Epidemiological and Clinical Characteristics of Neonatal Ureaplasma urealyticum Infection.

Purpose: To understand the epidemiology and clinical features of Ureaplasma urealyticum (UU) infection in hospitalized neonates due to vertical transmission from mother to child. Methods: Respiratory secretions were collected from neonates hospitalized in the neonatology department of the Maternal and Child Health Hospital of Hubei Province from July 2020 to June 2022, and PCR was used to detect UU-DNA in respiratory secretions. The neonates were divided into UU-positive and UU-negative groups, the epidemiological and clinical characteristics of two groups, were statistically analyzed. Results: A total of 7257 hospitalized neonates were included in this study, of whom 561 were UU positive and 6696 were UU negative, with a UU detection rate of 7.73%. The detection rate among female neonates was higher than male neonates, and the highest detection rate was found in the period from 1-7 days after birth; the detection rate was highest in spring and fall, and the lowest in winter, but the overall difference was not statistically significant (P>0.05). Compared with the UU-negative group, neonates in the UU-positive group were more likely to be preterm, have a lower birth weight, be delivered vaginally, and have maternal preterm rupture of membranes. In addition, neonates in the UU-positive group were more likely to be co-infected with pathogens and to have complications related to UU infections, which were all statistically significant (P<0.05). Conclusion: Neonatal UU infections are detected more frequently in female infants, with the highest detection rate occurring in 1-7 days after birth, and the most prevalent periods for infection being spring and fall. Vaginal delivery and premature rupture of membranes may lead to an increased risk of vertical UU transmission from mother to child, and UU infection is strongly associated with preterm labor, low birth weight, pathogen co-infection, and related complications.

Alterations in peripheral T- and B-cell subsets in patients with systemic sclerosis.

OBJECTIVES: To determine the alteration of peripheral T and B cell subsets in patients with systemic sclerosis (SSc) and to evaluate their correlation with the progression of SSc. METHODS: We recruited 47 SSc patients and 45 healthy controls (HCs) in this study. Demographic and clinical data were then collected. Flow cytometry was used to detect the proportions of 44 different T and B cell subsets in circulating blood. RESULTS: The proportion of total B cells (p = .043) decreased in SSc patients, together with similar frequencies of total T cells, CD4+ T cells, and CD8+ T cells in both groups. Several subsets of T and B cells differed significantly between these two groups. Follicular helper T cells-1 (Tfh1) (p < .001), helper T cells-1 (Th1) (p = .001), regulatory T cells (Treg) (p = .004), effector memory CD8+ T cells (p = .041), and cytotoxic T cells-17 (Tc17) (p = .01) were decreased in SSc patients. Follicular helper T cells-2 (Tfh2) (p = .001) and, helper T cells-2 (Th2) (p = .001) levels increased in the SSc group. Regulatory B cells (Breg) (p = .015) were lower in the SSc group, together with marginal zone (MZ) B cells (p < .001), memory B cells (p = .001), and non-switched B cells (p = .005). The modified Rodnan skin score (mRSS) correlated with helper T cells-17 (Th17) (r = -.410, p = .004), Tfh1 (r = -.321, p = .028), peripheral helper T cells (Tph) (r = -.364, p = .012) and plasma cells (r = -.312, p = .033). CONCLUSIONS: The alterations in T and B cells implied immune dysfunction, which may play an essential role in systemic sclerosis.

Differences in clinical characteristics of early-onset and late-onset severe acute respiratory syndrome coronavirus 2 infections in neonates.

