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Background: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide, and metastasis is the main cause of early recurrence and poor prognosis. However, the mechanism of metastasis remains poorly understood., Aim: To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC treatment., Methods: The candidate molecule lecithin-cholesterol acyltransferase (LCAT) was screened by gene microarray and bioinformatics analysis. The expression levels of LCAT in clinical cohort samples was detected by quantitative real-time polymerase chain reaction and western blotting. The proliferation, migration, invasion and tumor-forming ability were measured by Cell Counting Kit-8, Transwell cell migration, invasion, and clonal formation assays, respectively. Tumor formation was detected in nude mice after LCAT gene knockdown or overexpression. The immunohistochemistry for Ki67, E-cadherin, N-cadherin, matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on HCC. Gene set enrichment analysis (GSEA) on various gene signatures were analyzed with GSEA version 3.0. Three machine-learning algorithms (random forest, support vector machine, and logistic regression) were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO databases., Results: LCAT was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC tissues. LCAT was significantly downregulated in HCC tissues, which is correlated with recurrence, metastasis and poor outcome of HCC patients. Functional analysis indicated that LCAT inhibited HCC cell proliferation, migration and invasion both in vitro and in vivo . Clinicopathological data showed that LCAT was negatively associated with HCC size and metastasis (HCC size ≤ 3 cm vs 3-9 cm, P < 0.001; 3-9 cm vs > 9 cm, P < 0.01; metastatic-free HCC vs extrahepatic metastatic HCC, P < 0.05). LCAT suppressed the growth, migration and invasion of HCC cell lines via PI3K/AKT/mTOR signaling. Our results indicated that the logistic regression model based on LCAT, TNM stage and the serum level of α-fetoprotein in HCC patients could effectively predict high metastatic risk HCC patients., Conclusion: LCAT is downregulated at translational and protein levels in HCC and might inhibit tumor metastasis via attenuating PI3K/AKT/mTOR signaling. LCAT is a prognostic marker and potential therapeutic target for HCC., Competing Interests: Conflict-of-interest statement: The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Daurian ground squirrels (Spermophilus dauricus) experience various stress states during winter hibernation, but the impact on testicular function remains unclear. This study focused on the effects of changes in testicular autophagy, apoptosis, and mitochondrial homeostasis signaling pathways at various stages on the testes of Daurian ground squirrels. Results indicated that: (1) During winter hibernation, there was a significant increase in seminiferous tubule diameter and seminiferous epithelium thickness compared to summer. Spermatogonia number and testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were higher during inter-bout arousal, suggesting that the testes remained stable during hibernation. (2) An increased number of mitochondria with intact morphology were observed during hibernation, indicating that mitochondrial homeostasis may contribute to testicular stability. (3) DNA fragmentation was evident in the testes during the hibernation and inter-bout arousal stages, with the highest level of caspase3 enzyme activity detected during inter-bout arousal, together with elevated levels of Bax/Bcl-2 and Lc3 II/Lc3 I, indicating an up-regulation of apoptosis and autophagy signaling pathways during hibernation. (4) The abundance of DRP1, MFF, OPA1, and MFN2 proteins was increased, suggesting an up-regulation of mitochondrial dynamics-related pathways. Overall, testicular autophagy, apoptosis, and mitochondrial homeostasis-related signaling pathways were notably active in the extreme winter environment. The well-maintained mitochondrial morphology may favor the production of reproductive hormones and support stable testicular morphology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167-7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922-41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374-12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780-10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771-0.894) and 0.821 (95 % CI 0.720-0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Carnosine dipeptidase 1 (CNDP1), an enzyme integral to the hydrolysis of dipeptides containing histidine, plays an indispensable role in myriad physiological processes, including hydrolysis of proteins, maturation of specific biochemical functionalities within proteins, tissue regeneration, and regulation of cell cycle. However, the implications of CNDP1 in oncogenesis and its prognostic value are not yet fully elucidated. Initially, we procured the GSE40367 dataset from the Gene Expression Omnibus and established a protein-protein interaction network. Thereafter, we conducted functional and pathway enrichment analyses utilizing GO, KEGG, and GSEA. Moreover, we undertook an association analysis concerning the expression of CNDP1 with immune infiltration, along with survival analysis across various cancers and specifically in hepatocellular carcinoma (HCC). Our study uncovered a total of 2,248 differentially expressed genes, with a down-regulation of CNDP1 in HCC and other cancers. Our explorations into the relationship between CNDP1 and immune infiltration disclosed a negative correlation between CNDP1 expression and the presence of immune cells in HCC. Survival analyses revealed that diminished expression of CNDP1 correlates with an adverse prognosis in HCC and several other types of cancer. These observations intimate that CNDP1 holds promise as a novel prognostic biomarker for both pan-cancer and HCC., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Objectives: To study the left heart structure and functional characteristics of term neonates with intrauterine growth restriction (IUGR)., Methods: This study included 86 term neonates with IUGR admitted to the Neonatal Ward of Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2022 as the IUGR group, as well as randomly selected 86 term neonates without IUGR born during the same period as the non-IUGR group. The clinical data and echocardiographic data were compared between the two groups., Results: The analysis of left heart structure and function showed that compared with the non-IUGR group, the IUGR group had significantly lower left ventricular mass, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, end-diastolic interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic volume, left ventricular end-systolic volume, and stroke volume ( P <0.05) and significantly higher ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness, proportion of neonates with a mitral peak E/A ratio of ≥1, and cardiac index ( P <0.05). The Spearman correlation analysis suggested that stroke volume was positively correlated with birth weight and body surface area ( r s =0.241 and 0.241 respectively; P <0.05) and that the ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness was negatively correlated with birth weight and body surface area ( r s =-0.229 and -0.225 respectively; P <0.05)., Conclusions: The left ventricular systolic function of neonates with IUGR is not significantly different from that of neonates without IUGR. However, the ventricular septum is thicker in neonates with IUGR. This change is negatively correlated with birth weight and body surface area. The left ventricular diastolic function may be impaired in neonates with IUGR.

Fatty liver disease (FLD) is one of the major causes of chronic liver disease worldwide. With the increasing incidence of obesity and metabolic syndrome worldwide, FLD concomitant with other liver diseases is becoming more common, and multiple etiological overlap is associated with poor disease prognosis. Therefore, FLD concomitant with other liver diseases is a clinical concerning issue. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease continuum from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), and relative end stage liver disease, excluding other factors that may lead to fatty liver disease such as excessive alcohol consumption et. al. Following the nomenclature of NAFLD with metabolic associated fatty liver disease (MAFLD), an international panel of experts proposed a new name in June 2023 as Metabolic dysfunction - associated steatotic liver disease (MASLD), replacing the word "fatty" with "steatotic," The effect of lipid toxicity on FLD progression was highlighted. Compared with the concept of MAFLD, the disease spectrum of MASLD is broader, and the etiology and mechanism are more clear. The nomenclature of FLD brings some influence to the diagnosis and treatment of chronic liver diseases concomitant with FLD, including chronic hepatitis B, alcoholic fatty liver disease and genetic metabolic diseases. This article reviews the influence of renaming FLD on the diagnosis and treatment of FLD concomitant with other etiologies caused liver diseases.

