Genetic variation and evolutionary characteristics of Echovirus 11: new variant within genotype D5 associated with neonatal death found in China.

Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000-2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014-2019, D5-CHN2: 2016-2022, and D5-EUR: 2022-2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the VP1 region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.

Angiotensin II Type 2 Receptor Inhibits M1 Polarization and Apoptosis of Alveolar Macrophage and Protects Against Mechanical Ventilation-Induced Lung Injury.

Angiotensin II (Ang II) is associated with macrophage polarization and apoptosis, but the role of the angiotensin type 2 receptor (AT2R) in these processes remains controversial. However, the effect of AT2Rs on alveolar macrophages and mechanical ventilation-induced lung injury has not been determined. Mechanical ventilation-induced lung injury in Sprague‒Dawley (SD) rats and LPS-stimulated rat alveolar macrophages (NR8383) were used to determine the effects of AT2Rs, selective AT2R agonists and selective AT1Rs or AT2R antagonists. Macrophage polarization, apoptosis, and related signaling pathways were assessed via western blotting, QPCR and flow cytometry. AT2R expression was decreased in LPS-stimulated rat alveolar macrophages (NR8383). Administration of the AT2R agonist CGP-42112 was associated with an increase in AT2R expression and M2 polarization, but no effect was observed upon administration of the AT2R antagonist PD123319 or the AT1R antagonist valsartan. In mechanical ventilation-induced lung injury in Sprague‒Dawley (SD) rats, the administration of the AT2R agonist C21 was associated with attenuation of the pathological damage score, lung wet/dry weight, cell count and protein content in BALF. C21 can significantly reduce proinflammatory factor TNF-α, IL-1ß levels, increase anti-inflammatory factor IL-4, IL-10 levels in BALF, compared with the model group (p < 0.01). Similarly, compared with those at the same time points, the M1/M2 ratios in alveolar macrophages and apoptosis in peritoneal macrophages at 4 h, 6 h and 8 h in the mechanical ventilation models were lower after C21 administration. These findings indicated that the expression of AT2Rs in alveolar macrophages mediates M1 macrophage polarization and apoptosis and that AT2Rs play a protective role in mediating mechanical ventilation-induced lung injury.

The economic impact of international travel measures used during the COVID-19 pandemic: a scoping review.

INTRODUCTION: Assessment of the use of travel measures during COVID-19 has focused on their effectiveness in achieving public health objectives. However, the prolonged use of highly varied and frequently changing measures by governments, and their unintended consequences caused, has been controversial. This has led to a call for coordinated decision-making focused on risk-based approaches, which requires better understanding of the broader impacts of international travel measures (ITMs) on individuals and societies. METHODS: Our scoping review investigates the literature on the economic impact of COVID-19 ITMs. We searched health, social science and COVID-19-specific databases for empirical studies preprinted or published between 1 January 2020 and 31 October 2023. Evidence was charted using a narrative approach and included jurisdiction of study, ITMs studied, study design, outcome categories, and main findings. RESULTS: Twenty-six studies met the inclusion criteria and were included for data extraction. Twelve of them focused on the international travel restrictions implemented in early 2020. Limited attention was given to measures such as entry/exit screening and vaccination requirements. Eight studies focused on high-income countries, 6 on low-income and middle-income countries and 10 studies were comparative although did not select countries by income. Economic outcomes assessed included financial markets (n=13), economic growth (n=4), economic activities (n=1), performance of industries central to international travel (n=9), household-level economic status (n=3) and consumer behaviour (n=1). Empirical methods employed included linear regression (n=17), mathematical modelling (n=3) and mixed strategies (n=6). CONCLUSION: Existing studies have begun to provide evidence of the wide-ranging economic impacts resulting from ITMs. However, the small body of research combined with difficulties in isolating the effects of such measures and limitations in available data mean that it is challenging to draw general and robust conclusions. Future research using rigorous empirical methods and high-quality data is needed on this topic.

COVID-19 Omicron variant infection has minimal impact on maternal and neonatal outcomes: A cross-sectional cohort study.