Differences in clinical characteristics of early-onset and late-onset severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in neonates remain unclear. This study aimed to determine whether there are differences in the main clinical, radiological, and laboratory features of early-onset and late-onset SARS-CoV-2 infections in neonates. This single-center, prospective cohort study enrolled neonates with SARS-CoV-2 infection from December 7, 2022, to January 3, 2023, and evaluated their clinical characteristics during hospitalization. All neonates (N = 58) infected with SARS-CoV-2 within 28 days of birth who were admitted to the neonatal intensive care unit of Taizhou Hospital were included. These neonates were classified into the early-onset (diagnosed within 7 days of birth) and late-onset (diagnosed more than 7 days after birth) groups. The symptoms, treatment, and prognosis of SARS-CoV-2 infection were the main study outcomes. The incidence of hospitalization attributable to SARS-CoV-2 infection was 10.6% (58 of 546 neonates) in Linhai. Sixteen (28%) of the 58 SARS-CoV-2 infections were early-onset cases, and 42 (72%) were late-onset cases. The common symptoms among the late-onset group were fever (p < 0.001) and cough (p < 0.001). Neonates with late-onset SARS-CoV-2 infection (p < 0.001) were significantly more likely to develop pneumonia.  Conclusion: The clinical symptoms and rates of pneumonia caused by SARS-CoV-2 infection in neonates differed between the early-onset and late-onset groups. Different clinical management is necessary for neonates with early-onset and late-onset SARS-CoV-2 infections. What is Known: • Neonates are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). • Differences in clinical characteristics of early-onset and late-onset SARS-CoV-2 infections in neonates remain unclear. What is New: • Fever and cough were the most common symptoms among neonates with late-onset infection. • Neonates with late-onset SARS-CoV-2 infection were more likely to develop pneumonia.

Evaluation of causal associations between interleukin-18 levels and immune-mediated inflammatory diseases: a Mendelian randomization study.

BACKGROUND: Altered interleukin (IL)-18 levels are associated with immune-mediated inflammatory diseases (IMIDs), but no studies have investigated their causal relationship. This study aimed to examine the causal associations between IL-18 and IMIDs. METHODS: We performed a two-sample Mendelian randomization (MR) analysis. Genetic variants were selected from genome-wide association study datasets following stringent assessments. We then used these variants as instrumental variables to estimate the causal effects of IL-18 levels on the risk of developing five common IMIDs: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), and psoriasis. We used the inverse variance-weighted (IVW) method as the primary analysis, with sensitivity analyses performed to avoid potential bias. Reverse-direction MR analyses were performed to rule out the possibility of reverse associations. RESULTS: We found that genetically determined higher circulating IL-18 levels were causally associated with a higher risk for SLE (PIVW = 0.009; OR, 1.214; 95% CI, 1.049 - 1.404) and IBD (PIVW < 0.001; OR, 1.142; 95% CI, 1.062 - 1.228), but found no significant associations of IL-18 with RA (PIVW = 0.496; OR, 1.044; 95% CI, 0.923 - 1.180), AS (PIVW = 0.021; OR, 1.181; 95% CI, 1.025 - 1.361), or psoriasis (PIVW = 0.232; OR, 1.198; 95% CI, 0.891 - 1.611). In the reverse direction, no causal relationship existed between SLE or IBD and IL-18 levels. Globally, sensitivity studies using alternative MR methods supported the results that were robust and reliable. The Cochran's Q test, MR-Egger intercept, and MR-Pleiotropy RESidual Sum and Outlier excluded the influence of heterogeneity, horizontal pleiotropy, and outliers. CONCLUSIONS: We have demonstrated that elevated IL-18 levels increase the risk of SLE and IBD but not RA, AS, or psoriasis. The results enhanced our understanding of IL-18 in the pathology of IMIDs.

MiR-17-5p promoter methylation regulated by DNA methyltransferase 3 beta (DNMT3B) expedites endometriosis via the Krüppel-like factor 12 (KLF12)/Wnt/ß-catenin axis.

Endometriosis (EM) is a common chronic disease in women with a high incidence, and aberrant DNA methylation and circulating endometrial cells (CECs) have been reported to be involved in the development of EM. However, the underlying mechanisms by which DNA methylation regulates EM progression have not been fully elucidated. In our study, we demonstrated that the DNA methyltransferase 3 beta (DNMT3B)-mediated DNA methylation modification enhanced EM progression through regulating miR-17-5p/KLF12/Wnt/ß-catenin axis. In detail, expression levels of miR-17-5p were significantly downregulated in EM tissues and serums, and we found that DNMT3B elevated the methylation modification of the miR-17-5p promoter, thereby suppressing the expression of miR-17-5p. Subsequently, functional experiments showed that silencing DNMT3B inhibited cell viability and epithelial-mesenchymal transition (EMT) and promoted cell apoptosis in CECs, whereas this effect could be reversed by knocking down miR-17-5p. Besides, overexpression of miR-17-5p repressed EM progression in vivo. Moreover, we found that miR-17-5p could target negative regulation of Krüppel-like factor 12 (KLF12) and KLF12 overexpression could rescue the effect of over-miR-17-5p. Besides, miR-17-5p was able to suppress the Wnt/ß-catenin signaling pathway, and blocked Wnt/ß-catenin pathway by XAV-939 reversed the influence of knockdown of miR-17-5p. Overall, our data indicated that DNMT3B-mediated DNA methylation leading to miR-17-5p inhibition exacerbated the process of EM by targeting KLF12/Wnt/ß-catenin axis, which provided a new perspective on targeted therapies for EM.