Objective: To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease (CHB-MAFLD) and chronic viral hepatitis B alone (CHB alone), and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB. Methods: 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously. They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD. A retrospective case-control study was conducted. CHB-MAFLD was used as the case group, and 1:2 propensity score matching was performed with the CHB alone group according to age and gender, including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group. The body mass index (BMI), metabolic complications, laboratory indicators, and pathological characteristics of liver tissue were compared between the two groups. The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model. The measurement data between groups were compared using the t -test and rank sum test. The χ (2) test was used for the comparison of categorical data between groups. Results: Alanine aminotransferase (ALT, P = 0.032) and aspartate aminotransferase (AST, P = 0.003) levels were lower in the CHB-MAFLD group than those in the CHB alone group, while BMI ( P < 0.001), triglyceride (TG, P < 0.001), total cholesterol ( P = 0.016) and the incidence of metabolic syndrome ( P < 0.001) were higher in the CHB alone group. There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups ( P > 0.05). Histologically, the proportion of significant liver fibrosis (S2-S4) was higher in the CHB-MAFLD group than that in the CHB alone group (67.9% vs. 49.1%, χ (2) = 5.311, P = 0.021). Multivariate regression results showed that BMI ( OR = 1.258, 95% CI : 1.145 ~ 1.381, P = 0.001) and TG ( OR = 12.334, 95% CI : 3.973 ~ 38.286, P < 0.001) were the risk factors for hepatic steatosis occurrence in children with CHB. MAFLD ( OR = 4.104, 95% CI : 1.703 ~ 9.889, P = 0.002), liver inflammation ( OR = 3.557, 95% CI : 1.553 ~ 8.144, P = 0.003), and γ-glutamyl transferase ( OR = 1.019, 95% CI : 1.001 to 1.038, P = 0.038) were independent risk factors for significant hepatic fibrosis in children with CH. Conclusion: MAFLD occurrence is related to metabolic factors in children with CHB. Additionally, the combination of MAFLD may promote liver fibrosis progression in CHB patients.

Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.

Liver histological assessment is of great clinical significance for the diagnosis, classification, and prognosis prediction of drug-induced liver injury (DILI). Liver histological evaluation can effectively supplement RUCAM. The clinical phenotypes of DILI are complex and diverse, including acute, chronic and severe hepatic injury. DILI has multiple insult-targets, including hepatocytes, cholangiocytes, and vascular endothelial cells and others. The pathological damage patterns are similar to many types of non-DILI liver diseases, therefore making differential diagnosis difficult. New anti-tumor drugs such as immune checkpoints inhibitors and targeted therapy are widely used in clinical antineoplastic practice, thus the growing incidence of related liver injury occurs. Liver histological examination can effectively assess the pathological phenotypes and severity of DILI, so as to guide treatment. In uncommon conditions such as special types of DILI (such as hepatic vascular disease), DILI with other competitive etiology overlapping, chronic DILI, and DILI induced liver failure, liver histological assessment can provide strong support for identifying the cause, rational treatment, and prognosis. Currently, the histological evaluation system for drug-induced liver injury seems to be a lack of consensus, and the diagnosis of DILI is short of highly specific and sensitive serological markers. All in all, liver histological assessment plays a crucial role in the diagnosis and differential diagnosis of DILI.

Parathlasia gen. nov. , a new leafhopper genus and species of Ledrini, P.guizhouensis sp. nov. , from Guizhou, China are described. Morphological differences between the new genus to other related Chinese genera are discussed. A key to distinguish Parathlasia from other similar genera is given., (Yu-Jian Li, Li-Na Jiang, Zi-Zhong Li, Ji-Chun Xing.)

Purpose: Post hemorrhagic shock mesenteric lymph (PHSML) return contributes to CD4 + T cell dysfunction, which leads to immune dysfunction and uncontrolled inflammatory response. Tumor necrosis factor α induced protein 8 like-2 (TIPE2) is one of the essential proteins to maintain the immune homeostasis. This study investigated the role of TIPE2 in regulation of CD4 + T lymphocyte function in interaction of PHSML and TLR2/TLR4., Methods: The splenic CD4 + T cells were isolated from various mice (WT, TLR2 -/- , TLR4 -/- ) by immunomagnetic beads, and stimulated with PHSML, normal lymphatic fluid (NML), respectively. Application of TIPE2-carrying interfering fragments of lentivirus were transfected to WT, TLR4 -/- , and TLR2 -/- CD4 + T cells, respectively. After interference of TIPE2, they were stimulated with PHSML and NML for the examinations of TIPE2, TLR2, and TLR4 mRNA expressions, proliferation, activation molecules on surface, and cytokine secretion function., Results: PHSML stimulation significantly upregulated TIPE2, TLR2, and TLR4 mRNA expressions, decreased proliferation, CD25 expression, and IFN-γ secretion, and increased the secretion ability of IL-4 in WT CD4 + T cells. TIPE2 silencing enhanced proliferative capacity, upregulated CD25 expression, and increased IFNγ secretion in CD4 + T cells. PHSML stimulated TLR2 -/- CD4 + T or TLR4 -/- CD4 + T cells of which TIPE2 were silenced. TLR2 or TLR4 knockout attenuated PHSML-induced CD4 + T cells dysfunction; PHSML stimulation of silent TIPE2-expressing TLR2 -/- CD4 + T or TLR4 -/- CD4 + T revealed that the coexistence of low TIPE2 expression with lack of TLR2 or TLR4 eliminated this beneficial effect., Conclusion: TIPE2 improves the PHSML-mediated CD4 + T cells dysfunction by regulating TLR2/TLR4 pathway, providing a new intervention target following hemorrhagic shock-induced immune dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Du, Jiang, Zhao, Zhang, Zhang, Wang, Guo, Zhai, Wang, Zhao, Niu and Jiang.)

Migration of keratinocytes plays a crucial role in the re-epithelialization phase during wound healing. Circular RNA (circRNA) protein kinase, DNA-activated, catalytic subunit (circ&#95;PRKDC, hsa&#95;circ&#95;0084443) has been identified as a regulator of keratinocyte migration. However, the molecular basis governing it remains unclear. The levels of circ&#95;PRKDC, microRNA (miR)-20a-3p, and RAS p21 protein activator 1 (RASA1) were assessed by quantitative real-time PCR (qRT-PCR) or western blot. Subcellular localization, Actinomycin D, and Ribonuclease (RNase) R assays were performed to characterise circ&#95;PRKDC. Cell migration was gauged by transwell and wound-healing assays. A direct relationship between miR-20a-3p and circ&#95;PRKDC or RASA1 was verified by dual-luciferase reporter and RNA pull-down assays. Circ&#95;PRKDC expression was reduced in wound skin during wound healing. Circ&#95;PRKDC modulated migration of HaCaT keratinocytes. Mechanistically, circ&#95;PRKDC directly targeted miR-20a-3p. The regulation of circ&#95;PRKDC on HaCaT keratinocyte migration was mediated by miR-20a-3p. RASA1 was identified as a direct and functional target of miR-20a-3p, and miR-20a-3p-mediated inhibition of RASA1 impacted HaCaT keratinocyte migration. Circ&#95;PRKDC acted as a post-transcriptional modulator of RASA1 expression through miR-20a-3p. Moreover, circ&#95;PRKDC modulated migration of HaCaT keratinocytes by RASA1. Our findings demonstrated a novel molecular basis, the miR-20a-3p/RASA1 axis, for the regulation of circ&#95;PRKDC on HaCaT keratinocyte migration., (© 2021 The Wound Healing Society.)

