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Yuan-yuan Zhao,1,* Ying Tian,1,* Lin Liu,1,2,* Jian-hua Zhan,1 Xue Hou,1 Xi Chen,1 Ting Zhou,1 Yan Huang,1 Li Zhang1 1Department of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China; 2Zhaoqing Medical College, Zhaoqing, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Aim: Our previous research showed that AKT inactivation via small molecule inhibitors did not induce significant apoptosis, but rather markedly increased autophagy in nasopharyngeal carcinoma (NPC). The purpose of the current study was to determine whether autophagy inhibition can enhance the anticancer efficacy of an AKT inhibitor (MK-2206). Materials and methods: NPC cell lines CNE-2 (Epstein–Barr virus negative) and C666-1 (Epstein–Barr virus positive) were used to conduct the research. Autophagy induction effects were evaluated via Western blotting. Eukaryotic elongation factor-2 (eEF-2) kinase was specifically and stably knocked down using shRNA. The growth and proliferation of the cells were assessed by Cell Counting Kit-8. In CNE-2 xenograft tumors, the antitumor effects of an AKT inhibitor (MK-2206) combined with an eEF-2 kinase inhibitor (NH125) were tested. Results: MK-2206 induced eEF-2 kinase-dependent autophagy in NPC cell lines. Knockdown of eEF-2 kinase using shRNA blunted the autophagy activated by MK-2206. Compared with treatment with MK-2206 alone, shRNA or NH125 suppressed eEF-2 kinase and increased the growth-inhibitory effect of MK-2206 on the human NPC cell lines. The synergistic effects of eEF-2 kinase inhibition and MK-2206 were similar to those of the combination of hydroxychloroquine and MK-2206. Moreover, NH125 showed good synergistic effects with MK-2206 in vivo. Conclusion: eEF-2 kinase-mediated autophagy induced by AKT inhibition played a protective role in NPC cells. Inhibition of eEF-2 kinase may be an effective method for increasing the efficacy of an AKT inhibitor such as MK-2206 in NPC. Keywords: nasopharyngeal carcinoma, NPC, AKT, eEF-2 kinase, autophagy

Cong Xue,1 Ying Tian,2 Jing Zhang,3 Yuanyuan Zhao,1 Jianhua Zhan,2 Wenfeng Fang,1 Li Zhang1 1Department of Medical Oncology, 2Department of Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 3Department of Medical Oncology, The First Affiliated Hospital of Guangzhou Traditional Chinese Medicine University, Guangzhou, Guangdong, People’s Republic of China Purpose: Epidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC). We tested the antitumor effects of irreversible ErbB family inhibitor afatinib on human NPC using in vitro and in vivo models.Materials and methods: The effect of afatinib on NPC cells was evaluated using the Cell Counting Kit 8 (CCK8) assay, flow cytometry, and Western blot analyses. The effect of afatinib, as either a single agent or in combination with gemcitabine (GEM), on tumor growth was determined using NPC tumor xenografts in mice.Results: Afatinib inhibited cell growth in all three NPC cell lines tested in a dose-dependent manner. Afatinib promoted cell cycle arrest at the S and G2/M phases, and it significantly inhibited epidermal growth factor (EGF)-induced activation of EGFR and its downstream signaling factors. Co-treatment with afatinib and GEM more effectively inhibited tumor growth than either drug alone but was associated with increased toxicity.Conclusion: Afatinib induced cell cycle arrest and inhibited the proliferation of NPC cell lines. Afatinib in combination with GEM demonstrated significant antitumor effect in an NPC xenograft model. The administration of afatinib with GEM in NPC needs to be modified in order to be effective and tolerable. Keywords: nasopharyngeal carcinoma, EGFR, afatinib, gemcitabine, preclinical

Background: Oxidative stress is closely associated with hypertensive outcomes. The oxidative balance score (OBS) measures oxidative stress exposure from dietary and lifestyle elements. The objective of this study was to investigate the association between OBS and mortality in hypertensive patients., Methods: This study included 7823 hypertensive patients from the National Health and Nutrition Examination Survey (NHANES) 1999-2014. Several models, including Cox regression, restricted cubic splines (RCS), Kaplan‒Meier survival analysis, subgroup, and sensitivity analyses, were exploited to investigate the relationship between OBS and the risk of mortality., Results: Controlling for all potential confounders, a significantly inverse association was observed between elevated OBS and all-cause [hazard ratio (HR) = 0.90, 95% CI: 0.85-0.95] and cardiovascular mortality (HR = 0.85, 95% CI: 0.75-0.95). With adjustment for covariates, significant associations between lifestyle OBS and mortality risks diminished, whereas associations between dietary OBS and these mortality risks remained robust (all-cause mortality: HR = 0.91, 95% CI: 0.86-0.96; cardiovascular mortality: HR = 0.85, 95% CI: 0.76-0.96). RCS demonstrated a linear relationship between OBS and all-cause and cardiovascular mortality risk ( P nonlinear = 0.088 and P nonlinear = 0.447, respectively). Kaplan‒Meier curves demonstrated that the mortality rate was lower with a high OBS ( P < 0.001). The consistency of the association was demonstrated in subgroup and sensitivity analyses. RCS after stratification showed that among current drinkers, those with higher OBS had a lower risk of mortality compared with former or never drinkers., Conclusions: In hypertensive individuals, there was a negative association between OBS and all-cause and cardiovascular mortality. Encouraging hypertensive individuals, especially those currently drinking, to maintain high levels of OBS may be beneficial in improving their prognosis., (© 2024 JGC All rights reserved; www.jgc301.com.)

Background: Acral persistent papular mucinosis (APPM) is a rare idiopathic subtype of localized lichen myxedematosus. To date, there have been less than 41 APPM cases reported worldwide, however, almost all patients were older than 18 years of age. A 7-year-old child was first reported in this paper., Case Description: A 7-year-old boy was admitted to our hospital with a solitary skin-colored papule on the radial side of the middle segment of his right index finger. The patient wanted to know the exact diagnosis and remove it because the flexion movement of the middle segment had been affected. Thus, a surgery was performed. Histopathological examination of a biopsy specimen obtained from the papule on the radial side of the middle segment of his right index finger showed a focal and well-circumscribed deposit of mucin in the papillary and middermis. The deposit never extended deeply into the reticular dermis. Mucin spared a subepidermal area in the papillary dermis. Alcian blue stains can highlight the mucin. The papule was histologically diagnosed as an APPM and excised surgically. The wound gradually healed after the operation, and no obvious recurrence, scar or other discomfort was observed during follow-up so far., Conclusions: To the best of our knowledge, this is the rare case of a child APPM presenting as a solitary papule affecting the flexion movement of the middle segment. Since it is a rare disease, we report this case to contribute to future research on the diagnosis and pathogenesis of APPM., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-607/coif). The authors have no conflicts of interest to declare., (2024 Translational Pediatrics. All rights reserved.)

Unfolded protein response (UPR) signaling and endoplasmic reticulum (ER) stress have been linked to pulmonary fibrosis. However, the relationship between UPR status and pulmonary function and prognosis in idiopathic pulmonary fibrosis (IPF) patients remains largely unknown. Through a series of bioinformatics analyses, we established a correlation between UPR status and pulmonary function in IPF patients. Furthermore, thrombospondin-1 (TSP-1) was identified as a potential biomarker for prognostic evaluation in IPF patients. By utilizing both bulk RNA profiling and single-cell RNA sequencing data, we demonstrated the upregulation of TSP-1 in lung fibroblasts during pulmonary fibrosis. Gene set enrichment analysis (GSEA) results indicated a positive association between TSP-1 expression and gene sets related to the reactive oxygen species (ROS) pathway in lung fibroblasts. TSP-1 overexpression alone induced mild ER stress and pulmonary fibrosis, and it even exacerbated bleomycin-induced ER stress and pulmonary fibrosis. Mechanistically, TSP-1 promoted ER stress and fibroblast activation through CD47-dependent ROS production. Treatment with either TSP-1 inhibitor or CD47 inhibitor significantly attenuated BLM-induced ER stress and pulmonary fibrosis. Collectively, these findings suggest that the elevation of TSP-1 during pulmonary fibrosis is not merely a biomarker but likely plays a pathogenic role in the fibrotic changes in the lung.