Abnormal topology of cortical thickness covariance network and altered functional connectivity in patients with anti-N-methyl-D-aspartate receptor encephalitis / 中华行为医学与脑科学杂志

Objective:To explore the changes in topological attributes of structural covariance network based on cortical thickness and the brain functional activities in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis by graph theory and functional connectivity (FC) analyses, and to investigate whether these changes were correlated to cognitive impairment.Methods:A total of 33 patients with anti-NMDAR encephalitis from Department of Neurology of the First Affiliated Hospital of Guangxi Medical University(patient group) and 35 healthy controls(control group) with matched gender, age, and education were included from July 2018 to November 2021.All subjects received cognitive function assessments, structural and functional magnetic resonance imaging scans.Structural covariance networks were constructed in the two groups based on cortical thickness values and topological characteristics of networks were computed.A non-parametric permutation test which repeated 1 000 times was used to compare the characteristics of the networks between the two groups.Brain regions with abnormal topology were defined as region of interest(ROI), and FC values in global brain level were calculated.SPM 12 and RESTplus were used to identify the brain regions with significant differences in FC values between the two groups.Finally, Spearman correlation analysis between FC values of significant brain regions and cognitive scores were performed by SPSS 24.0.Results:The cognitive score of patients with anti-NMDAR encephalitis (27.0(23.5, 28.0)) was lower than that in control group(29.0(27.0, 30.0)) ( Z=-3.029, P=0.002). Graph theory analysis found that the patients showed significantly increased clustering coefficients ( P=0.004) and decreased global efficiency ( P=0.004) compared with healthy controls.Moreover, the nodal efficiency of left ventral posterior cingulate cortex (vPCC) and right dorsal posterior cingulate cortex (dPCC), as well as the nodal degree centrality of left vPCC and left polar planum of superior temporal gyrus (ppSTG) in patient group were significantly decreased ( P<0.05, FDR corrected) compared with control group.FC analysis showed the increased FC values between left vPCC and posterior cerebellum (MNI: x=6, y=-66, z=-21), as well as between left ppSTG and anterior cerebellum (MNI: x=6, y=-54, z=-12) (GRF corrected, voxel level P<0.001, cluster level P<0.05) in patient grooup.The FC values between left vPCC and posterior cerebellum were negatively correlated with the cognitive scores ( r=-0.403, P=0.020). Conclusion:Patients with anti-NMDAR encephalitis show abnormal topology of structural covariance network based on cortical thickness and altered FC values, some of which are correlated to cognition and may be the underlying neural mechanism of cognitive impairment in patients with anti-NMDAR encephalitis.

Daidzein affects proliferation and apoptosis in non-small cell lung cancer cells:role of p53 signaling pathway / 中国药理学通报

Aim To investigate the effects of daidzeinDD on the proliferation and apoptosis of non-small cell lung cancer cells,with a focus on the possible role of the p53 signaling pathway in this regard. Methods CCK-8 method and flow cytometry were used to detect the effects of soy isoflavone crude extract and DD on the viability and apoptosis of HELF and H1299 cells. Gene microarray was used to detect the changes in gene expression after treatment of H1299 cells with DD. GSEA and differential analysis were used to screen the major pathways and key genes. RT-qPCR and Western blot were performed to verify the differences in mRNA and protein expression of key genesp53 and CASP9 in the major pathways. After p53 inhibitor Pifithrin-α inhibited the expression of p53,the effect of DD on p53 mRNA and protein expression levels was examined,and the proliferative effect on H1299 cells was observed. Results Soy isoflavone crude extract and DD promoted proliferation and inhibited apoptosis of normal lung cells and inhibited proliferation and promoted apoptosis of lung cancer cells. p53 signaling pathway was significantly enriched in the DD-treated groupNES=1.78,P=0.000,and the expressions of p53 and CASP9 genes were found to be significantly up-regulated in the treated group. Compared with the control group,mRNA expression of CASP9 and p53 significantly increased in both HELF and H1299 cells treated with DDP<0.05,and p53 protein expression also increased in HELF cellsP<0.05. After inhibition of p53 expression,DD significantly increased the mRNA expression of p53 in H1299 and HELF cellsP<0.05 and also markedly increased the expression of p53 protein in H1299 cellsP<0.05,and it was observed that DD inhibited the proliferation of lung cancer cells. Conclusions DD inhibits the proliferation and promotes the apoptosis of lung cancer H1299 cells,and the mechanism mainly involves the p53 signaling pathway.