Severe hemorrhagic shock leads to excessive inflammation and immune dysfunction, which results in high mortality related to mesenteric lymph return. A recent study showed that stellate ganglion block (SGB) increased the survival rate in rats suffering hemorrhagic shock. However, whether SGB ameliorates immune dysfunction induced by hemorrhagic shock remains unknown. The aim of the present study was to verify the favorable effects of SGB on the proliferation and function of splenic CD4 + T cells isolated from rats that underwent hemorrhagic shock and to investigate the mechanism related to the SGB interaction with autophagy and posthemorrhagic shock mesenteric lymph (PHSML). Male rats underwent SGB or sham SGB and conscious acute hemorrhage followed by resuscitation and multiple treatments. After 3 h of resuscitation, splenic CD4 + T cells were isolated to measure proliferation and cytokine production following stimulation with ConA in vitro. CD4 + T cells isolated from normal rats were treated with PHSML drained from SBG-treated rats, and proliferation, cytokine production, and autophagy biomarkers were detected. Hemorrhagic shock reduced CD4 + T cell proliferation and production of interleukin (IL)-2, IL-4, and tumor necrosis factor-α-induced protein 8-like 2 (TIPE2). SGB or administration of the autophagy inhibitor 3-methyladenine (3-MA) normalized these indicators. In contrast, administration of rapamycin (RAPA) autophagy agonist or intravenous injection of PHSML inhibited the beneficial effects of SGB on CD4 + T cells from hemorrhagic shocked rats. Furthermore, PHSML incubation decreased proliferation and cytokine production, increased LC3 II/I and Beclin-1 expression, and reduced p-PI3K and p-Akt expression in normal CD4 + T cells. These adverse effects of PHSML were also abolished by 3-MA administration, as well as incubation with PHSML obtained from SGB-treated rats. SGB improves splenic CD4 + T cell function following hemorrhagic shock, which is related to the inhibition of PHSML-mediated autophagy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Patients with chronic schizophrenia present cognitive impairment, which affects their social function and prevents them from reintegrating into society. Yijinjing is a traditional Chinese aerobic exercise that has a putative psychosomatic effect on improving cognitive function. Methods: From January to May 2021, 40 patients with chronic schizophrenia were recruited and randomly divided into a control group and a Yijinjing group. In the 12-week intervention, the patients in the control group received conventional treatment, whereas patients in the Yijinjing group performed Yijinjing exercise (40 min/session, twice a week) in addition to receiving conventional treatment. The Positive and Negative Syndrome Scale (PANSS), the Insight and Treatment Attitude Questionnaire (ITAQ), the Rosenberg Self-esteem Scale (SES), and the Mini Mental State Examination (MMSE) were used to measure clinical symptoms and cognitive function at 0, 6, and 12 weeks. Results: The demographic information was not significantly different between groups. At baseline, the scores of all the scales were not statistically different between groups. After 12 weeks of intervention, compared to those at baseline, the scores of the negative scale ( t = 19.00, p < 0.0001), general psychopathology scale ( t = 15.98, p < 0.0001), and total score ( t = 15.47, p < 0.0001) of the PANSS and SES ( t = 5.378, p < 0.0001) had significantly decreased, and the scores of the ITAQ ( t = 7.984, p < 0.0001) and MMSE ( t = 6.750, p < 0.0001) had significantly increased in Yijinjing group; the score of the MMSE increased in the control group as well ( t = 2.491, p = 0.0222). Compared to the respective scores in the control group, the negative scale score ( t = 2.953, p = 0.0054) significantly decreased, and the ITAQ ( t = 3.043, p = 0.0042) and MMSE ( t = 2.2.68, p = 0.0291) scores significantly increased in the Yijinjing group after 12 weeks of intervention. Conclusion: These results provide a preliminary indication that Yijinjing exercise had the potential to improve cognitive function and negative symptoms in patients with chronic schizophrenia. A larger-scale study to determine the trajectory of change in the longer term should be undertaken., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gao, Luo, Tu, Lu, Jiang, Qiao, Lin, Li and Chen.)

Abstract: Vascular hypo-reactivity plays a critical role inducing organ injury during hemorrhagic shock. 17β-estradiol (E2) can induce vasodilation to increase blood flow in various vascular beds. This study observed whether E2 can restore vascular hypo-reactivity induced by hemorrhagic shock, and whether E2 effects are associated with RhoA-Rho kinase (ROCK)-myosin light chain kinase phosphatase (MLCP) pathway. The hemorrhagic shock model (40 ± 2 mm Hg for 1 h, resuscitation for 4 h) was established in ovary intact sham operation (OVI), ovariectomized (OVX), and OVX plus E2 supplement female mice. Intestinal microvascular loop was used to assess blood flow in vivo, mRNA expression and vascular reactivity in vitro. Hemorrhagic shock significantly reduced norepinephrine microvascular reactivity. Decreased microvascular reactivity was exacerbated by OVX and reversed by E2 supplement. U-46619 (RhoA agonist) increased microvascular reactivity, and C3 transferase (an ADP ribosyl transferase that selectively induces RhoA ribosylation) or Y-27632 (ROCK inhibitor) inhibited sham mice microvascular reactivity. Similarly, U-46619 increased microvascular reactivity in OVI and OVX mice following hemorrhagic shock, which was abolished by Y-27632 or concomitant incubation of okadaic acid (OA) (MLCP inhibitor) and Y-27632. In OVX plus E2 supplement mice with hemorrhagic shock, Y-27632 inhibited microvascular reactivity, which was abolished by concomitant U-46619 application. Lastly, hemorrhagic shock remarkably decreased intestinal loop blood flow, RhoA and ROCK mRNA expressions in vascular tissues in OVX females, but not in OVI females, which were reversed by E2 supplement. These results indicate that estrogen improves microvascular reactivity during hemorrhagic shock, and RhoA-ROCK signaling pathway may mediate E2 effects., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Objective: To study the effect of intestinal microecology on postnatal weight gain of very preterm infants in neonatal intensive care unit (NICU)., Methods: Very preterm infants who met the inclusion criteria were enrolled. The subjects were divided into the extrauterine growth retardation (EUGR) group(defined as a body weight less than the 10th percentile of the corresponding gestational age or a weight loss between birth and a given time of  >  2SD were considered EUGR) and normal growth group, and the growth was evaluated at 2 and 4 weeks after birth. Meanwhile, the stool samples were taken to perform16S ribosomal RNA (rRNA) high -throughput 16S rRNA sequencing of the intestinal microflora was performed on stool samples., Results: A total of 22 infants were included. There was no significant difference in the alpha diversity indexes indices between the two groups at 2 weeks or 4 weeks after birth. The beta diversity analysis showed that the two groups had similar principal components of the intestinal microflora were similar between the two groups. Linear discriminant analysis (LDA) effect size (LEfSe) showed that 2 weeks after birth, the bacteria with an absolute LDA score (log10) higher than 4 included Streptococcaceae, Streptococcus, Bacteroidetes, Bacteroidales and Stenotrophomonas in the EUGR group and Enterococcaceae and Enterococcus in the control group. At the 4th week after birth, the bacteria with an absolute LDA score (log10) higher than 3 in the EUGR group includedwere Clostriaceae, Eubacteriaceae and Eubacterium. TheBy comparing the composition of the microbial community composition comparison showed, significant differences were found in the principal components of Enterococcus and Streptococcus on the family and genus levels at 2 weeks after birth. No Bifidobacterium was found in either group at 4 weeks after birth., Conclusion: Intestinal microecology is different between infants with EUGR and those with normal growth. The diversity and richness of the intestinal microflora in preterm infants at the NICU are significantly insufficient and change dynamically with time, and the establishment of intestinal homeostasis is obviously delayed., (© 2021. The Author(s).)