Importance: Multiple studies indicate a possible correlation between ADD3 rs2501577 and biliary atresia susceptibility; however, a conclusive determination has yet to be made., Objective: Investigate the role of ADD3 rs2501577 in biliary atresia susceptibility across diverse populations., Data Sources: The study protocol has been registered on PROSPERO, an international platform for systematic review registration (PROSPERO ID: CRD42023384641). The following databases will be searched until February 1, 2023: PubMed, Embase, Cochrane, CBM, Web of Science, and CNKI., Study Selection: Eight studies were selected from seven papers to assess the data. A total of 7651 participants were included, consisting of 1662 in the BA group and 5989 in the NC group., Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed while conducting the systematic reviews and meta-analyses. Two authors independently assessed the quality of the included studies using the Newcastle-Ottawa Quality Assessment Scale. The significance of the pooled odds ratio (OR) was evaluated with a Z test, and statistical heterogeneity across studies was assessed using the I2 and Q statistics. Publication bias was assessed using Egger's and Begg's tests., Main Outcome(s) and Measure(s): The primary study outcome was the development of biliary atresia. Subgroup analysis was performed based on race, region, and assessment of Hardy-Weinberg equilibrium (HWE)., Results: The studies indicate that the ADD3 rs2501577 susceptibility locus increases the risk of developing biliary atresia, regardless of allelic, homozygote, dominant, and recessive gene inheritance models. Furthermore, ADD3 has been found to be associated with apoptosis, cell cycle, and cell damage repair based on functional analysis., Conclusions and Relevance: The ADD3 rs2501577 polymorphic locus is associated with an increased risk of biliary atresia, particularly in Asian populations. This study recommends further investigation of the ADD3 rs2501577 locus in Asian populations to validate its role in the diagnosis of biliary atresia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Invasive fungal infection (IFI) is one of the serious complications in burn patients. The gradual development and application of broad-spectrum antibiotics in recent years has led to a serious dysbiosis of the flora, while the widespread prophylactic use of antifungal drugs has led to an increasing number of drug-resistant fungi. The clinical treatment of IFI is difficult and the prognosis is poor. The mortality of burn patients caused by IFI is increasing year by year. This paper reviews the epidemiologic characteristics, related risk factors, diagnostic methods, and treatment progress of IFI after burns, aiming to provide new ideas and reference for the prevention and treatment of IFI after burns.

Background: Sepsis is one of the most common complications in burn patients and causes high morbidity, especially in those with severe burns. Nevertheless, there are no formal criteria for diagnosing and treating burn sepsis. Therefore, this bibliometric analysis is applied to reveal research trends in this field and predicts its possible hot spots., Methods: We screened relevant literature on burn sepsis that met the inclusion criteria of the Web of Sciences (WOS) database and analyzed publication trends and research hot spots in related fields using VOSviewer software., Results: From 1981 to 2022, we screened 2,486 documents that met the requirements and analyzed them bibliometrically. The American scholar Herndon DN had a much higher h-index [47] than other authors. Most published, cited, and h-indexed publications are from the USA (Np: 1193, Nc: 42154, H: 98). The second most publishing country is China, but the second most cited and h-indexed country is Germany. Burns also outperforms other journals in this field (Np: 376, Nc: 8019, H: 46). "Biomarkers" is a newly emerging keyword (cluster "clinical research," APY was 2018.16), and clinically relevant research in burn sepsis maybe a future research trend., Conclusions: Sepsis in burn patients has unique pathophysiological characteristics and the general diagnostic criteria for sepsis lack specificity. Consequently, we must establish a database and construct an intelligent predictive model to help achieve a more individualized and precise early diagnosis and treatment of burn sepsis. This may also be an important development direction for future research in this field., 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 Cao, Zhang, Luo, Liao, Cheng and Zhan.)

The response to immune checkpoint inhibitors (ICIs) monotherapy remains unsatisfactory in patients with NSCLC. Thus, combining ICIs with other potential modalities is of great significance to enhance the response of single drug alone. Here, we identified that HIF-1α inhibition was capable of promoting anti-tumor immunity in NSCLC. We applied NSCLC cell lines and mouse models to evaluate the synergy of combined HIF-1α inhibition and PD-1 blockade on tumor growth and the function of tumor infiltrating lymphocytes (TILs). Public datasets were utilized to investigate patients' prognosis based on expressions of HIF-1α and LOXL2 as well as EMT-associated markers and CD8 + TILs. Moreover, we explored the correlation between HIF-1α and LOXL2 levels and CD8 + TILs in tumor samples from patients with NSCLC by immunohistochemistry, as well as their association to patients' survival. In vitro, PX-478, an HIF-1α inhibitor, promoted tumor cell apoptosis induced by T cells when combined with ICIs. Furthermore, mice treated with PX-478 and anti-PD-1 antibodies exhibited a marked delay in tumor growth and prolonged survival, which correlated with increased TILs and granzyme B secretion. Besides, patients with high HIF-1α expression exhibited high levels of EMT-related markers and low TILs, indicating an immunosuppressive phenotype. Mechanistically, we observed that HIF-1α inhibition suppressed the EMT phenotypes induced by hypoxia and further alleviated tumor immunosuppression, which was related to blockage of HIF-1α/LOXL2 signaling pathway. In summary, we identified that HIF-1α inhibition could synergize with anti-PD-1 to impair tumor growth in vitro and in vivo. Our data suggest that HIF-1α inhibitors represent a promising treatment to enhance anti-tumor immunity and provide preclinical rationale to evaluate the combination of ICIs with HIF-1α inhibition clinically in NSCLC., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of Modified Sijunzi Decoction on the diversity of intestinal microflora of in severe scald rabbits based on 16S ribosomal RNA (16S rRNA) high-throughput sequencing. Methods: The experimental research method was adopted. Ninety Japanese big-ear rabbits regardless gender, aged 6 to 8 months, were randomly divided into normal control group, scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group, with 18 rabbits in each group. The rabbits in normal control group were free to eat and drink, and the rabbits in scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group were intragastrically administered normal saline, 0.2 g/mL Modified Sijunzi Decoction, 1.0 g/mL Modified Sijunzi Decoction, and 5.0 g/mL Modified Sijunzi Decoction, respectively for 7 days after sustaining full-thickness scalding of 30% total body surface area. On the 1 st , 3 rd , and 7 th day after grouping, the levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-10 in ileal mucosa tissue of rabbits in each group were determined by enzyme-linked immunosorbent assay, and the number of samples in each group at each time point was 6. According to the above experimental results, another 9 rabbits were selected and divided into normal control group, scald alone group and scald+medium-dose group, with 3 rabbits in each group. The grouping and treatment methods of rabbits in each group were the same as before. On the 7 th day after grouping, the V3, V4 region of 16S rRNA of ileum mucosa of rabbits in three groups were sequenced by high-throughput sequencing technology. The number of quality bacteria was counted by QIME software. The classifications of phylum, class, order, family and genus of microflora were analyzed by RDP Classifier software. The α diversity (Ace, Chao1, Simpson, and Shannon indexes) and β diversity were analyzed by Illumina MiSeq sequencing technology, and the number of experiment samples in each group was 3. Data were statistically analyzed with analysis for variance of factorial design, SNK test, and Bonferroni correction. Results: Compared with that in normal control group, the levels of TNF-α of ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, and scald+high-dose group on the 1 st , 3 rd , and 7 th day after grouping and scald+medium-dose group on the 1 st and 3 rd day after grouping were all significantly increased ( P <0.01), the levels of IL-1β in ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, scald+medium-dose group and scald+high-dose group on the 1 st , 3 rd , and 7 th day after grouping were all significantly increased ( P <0.05 or P <0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 1 st , 3 rd , and 7 th day after grouping were all significantly decreased ( P <0.01). Compared with that in scald alone group, the levels of TNF-α in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 3 rd and 7 th day after grouping, and scald+medium-dose group on the 1 st day after grouping were all significantly decreased ( P <0.01), and the levels of IL-1β in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 3 rd and 7 th day after grouping and scald+medium-dose group on the 1 st day after grouping were all significantly decreased ( P <0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+low-dose group on the 7 th day after grouping and scald+medium-dose group on the 1 st , 3 rd , and 7 th day after grouping and scald+high-dose group on the 3 rd and 7 th day after grouping were all significantly increased ( P <0.05 or P <0.01). Compared with that in scald+low-dose group, the levels of TNF-α in ileal mucosa tissue of rabbits in medium-dose scald alone group on the 1 st , 3 rd , and 7 th day after grouping and in high-dose scald alone group on the 3 rd and 7 th day after grouping were significantly decreased ( P <0.01), and the levels of IL-1β in ileal mucosa tissue of rabbits in medium-dose scald alone group on the 1 st , 3 rd , and 7 th day after grouping and in high-dose scald alone group on the 3 rd and 7 th day after grouping were all significantly decreased ( P <0.05 or P <0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+medium-dose group on the 1 st , 3 rd , and 7 th day after grouping and in scald+high-dose group on the 7 th day after grouping were all significantly increased ( P <0.05 or P <0.01). Compared with that in scald medium-dose group, the levels of TNF-α in ileal mucosa tissue of rabbits in scald+high-dose group on the 1 st , 3 rd , and 7 th day after grouping were all significantly increased ( P <0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+high-dose group on the 1 st , 3 rd , and 7 th day after grouping were all significantly decreased ( P <0.01), and the levels of IL-1β in ileal mucosa tissue of rabbits in scald+high-dose group on the 7 th day after grouping was significantly decreased ( P <0.01). Compared with that on the 1 st day after grouping, the levels of TNF-α in ileal mucosa tissue of rabbits in scald alone group on the 3 rd and 7 th day after grouping and in normal control group on the 3 rd day after grouping were all significantly increased ( P <0.05 or P <0.01), and the levels of IL-1β in ileal mucosa tissue of rabbits in scald alone group both on the 3 rd and 7 th day after grouping were significantly increased ( P <0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in both scald+low-dose group and scald+high-dose group on the 7 th day after grouping and scald+medium-dose group both on the 3 rd and 7 th day after grouping were significantly increased ( P <0.05 or P <0.01), and the levels of TNF-α in ileal mucosa tissue of rabbits in scald+high-dose group on the 3 rd and 7 th day after grouping and in scald+medium-dose group on the 7 th day after grouping were all significantly decreased ( P <0.05 or P <0.01), and the level of IL-1β in ileal mucosa tissue of rabbits in scald+medium-dose group on the 7 th day after grouping was significantly decreased ( P <0.01), and the level of IL-10 in ileal mucosa tissue of rabbits in scald alone group on the 7 th day after grouping was significantly decreased ( P <0.01). Compared with that on the 3 rd day after grouping, the levels of TNF-α and IL-1β in ileal mucosa tissue of rabbits in scald alone group and the levels of IL-10 in ileal mucosa tissue of rabbits in normal control group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 7 th day after grouping were all significantly increased ( P <0.05 or P <0.01); and the levels of TNF-α in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 7 th day after grouping were all significantly decreased ( P <0.05), and the levels of IL-1β in ileal mucosa tissue of rabbits both in scald+medium-dose group and scald+high-dose group on the 7 th day after grouping were significantly decreased ( P <0.05 or P <0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald alone group on the 7 th day after grouping was significantly decreased ( P <0.01). On the 7 th day after grouping, the high-quality sequences obtained from the microflora in ileum mucosa of rabbits in normal control group, scald alone group, and scald+medium-dose group were 96 023, 107 365, and 95 921, respectively. At the classification level of phylum, class, order, family, and genus of the microflora in ileum mucosa of rabbits in three groups were all Bacteroidetes and Firmicutes , Clostridium and Bacteroidetes, Clostridium and Bacteroidetes , Rumenobacteriaceae and Clostridium and Bacteroideaceae , Clostridium and Bacteroidetes and rumen bacteria mainly, while the percentage of microflora in each group was different. There were no significant differences in Ace, Chao1, Simpson, Shannon indices ( P >0.05), and no obvious difference in β diversity of microflora in ileal mucosa tissue of rabbits among three groups. Conclusions: After severe scalding, the inflammatory response of rabbit ileal mucosa tissue is obvious and increased in a time-dependent manner. Modified Sijunzi Decoction can reduce inflammation with optimal therapeutic concentration of 1.0 g/mL. The technology of high-throughput sequencing can reflect the structural composition of the intestinal microflora accurately. The ileal microflora of the severe scald rabbit can be regulated by the administration of Modified Sijunzi Decoction.