AIM: To explore the impact of the Omicron variant on maternal and neonatal outcomes. DESIGN: Cross-sectional cohort study of women giving live birth in a single hospital in Shanghai in December 2022. METHODS: Demographic characteristics, maternal and neonatal outcomes and laboratory testing results were retrieved from medical records. Propensity score matching was used to match COVID-19-positive and -negative women. Differential analysis was used to assess associations between COVID-19 and in-hospital maternal and neonatal outcomes. RESULTS: A total of 1508 women were included, comprising 729 natural births, 741 caesarean sections and 38 forceps deliveries. After 1:1 matching, 310 clients were included for analysis with each 155 in COVID-19-positive and -negative groups. Higher maternal fever was found in all modes of delivery, and higher preterm birth and lower pH value of blood gas of the umbilical artery in the vaginal delivery subgroup (p < 0.05). Other maternal and neonatal outcomes showed no significant difference between COVID-19-positive and -negative clients.

Prognostic significance of positive lymph node regression grade to neoadjuvant chemoradiation for esophageal squamous cell carcinoma.

BACKGROUND AND PURPOSE: To assess the relationship between metastatic lymph node (LN) responder status and recurrence-free survival (RFS) in patients undergoing neoadjuvant chemoradiotherapy (NCRT). MATERIALS AND METHODS: We retrospectively reviewed 304 patients with local advanced esophageal squamous cell carcinoma received NCRT followed by esophagectomy. For 112 patients with positive node, according to the proportion of residual viable tumor cells area within the whole tumor beds of all metastatic LNs, we classified LN-tumor regression grade (LN-TRG) into four categories: grade 1, 0%; 2, <10%; 3, 10%-50%; 4, >50%. Patients with grade 1-2 LN-TRG of were considered LN responders, and those with grades 3-4, as LN nonresponders. Univariate and multivariate analyses of RFS were estimated by a Cox regression model, Kaplan-Meier curve, and log-rank test. RESULTS: The median follow-up time of a total of 112 patients was 29.6 months. Fifty-two (46.4%) patients have experienced recurrence. In Cox univariate analysis, differentiation, AJCC stage LN responder status, nerve invasion, and lymphovascular invasion significantly correlated with RFS. Multivariate analysis for RFS revealed that LN responder status and AJCC stage (p < 0.05) were independent prognostic factor. The 3-year RFS rates for patients with LN-TRG of 1-4 grades were 72.7%, 76.5%, 37.4%, and 28.5%, respectively, and the median RFS times were not reach, 43.56, 28.09, and 22.77, respectively. CONCLUSIONS: LN responder status is an independent prognostic factor for RFS in esophageal cancer patients who received NCRT.

Plant-plant interactions vary greatly along a flooding gradient in a dam-induced riparian habitat.

Plant-plant interactions under extreme environmental stress are still controversial. The stress gradient hypothesis (SGH) proposes that facilitation prevails under extreme environmental stresses, while an alternative view states that facilitation collapses or even switches back to competition at the extreme end of stress gradients. However, how the relationship between plant-plant interaction and periodic extreme flooding stress varies and its underlying mechanism are still unclear in a dam-regulated riparian ecosystem. We established a controlled experiment using two dominant species pairs (Cynodon dactylon-Cyperus rotundus and C. dactylon-Xanthium sibiricum) in the water level fluctuating zone of the Three Gorges Dam to examine their growth responses to the periodic extreme flooding stress. The results showed that as flooding stress increased, the competitive effect of C. dactylon on X. sibiricum shifted to facilitation, whereas the effect of X. sibiricum on C. dactylon maintained a strong inhibition. The plant height of X. sibiricum was the most important driver of the interaction between X. sibiricum and C. dactylon along the flooding gradient. The net effect of C. dactylon on C. rotundus shifted from neutral to negative, and the inhibitory effect of C. rotundus on C. dactylon became stronger at the extreme end of flooding stress. The root biomass of the two species was the key trait regulating their interaction with increasing flooding stress. Overall, the SGH was partially supported along our periodic extreme flooding stress gradient. Aboveground resource (light) might be the dominant factor driving the response of the interaction between annual plants and perennial clonal plants to periodic flooding stress, whereas belowground resource (water and nutrients) was probably the dominant factor for perennial clonal plants. Our study will help to further understand the environmental responses of plant-plant relationships and their regulatory mechanism, and the succession of riparian plant communities under extreme environmental changes, providing a basic theoretical basis and data support for the ecological restoration and management of riparian wetland vegetation.

The changes and causes of asthenopia after ICL implantation.