Objective: To analysis effectiveness of the "14 plus 7 day quarantine" and "nucleic acid plus total antibody testing" strategy (combined screening strategy) for screenin the imported patients with COVID-19 in Xiamen. Methods: The study populations were overseas travelers arriving in Xiamen from March 17 to December 31, 2020, and overseas travelers who had quarantine outside Xiamen for less than 21 days from July 18 to December 31, 2020. Data were collected and analyzed on the timing of detection, pathways, and test results of the imported patients with COVID-19 after implementing combined screening strategy. Results: A total of 304 imported patients with COVID-19 were found from 174 628 overseas travelers and 943 overseas travelers from other cities. A total of 163 cases (53.6%) were diagnosed by multitime, multisite intensive nucleic acid testing after positive finding in total antibody testing. Among them, 27 (8.9%) were first positive for nucleic acid in 14 plus 7 day quarantine and 136 were first positive for nucleic acid in 14-day quarantine. Only 8 of these individuals were tested positive for nucleic acid after positive total antibody testing. The other 128 individuals were tested positive for nucleic acid after being negative for average 2.3 times (maximum of 6 times). Aditional 155 cases might be detected by using the combined "14 plus 7 day quarantine" and " nucleic acid plus total antibody testing" strategy compared with "14-day quarantine and nucleic acid testing" strategy, accounting for 51.0% of the total inbound infections. So the combined screening strategy doubled the detection rate for imported patients with COVID-19. No second-generation case caused by overseas travelers had been reported in Xiamen as of February 26, 2021. Conclusions: Xiamen's combined screening strategy can effectively screen the imported patients with COVID-19 who were first positive for nucleic acid after 14 day quarantine. Compared with "14 day quarantine and nucleic acid testing", the combined screening strategy improved detection rate and further reduced the risk of the secondary transmission caused by the imported patients with COVID-19.

The aim is to investigate that 17β-estradiol (E2)/estrogen receptors (ERs) activation normalizes splenic CD4 + T lymphocytes proliferation and cytokine production through inhibition of endoplasmic reticulum stress (ERS) following hemorrhage. The results showed that hemorrhagic shock (hemorrhage through femoral artery, 38-42 mmHg for 90 min followed by resuscitation of 30 min and subsequent observation period of 180 min) decreased the CD4 + T lymphocytes proliferation and cytokine production after isolation and incubation with Concanavalin A (5 μg/mL) for 48 h, induced the splenic injury with evidences of missed contours of the white pulp, irregular cellular structure, and typical inflammatory cell infiltration, upregulated the expressions of ERS biomarkers 78 kDa glucose-regulated protein (GRP78) and activating transcription factor 6 (ATF6). Either E2, ER-α agonist propyl pyrazole triol (PPT) or ERS inhibitor 4-Phenylbutyric acid administration normalized these parameters, while ER-β agonist diarylpropionitrile administration had no effect. In contrast, administrations of either ERs antagonist ICI 182,780 or G15 abolished the salutary effects of E2. Likewise, ERS inducer tunicamycin induced an adverse effect similarly to that of hemorrhagic shock in sham rats, and aggravated shock-induced effects, also abolished the beneficial effects of E2 and PPT, respectively. Together, the data suggest that E2 produces salutary effects on CD4 + T lymphocytes function, and these effects are mediated by ER-α and GPR30, but not ER-β, and associated with the attenuation of hemorrhagic shock-induced ERS.

Background: Immune dysfunction is associated with posthemorrhagic shock mesenteric lymph (PHSML) return. To determine the proliferation and cytokine production capacity of CD4 + T lymphocytes, the effect of PHSML drainage on spleen CD4 + T lymphocytes in a mouse model of hemorrhagic shock was assessed., Methods: The normal spleen CD4 + T lymphocytes were in vitro incubated with either drained normal mesenteric lymph (NML), PHSML during hypotension (PHSML-H), or PHSML from 0 h to 3 h after resuscitation (PHSML-R) to verify direct proliferation effects of PHSML., Results: Hemorrhagic shock led to reduction of proliferation and mRNA expression of interleukin 2 (IL-2) and IL-2 receptor in CD4 + T lymphocytes and to decrease in IL-2 and interferon γ (IFN-γ) levels in supernatants. In contrast, the interleukin-4 levels were increased. These effects were reversed by PHSML drainage. Moreover, NML incubation promoted CD4 + T lymphocyte proliferation, whereas both PHSML-H and PHSML-R treatment had a biphasic effects on CD4 + T lymphocyte proliferation, exhibiting an enhanced effect at early stages and an inhibitory effect at later stages. Compared with NML, PHSML-H increased IL-2 expression at 12 h, but decreased expression of both IL-2 and IFN-γ at 24 h. By contrast, PHSML-R induced significant increases in IL-2 and IFN-γ levels at 24 h. Interleukin-4 expression in CD4 + T lymphocytes was reduced at 12 h, but augmented at 24 h after incubation with either PHSML-H or PHSML-R., Conclusions: The results indicate that PHSML has a direct inhibitory effect on CD4 + T lymphocyte proliferation that induces an inflammatory response, which is associated with cellular immune dysfunction., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To clarify the clinical characteristics of chest infections caused by streptococcus anginosus group (SAG). Methods: A total of 26 patients diagnosed in Affiliated Hospital of Jining Medical University from January 2014 to October 2019 were enrolled. The analyzed clinical data included baseline data, clinical symptoms, imaging manifestations, therapies, and outcomes. The microbiological diagnosis was established based on the specimens collected by lung needle biopsy, bronchoscopy, artificial airway aspiration, thoracentesis or thoracoscopy. Results: Among the 26 patients, there were 23 (88.5%) males and 3 (11.5%) females aged (63.0±12.5) years, and 21 cases (80.8%) had potential diseases. The distribution of clinical manifestations included 21 cases (80.8%) with fever, 13 cases (50.0%) with pectoralgia, 13 cases (50.0%) with cough, and 13 cases (50.0%) with expectoration. Chest CT displayed 18 cases (69.2%) with nodules, 18 cases (69.2%) with pleural effusion, 17 cases (65.4%) with patchy shadows, 12 cases (46.2%) with consolidation, 4 cases (15.4%) with cavity, 3 cases (11.5%) with spontaneous pneumothorax. 13 cases (50.0%) of Streptococcus constellatus , 12 cases (46.2%) of Streptococcus anginosus and 1 case (3.8%) of Streptococcus intermadius were observed through the bacterial culture. After anti-infection treatment and invasive operation (including tracheoscopy, thoracoscopy, lung puncture, and thoracic puncture drainage), the prognosis of 24 cases (92.3%) became satisfactory, and 2 (7.7%) died. Conclusion: Pulmonary infection caused by SAG is mainly seen in male patients with underlying diseases. No specificity is displayed in clinical manifestations. CT manifestations usually show intrapulmonary nodules, patchy shadows, consolidation and pleural effusion.