Bladder cancer is one of the most frequent cancers among males, and a poor survival rate reflects problems with aggressiveness and chemo-resistance. Accumulating evidence indicates that SIRT1 is involved in bladder cancer tumorigenesis and is positively associated with chemo-resistance and poor prognosis. We recently synthesized water-soluble chemical derivatives of heliomycin, an antibiotic from Streptomyces resistomycificus , and demonstrated that they possess anticancer properties. In this present study, we used the cellular thermal shift assay (CETSA) in T24 bladder cancer cells to show that heliomycin (designated compound (H1)) and its 4-( tert -butylamino)methyl derivative (HD2) directly engaged with SIRT1 in the native cellular environment, whereas another derivative (HD3) did not. Upon binding, heliomycin downregulated SIRT1 protein expression without altering its transcript level, and subsequently induced autophagy. Interestingly, the derivative (HD2) triggered apoptosis. The interaction between SIRT1 protein and heliomycin or its derivatives was also speculated by a molecular docking simulation, suggesting heliomycin (H1) and derivative (HD2) acting with the different binding modes to SIRT1. Given the increased water-solubility, hydrogen bonds were found on Ala262 and Ile347 residues in the docked complex of derivative (HD2) to produce more steady interaction and initiate signaling pathways that were not observed in the case of heliomycin. Meanwhile, it is evident that derivative (HD3) did not engage with SIRT1 by CETSA or molecular docking studies, nor did it downregulate SIRT1 expression. Taken together, these findings clearly show that SIRT1 is targeted and downregulated by heliomycin and its water-soluble 4-aminomethylated derivative (HD2) possibly through autophagic and/or proteasomal degradation, leading to cell death and growth suppression of T24 bladder cancer cells., Competing Interests: None., (AJCR Copyright © 2022.)

Ethnopharmacological Relevance: Korean red ginseng (KRG), a processed product of Panax ginseng C. A. Mey, show significant anti-depressive effect in clinic. However, its mechanism is still unclear., Aim of the Study: Gap junction intercellular communication (GJIC) dysfunction is a potential pathogenesis of depression. Therefore, this study's objective is to investigate whether the antidepressant effect of KRG is related to GJIC., Materials and Methods: Rat were restraint 8 h every day for 28 consecutive days to prepare depression models, and meanwhile, rats were intragastrically administrated with normal saline, KRG solutions (25, 50 or 100 mg/kg) or fluoxetine (10 mg/kg) 1 h before stress. The behavioral performance was determined by forced swimming test, sucrose preference test and open field test. GJIC was determined by the Lucifer yellow (LY) diffusion distance in prelimb cortex (PLC). In addition, the level of Cx43, one of executors of GJIC, was tested by Western blot. To find out the protective effect of KRG against GJIC dysfunction directly, rats were intracranially injected with carbenoxolone (CBX, blocker of GJIC), and meanwhile normal saline, KRG (100 mg/kg) or fluoxetine (10 mg/kg) was administered daily. The behavioral performance of these rats was detected, and the LY localization injection PLC area was used to detect the gap junction function., Results: Chronic resistant stress (CRS) induced depressive symptoms, as manifested by prolonged immobility time in forced swimming test and decreased sucrose consumption ratio. Administration of KRG alleviated these depressive symptoms significantly. GJIC determination showed that KRG improved the LY diffusion and increased Cx43 level in prefrontal cortex (PFC) significantly, indicated that GJIC dysfunction was alleviated by the treatment of KRG. However, the astrocytes number was also increased by the treatment of KRG, which maybe alleviate depression-like symptoms by increasing the number of astrocytes rather than improving GJIC. Injection of CBX produced depressive symptoms and GJIC dysfunction, as manifested by decreased sucrose consumption ratio and prolonged immobility time in forced swimming test, but no astrocytes number changes, KRG also reversed depressive symptoms and GJIC dysfunction, suggested that the improvement of depressive-like symptoms was improved by GJIC., Conclusions: KRG alleviate depressive disorder by improving astrocytic gap junction function., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Sophorae Flavescentis Radix, the root of Sophora flavescens Ait., has been widely applied in the medical field due to its anti-inflammatory, analgesic, bacteriostatic, antiviral, antitumor, and other pharmacological effects. The present study investigated the anti-rheumatoid arthritis effect of oxymatrine(OMT), the active component of Sophorae Flavescentis Radix by observing its effect on the function of B lymphocytes in collagen-induced arthritis(CIA) mice through the Toll-like receptor 9(TLR9)/myeloid differentiation factor 88(MyD88)/signal transducer and activator of transcription 3(STAT3) pathway. The CIA model in DBA/1 J mice was induced by bovine type Ⅱ collagen and complete Freund's adjuvant(CFA). Fifteen days after the primary immunization, mice were treated with OMT for 30 days by intraperitoneal injection. Paw swelling and arthritis index(AI) score were evaluated every 3 days. Joint histopathologic changes were observed by HE staining. Magnetic-activated cell sorting(MACS) was used to isolate B lymphocytes from the spleen of CIA mice spleen. The serum expression level of interleukin(IL)-21 was examined by the enzyme-linked immunosorbent assay(ELISA). The expression of TLR9, STAT3, p-STAT3, and IL-21 in B lymphocytes was detected by Western blot. The mRNA expression of TLR9, STAT3, and IL-21 in B lymphocytes was detected by real-time fluorescence-based quantitative PCR(qRT-PCR). The results showed that OMT could significantly alleviate the paw swelling, decrease the AI score, relieve synovial inflammatory cell infiltration and hyperplasia, reduce the level of inflammatory cytokines, and inhibit the expression of TLR9, STAT3, p-STAT3, and IL-21 of B lymphocytes in CIA mice. Therefore, OMT may alleviate rheumatoid arthritis by regulating TLR9/MyD88/STAT3 pathway in B lymphocytes, providing a valuable reference for the application of OMT in the clinical treatment of rheumatoid arthritis.