Transformation Kinetics of LiBH4-MgH2 for Hydrogen Storage.

The reactive hydride composite (RHC) LiBH4-MgH2 is regarded as one of the most promising materials for hydrogen storage. Its extensive application is so far limited by its poor dehydrogenation kinetics, due to the hampered nucleation and growth process of MgB2. Nevertheless, the poor kinetics can be improved by additives. This work studied the growth process of MgB2 with varying contents of 3TiCl3·AlCl3 as an additive, and combined kinetic measurements, X-ray diffraction (XRD), and advanced transmission electron microscopy (TEM) to develop a structural understanding. It was found that the formation of MgB2 preferentially occurs on TiB2 nanoparticles. The major reason for this is that the elastic strain energy density can be reduced to ~4.7 × 107 J/m3 by creating an interface between MgB2 and TiB2, as opposed to ~2.9 × 108 J/m3 at the original interface between MgB2 and Mg. The kinetics of the MgB2 growth was modeled by the Johnson-Mehl-Avrami-Kolmogorov (JMAK) equation, describing the kinetics better than other kinetic models. It is suggested that the MgB2 growth rate-controlling step is changed from interface- to diffusion-controlled when the nucleation center changes from Mg to TiB2. This transition is also reflected in the change of the MgB2 morphology from bar- to platelet-like. Based on our observations, we suggest that an additive content between 2.5 and 5 mol% 3TiCl3·AlCl3 results in the best enhancement of the dehydrogenation kinetics.

Etanercept/celecoxib on improving MRI inflammation of active ankylosing spondylitis: A multicenter, open-label, randomized clinical trial.

Objective: To investigate the efficacy and safety of clinical, magnetic resonance imaging (MRI) changes in active ankylosing spondylitis (AS) patients with etanercept and celecoxib alone/combined treatment. Methods: A randomized controlled trial was conducted in three medical centers in China. Adult AS patients with BASDAI ≥4 or ASDAS ≥2.1, CRP >6 mg/L, or ESR 28 mm/1st hour were randomly assigned (1:1:1 ratio) to celecoxib 200 mg bid or etanercept 50 mg qw or combined therapy for 52 weeks. The primary outcomes were SPARCC change of the sacroiliac joint (SIJ) and spine and the proportion of patients achieving ASAS20 response at 52 weeks. Results: Between September 2014 and January 2016, we randomly assigned 150 patients (mean age, 32.4 years; mean disease duration, 109 months), and 133 (88.6%) completed the study. SPARCC inflammation scores of the SIJ and spine decreased in the three groups, and significant differences were found between the combined group and the celecoxib group [between-group difference: -6.33, 95% CI (-10.56, -2.10) for SIJ; -9.53, 95% CI (-13.73, -5.33) for spine] and between the etanercept group and the celecoxib group [between-group difference: -5.02, 95% CI (-9.29, -0.76) for SIJ; -5.80, 95% CI (-10.04, -1.57) for spine]. The ASAS20 response rates were 44%, 58%, and 84% in the celecoxib, etanercept, and combined groups, respectively, and a significant difference was only found between the combined and the celecoxib groups. Conclusion: Etanercept with or without celecoxib decreases inflammation detected by MRI at 1 year compared to celecoxib alone in active AS patients. The combination of etanercept and celecoxib was superior to celecoxib alone for the primary clinical response. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01934933.

Association of Plasma Anion Gap with 28-Day Inhospital Mortality and 1-Year Mortality of Patients with Alcohol Use Disorder at ICU Admission: A Retrospective Cohort Study.