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell-in-cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty-six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early-stage PBC (stages I and II, n = 39) and late-stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin-eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3 + and CD8 + T cells correlated with the advancement of emperipolesis (R 2  = 0.318, P < .001; R 2  = 0.060, P < .05). The cell numbers of TUNEL-positive BECs and double staining for CK19 and Ki67 showed a significant positive correlation with emperipolesis degree (R 2  = 0.236, P < .001; R 2  = 0.267, P < .001). We conclude that emperipolesis mediated by CD8 + T cells appears to be relevant to apoptosis of BEC and thus may aggravate the further injury of interlobular bile ducts., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: Acute hemorrhage-induced excessive excitation of sympathetic-adrenal-medullary system (SAS) leads to gut hypoperfusion and barrier dysfunction, which is a critical event during hemorrhagic shock-induced multiple organ injury. Stellate ganglion blockade (SGB) has been widely used for suppression of sympathetic-adrenal-medullary system in the clinical practice. However, whether SGB improves intestinal barrier function after hemorrhagic shock remains unclear. Here, we hypothesized that the implementation of SGB restores intestinal barrier function and reduces gut injury., Materials and Methods: Male rats received the SGB pretreatment and underwent hemorrhagic shock followed by resuscitation. The 96-h survival rate, intestinal permeability and morphology, D-lactic acid concentration and diamine oxidase activity in plasma, and expressions of F-actin, Claudin-1, and E-cadherin in intestinal tissues were observed., Results: Pretreatment with SGB significantly enhances the 96-h survival rate in rats subjected to hemorrhagic shock (from 8.3% to 66.7%). Hemorrhagic shock reduced the coverage scale of intestinal mucus and intestinal villus width and height, enhanced the intestinal permeability to fluorescein isothiocyanate-dextran 4 and D-lactic acid concentration in plasma, and decreased the expressions of F-actin, Claudin-1, and E-Cadherin in intestinal tissue. These hemorrhagic shock-induced adverse effects were abolished by SGB treatment., Conclusions: SGB treatment has a beneficial effect during hemorrhagic shock, which is associated with the improvement of intestine barrier function. SGB may be considered as a new therapeutic strategy for treatment of hemorrhagic shock., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate the effect of mesenteric lymph drainage on the spleen injury and the expressions of inflammatory cytokines in splenic tissue in mice following hemorrhagic shock., Methods: Male C57 mice were randomly divided into the sham shock, shock and shock+drainage groups. The mice in both shock and shock+drainage groups suffered femoral artery bleeding, maintained mean arterial pressure (MAP) of 40±2 mmHg for 90 min, and were resuscitated. And mesenteric lymph drainage was performed in the shock+drainage group at the time of resuscitation. After three hours of resuscitation, the splenic tissues were harvested for the histological observation and protein and mRNA expression analysis of cytokines., Results: The spleen in the shock group revealed a significantly structural damage and increased mRNA expressions of MyD88 and TRAF6 and protein expressions of TIPE2, MyD88, TRIF and TRAF3 compared to the sham group. By contrast, the splenic pathological injury in the shock+drainage group was alleviated significantly, and the mRNA and protein expressions of TIPE2, MyD88, TRIF, TRAF3 and TRAF6 were significantly lower than those in the shock group., Conclusion: These results indicate that post-hemorrhagic shock mesenteric lymph drainage alleviates hemorrhagic shock-induced spleen injury and the expressions of inflammatory cytokines.

Lycopene is a natural compound that alleviates oxidative stress and inflammation, exerting therapeutic effects in a number of cancers. The aim of this study is to investigate the efficacy of lycopene in inhibiting prostate cancer. Cell viability assays indicated the dose- and time-dependent toxicity of lycopene in prostate cancer cells. Annexin V/propidium iodide double-staining assays revealed the strong apoptotic effects of lycopene. The levels of inflammatory factors, including interleukin-1 (IL1), IL6, IL8, and tumor necrosis factor-α (TNF-α), in lycopene-treated cells were also reduced by lycopene treatment. With the increasing dose of lycopene, the survival of mice bearing prostate cancer xenografts was significantly improved ( P < 0.01), and the tumor burden was significantly reduced ( P < 0.01). Our results indicate that lycopene is a promising chemotherapy drug, which inhibits prostate cancer progression by suppressing the inflammatory response., (Copyright © 2019 Asian Journal of Andrology | Published by Wolters Kluwer – Medknow.)

The pectin gel has been proved to be an effective material for methylene blue (MB) removal, but it presented low adsorption rate. To get over the vice, the pectin microgel particles (PMP) was prepared. No matter high or low initial MB concentration, the PMP presented high adsorption rate with equilibrium time of 20min. The adsorption process based on monolayer adsorption and adsorbance of 284.09mg/g was obtained. What's more, the adsorption process was electrostatic adsorption with mean free energy of 74.223kJ/mol. The pseudo-second-order kinetic model fitted perfectly to the experimental data. The MB uptake was controlled by film diffusion mechanism. Furthermore, the recovery efficiency of regenerated PMP were higher than 80% after three cycles. The present study showed the PMP presented acceptable adsorbance, high adsorption rate and recovery efficiency. Thus, we believe that the PMP was a promising candidate for MB cleanup., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Rationale: Medulla oblongata dysplasia is an extremely rare form of neurodevelopmental immaturity in premature infants. Intracranial hemorrhage in premature infants may be closely related to neurodevelopmental immaturity., Diagnoses: We report a female premature infant who succumbed to intracranial hemorrhage caused by medulla oblongata dysplasia., Patient Concerns: The infant was born at 31 weeks gestation. The onset manifestation was symptomatic epilepsy associated with subependymal hemorrhage., Interventions: Levetiracetam and sodium valproate were administered. During the hospitalization, hydrocephalus developed and the intracranial hemorrhage aggravated., Outcomes: The infant died on day 171 after birth., Lessons: Early identification and prompt treatment should be emphasized. Clinicians should be aware of this condition, as it can potentially cause neonatal intracranial hemorrhage.