A series of sulfonamide derivatives were synthesized, and the enzyme inhibitory activity of the synthesized compounds on carbonic anhydrase II was evaluated. Through molecular docking studies, it was found that compounds 1b , 1e , 2a , 2b , 3a have a strong binding affinity to carbonic anhydrase II. The IC 50 values of the four compounds 1e , 2b , 3a , and 3b were lower than that of the positive control drug acetazolamide. What's more, the compounds had a high inhibitory activity for A549 lung cancer cell growth, among them, 1e and 3a could inhibit both carbonic anhydrase II and lung cancer cell proliferation.

Metalation of covalent organic frameworks (COFs) is a critical strategy to functionalize COFs for advanced applications yet largely relies on the pre-installed specific metal docking sites in the network, such as porphyrin, salen, 2,2'-bipyridine, etc. We show in this study that the imine linkage of simple imine-based COFs, one of the most popular COFs, readily chelate transition metal (Ir in this work) via cyclometalation, which has not been explored before. The iridacycle decorated COF exhibited more than 10-fold efficiency enhancement in (photo)catalytic hydrogen evolution from aqueous formate solution than its molecular counterpart under mild conditions. This work will inspire more functional cyclometallated COFs to be explored beyond catalysis considering the large imine COF library and the rich metallacycle chemistry., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Despite the progress that has been made in diagnosing and treating oral cancers, they continue to have a poor prognosis, with a 5-year overall survival rate of approximately 50%. We have intensively studied the anticancer properties of capsaicin (a burning constituent of chili pepper), mainly focusing on its apoptotic properties. Here, we investigated the interplay between apoptosis and autophagy in capsaicin-treated oral cancer cells with either functional or mutant p53. Cytotoxicity was determined by cell impedance measurements and WST-1 assays, and cell death was analyzed by flow cytometry. The interaction between capsaicin and tumor-associated NADH oxidase (tNOX, ENOX2) was studied by cellular thermal shift assay (CETSA) and isothermal dose-response fingerprint curves (ITDRF CETSA ). Our CETSA data suggested that capsaicin directly engaged with tNOX, resulting in its degradation through the ubiquitin-proteasome and the autophagy-lysosome systems. In p53-functional SAS cells, capsaicin induced significant cytotoxicity via autophagy but not apoptosis. Given that tNOX catalyzes the oxidation of NADH, the direct binding of capsaicin to tNOX also inhibited the NAD + -dependent activity of sirtuin 1 (SIRT1) deacetylase, we found that capsaicin-induced autophagy involved enhanced acetylation of ULK1, which is a key player in autophagy activation, possibly through SIRT1 inhibition. In p53-mutated HSC-3 cells, capsaicin triggered both autophagy and apoptosis. In this case, autophagy occurred before apoptosis: during this early stage, autophagy seemed to inhibit apoptosis; at a later stage, in contrast, autophagy appeared to be essential for the induction of apoptosis. Western blot analysis revealed that the reduction in tNOX and SIRT1 associated with enhanced ULK1 acetylation and c-Myc acetylation, which in turn, reactivated the TRAIL pathway, ultimately leading to apoptosis. Taken together, our data highlight the potential value of leveraging capsaicin and tNOX in therapeutic strategies against oral cancer., Competing Interests: None., (AJCR Copyright © 2020.)

Vascular dementia (VD) is the second most common dementia disease after Alzheimer's diseases (AD) in the world. Donepezil is used to treat mild to moderate AD, and it has been shown to treat cognitive impairment and memory deficits caused by VD. However, the action mechanism of donepezil against VD has not been clarified. In this study, a bilateral common carotid artery occlusion (BCCAO) model was established in rats to simulate the pathology of VD. Two weeks after the surgery, the rats were administered donepezil (10 mg · kg -1  · d -1 , ig) for 3 weeks, and then subjected to behavioral tests. We showed that donepezil treatment significantly improved the performance of BCCAO rats in Morris Water Mazes test and Step-down test. Furthermore, we showed that donepezil treatment significantly attenuated neurodegeneration and restored the synapse dendritic spines density in cortex and hippocampus. We revealed that donepezil treatment significantly increased BDNF expression in cortex and hippocampus. Interestingly, donepezil treatment significantly decreased nuclear translocation of HDAC6 and the binding between HDAC6 and BDNF promoter IV in cortex, but not in the hippocampus. The attenuated neurodegeneration by donepezil in cortex and hippocampus might due to the reduced ROS levels and increased phosphorylation of AMPK, whereas increased phosphorylation of AKT was only detected in cortex. In conclusion, our results demonstrate that donepezil attenuates neurodegeneration in cortex and hippocampus via increasing BDNF expression; the regulation of donepezil on HDAC6 occurred in cortex, but not in the hippocampus. This study further clarifies the pharmacological mechanism of donepezil, while also emphasizes the promising epigenetic regulation of HDAC6.

Objective: To explore the effect of alprostadil in early wound healing of rats with deep partial-thickness scald. Methods: Ninety specific pathogen free healthy Sprague-Dawley rats (half males and half females) were divided into sham scald group, simple scald group, and alprostadil group using the random number table with 30 rats in each group. Rats in sham scald group were sham injured, and rats in the other 2 groups were inflicted with deep partial-thickness scald of 30% total body surface area on the back. Immediately after scald, rats in the 3 groups received anti-shock treatment. Two hours post scald, rats in sham scald group and simple scald group were injected intraperitoneally with 1 mL normal saline, and rats in alprostadil group were injected intraperitoneally with 1 mL alprostadil injection, once a day and continued for 14 days. On post scald day (PSD) 3, 7, and 14, 10 rats in each group were collected for observing the general wound conditions and the wound healing rates of rats in 2 scald groups were calculated, abdominal aortic blood of 2 mL from each rat were collected to detect serum thromboxane B2 by enzyme-linked immunosorbent assay, and wound tissue on the back was collected to examine pathomorphological change by hematoxylin-eosin staining and to detect wound microvessel density (MVD) by immunohistochemical staining. Data were statistically analyzed with analysis of variance of factorial design, t test, Kruskal-Wallis H test, Mann-Whitney U test, and Bonferroni correction. Results: (1) There was no scald wound in rats in sham scald group. On PSD 3, wounds of rats in simple scald group and alprostadil group formed dry eschar. On PSD 7 and 14, wound areas of rats in alprostadil group were significantly smaller than those of rats in simple scald group, and with less exudation. (2) On PSD 3, the wound healing rates of rats in simple scald group and alprostadil group were similar ( t =1.167, P >0.05). On PSD 7 and 14, the wound healing rates of rats in alprostadil group were significantly higher than those in simple scald group ( t =8.657, 33.050, P <0.01). (3) On PSD 3, 7, and 14, the levels of serum thromboxane B2 of rats in simple scald group and alprostadil group were (541±22), (607±47), (688±21), (326±25), (271±21), (135±27) pg/mL, significantly higher than (17±6), (16±4), (16±4) pg/mL of rats in sham scald group ( t =72.977, 39.685, 102.076, 37.033, 37.253, 13.845, P <0.01). On PSD 3, 7, and 14, the levels of serum thromboxane B2 of rats in alprostadil group were significantly lower than those in simple scald group ( t =20.637, 20.651, 51.680, P <0.01). (4) Normal epidermis and dermis were seen in rats in sham scald group. On PSD 3, a large number of necrotic tissue and inflammatory cells infiltration were seen in wounds of rats in simple scald group, while a little new epithelium formation and some inflammatory cells infiltration were seen in wounds of rats in alprostadil group. On PSD 7 and 14, the new epithelium of rats in alprostadil group was significantly thicker than that in simple scald group, and epidermis formed gradually in alprostadil group. (5) On PSD 3, 7, and 14, the wound MVD of rats in simple scald group and alprostadil group were significantly higher than those in sham scald group ( Z =-3.780, -3.781, -3.780, -3.780, -3.781, -3.780, P <0.01). On PSD 3, the wound MVD of rats in simple scald group and alprostadil group were similar ( Z =-1.965, P >0.05). On PSD 7 and 14, the wound MVD of rats in alprostadil group were significantly higher than those in simple scald group ( Z =-3.780, -3.780, P <0.01). Conclusions: The early intervention with alprostadil can significantly improve microcirculation of deep partial-thickness scald wound, reduce inflammatory cell infiltration, promote the formation of new blood vessels, thus promoting wound healing.