OBJECTIVE: To detect the presence of asthenopia after implantation of Implantable Collamer Lens (ICL). METHOD: Design: prospective observational case series. Patients with myopia and/or astigmatism who underwent ICL surgeries and completed 3-month follow-up were enrolled. Asthenopia scores, amplitude of accommodation (AA), positive/negative relative accommodation (PRA/NRA), accommodative facility (AF), the ratio of accommodative convergence and accommodation (AC/A), Schirmer test, noninvasive breakup time (NBUT), and HOA were examined before surgeries and at 1 week, 1 month and 3 months postoperatively then statistically analyzed. RESULTS: Symptoms of asthenopia were significantly decreased at 1 week after ICL surgeries than those before surgeries, but increased gradually as time went by, eventually recovered at 3 months postoperatively. AA, AF, AC/A decreased 1 week postoperatively, returned to the baseline at 1 month and were improved at 3 months after surgeries. NBUT at 1 week, 1 month and 3 months after surgeries were significantly decreased and was the lowest at 1 week postoperatively. PRA, NRA, Schiermer values and HOA had no significant change. Correlation analysis showed that the lower AF and NBUT after ICL surgeries, the more severe the asthenopia symptoms. CONCLUSION: The symptoms of asthenopia aggravated transiently after ICL implantation surgeries, but improved gradually with time. AF and NBUT were important factors affecting the changes of asthenopia.

Protective effects and mechanism of curcumin in animal models of pulmonary fibrosis: a preclinical systematic review and meta-analysis.

Introduction: At present, there is a lack of effective treatment for pulmonary fibrosis (PF), and a number of studies have confirmed that curcumin (CUR) has a good effect on PF. Research Qusetion: Is CUR effective in preclinical trials for PF and what is its mechanism of action? Methods: Animal reports of PF treated with CUR were searched from Pubmed, Embase, Web of Science and Cochrane Library from 1 January 2000 to 19 April 2023 to compare CUR treatment of PF with a no-intervention model group. A previous registration (nsply registration number: INPLASY202360084) of this review protocol was undertaken. Results: The meta-analysis included 27 publications and 29 studies involving 396 animals. CUR significantly improved the degree of fibrosis, levels of inflammation, and oxidative imbalances in lung tissue in animal models of PF. In terms fibrosis, such as HYP content (SMD = -4.96; 95% CI = -6.05 to -3.87; p = 0.000).In terms of inflammatory indicators, such as MPO activity (SMD = -2.12; 95% CI = -4.93 to 0.69; p = 0.000). In terms of oxidation index, such as MDA (SMD = -5.63; 95% CI = -9.66 to -1.6; p = 0.000). Conclusion: CUR significantly improved the degree of fibrosis, levels of inflammation, and oxidative imbalances in lung tissue in animal models of PF. Due to the quantitative and qualitative limitations of current research, more high-quality studies are needed to verify the above conclusion.

Identification of QTLs and their candidate genes for the number of maize tassel branches in F2 from two higher generation sister lines using QTL mapping and RNA-seq analysis.

Tassel branch number is an important agronomic trait that is closely associated with maize kernels and yield. The regulation of genes associated with tassel branch development can provide a theoretical basis for analyzing tassel branch growth and improving maize yield. In this study. we used two high-generation sister maize lines, PCU (unbranched) and PCM (multiple-branched), to construct an F2 population comprising 190 individuals, which were genotyped and mapped using the Maize6H-60K single-nucleotide polymorphism array. Candidate genes associated with tassel development were subsequently identified by analyzing samples collected at three stages of tassel growth via RNA-seq. A total of 13 quantitative trait loci (QTLs) and 22 quantitative trait nucleotides (QTNs) associated with tassel branch number (TBN) were identified, among which, two major QTLs, qTBN6.06-1 and qTBN6.06-2, on chromosome 6 were identified in two progeny populations, accounting for 15.07% to 37.64% of the phenotypic variation. Moreover, we identified 613 genes that were differentially expressed between PCU and PCM, which, according to Kyoto Encyclopedia of Genes and Genomes enrichment analysis, were enriched in amino acid metabolism and plant signal transduction pathways. Additionally, we established that the phytohormone content of Stage I tassels and the levels of indole-3-acetic acid (IAA) and IAA-glucose were higher in PCU than in PCM plants, whereas contrastingly, the levels of 5-deoxymonopolyl alcohol in PCM were higher than those in PCU. On the basis of these findings, we speculate that differences in TBN may be related to hormone content. Collectively, by combining QTL mapping and RNA-seq analysis, we identified five candidate genes associated with TBN. This study provides theoretical insights into the mechanism of tassel branch development in maize.