Background: Alcohol use disorder (AUD) is common in critically ill patients. Plasma anion gap (AG) was known as a feasible parameter and was associated with outcomes of various diseases. This study is intended to explore whether AG is related to 28-day inhospital mortality and 1-year mortality of critically ill patients with AUD. Method: We extracted data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The association of plasma AG with 28-day inhospital mortality and 1-year mortality of critically ill AUD patients was assessed using Cox proportional hazard regression models and stratification analyses, allowing AG as a time-varying covariate in the models. To evaluate the accuracy of AG in predicting different endpoints, receiver operator characteristic (ROC) curves were used. Result: Among the 3993 critically ill patients with AUD, AG was positively associated with 28-day inhospital mortality and 1-year mortality after adjusting confounders (p < 0.001 for all). Compared with lower AG (<12 mmol/L), patients in different groups (12 ≤ AG < 14 mmol/L, 14 ≤ AG < 17 mmol/L, 17 ≤ AG < 20 mmol/L, and AG ≥ 20 mmol/L) had different HRs (95% CIs) for 28-day inhospital mortality (1.105, (0.906, 1.347); 1.171, (0.981, 1.398); 1.320, (1.108, 1.573); and 1.487, (1.254, 1.763), respectively) and 1-year mortality (1.037 (0.898, 1.196); 1.091 (0.955, 1.246); 1.201 (1.052, 1.371); and 1.3093 (1.149, 1.492), respectively). Conclusion: Increased AG is associated with greater 28-day inhospital mortality and 1-year mortality. The effect of AG on all-cause mortality is linear in critically ill AUD patients.

A yeast-based system to study SARS-CoV-2 Mpro structure and to identify nirmatrelvir resistant mutations

The SARS-CoV-2 main protease (Mpro) is a major therapeutic target. The Mpro inhibitor, nirmatrelvir, is the antiviral component of Paxlovid, an orally available treatment for COVID-19. As Mpro inhibitor use increases, drug resistant mutations will likely emerge. We have established a non-pathogenic system, in which yeast growth serves as a proxy for Mpro activity, enabling rapid identification of mutants with altered enzymatic activity and drug sensitivity. The E166 residue is known to be a potential hot spot for drug resistance and yeast assays showed that an E166R substitution conferred strong nirmatrelvir resistance while an E166N mutation compromised activity. On the other hand, N142A and P132H mutations caused little to no change in drug response and activity. Standard enzymatic assays confirmed the yeast results. In turn, we solved the structures of Mpro E166R, and Mpro E166N, providing insights into how arginine may drive drug resistance while asparagine leads to reduced activity. The work presented here will help characterize novel resistant variants of Mpro that may arise as Mpro antivirals become more widely used.

Microstructural Study of MgB2 in the LiBH4-MgH2 Composite by Using TEM.

The hampered kinetics of reactive hydride composites (RHCs) in hydrogen storage and release, which limits their use for extensive applications in hydrogen storage S1and energy conversion, can be improved using additives. However, the mechanism of the kinetic restriction and the additive effect on promoting the kinetics have remained unclear. These uncertainties are addressed by utilizing versatile transmission electron microscopy (TEM) on the LiBH4-MgH2 composite under the influence of the 3TiCl3·AlCl3 additives. The formation of the MgB2 phase, as the rate-limiting step, is emphatically studied. According to the observations, the heterogeneous nucleation of MgB2 relies on different nucleation centers (Mg or TiB2 and AlB2). The varied nucleation and growth of MgB2 are related to the in-plane strain energy density at the interface, resulting from the atomic misfit between MgB2 and its nucleation centers. This leads to distinct MgB2 morphologies (bars and platelets) and different performances in the dehydrogenation kinetics of LiBH4-MgH2. It was found that the formation of numerous MgB2 platelets is regarded as the origin of the kinetic improvement. Therefore, to promote dehydrogenation kinetics in comparable RHC systems for hydrogen storage, it is suggested to select additives delivering a small atomic misfit.

The pattern and trends of disease burden due to low bone mineral density from 1990 to 2019 in China: findings from the Global Burden of Disease Study 2019.