Context: Women with obesity usually need larger doses of FSH for ovarian stimulation, resulting in poor outcomes; however, the mechanism is still unclear., Objective: To investigate the molecular regulation of FSH receptor (FSHR) expression associated with obesity., Design: Case-control study to improve in vitro fertilization (IVF) outcomes., Patients: Women with obesity (82) and women who were overweight (457) undergoing IVF and 1790 age-matched controls with normal weight from our reproductive medicine center., Main Outcome Measures: FSHR expression was decreased in parallel with body mass index (BMI), whereas the estradiol (E2) level on the human chorionic gonadotropin (hCG) trigger day was significantly lower., Results: FSHR expression in human granulosa cells (hGCs), both mRNA (P = 0.02) and protein (P = 0.001) levels, was decreased in women who were overweight or obese. Both insulin (P < 0.001) and glucose (P = 0.0017) levels were positively correlated with BMI in fasting blood and follicle fluids (FFs) but not with FFs leptin level. We treated human granulosa-like tumor cells (KGN) cells with insulin; E2 production was compromised; the level of phosphorylated (p)-protein kinase B (p-Akt2) decreased, whereas p-glycogen synthase kinase 3 (GSK3) increased; and there were similar changes in hGCs from women with obesity. Stimulated hGCs from women with obesity with compound 21 (CP21), an inhibitor of GSK3β, resulted in upregulated β-catenin activation and increased FSHR expression. CP21 also increased the expression of insulin receptor substrate 1 and phosphatidylinositol 3-kinase (PI3K), as well as p-Akt2., Conclusions: Women with obesity in IVF were associated with reduced FSHR expression and E2 production caused by a dysfunctional insulin pathway. Decreased FSHR expression in hGCs from women with obesity and insulin-treated KGN cells could be rescued by an inhibitor of GSK3β, which might be a potential target for the improvement of the impaired FSH-stimulation response in women with obesity., (Copyright © 2019 Endocrine Society.)

The potential role of total saponins extracted from Lilium lancifolium bulbs (TSLL) on the proliferation, apoptosis, migration and invasion of human lung cancer A549 cells and its possible mechanism were discussed. Effect of TSLL on proliferation of A549 cells were detected by CCK-8, clone formation assay and EdU staining. Effect of TSLL on apoptosis morphology of A549 cells was observed by fluorescence microscope using Annexin V/PI double staining and Hoechst 33342 staining. Effect of TSLL on cell migration and invasion was detected by Transwell migration test and Transwell invasion test, respectively. Western blot was used to detect TSLL on the expression change of intracellular associated proteins. Results showed that TSLL intervention in A549 cells within 24, 48 or 72 h significantly inhibited cell growth, and its IC₅₀values were about 229, 173 and 71 mg·L⁻¹, respectively. TSLL significantly reduced the clone formation rate of A549 cells and decreased the DNA synthesis rate of A549 cells in a concentration dependent manner. TSLL induced A549 cells apoptosis and reduced the migratory behavior of A549 cells. TSLL decreased invasion of A549 cells to the artificial basement membrane. The expression level of intracellular PCNA and the ratio of Bcl-2/Bax protein were down-regulated and procaspase 3 was activated. In addition, TSLL had no obvious effect on epithelial mesenchymal transition (EMT) related marker proteins E-cadherin and vimentin expression. The above results indicated that TSLL possess inhibitory effects against proliferation, migration and invasion of lung cancer A549 cells and apoptosis-induced effect. The anti-proliferation effect of TSLL is very likely by inhibiting intracellular DNA synthesis through reducing the expression of PCNA in lung cancer cells. And the apoptosis induction of TSLL on lung cancer cells is associated with the regulation of Bcl-2 and Bax proteins expression. Nevertheless, there is no incontestable correlation between anti-invasion and metastasis effects of TSLL and EMT in lung cancer cells., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To explore effect of alprostadil on wound healing of scalded rats and the mechanism. Methods: According to random number table method, forty-eight Sprague Dawley rats were divided into sham scald group, simple scald group, lithium chloride group, and alprostadil group, with 12 rats in each group. Rats in sham injury group were sham injured on the back, and rats in the other three groups were inflicted with 30% total body surface area deep partial thickness scald on the back.Immediately after scald, rats in sham scald group and simple scald group were injected with 1 mL saline through caudal vein, and rats in lithium chloride group and alprostadil group were injected respectively with 1 mL lithium chloride and alprostadil through caudal vein. Saline, lithium chloride, and alprostadil were injected once in a day and lasted for 14 days. General wound appearance and wound healing rate on post scald day (PSD) 7, 10, 14 were observed and calculated. Expressions of protein and mRNA of Wnt1 and β-catenin on PSD 14 were detected. Data were processed with analysis of variance of factorial design, one-way analysis of variance, Student Newman Keuls q test, t test, and Bonferroni correction. Results: (1) On PSD 7, wounds of scalded rats in each group formed dry eschar and had little exudation. On PSD 10, wounds of rats in simple scald group were covered with eschar, with little exudation, and wounds of rats in lithium chloride group were covered with eschar, and partial wounds healed under the eschar. On PSD 10, partial eschar of rats in alprostadil group desquamated; partial wounds healed; newly burned skin was ruddy. On PSD 14, partial wounds of rats in simple scald group were healed under eschar with little exudation. On PSD 14, most of the eschar of rats in lithium chloride group were desquamated with patial wounds healed and little exudation. On PSD 14, wounds of rats in alprostadil group were basically healed with vigorously growing hair on the back. (2) On PSD 7, the wound healing rates of rats in simple scald group, lithium chloride group, and alprostadil group were close ( F =0.41, P >0.05). On PSD 10 and 14, wound healing rate of rats in lithium chloride group and alprostadil group were significantly higher than that in simple scald group ( q =5.73, 17.45, 26.30, 11.28, P <0.05), and wound healing rate of rats in alprostadil group was significantly higher than that in lithium chloride group ( q =32.03, 28.73, P <0.05). (3) On PSD 14, the mRNA expressions of Wnt1 and β-catenin of rats in lithium chloride group and alprostadil group were significantly higher than those in simple scald group ( q =65.40, 19.16, 66.79, 18.41, P <0.05), and the mRNA expressions of Wnt1 and β-catenin of rats in simple scald group was significantly higher than those in sham scald group ( t =14.86, 4.46, P <0.05). (4) On PSD 14, the protein expressions of Wnt1 and β-catenin of rats in lithium chloride group and alprostadil group were 0.98±0.05, 0.98±0.06, 0.97±0.06, and 1.00±0.06, which were significantly higher than 0.49±0.04 and 0.66±0.04 of rats in simple scald group ( q =34.62, 22.38, 33.61, 23.47, P <0.05). On PSD 14, the protein expressions of Wnt1 and β-catenin of rats in simple scald group was significantly higher than 0.29±0.03 and 0.31±0.03 of rats in sham scald group ( q =14.73, 23.88, P <0.05). Conclusions: Alprostadil can accelerate wound healing through activating Wnt/β-catenin signal pathway and upregulating the expressions of Wnt1 and β-catenin.