Rapid detection of Heterobasidion annosum using a loop-mediated isothermal amplification assay.

Heterobasidion annosum is one of the most aggressive pathogens of Pinus forests in Europe, causing considerable economic losses. To detect H. annosum for disease diagnosis and control, we developed a loop-mediated isothermal amplification (LAMP) reaction with a primer set designed from the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) DNA sequences of H. annosum. In our study, this LAMP assay was found to be capable of efficiently amplifying the target gene within 60 min at 63°C. In specificity tests, H. annosum was positively detected, and other species were negative. The detection limit of this assay was found to be 100 pg·µL-1, and the assay was also successfully tested for use with basidiospore suspensions and wood samples. This study provides a rapid method for diagnosing root and butt rot caused by H. annosum, which will be of use in port surveillance of logs imported from Europe.

Can precancerous stem cells be risk markers for malignant transformation in the oral mucosa?

Accurate assessment of the carcinogenic potential of oral mucosal diseases can significantly reduce the prevalence of oral cancer. We speculate that precancerous stem cells (pCSCs) arise during the evolution of carcinomas based on long-term experimental findings, published literature, and the cancer stem cell (CSC) theory, wherein pCSCs exist in precancerous lesions and have characteristics of both CSCs and normal stem cells. This apparently contradictory feature may be the foundation of the reversible transformation of precancerous lesions. Predicting malignant transformation in potentially malignant oral illnesses would allow for focused treatment, prognosis, and secondary prevention. Currently available clinical assays for chromosomal instability and DNA aneuploidy have several deficiencies. We hope that our study will increase attention to pCSC research and lead to the development of novel strategies for the prevention and treatment of oral cancer by identifying pCSC markers.

Prevention of skin damages related to personal protective equipment among healthcare workers: Summary of best-evidence practiced strategies.

AIM: To conduct a quality evaluation of the literature for the prevention of skin damage caused by personal protective equipment among healthcare workers and to summarise the best-evidence practice strategies to prevent it. DESIGN: Review. METHODS: Two researchers retrieved the literature from Web of Science, Public Medicine, etc., from the establishment of the database until 24 June 2022. Appraisal of Guidelines, Research and Evaluation II was used to assess the methodological quality of the guidelines. Expert consensus was assessed by the 2016 version of the Australian Joanna Briggs Institute Evidence-based Health Care Center corresponding evaluation standards. By tracking the original study, the quality of practice recommendations and best-practice evidence information sheets were evaluated by the 2016 version of the Australian Joanna Briggs Institute Evidence-based Health Care Center corresponding evaluation standards. The classification of evidence and recommendation level adopted the 2014 version of the Australian Joanna Briggs Institute evidence pre-grading and recommending level system. RESULTS: A total of 5476 studies were retrieved after duplications were eliminated. After the quality evaluation, 10 qualified studies were finally included. All consisted of two guidelines, one best practice information sheet, five practice recommendations, and one expert consensus. The evaluation results of the guidelines were both B-level recommendations. The consistency strength of expert consensus was moderate (Cohen's kappa coefficient = .571). Thirty best-evidence practised strategies were compiled for four elements, including cleaning, moisturising, prophylactic dressings and others. CONCLUSION: Our study evaluated the quality of the included studies and summarised the preventive measures of PPE-related skin lesions according to the recommendation level. The main preventive measures were divided into 4 parts and 30 items. However, the associated literature was rare, and the quality was slightly low. More high-quality research is needed to focus on healthcare workers' health and not just skin in the future.

Light-acquisition traits link aboveground biomass and environment in inner saline-alkaline herbaceous marshes.

