by high performance liquid chromatography（HPLC）.The partial least squares regression（PLSR）method was employed to correlate the colors with component contents in G.uralensis. The results showed that there were no significant differences in the colors of root bark but significant or very significant differences（P<0.05,P<0.01）in the colors of transverse section between the wild and cultivated G. uralensis. Compared with those in the cultivated G. uralensis, the contents of liquiritin, isoliquiritin isoliquiritigenin and the contents of ammonium glycyrrhizinate, glycyrrhetinic acid were obviously significant or remarkably significant in the wild G. uralensis.The correlation results showed that there was a significant or very significant correlation between the colors and the effective component contents. This study provides a scientific basis to evaluate the quality of G.uralensis by color and a new reference for the traditional evaluation methods for Chinese drugs.

The Wnt/ß-catenin and PI3K/Akt signaling pathways promote EMT in gastric cancer by epigenetic regulation via H3 lysine 27 acetylation.

In this study, we investigated the underlying mechanism of the phosphoinositide 3-kinase/Akt- and Wnt/ß-catenin-mediated promotion of epithelial-to-mesenchymal transition by epigenetic regulation of histone acetylation in gastric cancer. First, we used immunohistochemistry to detect the expression of phosphorylated Akt, phosphorylated glycogen synthase kinase 3 beta, and ß-catenin in gastric cancer tissues and adjacent tissues. In addition, we confirmed that the phosphoinositide 3-kinase/Akt and Wnt/ß-catenin signaling pathways were correlated with tumorigenesis, progression, and maintenance of gastric cancer using the phosphoinositide 3-kinase inhibitor LY294002 and an inhibitor of the ß-catenin/TCF4 complex, FH535. Epithelial-to-mesenchymal transition-related gene expression was measured by western blotting and quantitative real-time polymerase chain reaction assays. Furthermore, we detected the acetylation of histone H3 lysine 4 and lysine 27 using the FH535 and LY294002 inhibitors at different concentrations for 24 and 48 h. Finally, chromatin immunoprecipitation-quantitative polymerase chain reaction was performed to detect the specific binding of H3K27ac to the promoter of the epithelial-to-mesenchymal transition-related factor, Twist. Taken together, abnormal activation of the phosphoinositide 3-kinase/Akt and Wnt/ß-catenin signaling pathway was correlated with the gastric cancer progression and contributed to epithelial-to-mesenchymal transition regulation by controlling histone acetylation.

Kinetic analysis and degradation pathway for m-dichlorobenzene removal by Brevibacillus agri DH-1 and its performance in a biotrickling filter.

A strain, Brevibacillus agri DH-1, isolated from dry lands was used to remove m-dichlorobenzene. After 48h culturing, the concentrations of m-dichlorobenzene decreased from 26-130 to 7.87-28.87mg/L and dry cell weight for bacterial growth reached 52.43-75.05mg/L. The growth and degradation kinetics were analyzed by the fitting of Haldane-Andrews model and pseudo first-order model. A degradation pathway was proposed according to major intermediates (phenol), chloride ion variation, ring-opening enzyme activity, and high mineralization (0.47gCl-/gm-dichlorobenzene, 0.65 gco2/gm-dichlorobenzene, 0.15 gDCW/gm-dichlorobenzene). In addition, the performance in a biotrickling filter (BTF) was evaluated through removal efficiency and pressure drop values with increasing inlet loading rate from 4.10 to 122.57g/m3/h at three empty bed residence time points (30s, 60s, and 90s). The results demonstrated that strain DH-1 possessed high removal efficiency and stable operation in a BTF.

Inhibition of smoothened decreases proliferation of synoviocytes in rheumatoid arthritis.

Fibroblast-like synoviocytes (FLSs) contribute to synovial hyperplasia in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist (GDC-0449) and small interfering RNA (siRNA) targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls (P < 0.05). Incubation with GDC-0449 or transfection with Smo-siRNA resulted in a significant increase of G1 phase cells compared to controls (P < 0.05). Cell cycle arrest was validated by the significant increase in cyclin D1 and E1 mRNA expression, decrease in cyclin-dependent kinase p21 mRNA expression in Smo-siRNA transfected cells (P < 0.05). Protein expression of cyclin D1 was also downregulated after Smo gene knockdown (P < 0.05). The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA.

[Analysis of immune suppression in patients with systemic lupus erythematosus complicated by herpes zoster virus infection].

OBJECTIVE: To explore the changes in cellular immune function and the safety of physical therapy in patients with systemic lupus erythematosus (SLE) complicated by herpes zoster (HZ) virus infection. Methods A retrospective analysis was conducted among 10 SLE pateints with HZ virus infection, with 30 SLE patients without HZ infection as the control group. The results of routine laboratory tests and T lymphocyte subset counts (before and during infection and after cure of infection) were compared between the two groups. RESULTS: The proportion of patients with significantly increased absolute neutrophil count and white blood cell count before HZ infection, and those with decreased lymphocyte percentage and elevated C-reactive protein during infection differed significantly between the two groups (P<0.05). Before HZ infection, the proportions of patients with increased CD3+%, decreased CD16+CD56+%, abnormal 4/8 ratio (P<0.01) and those with increased CD8+% and CD8+ count and decreased CD16+CD56+ count differed significantly between the two groups (P<0.05). During HZ infection, the proportion of patients with increased CD3+% and CD8+% and decreased CD4+% and 4/8 ratio count (P<0.05) and those with decreased CD16+CD56+% and increased CD8+ count differed significantly between the two groups (P<0.01). After cure of HZ infection, the proportion of patients with decreased CD16+CD56+% was significantly different between the two groups (P<0.01). The treatment time of HZ infection averaged 5∓1.3 days with a cure rate of 100% postherpetic neuralgia occurred in none of the patients after the treatment. CONCLUSION: Patients with SLE complicated by HZ infection are in an immunosuppressive state, suggesting the need of monitoring T lymphocyte subsets in SLE treatment. The combined use of antiviral drugs and physical therapy can be safe and effective for treatment of SLE complicated by HZ infection.

Maternal Coffee Consumption During Pregnancy and Neural Tube Defects in Offspring: A Meta-Analysis.

PURPOSE: To examine the association between maternal coffee consumption during pregnancy and the occurrence of neural tube defects (NTDs) in offspring. METHODS: PubMed, Springer Link and Elsevier databases were searched up to August, 2014. Case-control and cohort studies published on the association between maternal coffee consumption during pregnancy and the occurrence of NTDs in offspring were included. Meta-analysis was applied to calculate the pooled effect estimates and their 95% confidence intervals (CIs) using a random-effects model. RESULTS: A total of six case-control studies and one cohort study were included. The pooled effect estimate of maternal coffee consumption during pregnancy was 0.86 for total NTDs (95% CI: 0.51- 1.45) and 1.30 (95% CI: 0.67- 2.52) for NTDs subtype of spina bifida. CONCLUSIONS: Our findings suggested that maternal coffee consumption during pregnancy was not significantly associated with the occurrence of total NTD or the spina bifida subtype of NTD.