Background: The standard first-line chemotherapy for patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has not been well established. We conducted a pooled meta-analysis to evaluate the efficacy of commonly used first-line chemotherapy in this disease., Methods: Electronic databases including PubMed, Embase, and Corchrane library were searched for eligible literatures. Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS) were pooled with the 95% confidence interval (CI) using R software., Results: Totally 973 patients were available for analysis from 14 phase II single arm clinical trials and 2 phase III randomized clinical trials. Four regimens were identified including 5-fluorouracil plus platinum (FP), gemcitabine plus platinum (GP), taxanes plus platinum (TP), and triplet combination regimen. Of these four regimens, triplet combination regimen demonstrated best short-term efficacy with a highest ORR (0.74; 95% CI, 0.62-0.87), DCR (0.91; 95% CI, 0.87-0.95), and 6-month PFS rate (0.83; 95% CI, 0.75-0.91), while 1-year OS rate (0.74; 95% CI, 0.61-0.87) was a little lower than TP regimen. Meanwhile, TP regimen showed best prognosis with a highest 1-year OS rate of 0.79 (95% CI, 0.65-0.92) and pretty good short-term efficacy with an ORR of 0.60 (95% CI, 0.48-0.72) and a DCR of 0.92 (95% CI, 0.86-0.98) comparable with triplet combination therapy. FP regimen had the lowest ORR (0.52; 95% CI, 0.38-0.65) and 1-year OS rate (0.63; 95% CI, 0.57-0.69). Efficacy of GP regimen fell between FP and TP regimens with an ORR of 0.54 (95% CI, 0.38-0.65), a DCR of 0.85 (95% CI, 0.71-0.93), a 6-month PFS rate of 0.69 (95% CI, 0.60-0.78) and a 1-year OS rate of 0.71 (95% CI, 0.61-0.80)., Conclusions: Among four commonly used first-line chemotherapy regimens for R/M NPC, triplet combination regimen showed best short-term efficacy but failed to improve prognosis. TP regimen demonstrated fairly good short-term efficacy and best long-term efficacy, followed by GP regimen, while FP regimen was the lowest., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objective: To investigate the effects of astragalus polysaccharide (AP) on cardiac dysfunction in rabbits with severe scald injury. Methods: Sixty-four New Zealand white rabbits were divided into pure scald group and AP group according to the random number table, with 32 rabbits in each group. Rabbits in the two groups were all inflicted with 30% total body surface area full-thickness scald on the back. Immediately after injury, rabbits in two groups were intraperitoneally injected with lactated Ringer's solution once for antishock. Rabbits in AP group were intraperitoneally injected with 10 mL AP solution with the dosage of 200 mg/kg 10 min after injury and the following 6 days respectively, once a day. Rabbits in pure scald group were injected with 10 mL normal saline instead. Eight rabbits of each group were respectively selected before injury hour (BIH) 1 and on post injury day(PID) 1, 3, 7, and 14 to collect blood samples from ear marginal vein, and then sacrificed immediately to collect hearts at each time point post injury. The morphology of myocardium was observed after HE staining. The serum content of cardiac troponin I (cTnI) was detected by enzyme-linked immunosorbent assay (ELISA). The serum content of aspartate transaminase (AST), creatine kinase (CK), CK isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH) was detected by fully automatic chemistry analyzer. The content of angiotensin Ⅱ (Ang Ⅱ) in serum and myocardium was detected with radioimmunoassay and the content of endothelin 1 (ET-1) in serum and myocardium was detected by ELISA. Another 8 normal rabbits were sacrificed to detect the content of Ang Ⅱ and ET-1 in the myocardium as the value of the two groups of scalded rabbits at BIH 1. The serum content of superoxide dismutase (SOD) and malondialdehyde (MDA) was detected by ELISA. The values of whole blood viscosity (ηb), reductive viscosity of whole blood (ηr), plasma viscosity (ηp), hematocrit (HCT), erythrocyte rigidity index (TK), erythrocyte aggregation index (EAI), and erythrocyte sedimentation rate (ESR) were detected by fully automatic hematology analyzer. Data were processed with analysis of variance of factorial design, independent sample t test, and Dunnett test. Results: (1) Compared with those in pure scald group, the degrees of cardiomyocyte swelling, steatosis, necrosis and rupture of muscle fiber were significantly alleviated in rabbits of AP group on PID 1 and 3. There was no obvious increase in cell size, no breakage of muscle fiber or infiltration of inflammatory cells in myocardial interstitium on PID 7. The myocardial tissue structure and muscle fiber arrangement returned to normal condition on PID 14, with no interstitial fibroblast hyperplasia or excessive extra cellular matrix deposition. (2) Serum content of cTnI, CK, and LDH of rabbits in AP group was significantly lower than that in pure scald group on PID 1, 3, and 7 (with t values from 2.69 to 13.99, P <0.05 or P <0.01), while there was no significant difference between the two groups on PID 14 (with t values from -0.32 to 0.68, P values above 0.05). Serum content of AST and CK-MB of rabbits in AP group was significantly lower than that in pure scald group on PID 1 and 3 (with t values from 2.21 to 12.65, P <0.05 or P <0.01), while there was no significant difference between the two groups on PID 7 and 14 (with t values from 0.03 to 1.67, P values above 0.05). (3) Serum content of Ang Ⅱ of rabbits in AP group was significantly lower than that in pure scald group from PID 1 to 14 (with t values from 3.38 to 32.58, P values below 0.01). Serum content of ET-1 of rabbits in AP group was significantly lower than that in pure scald group from PID 3 to 14 (with t values from 3.54 to 11.02, P values below 0.01), while there was no obvious difference on PID 1 ( t =0.39, P >0.05). Content of Ang Ⅱ and ET-1 in myocardial tissue of rabbits in AP group was significantly lower than that in pure scald group from PID 1 to 7 (with t values from 1.27 to 13.79, P values below 0.01), while there was no obvious difference on PID 14 (with t values respectively 0.07 and 0.81, P values above 0.05). (4) Serum content of SOD of rabbits in AP group was respectively (15.65±2.64), (14.67±0.74), and (8.43±0.56) ng/mL on PID 1, 3, and 7, which was significantly higher than (6.35±0.83), (2.62±0.75), and (2.84±0.41) ng/mL in pure scald group (with t values from -29.79 to -9.10, P values below 0.01); while there was no obvious difference on PID 14 [with (4.02±0.26) ng/mL in pure scald group and (4.11±0.52) ng/mL in AP group, t =-0.01, P >0.05]. Serum content of MDA of rabbits in AP group was respectively (1.31±0.61), (1.72±0.64), and (0.65±0.42) μmol /mL on PID 1, 3, and 7, which was significantly lower than (1.68±0.57), (2.34±0.79), and (1.06±0.32) μmol/mL in pure scald group (with t values from 1.63 to 3.16, P <0.05 or P <0.01), while there was no obvious difference on PID 14 [with (0.31±0.09) μmol/mL in pure scald group and (0.24±0.08) μmol/mL in AP group, t =2.11, P >0.05]. (5) Values of ηb1 and EAI of rabbits in AP group were significantly lower than those in pure scald group from PID 1 to 7 (with t values from 2.718 to 11.170, P <0.05 or P <0.01), while there were no obvious differences on PID 14 (with t values respectively 2.078 and -1.423, P values above 0.05). Values of ηb2 and ηr2 of rabbits in AP group were significantly lower than those in pure scald group on PID 3 and 7 (with t values from 2.178 to 19.205, P <0.05 or P <0.01), while there were no obvious differences on PID 1 and 14 (with t values from -0.730 to 1.320, P values above 0.05 ). Values of ηr1 and ESR of rabbits in AP group were significantly lower than those in pure scald group on PID 3, 7, and 14 (with t values from 3.021 to 8.058, P values below 0.01), while there were no obvious differences on PID 1 (with t values respectively 1.200 and 1.263, P values above 0.05 ). Value of ηp of rabbits in AP group was significantly lower than that in pure scald group on PID 1 ( t =2.430, P <0.05), while there were no obvious differences on PID 3, 7, and 14 (with t values from 0.002 to 1.446, P values above 0.05 ). Value of HCT of rabbits in AP group was close to that in pure scald group on PID 1 ( t =1.079, P >0.05), and the values were significantly lower than those in pure scald group on PID 3 and 14 (with t values respectively 3.849 and 4.208, P values below 0.01), while the value was significantly higher than that in pure scald group on PID 7 ( t =-4.925, P <0.01). Value of TK of rabbits in AP group was lower than that in pure scald group on PID 7 ( t =2.847, P <0.05), while there were no obvious differences on PID 1, 3, and 14 (with t values from -1.102 to 0.875, P values above 0.05). Conclusions: AP can alleviate the damage of myocardium of rabbits with severe scald by reducing the production of vasoactive substances Ang Ⅱ and ET-1, decreasing oxidative stress injury by increasing the content of SOD and decreasing the production of MDA, improving blood flow performance and microcirculation perfusion.