A functional response-effect approach could predict how environmental changes affect ecosystem functioning. However, few studies have applied this approach to inner saline-alkaline marsh ecosystems where soil saline-alkaline, flooding/drought and nutrients stresses threat ecological functioning. To disentangle the relationships between environmental conditions and ecosystem functioning, a total of 81 plots were investigated across 22 marsh sites dominated by Phragmites australis and Bolboschoenus planiculmis in Western Songnen Plain wetlands, China. For both plant communities combined, deep flooding supported communities with higher specific leaf area (SLA), plant height and leaf nitrogen (N) content but lower leaf thickness. On the contrary, high soil salt content induced low leaf N and phosphorus (P) content, SLA and plant height. Only light acquisition-related trait, plant height and SLA, was the key traits which determined the relationships between ecosystem functioning (aboveground biomass) and saline-alkaline wetland environment. Yet indirect key traits related nutrient and water acquisition such as leaf thickness, N and P content were also found, and mediated the response of aboveground biomass through the allometric relationships with plant height or SLA. For the individual species community, only plant height was the key trait shared by P. australis and B. planiculmis, indicating the universality of plant height as a key trait for grass and sedge plants to explain how ecosystem functioning responds to abiotic factors. Hence, our findings suggest that saltmarsh plants are more inclined to alter light-acquisition traits to mediate the response of ecosystem functioning to environmental changes and that plant height is a particularly useful trait to predict plant productivity in earth system models under future environmental changes in inner saline-alkaline wetlands.

Retinal development and the expression profiles of opsin genes during larval development in Takifugu rubripes.

The light-sensitive capacity of fish larvae is determined by the structure of the retina and the opsins expressed in the retinal and nonretinal photoreceptors. In this study, the retinal structure and expression of opsin genes during the early developmental stage of Takifugu rubripes larvae were investigated. Histological examination showed that at 1 days after hatching (dah), seven layers were observed in the retina of T. rubripes larva, including the pigment epithelial layer [retinal pigment epithelium layer (RPE)], photoreceptor layer (PRos/is), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL) and ganglion cell layer (GCL). At 2 dah, optic fibre layer (OFL) can be observed, and all eight layers were visible in the retina. By measuring the thickness of each layer, opposing developmental trends were found in the thickness of ONL, OPL, INL, IPL, GCL and OFL. The nuclear density of ONL, INL and GCL and the ratios of ONL/INL, ONL/GCL and INL/GCL were also measured and the ratio of ONL/GCL ranged from 1.9 at 2 dah to 3.4 at 8 dah and no significant difference was observed between the different developmental stages (P > 0.05). No significant difference was observed for the INL/GCL ratio between the different developmental stages, which ranged from 1.2 at 2 dah to 2.0 at 18 dah (P > 0.05). The results of quantitative real-time polymerase chain reaction (PCR) showed that the expression of RH1, LWS, RH2-1, RH2-2, SWS2, rod opsin, opsin3 and opsin5 could be detected from 1 dah. These results suggest that the well-developed retina and early expression of the opsins of T. rubripes during the period of transition from endogenous to mixed feeding might be critical for vision-based survival skills during the early life stages after hatching.

CNTF induces Clcf1 in astrocytes to promote the differentiation of oligodendrocyte precursor cells.

NSCs play an essential role in the regeneration process of the central nervous system. However, due to the influence of the harsh pathological microenvironment, the viability of neural stem cells is limited, and the therapeutic effect needs improvement. Previous studies have found that stem cells overexpressing ciliary neurotrophic factor (CNTF) have apparent therapeutic effects on remyelination, but the specific mechanism of action still needs to be further explored. We found that astrocytes, the most numerous groups in the CNS, exhibited a pathological role in the experimental autoimmune encephalomyelitis model, but after stimulation with CNTF-NSCs, a phenotypic switch occurred and induced the neurotrophic factor cardiotrophin-like cytokine 1 (Clcf1) production. Mechanistically, Clcf1 can significantly promote the differentiation of oligodendrocyte precursor cells (OPCs), and the advanced effect can attenuate by the Clcf1 antibody. Therefore, this study was conducted to investigate the pathway by which CNTF-NSCs exert their therapeutic effects by affecting astrocytes. It is expected to identify a potential therapeutic factor, Clcf1, for the treatment of demyelinating diseases.

Wenshen Jianpi recipe induced immune reconstruction and redistribution of natural killer cell subsets in immunological non-responders of human immunodeficiency virus/acquired immune deficiency syndrome: a randomized controlled trial.