The histological assessment of liver biopsy in chronic hepatitis C patients after direct-acting antiviral agents(DAAs) treatment plays a key role in evaluation of response to therapy. Liver necro-inflammation gradually subsides in patients who achieved sustained virologic response after DAAs treatment, thus the histological assessment focus on evaluating remission of liver fibrosis and other lesions. However, the evaluation of liver inflammation and fibrosis are usually inconsistent when the histological scoring systems are recommended by the clinical practice guidelines and applied in chronic hepatitis C patients who achieved viral clearance after DAAs therapy. Therefore, an immunohistochemical staining of α-smooth muscle actin is recommended to evaluate the activity of liver fibrosis. The gold standard for determining the complete clearance of virus after DAAs treatment is detection of HCV RNA in liver tissues. RNAscope technology and RT-PCR technique and other technologies are the powerful means of detecting HCV RNA in liver tissues. The implementation of non-invasive diagnostic techniques in clinic for the screening of liver fibrosis after DAAs therapy is problematic.

Accumulating studies have shown that bats could harbor various important pathogenic viruses that could be transmitted to humans and other animals. Extensive metagenomic studies of different organs/tissues from bats have revealed a large number of novel or divergent viruses. To elucidate viral diversity and epidemiological and phylogenetic characteristics, six pooled fecal samples from bats were generated (based on bat species and geographic regions characteristic for virome analysis). These contained 500 fecal samples from six bat species, collected in four geographic regions. Metagenomic analysis revealed a plethora of divergent viruses originally found in bats. Multiple contigs from influenza A virus and coronaviruses in bats shared high identity with those from humans, suggesting possible cross-species transmission, whereas a number of contigs, whose sequences were taxonomically classifiable within Alphapapillomavirus, Betaretrovirus, Alpharetrovirus, Varicellovirus, Cyprinivirus, Chlorovirus and Cucumovirus had low identity to viruses in existing databases, which indicated possible evolution of novel viral species. None of the established caliciviruses and picornaviruses were found in the 500 fecal specimens. Papillomaviruses with high amino acid identity were found in Scotophilus kuhlii and Rhinolophus blythi, challenging the hypotheses regarding the strict host specificity and co-evolution of papillomaviruses. Phylogenetic analysis showed that four bat rotavirus A strains might be tentative G3 strains, according to the Rotavirus Classification Working Group classification.

Mucin 1 (MUC1), as an oncogene, is overexpressed in hepatocellular carcinoma (HCC) cells and promotes the progression and tumorigenesis of HCC through JNK/TGF-β signaling pathway. In the present study, RNA interference (RNAi) and JNK inhibitor SP600125, which target MUC1 and/or JNK, were used to treat HCC cells in vitro, and the results showed that both silencing the expression of MUC1 and blocking the activity of JNK inhibited the proliferation of HCC cells. In addition, MUC1-stable-knockdown and SP600125 significantly inhibited the growth of tumors in the subcutaneous transplant tumor models that established in BALB/c nude mice rather than MUC1 or JNK siRNAs transiently transfection. Furthermore, the results from immunohistochemical staining assays showed that the inhibitory effects of MUC1 gene silencing and SP600125 on the proliferation of HCC cells in vivo were through the JNK/TGF-β signaling pathway. These results indicate that MUC1 and JNK are attractive targets for HCC therapy and may provide new therapeutic strategies for the treatment of HCC., (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

A series of diphenyl ether-containing pyrazole-carboxamide derivatives was designed and synthesized as new succinate ubiquinone oxidoreductase (SQR) inhibitors. This highly potent molecular scaffold was developed from a moderately activie hit 3, obtained from our previous pharmacophore-linked fragment virtual screening (PFVS) method. The results of greenhouse tests indicated that some analogues showed good SQR inhibitory activity, with promising fungicidal activity against Rhizoctonia solani and Sphaerotheca fuliginea at a dosage of 200 mg/L. Most surprisingly, compound 62 showed the highest SQR inhibitory activity with a K i value of 0.081 μM, about 4-fold more potent than penthiopyrad (K i = 0.307 μM). In addition, compounds 43 and 62 displayed excellent fungicidal activity even at a dosage as low as 6.25 mg/L, which was superior to thifluzamide. Moreover, compound 62 exhibited excellent protection effect against R. solani and provided about 81.2% protective control efficancy after 21 days with two sprayings. The present work indicated that these two compounds could be used as potential agricultural fungicides targeting SQR.

Objective: To observe the change of angiotensin converting enzyme (ACE) and ACE2 in the murine myocardium followed hemorrhagic shock and the role of post-hemorrhagic shock mesenteric lymph (PHSML) drainage., Methods: Twenty-four male mice were ran-domly divided into control, sham, shock, and shock + drainage groups. A hemorrhagic shock model was established and then fluid resuscita-tion was performed to the mice in the shock and shock + drainage groups, and the PHMSL was drained in the shock + drainage group after fluid resuscitation. After 6 h of resuscitation in the shock and shock + drainage groups or corresponding time in the sham group, or after anesthesia in the control group, the myocardial tissues were harvested for the determination of the mRNA expressions of ACE, ACE2, angiotensin Ⅱ (Ang Ⅱ) type 1 receptor (AT1R), and Mas related G protein coupled receptor (Mas1R) using the method of qRT-PCR, and the levels of Ang Ⅱ and Ang (1-7) using the method of ELISA., Results: In the myocardial tissue of shock group, the ACE and AT1R mRNA expressions and Ang Ⅱ level were significantly increased than those of the control and sham groups, the ACE2 and Mas1R mRNA expressions were significantly de-creased than that of the control and sham groups, the Ang (1-7) level was decreased compared with the control group, the ratios of ACE/ACE2, Ang Ⅱ/Ang (1-7), and AT1R/Mas1R in the shock group were significantly increased than the control and sham groups. Meanwhile, PHSML drainage obviously suppressed the effects of hemorrhagic shock on these indices., Conclusions: Hemorrhagic shock up-regulated the ACE-Ang Ⅱ-AT1R axis, down-regulated the ACE2-Ang (1-7)-Mas1R axis, and induced the unbalance of ACE and ACE2 in myocardial tis-sue. PHSML drainage decreased the ACE-Ang Ⅱ-AT1R axis and increased the ACE2-Ang (1-7)-Mas1R axis, resulted in the balance of ACE and ACE2.