Osteoporosis is becoming increasing important health problem in China. This study shows that the disease burden of low bone mineral density (BMD) in China is large and will remain increasing with the growth of aging population. In addition, male low BMD should not be ignored. Although burden of low BMD is partially representative of the real burden of osteoporosis, the information provided in our study could be used to better inform targeted public health prevention and management programs for osteopososis. PURPOSE: We aim to investigate the pattern and trends of disease burden due to low BMD by gender, year, and age in China from 1990 to 2019. METHODS: Data on summary exposure value (SEV) and disability-adjusted life years (DALYs) due to low BMD was obtained from the Global Burden of Disease Study 2019, and analyzed by gender, age, and years. Average annual percent change (AAPC) and annual percent change (APC) were calculated to qualify the trends of burden due to low BMD. RESULT: In 2019, the age-standardized SEV was higher in females than that in males (23.04, 95% UI = [17.25-29.83] and 12.50, 95% UI = [7.71-19.25], respectively), while the total number of DALYs was higher in males than females with 1,698,705.92 (95% UI = 1,281,580.79 to 2,076,364.25) and 1,621,569 (95% UI = 1,266,284.89 to 2,016,399.16), respectively. Though SEV exhibited decreasing trends during 1990 to 2019 in both sexes, the absolute number of DALYs due to low BMD increased steadily and almost doubled in 2019 compared to that in 1990. CONCLUSION: The burden of low BMD remains large and continues to increase. Although females are prone to low BMD, the disease burden for males should not be ignored.

Adalimumab Therapy Restores the Gut Microbiota in Patients With Ankylosing Spondylitis.

Growing evidence suggests that the gut microbiota is involved in the initiation and progression of ankylosing spondylitis (AS). In this study, we aimed to explore the gut microbiome alterations during adalimumab therapy and verify microbiome biomarkers predicting treatment response. By evaluating the gut microbial features of 30 AS patients before and after adalimumab therapy for 6 months and 24 healthy controls, we confirmed that the microbiome was restored remarkably after 6 months of adalimumab therapy in AS patients. We then compared the baseline gut microbiome of 22 adalimumab responders with 8 non-responders, a higher abundance of Comamonas was revealed in the latter, although no statistical difference was found after adjusting for the false discovery rate. These results suggested that adalimumab therapy restored the gut microbiome in AS patients and indicated the utility of gut microbiome to be potential biomarkers for therapeutic evaluation. These findings provided an insight into the development of predictive tools and the establishment of precise medical interventions for clinical practice.

TNF-α inhibitor therapy can improve the immune imbalance of CD4+ T cells and negative regulatory cells but not CD8+ T cells in ankylosing spondylitis.

BACKGROUND: Studies into ankylosing spondylitis (AS) and its relationship with immune imbalance are controversial, and the correlation between the efficacy of TNF-α inhibitor and changes in immune imbalance is unclear. METHODS: A total of 40 immune cells were tested with flow cytometry, and the results of 105 healthy control (HC) subjects, 177 active-stage AS patients, and 23 AS cases before and after 12 weeks of TNF-α inhibitor therapy (Anbainuo) were analyzed. RESULTS: Compared with the HC group, the proportion of immune cells, such as naïve and central memory CD4+T cells, in AS increased (P < 0.0001), but effector memory and terminally differentiated CD4+T cells were decreased (P < 0.01 and 0.0001, respectively). Naïve, central memory, and effector memory CD8+T cells were increased (P < 0.0001, 0.001, and 0.01, respectively), but terminally differentiated CD8+T cells were decreased (P < 0.0001). Th1 cells (helper T cells-1), Tfh1 cells (follicular helper T cells-1), Tc1 cells (cytotoxic T cells-1), and Tregs (regulatory T cells) were lower (P < 0.01, 0.05, 0.0001, and 0.001, respectively), but Th17 cells, Tfh17 cells, and Tc cells were higher (P < 0.001, 0.0001, and 0.001, respectively). The proportions of total B cells and class-switched B cells were increased (P < 0.05), but non-switched B cells, plasma cells, memory B cells, and immature Bregs (regulatory B cells) were lower (P < 0.01, 0.0001, 0.0001, and 0.0001, respectively). After Anbainuo therapy, the percentage of naïve CD4+ T cells had decreased (P < 0.05) but Tregs and B10 cells (IL-10-producing regulatory B cells) had increased (P < 0.01 and 0.05, respectively), and the increase in Tregs was positively correlated with the decrease in C-reactive protein (CRP) (r = 0.489, P = 0.018). CONCLUSIONS: We found that active-stage AS patients have an immunity imbalance of frequency involving multiple types of immune cells, including CD4+T cells, CD8+T cells, Th cells, Tfh cells, Tc cells, Tregs, Bregs, and B cells. TNF-α inhibitor Anbainuo can not only help to inhibit disease activity but can also improve the immune imbalance of CD4+ T cells and negative regulatory cells in frequency. But CD8+ T cells have not been rescued.