OBJECTIVE: To evaluate the effects of the Wenshen Jianpi recipe (, WJR) on immune reconstruction and natural killer (NK) cells in immunological non-responders (INRs) of people living with human immunodeficiency virus (HIV) (PLWH) and propose new therapeutic strategies for HIV. METHODS: Based on Traditional Chinese Medicine treatment principle "invigorating and warming in the spleen and kidneys", WJR combined with antire-troviral therapy (ART) therapy was performed in a randomized, double-blind, placebo-controlled study of 60 patients with non-responders. The randomized process was executed by the Clinical Evaluation Center of China Academy of Chinese Medical Sciences. Sixty patients who met the inclusion criteria obtained random numbers (that is the drug number) was randomly divided into a treatment group and a placebo control group according to a 1∶1 ratio. CD4+T cell counts and natural killer (NK) cells counts were evaluated at baseline and 12-week, 24-week follow-ups. RESULTS: Four participants received random numbers and did not enter the group due to the patient's own reasons. A total of 56 patients were enrolled, including 28 in the treatment group and 28 in the control group. CD4+T cell counts in the treatment group were significantly increased at week 24 ( = 0.01 < 0.05), which were significantly higher than those in the control group (= 0.01 < 0.05). Although no significant differences were observed between two groups, the CD56briCD16- NK cell counts in the treatment group were significantly increased after duration. and CD56dimCD16+ NK cell counts in the treatment group were significantly higher than those in the control group after 24 weeks of treatment (= 0.025 < 0.05). As compared with the control group, the treatment group had significantly lower CD56negCD16+ NK cell counts after 24 weeks of treatment (= 0.023 < 0.05). CONCLUSIONS: WJR promotes the immune reconstruction of INRs and redistribution of NK cell subsets, notably decreasing CD56negCD16+ NK cell counts in INRs. However, the redistribution of NK cell subsets is not beneficial for immune reconstruction in INRs. Further large-scale RCTs are required to evaluate the effect of WJR on immune recovery in INRs and decipher the underlying mechanism.

The Experience Among College Students with Social Anxiety Disorder in Social Situations: A Qualitative Study.

Background: Few individuals have focused on the experience of students during social events, especially among college students with social anxiety disorder. This study aimed to explore the anxiety experience among college students with social anxiety disorder in social situations. Methods: This qualitative interpretive study was conducted on college students who were diagnosed with social anxiety disorder (SAD) and recruited from two colleges in Heilongjiang Province, China. A total of 7 participants were selected by purposive sampling with maximum variability. Data were collected through semistructured individual interviews, and data analysis was performed by using Colaizzi's 7-step analysis method. Results: The findings from the analysis of the interviews were classified into 4 themes and several main categories, including distorted self-awareness (3 main categories), fear of negative reaction from others (2 main categories), adverse reaction of body and mind (4 main categories) and strong desire to seek treatment. Conclusion: In our study, we sought to understand the anxiety experience among college students with social anxiety disorder in social situations. The study results provide a reference for psychologists and clinical medical staff and establish a scientific basis for the prevention and intervention of social anxiety disorder.

Butyrate Ameliorates Intestinal Epithelial Barrier Injury Via Enhancing Foxp3+ Regulatory T-Cell Function in Severe Acute Pancreatitis Model.

BACKGROUND: This study aimed to examine the effect of sodium butyrate on severe acute pancreatitis-related gut barrier injury in a rat model and explore its mechanism. METHODS: Male rats randomly fell into 3 groups, that is, the control, the severe acute pancreatitis group, and the severe acute pancreatitis+butyrate group. Rats in the control group received sham operation, while rats in the severe acute pancreatitis group and severe acute pancreatitis+butyrate group received severe acute pancreatitis induction by intraductal infusion of 4% sodium taurocholate. After that, rats in the severe acute pancreatitis+butyrate group were fed with sodium butyrate solution with free access. Intestinal barrier injury was measured based on the expression of tight junction proteins by reverse transcription polymerase chain reaction, Western blotting assay as well as immunohistochemical staining. The variation of Treg cells was measured by reverse transcription polymerase chain reaction, Western blotting assay, immunohistochemical staining, and flow cytometry analysis. RESULTS: Compared to rats in the control, rats in the severe acute pancreatitis group showed significantly higher pathohistological scores (P < .001) in the intestine, as well as decreased expression of occludin and ZO-1. While, rats in the severe acute pancreatitis+butyrate group showed mitigated histologic lesions (P < .05) and increased expressions of occludin and ZO-1. In addition, rats in the severe acute pancreatitis group showed the obvious reduction in the expressions of Foxp3 and GPR109a and the decreased percentage of Treg cells in the intestine (P < .001) compared to rats in the control. However, rats in the severe acute pancreatitis+butyrate group showed markedly increased expressions of Foxp3 and GPR109a and the upregulated percentage of Treg cells (P < .01). CONCLUSION: Butyrate could significantly mitigate the intestinal injury induced by severe acute pancreatitis, probably by inducing the differentiation of Treg cells.