Background: Japanese encephalitis caused by Japanese encephalitis virus (JEV) is an endemic zoonotic disease of high public health importance in the Asian Pacific region. The aim of this study was to investigate the presence of JEV infection in commensal and field rodents in South China., Materials and Methods: RNA copies of JEV were detected in brain samples of rodents using real-time RT-PCR. Detection of serum against JEV-reactive antibodies was performed using indirect enzyme-linked immunosorbent assay and microneutralization test., Results: In total, 198 rodents were collected from Guangzhou City and Xiamen City between November 2013 and May 2014. JEV RNA was not detected in 188 brain samples. Forty-four in 96 serum samples (45.8%) were positive for JEV-reactive IgG antibodies. The prevalence of neutralizing antibodies to against JEV-reactive in these serum samples was 61.5% (24/39), with titers ranging from 1:10 to 1:56., Conclusion: Rodents are not known to play a role in transmission of JEV in Asia, nor is there an evidence to support a role for rodents in transmission of other related flaviviruses in China. However, in the current study, we detected evidence of JEV-reactive antibodies in large numbers of Rattus norvegicus and Rattus losea Swinhoe. Further studies of rodents as potential hosts of JEV or other related flaviviruses are warranted.

Objective: To initially explore MRI features and its changing trends including of lung tumors after Argon-Helium cryoablation therapy, and enhance the recognition of MR findings of lung tumors postcryoablation. Methods: Twenty-three cases of patients with twenty six nodules of pulmonary malignance who received Argon-Helium cryoablation therapy in Henan Cancer Hospital from July 2014 to January 2016 were enrolled.All patients underwent unenhanced and dynamic contrast-enhanced MRI scans at pre-and 1-day, 1-week, 1-, 3-, 6-, 12-month postcryoablation. Two radiologists independently reviewed MRI images, signal intensity in the ablated zone on T 1 WI and T 2 WI were assessed by a 5-point scale.The changing trends of size and signal intensity with time were showed by time-maximum diameter and time-score curve.Time-signal intensity curves based on dynamic enhanced sequence were also performed. Results: Typical MRI findings includes: heterogeneous signal intensity on both T 1 WI and T 2 WI at 1-day postcryoablation(26/26, 100%). Hyper-intense on T 1 WI(22/26, 84.6%) and T 2 WI(17/26, 65.4%) with a hypo-intense rim at 1-week postcryoablation.Decreasing signal intensity on T 1 WI(17/26, 65.4%) and increasing signal intensity on T 2 WI(22/26, 84.6%) at 1-month.Signal intensity declined to the level of muscle on both T 1 WI(18/26, 69.2%) and T 2 WI(19/26, 73.1%) at 3-month, nineteen ablated zone turned into patchy shape(19/26, 73.1%). The maximum diameter was largest at 1-day and gradually shrunk with time. The mean score value toped at 1-week and gradually decreased. A straight line type without definite enhancement was found from 1-day to 1-month postcryoablation, an inflow curve with a mild delayed enhancement was seen from 3- to 12- month. Totally 4 recurrence (4/26, 15.4%) all occurred at 3-month and were lack of a complete hypo-intense rim at 1-week postcryoablation. Conclusion: MRI findings of lung tumors postcryoablation are characteristic, a complete hypo-intense rim at 1-week is helpful to determine further recurrence, 1-week to 3-month is an important period to observe significant change of the ablation zone, MRI is valuable in identifying the ablation zone and can reflect its evolution with time.

Herpesviruses (HVs) can cause asymptomatic, benign, or fatal infections in a variety of animal species. However, the prevalence and phylogenetic characteristics of HVs in rodents and shrews in China are poorly understood. We thus performed a molecular detection and phylogenetic analysis of rat and shrew HVs in southern China between 2012 and 2014. Seventeen (6.7%) of 255 rectal swab specimens from rats and six (6.7%) of 90 rectal swab specimens from shrews tested positive for HVs. Phylogenetic analysis revealed that rodent and shrew HVs detected in this study were species specific, clustering in the Betaherpesvirinae and Gammaherpesvirinae clade. Novel Macavirus was detected in Rattus norvegicus (RN/13YX52/24 and RN/14HC50) and gammaherpesviruses in Suncus murinus (SM/14BY7/16/20/97/99/106).These findings have contributed to our understanding of the taxonomy, phylogeny, and biology of HVs.

Succinate-ubiquinone oxidoreductase (SQR) is an attractive target for fungicide discovery. Herein, we report the discovery of novel SQR inhibitors using a pharmacophore-linked fragment virtual screening approach, a new drug design method developed in our laboratory. Among newly designed compounds, compound 9s was identified as the most potent inhibitor with a Ki value of 34 nM against porcine SQR, displaying approximately 10-fold higher potency than that of the commercial control penthiopyrad. Further inhibitory kinetics studies revealed that compound 9s is a noncompetitive inhibitor with respect to the substrate cytochrome c and DCIP. Interestingly, compounds 8a, 9h, 9j, and 9k exhibited good in vivo preventive effects against Rhizoctonia solani. The results obtained from molecular modeling showed that the orientation of the R(2) group had a significant effect on binding with the protein.

Several novel adenoviruses (AdVs) have recently been identified in humans and other animal species. In this study, we report the molecular detection of and phylogenetically characterize bat and human AdVs detected in fecal or rectal swab samples collected in southern China. To detect AdVs, a 252-261 bp fragment of the DNA polymerase (DPOL) gene was amplified using nested PCR. A total of 520 rectal swab samples were collected from eight bat species in four geographic regions of southern China (Guangzhou, Yunfu, Huizhou, and Haikou city). Thirty-six (6.9%) samples from the following species tested positive for AdVs: Myotis ricketti, Miniopterus schreibersii, Scotophilus kuhlii, Taphozous melanopogon, Rhinolophus blythi, and Cynopterus sphinx. Eight novel AdVs were detected in 13.3% of the samples from C. sphinx. Of 328 fecal samples from patients with diarrhea, 16 (4.9%) were positive for classical human AdVs. Phylogenetic analysis showed that human AdVs shared low similarity (57.1-69.3%) with bat AdVs in deduced amino acid sequences of the AdV DPOL region. Thus, our study indicated that bat AdVs and human AdVs are species specific. As such, there is no evidence of cross-species transmission of AdV between bats and humans based on current data.

Telomerase is composed of the catalytic subunit TERT (Telomerase reverse transcriptase),RNA subunit TERC (Telomerase RNA component) and other telomerase associated proteins. These two compartments with other telomerase subunits can assemble a holoenzyme, which maintain the length of telomeres. Telomerase plays important roles in cell senescence and tumor formation. The molecular mechanisms of the regulation of telomerase are very complicated. These processes comprise the regulation of transcription, post-transcription, post-translation and subcellular localization. Trafficking and assemble of TERT and TERC, as well as recruitment to telomeres, are also involved in this process. Here we review the regulation mechanism of telomerase from these aspects, and aim to laid a foundation for telomerase associated research and the drug targeting the telomerase.

NAC transcription factors are one of plant-specific gene families with diverse functions, and they regulate plant development, organ formation and stress responses. Currently, the researches about NAC transcription factors mainly focus on model plants, Arabidopsis and rice, whereas such studies are hardly reported in wheat and other plants. In this study, the full-length coding sequences (CDS) of NAC transcription factors from Triticum urartu (TuNAC) were identified through bioinformatic analysis. Their biological function, evolutionary relationship, gene duplication and chromosomal locations were further predicted and analyzed. The quantitative real-time PCR (qRT-PCR) assay was used to verify the expression pattern of abiotic-related TuNAC transcription factors. A total of 87 TuNAC transcription factors with full-length CDS were identified, which were divided into seven subgroups through phylogenetic analysis. Thirty-nine TuNAC transcription factors were located on seven chromosomes, and five pairs of TuNAC transcription factors were duplicated. The expression of four TuNAC transcription factors was consistently increased under diverse abiotic stress by qRT-PCR assay. Our study thus provides basis for further functional investigations of TuNAC transcription factors.