Alterations in intra- and internetwork functional connectivity associated with levetiracetam treatment in temporal lobe epilepsy.

OBJECTIVE: Levetiracetam (LEV) is an antiepileptic drug with a novel pharmacological mechanism. Advances in functional magnetic resonance imaging (fMRI) enable researchers to explore the cognitive effects of antiepileptic drugs on the living brain. This study aimed to explore how the functional connectivity patterns of the cognitive networks changed in association with LEV treatment. METHODS: Patients with temporal lobe epilepsy (TLE), including both users and nonusers of LEV, were included in this study along with healthy controls. Core cognitive networks were extracted using an independent component analysis approach. Functional connectivity patterns within and between networks were investigated. The relationships between functional connectivity patterns and clinical characteristics were also examined. RESULTS: The patterns of intranetwork connectivity in the default mode network (DMN), left executive control network (lECN), and dorsal attention network (DAN) differed among the three groups. The internetwork interactions did not show intergroup differences once corrected for multiple comparisons. No correlation between functional connectivity and clinical characteristics was found in patients with TLE. CONCLUSIONS: Changes in intranetwork connectivity are a key effect of LEV administration. SIGNIFICANCE: Alterations in intranetwork connectivity patterns may underlie the cognitive effects of LEV administration; this finding improves our understanding of the neural mechanisms of LEV therapy.

Correction to: Role of community-based active case finding in screening tuberculosis in Yunnan province of China.

In the original publication of this article [1] we noticed the Fig. 4 was incorrect. The correct Fig. 4 is as below.

Granulocyte colony-stimulating factor and stromal cell-derived factor-1 combination therapy: A more effective treatment for cerebral ischemic stroke.

BACKGROUND: Drugs that promote angiogenesis include statins, recombinant human granulocyte colony-stimulating factor, and stromal cell-derived factor-1. Low doses of atorvastatin could significantly increase the vascular expressions of endothelial growth factor, and the number of peripheral blood endothelial progenitor cells (EPCs), thus improving angiogenesis and local blood flow. G-CSF is an EPC-mobilization agent used in ischemia studies for targeting angiogenesis after cerebral ischemia via EPCs. In previous clinical trials, consistent conclusions have not been reached about the effectiveness of G-CSF on ischemic stroke. Therefore, the therapeutic effect of G-CSF and its combination with other medicines need further experimental verification. It is known that atorvastatin, rhG-CSF, and SDF-1 are considered the most promising neuroprotective candidates, but a comprehensive comparison of their effects is lacking. AIMS: To compare the effects of atorvastatin, stromal cell-derived factor-1, and recombinant human granulocyte colony-stimulating factor on ischemic stroke. METHODS: Adult male Sprague-Dawley rats were randomly allocated to three groups: normal, sham-operated, and middle cerebral artery occlusion operated. Middle cerebral artery occlusion operated rats were further allocated into saline, atorvastatin, recombinant human granulocyte colony-stimulating factor, and recombinant human granulocyte colony-stimulating factor + stromal cell-derived factor-1 groups. Neurological function evaluation, cerebral infarction and the blood-brain barrier integrity analysis, identification of angiogenic factors, assessment of angiogenesis, expression of growth-associated protein-43, neuroglobin, glial cell-derived neurotrophic factor, and cleaved caspase 3, were performed. RESULTS: Compared with atorvastatin or recombinant human granulocyte colony-stimulating factor alone, recombinant human granulocyte colony-stimulating factor + stromal cell-derived factor-1 treatment improved neurological performance, reduced cerebral infarction and blood-brain barrier disruption after stroke, and increased the content of stromal cell-derived factor-1, vascular endothelial growth factor, monocyte chemotactic protein 1, and basic fibroblast growth factor in peripheral blood. In addition, recombinant human granulocyte colony-stimulating factor + stromal cell-derived factor-1 promoted greater angiogenesis than atorvastatin or recombinant human granulocyte colony-stimulating factor alone and increased the expression of growth-associated protein-43, neuroglobin, and glial cell-derived neurotrophic factor, while decreasing the levels of cleaved caspase 3 in the brain after ischemic stroke. CONCLUSIONS: Combination therapy with recombinant human granulocyte colony-stimulating factor and stromal cell-derived factor-1 is more effective than atorvastatin or recombinant human granulocyte colony-stimulating factor alone in protecting against stroke-induced damage and could be an optimal therapeutic strategy for stroke.