Efficacy and safety of Mianyi granules (+mianyi+) for reversal of immune nonresponse following antiretroviral therapy of human immunodeficiency virus-1: a randomized, double-blind, multi-center, placebo-controlled trial.

OBJECTIVE: To investigate whether Mianyi granules (+mianyi+) are effective and safe in reversing immune nonresponse following antiretroviral therapy (ART) in individuals with human immunodeficiency virus (HIV) infection. METHODS: Randomized, double-blind, multi-center, placebo-controlled trial (factorial design) of daily oral Mianyi granules versus placebo for 72 weeks. A total of 361 HIV-positive individuals receiving ART at five Class III Grade I hospitals in China between September 2013 and January 2016 completed the study. The primary endpoints were frequencies of CD3+, CD4+, CD8+, and CD45RA+ cells at seven timepoints over the 72 weeks. Secondary endpoints included viral loads, clinical symptoms, and quality of life at 72 weeks. RESULTS: A total of 400 participants were enrolled in the study and randomized, of whom 361 completed the study: 189 individuals (140 men and 49 women) in the Mianyi granule group and 172 individuals (135 men and 37 women) in the placebo group. In the intent-to-treat population, CD4+ T cell counts increased from (193 ± 71) cells/mm at baseline to (288 ± 131) cells/mm post-treatment in the Mianyi granule group and from (200 ± 75) cells/mm at baseline to (264 ± 124) cells/mm post-treatment in the placebo group. Patients treated with Mianyi granule had higher increases in CD4+ T cell counts than those treated with placebo ( = 0.045). Reversal of immune nonresponse was defined as a CD4+ T cell increase of more than 100 cells/mm3. After treatment for 72 weeks, Mianyi granule was effective in reversing immune nonresponse in a higher proportion of individuals (20.2%) compared with placebo (9.7%). CD45RA+ cell counts increased from (34 ± 32) cell/mm at baseline to (51 ± 61) cells/mm post-treatment in the Mianyi granule group and from (37 ± 33) cells/mm at baseline to (48 ± 37) cells/mm post-treatment in the placebo group. Mianyi granules were more effective than placebo in increasing CD45RA+ cell counts. CONCLUSIONS: In ART-treated HIV-positive adults with immune nonresponse, treatment with Mianyi granules for 72 weeks was safe and significantly increased CD4+ and CD45RA+ cell counts, thereby promoting immune reconstitution.

Childhood trauma and the plasma levels of IL-6, TNF-α are risk factors for major depressive disorder and schizophrenia in adolescents: A cross-sectional and case-control study.

BACKGROUND: It has been reported that childhood trauma and inflammation are associated with major depressive disorder (MDD) and schizophrenia (SZ), but previous researches were almost aimed at adults. The aim of the present research is to observe the alteration of peripheral interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in adolescents (12-20 years) with MDD and SZ, to investigate the impact of childhood abuse in early-onset MDD and SZ, and to furtherly explore the correlation between childhood maltreatment and plasma IL-6, TNF-α levels. SUBJECTS AND METHODS: Enzyme-linked immunosorbent assay (ELISA) is applied to obtain the plasma concentrations of IL-6 and TNF-α in 55 patients with MDD, 51 patients with SZ and 47 healthy minors. The short form of the Childhood Trauma Questionnaire (CTQ-SF) is used to assess the severity of early trauma. RESULTS: Plasma IL-6 and TNF-α levels are significantly elevated in patients with early-onset MDD and SZ compared with healthy subjects (p <0.01), whose results display that the correlation between IL-6 and TNF-α is significantly positive (γ=0.787, p <0.01) in all participants. Compared with the healthy adolescents, patients with MDD and SZ show more serious childhood trauma, and the plasma IL-6, TNF-α concentrations are closely related to childhood maltreatment. CONCLUSIONS: Early trauma and peripheral inflammatory response play an important role in the pathophysiology of early-onset MDD or SZ. The current findings provide effective targets for the prevention, diagnosis, and treatment of major depressive disorder and schizophrenia in adolescents.