Although inherited and immune disorder factors are known to be involved in autism spectrum disorders (ASD), controversy still exists as to whether maternal autoimmune disease is an independent risk of ASD in offspring. We aimed to quantitatively summarize the risk of ASD in offspring in relation to maternal autoimmune diseases. A literature search in Pubmed, Web of science, Embase, and China national knowledge internet was conducted to identify relevant studies. Pooled odd ratio (OR) and its 95% confidence interval (CI) were computed by STATA version 12.0. Nine case-control studies and one cohort studies comprising 9775 cases and 952,211 controls were included in this study. A positive association between maternal autoimmune diseases and the risk of ASD in offspring was identified assuming a fixed effect model (pooled OR, 1.34; 95% CI, 1.23-1.46; I(2), 27.9%). There were statistically significant associations between maternal autoimmune diseases developed during pregnancy or maternal thyroid disease and the risk of ASD in offspring (pooled OR, 1.30, 1.29, respectively). Maternal autoimmune disease is likely to be an independent risk factor of ASD in offspring., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Excessively inflammatory response is one of mechanisms that underlie the acute kidney injury (AKI) induced by severe hemorrhagic shock, which could be ameliorated by post-hemorrhagic shock mesenteric lymph (PHSML) blockage. Recent studies demonstrate that high mobility group box 1 (HMGB1) and the receptor for advanced glycation end products (RAGE) are critical mediators of local inflammations. The present study was sought to investigate whether the PHSML drainage inhibits the HMGB1 and RAGE in mouse kidney to ameliorate the renal inflammatory responses., Methods: A mouse hemorrhagic shock model (40 ± 2 mmHg for 90 min, fluid resuscitation for 30 min) was employed, and the PHMSL drainage was performed at the end of the resuscitation. After 3 h of resuscitation, the expressions of mRNA and protein for the renal HMGB1 and RAGE and the levels of interleukin (IL)-1β and IL-18 were assessed by the real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively., Results: Hemorrhagic shock elicited significant increases in the mRNA expressions of HMGB1 and RAGE and in the protein expressions of HMGB1, RAGE, IL-1β and IL-18 in kidney. The PHSML drainage abolished these potentiating effects., Conclusion: The present study demonstrates that PHSML blockade reduces the increased HMGB1 and RAGE and pro-inflammatory factors following hemorrhagic shock, suggesting that the PHSML elicits the inflammatory responses via enhancing the HMGB1 and RAGE production in the kidney.

Several studies have reported the detection of herpesviruses (HVs) in bats. However, the prevalence and phylogenetic characteristics of HVs in bats are still poorly understood. To elucidate the epidemiological characteristics of bat HVs in southern China, 520 fecal samples from eight bat species were collected in four geographic regions of southern China. Of these samples, 73 (14.0 %) tested positive for HVs using nested polymerase chain reaction assay. Phylogenetic analysis revealed a high degree of molecular diversity of HVs in bats of different species from different geographic regions. Our study provides evidence for co-evolution of bats and HVs.

Background: Air pollution constitutes a significant stimulus of asthma exacerbations; however, the impacts of exposure to major air pollutants on asthma-related hospital admissions and emergency room visits (ERVs) have not been fully determined., Objective: We sought to quantify the associations between short-term exposure to air pollutants [ozone (O3), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and particulate matter ≤10 μm (PM10) and PM2.5] and the asthma-related emergency room visits (ERV) and hospitalizations., Methods: Systematic computerized searches without language limitation were performed. Pooled relative risks (RRs) and 95% confidence intervals (95%CIs) were estimated using the random-effect models. Sensitivity analyses and subgroup analyses were also performed., Results: After screening of 246 studies, 87 were included in our analyses. Air pollutants were associated with significantly increased risks of asthma ERVs and hospitalizations [O3: RR(95%CI), 1.009 (1.006, 1.011); I2 = 87.8%, population-attributable fraction (PAF) (95%CI): 0.8 (0.6, 1.1); CO: RR(95%CI), 1.045 (1.029, 1.061); I2 = 85.7%, PAF (95%CI): 4.3 (2.8, 5.7); NO2: RR(95%CI), 1.018 (1.014, 1.022); I2 = 87.6%, PAF (95%CI): 1.8 (1.4, 2.2); SO2: RR(95%CI), 1.011 (1.007, 1.015); I2 = 77.1%, PAF (95%CI): 1.1 (0.7, 1.5); PM10: RR(95%CI), 1.010 (1.008, 1.013); I2 = 69.1%, PAF (95%CI): 1.1 (0.8, 1.3); PM2.5: RR(95%CI), 1.023 (1.015, 1.031); I2 = 82.8%, PAF (95%CI): 2.3 (1.5, 3.1)]. Sensitivity analyses yielded compatible findings as compared with the overall analyses without publication bias. Stronger associations were found in hospitalized males, children and elderly patients in warm seasons with lag of 2 days or greater., Conclusion: Short-term exposures to air pollutants account for increased risks of asthma-related ERVs and hospitalizations that constitute a considerable healthcare utilization and socioeconomic burden.

Background: Considering the febrile seizure rate, there is no longer a clear preference for use of measles-mumps-rubella-varicella (MMRV) vaccine over separate measles-mumps-rubella (MMR) and varicella (V) vaccine. This work was undertaken to assess the risk of febrile seizure after MMRV vaccine in children., Methods: We searched PubMed, Embase, BIOSIS Previews, Scopus, Web of Science, Cochrane Library and other databases through 12 December 2014. Meta-analysis was conducted using R version 3.1.2 and Stata version 12.0., Results: A total of thirty-nine studies were included. Thirty-one published or unpublished clinical trials involving about 40,000 subjects did not show significant differences in incidence of febrile seizure or vaccine related febrile seizure between MMRV and MMR with or without varicella vaccine after any doses, in the risk windows of 0-28, 0-42 or 0-56 days and 7-10 days. In addition, these studies showed that the receipt of concomitant use of MMRV and other pediatric vaccines was not a significant predictor of febrile seizure. Eight post-marketing observations involving more than 3,200,000 subjects were included. No evidence suggested elevated risk of febrile seizure associated with MMRV vaccine among children aged 4-6 years old during 7-10 days or 0-42 days after vaccination. However, an approximately 2-fold increase in risk of seizure or febrile seizure during 7-10 days or 5-12 days after MMRV vaccination was found among children aged 10-24 months, although the highest incidence of seizure was still lower than 2.95‰., Conclusions: First MMRV vaccine dose in children aged 10-24 months was associated with an elevated risk of seizure or febrile seizure. Further post-marketing restudies based on more rigorous study design are needed to confirm the findings., (Copyright © 2015 Elsevier Ltd. All rights reserved.)