Role of community-based active case finding in screening tuberculosis in Yunnan province of China.

BACKGROUND: The barriers to access diagnosis and receive treatment, in addition to insufficient case identification and reporting, lead to tuberculosis (TB) spreads in communities, especially among hard-to-reach populations. This study evaluated a community-based active case finding (ACF) strategy for the detection of tuberculosis cases among high-risk groups and general population in China between 2013 and 2015. METHODS: This retrospective cohort study conducted an ACF in ten communities of Dongchuan County, located in northeast Yunnan Province between 2013 and 2015; and compared to 136 communities that had passive case finding (PCF). The algorithm for ACF was: 1) screen for TB symptoms among community enrolled residents by home visits, 2) those with positive symptoms along with defined high-risk groups underwent chest X-ray (CXR), followed by sputum microscopy confirmation. TB incidence proportion and the number needed to screen (NNS) to detect one case were calculated to evaluate the ACF strategy compared to PCF, chi-square test was applied to compare the incidence proportion of TB cases' demography and the characteristics for detected cases under different strategies. Thereafter, the incidence rate ratio (IRR) and multiple Fisher's exact test were applied to compare the incidence proportion between general population and high-risk groups. Patient and diagnostic delays for ACF and PCF were compared by Wilcoxon rank sum test. RESULTS: A total of 97 521 enrolled residents were visited with the ACF cumulatively, 12.3% were defined as high-risk groups or had TB symptoms. Sixty-six new TB patients were detected by ACF. There was no significant difference between the cumulative TB incidence proportion for ACF (67.7/100000 population) and the prevalence for PCF (62.6/100000 population) during 2013 to 2015, though the incidence proportion in ACF communities decreased after three rounds active screening, concurrent with the remained stable prevalence in PCF communities. The cumulative NNS were 34, 39 and 29 in HIV/AIDS infected individuals, people with positive TB symptoms and history of previous TB, respectively, compared to 1478 in the general population. The median patient delay under ACF was 1 day (Interquartile range, IQR: 0-27) compared to PCF with 30 days (IQR: 14-61). CONCLUSIONS: This study confirmed that massive ACF was not effective in general population in a moderate TB prevalence setting. The priority should be the definition and targeting of high-risk groups in the community before the screening process is launched. The shorter time interval of ACF between TB symptoms onset and linkage to healthcare service may decrease the risk of TB community transmission. Furthermore, integrated ACF strategy in the National Project of Basic Public Health Service may have long term public health impact.

Long noncoding RNA LINC00473 drives the progression of pancreatic cancer via upregulating programmed death-ligand 1 by sponging microRNA-195-5p.

Pancreatic cancer (PC) is a great health burden to patients owing to its poor overall survival rate. Long noncoding RNAs (lncRNAs) interact with microRNAs (miRs) to participate in tumorigenesis. Therefore, we aim to uncover the role and related mechanism of LINC00473 in PC through the modulation of miR-195-5p and programmed death-ligand 1 (PD-L1). Increased LINC00473 and PD-L1 but declined miR-195-5p were determined in PC tissues and cell lines, and it was found that LINC00473 mainly situated in the cytoplasm. Also, miR-195-5p was verified to bind with both LINC00473 and PD-L1. Next, with the aim to examine the ability of LINC00473, miR-195-5p, and PD-L1 on the PC progression, the expression of LINC00473, miR-195-5p and PD-L1 were altered with mimics, inhibitors, overexpression vectors or siRNAs in PC cells and cocultured CD8+ T cells. It was demonstrated that LINC00473 sponged miR-195-5p to upregulate PD-L1 expression. More important, the obtained results revealed that LINC00473 silencing or miR-195-5p upregulation elevated the expression of Bcl-2 associated X protein (Bax), interferon (IFN)-γ, and interleukin (IL)-4 but reduced the expression of B-cell lymphoma-2 (Bcl-2), matrix metalloproteinase (MMP)-2, MMP-9, and IL-10, thus inducing the enhancement of the apoptosis as along with the inhibition of proliferation, invasion, and migration of the PC cells. LINC00473 silencing or miR-195-5p elevation activated the CD8+ T cells. Taken together, LINC00473 silencing blocked the PC progression through enhancing miR-195-5p-targeted downregulation of PD-L1. This finding offers new therapeutic options for treating this devastating disease.