Background: To investigate the role of PD-L1 expression in tumor recurrence and metastasis in Chinese patients with breast cancer., Methods: Suitable tissue samples were available from 870 patients with breast cancer. Paraffin-embedded tumor sections were stained with PD-L1 antibody. The correlations between PD-L1 expression and clinical characteristics, ER/PR/HER2 status and survival parameters were analyzed. Kaplan-Meier and univariate Cox proportional hazards model analyses were used to compare the survival of patients with high PD-L1 expression and patients with no PD-L1 expression., Results: The median follow-up time was 98 months(range, 17-265 months).The positive rate of PD-L1 expression in breast cancer was 21.7% (189/870). PD-L1 high expression was inversely associated with larger tumor size, higher tumor grade, more positive lymph node number, as well as negative ER and PR status. PD-L1 expression was particularly higher in TNBC compared with non-TNBC, although no statistical significance was observed. Nomogram logistic regression results based on clinical and pathological features showed that the following factors were more likely associated with high PD-L1 expression: patient age younger than 35 years, larger tumor size, lymphovascular invasion and advanced stage. Our data indicated that patients with high PD-L1 expression had poor DFS, DMFS and overall survival compared with those with no PD-L1 expression. Univariate Cox proportional hazards model analysis showed that PD-L1 was an independent prognostic factor for tumor prognosis., Conclusions: PD-L1 expression is an important indicator of unfavorable prognosis in breast cancer patients.

Intestinal ischemia/reperfusion (I/R) injury, in which macrophages play a key role, can cause high morbidity and mortality. The switch from classically (M1) to alternatively (M2) activated macrophages, which is dependent on the activation of STAT6 signaling, has been shown to protect organs from I/R injuries. In the current study, the effects of recombinant Trichinella spiralis cathepsin B-like protein (rTsCPB) on intestinal I/R injury and the potential mechanism related to macrophage phenotypes switch were investigated. In a mouse I/R model undergoing 60-min intestinal ischemia followed by 2-h or 7-d reperfusion, we demonstrated that intestinal I/R caused significant intestinal injury and induced a switch from M2 to M1 macrophages, evidenced by a decrease in levels of M2 markers (arginase-1 and found in inflammatory zone protein), an increase in levels of M1 markers (inducible NO synthase and CCR7), and a decrease in the ratio of M2/M1 macrophages. RTsCPB reversed intestinal I/R-induced M2-M1 transition and promoted M1-M2 phenotype switch evidenced by a significant decrease in M1 markers, an increase in M2 markers, and the ratio of M2/M1 macrophages. Meanwhile, rTsCPB significantly ameliorated intestinal injury and improved intestinal function and survival rate of animals, accompanied by a decrease in neutrophil infiltration and an increase in cell proliferation in the intestine. However, a selective STAT6 inhibitor, AS1517499, reversed the protective effects of rTsCPB by inhibiting M1 to M2 transition. These findings suggest that intestinal I/R injury causes a switch from M2 to M1 macrophages and that rTsCPB ameliorates intestinal injury by promoting STAT6-dependent M1 to M2 transition., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Background: Differentiating morphologic features based on hematoxylin-eosin (HE) staining is the most common method to classify pathological subtypes of non-small-cell lung cancer (NSCLC). However, its accuracy and inter-observer reproducibility in pathological diagnosis of poorly differentiated NSCLC remained to be improved., Materials and Methods: We attempted to explore the role of immunohistochemistry (IHC) staining in diagnosing pulmonary squamous cell carcinoma (SQCC) with poorly differentiated features by HE staining or with elevated serum adenocarcinoma-specific tumor markers (AD-TMs). We also compared the difference of epidermal growth factor receptor (EGFR) mutation rate between patients with confirmed SQCC and those with revised pathological subtype. Logistic regression analyses were used to test the association between different factors and diagnostic accuracy., Results: A total of 132 patients who met the eligible criteria and had adequate specimens for IHC confirmation were included. Pathological revised cases in poor differentiated subgroup, biopsy samples and high-level AD-TMs cases were more than those with high/moderate differentiation, surgical specimens and normal-level AD-TMs. Moreover, biopsy sample was a significant factor decreasing diagnostic accuracy of pathological subtype (OR, 4.037; 95% CI 1.446-11.267, p=0.008). Additionally, EGFR mutation rate was higher in patients with pathological diagnostic changes than those with confirmed SQCC (16.7% vs 4.4%, p=0.157)., Conclusions: Diagnosis based on HE staining only might cause pathological misinterpretation in NSCLC patients with poor differentiation or high-level AD-TMs, especially those with biopsy samples. HE staining and IHC should be combined as pathological diagnostic standard. The occurrence of EGFR mutations in pulmonary SQCC might be overestimated.

In this paper, we cloned a novel full-length cDNA that encodes a Trichinella spiralis cathepsin B-like protease gene (TsCPB) using 3'-RACE PCR. The recombinant mature TsCPB protein (rTsCPB) was then expressed in an Escherichia coli expression system and purified with Ni-affinity chromatography. Real-time quantitative PCR revealed that TsCPB was expressed across all development stages of the parasite but had the highest expression level during the adult stage. Furthermore, rTsCPB was detected in Trichinella excretory-secretory products with anti-rTsCPB rabbit polyclonal antibodies. Interestingly, rTsCPB was strongly recognized by the T. spiralis-infected sera in Western blotting, implying that TsCPB protein appeared in the peripheral blood of Trichinella-infected mice as circulating antigens (CAg). We then analyzed the dynamic levels of TsCPB CAg and its antibodies in T. spiralis-infected sera by using an improved double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) and indirect ELISA, respectively. The results showed that TsCPB CAg can be detected much earlier compared to antibody detection in Trichinella-infected mice. In addition, we monitored the effects of albendazole drug therapy (a dosage of 370 mg/kg body weight, twice a day) on T. spiralis-infected mice by detecting the levels of TsCPB CAg and its antibody in the sera of drug-treated mice. The results showed that the levels of CAg dramatically decreased after successful drug treatment, while the antibody level remained unchanged. Overall, the novel Trichinella antigen TsCPB could be a promising novel circulating antigen molecule for the detection of Trichinella infection and for monitoring the efficacy of drug treatment of trichinellosis.

"Synergistic effect" is prevalent in natural metalloenzymes in activating small molecules, and the success has inspired the development of artificial catalysts capable of unprecedented organic transformations. In this work, we found that the attractive π-π interaction between organic additives (as electron-donors) and the perfluorinated arenes (as electron acceptors) is effective in gold hydride catalyzed activation of C-F bonds, specifically hydrodefluorination (HDF) of perfluoroarenes catalyzed by the Sadighi's gold hydrides [(NHC)AuH] (NHC = N-heterocyclic carbene). Although a weak interaction between [(NHC)AuH] and perfluoroarenes was observed from (1)H NMR and UV-vis spectroscopies, low reactivity of [(NHC)AuH] toward HDF was found. In contrast, in the presence of p-N,N-dimethylaminopyridine (DMAP), the HDF of perfluoroarenes with silanes can be efficiently catalyzed by [(NHC)AuH], resulting in mainly the para-hydrodefluorinated products with up to 90% yield and 9 turnovers. The yield of the reaction increases with the more electron-withdrawing groups and degree of fluorination on the arenes, and the HDF reaction also tolerates different function groups (such as formyl, alkynyl, ketone, ester, and carboxylate groups), without reduction or hydrogenation of these function groups. To reveal the role of DMAP in the reactions, the possible π-π interaction between DMAP and perfluoroarenes was suggested by UV-vis spectral titrations, (1)H NMR spectroscopic studies, and DFT calculations. Moreover, (1)H and (19)F-NMR studies show that this π-π interaction promotes hydrogen transfer from [(NHC)AuH] to pyridyl N atom, resulting in C-F bond cleavage. The interpretation of π-π interaction assisted C-F activation is supported by the reduced activation barriers in the presence of DMAP (31.6 kcal/mol) than that in the absence of DMAP (40.8 kcal/mol) for this reaction. An analysis of the charge distribution and transition state geometries indicate that this HDF process is controlled by the π-π interaction between DMAP and perfluoroarenes, accompanied with the changes of partial atomic charges.

Objective: To explore the effect of bone marrow mesenchymal stem cells (MSCs) engraftment on secretion of tumor necrosis factor-α (TNF-α), interleukins (IL-1β, IL-6, IL-10) in peripheral blood and lung homogenates in the early stages of smoke inhalation injury., Methods: MSCs were proliferated by the method of whole marrow culture and identified by flow cytometry. Fifty-six healthy New Zealand rabbits were randomly divided into control group (C group, n=8), smoke inhalation injury group (S group, n=24) and smoke inhalation injury+MSCs engraftment group (M group, n=24). The latter two groups were subdivided into 2, 4, 6 hours after injury subgroups, with 8 rabbits in each group. The levels of TNF-α, IL-1β, IL-6 and IL-10 in peripheral blood and lung homogenates were measured by enzyme-linked immunosorbent assay (ELISA)., Results: Compared with C group, concent of pro-inflammatory and anti-inflammatory cytokines in peripheral blood at each time point in S group were increased significantly. The concent of pro-inflammatory cytokines in lung homogenate at each time point in S group was significantly higher than those in C group, and that of anti-inflammatory cytokines showed no significant changes. Compared with the S group, concent of pro-inflammatory cytokines in peripheral blood in M group was decreased significantly, and that of anti-inflammatory cytokines was increased significantly [6 hours TNF-α (μg/L): 1.7±1.7 vs. 4.1±1.6, IL-1β (ng/L): 9.9±1.7 vs. 21.2±2.6, IL-6 (μg/L): 1.0±0.3 vs. 1.3±0.2, IL-10 (ng/L): 15.2±4.4 vs. 7.9±3.5, all P<0.05]. Concent of pro-inflammatory cytokines at each time point in M group was decreased significantly when compared with S group in lung homogenate, while only anti-inflammatory cytokine at 4 hours and 6 hours was increased significantly [6 hours TNF-α (ng/L): 503.0±156.4 vs. 587.7±171.2, IL-1β (ng/L): 0.4±0.2 vs. 0.6±0.2, IL-6 (ng/L): 155.2±13.7 vs. 350.2±20.3, IL-10 (ng/L): 23.3±5.4 vs. 11.0±5.6, all P<0.05]., Conclusion: MSCs engraftment could decrease pro-inflammatory cytokines and increase anti-inflammatory cytokines in the early stages of smoke inhalation injury, thus ameliorates inflammatory response, which confers protective effect on smoke inhalation injury.

Objective: To explore the effect of bone marrow mesenchymal stem cells (MSCs) engraftment on lung tissue at early stage of smoke inhalation injury in rabbits., Methods: MSCs were proliferated by the method of whole marrow culture and identified by flow cytometry. Forty-eight rabbits were randomly divided into smoke inhalation group (S group) and MSCs group (M group) after reproduction of rabbit smoke inhalation injury model. 10 ml of phosphate buffer saline (PBS) containing 1×10(7)/ml MSCs was intravenously injected in M group, meanwhile 10 ml PBS was injected intravenously in S group. Eight rabbits were sacrificed at 2, 6 and 24 hours after intervention, and the lung tissue was harvested for morphological and pathological observation, and lung injury score was used to evaluate smoke inhalation injury., Results: Cultured cells were confirmed to be MSCs with flow cytometry. Lung injury in rabbits of M group was less serious in morphology and histopathology than that in S group. Though there was no significance in lung injury score between M group and S group at 2 hours after injury (4.0±0.7 vs. 4.5±0.6, P>0.05), the lung injury scores in M group at 6 hours and 24 hours after injury were significantly lower than those in S group (6 hours: 6.1±0.9 vs. 8.2±0.9, 24 hours: 4.6±0.9 vs. 10.4±0.8, both P<0.01)., Conclusion: Intravenous engraftment of MSCs could ameliorate lung injury induced by smoke inhalation, and improve lung injury score significantly.

To synthesize salbutamol immunogen and develop an enzyme immunoassay (ELISA), a new salbutamol immunogen was synthesized using 4-aminobenzoic acid as a linker to connect hapten with carrier protein. An enzyme immunoassay based on the antibody prepared was developed and applied to detect salbutamol residue spiked in swine liver. An unusual coating antigen, clenbuterol-ovalbumin (OVA) conjugate instead of salbutamol-OVA conjugate, was used in the immunoassay and the results were discussed based on the structures of related compounds. The antibodies showed high sensitivity in the heterologous assay when using clenbuterol-OVA as a coating antigen, with an IC50 value of 8.97 ng mL(-1) toward salbutamol. The antibodies prepared showed high cross-reactivity with clenbuterol (107%) and were promising for the simultaneous determination of salbutamol and clenbuterol residues in food and food products. Recovery rates from the salbutamol-spiked swine liver samples were in the range of 70%-99%, while the intra-assay and inter-assay coefficients of variation were <13.3% and <14.3%, respectively. In summary, the antibodies of salbutamol have been successfully prepared. Sensitive and stable analysis for the detection of salbutamol residues in swine liver was obtained based on the competitive ELISA methods developed in this study.

Objective: To investigate the effects of arginine enriched enteral nutrition (EN) on nutritional status and cellular immunity of severely burned patients., Methods: Randomized, single blind, parallel and positive control investigation was employed in the study. Thirty severely burned patients were divided into enteral immune nutrition (EIN) group and EN group. Sixteen patients in EIN group received enteral nutrition enriched with arginine, while the other 14 patients in EN group received standard enteral nutrition. Nutritional support was continued for 14 days. Gastrointestinal reaction of patients in 2 groups was observed. Fasting venous blood was drawn from patients of both groups before receiving nutrition treatment and on the morning of 7th, 14th day of treatment. Level of serum protein, hepatic function parameters, renal function parameters, fasting-blood glucose, and subpopulations of T lymphocytes in peripheral blood were determined., Results: (1) Incidence of gastrointestinal side effect in EIN group (25.0%) was close to that of EN group (21.4% , P > 0.05). (2) Compared with pre-treatment days, levels of prealbumin and transferrin in serum of patients in 2 groups on 7th and 14th post-treatment days were significantly increased (P < 0.05 or P < 0.01), but there was no significant difference between 2 groups. The level of total serum protein on 14th day of treatment of patients was significantly increased in both groups, and that of EIN group (66 +/- 7 g/L) was significantly higher compared with that in EN group (64 +/- 11 g/L, P < 0.05). The level of serum albumin (29 +/- 5, 32 +/- 5 g/L, respectively) of patients in EIN group on 7th and 14th day of treatment were significantly higher than that (26 +/- 4 g/L, P < 0.05) in pre-treatment days, however there was no significant difference in EN group. (3) There was no significant difference in respect of hepatic function, renal function, and fasting-blood glucose between pre-treatment and post-treatment periods in both groups (P > 0.05). (4) The ratio of CD4(+), CD8(+) on 14th day of treatment in EIN group was close to that of pretreatment level. In EN group, cell percentage of CD4(+) significantly decreased, while that of CD8(+) significantly increased (P < 0.05), and CD4(+) was significantly higher [(56 +/- 8)%] in EIN group than that in EN group [(55 +/- 12)%, P < 0.05]. In both groups, cell percentage of CD3(+) was significantly higher than that in pre-treatment days (P < 0.05), while there was no obvious change in CD4(+)/CD8(+)., Conclusions: Arginine enriched enteral nutrition can effectively improve nutritional status and cellular immune function of burn patients.

Objective: To investigate the influence of heat shock (HS) preconditioning on the ultra-structure of gastric mucosal cells and the activity of cytochrome oxidase (CCO) and superoxide dismutase (SOD) in mitochondria isolated from gastric mucosa of burned rats in order to investigate its protective mechanism on burn-induced acute gastric mucosal lesion., Methods: Ninety-six Wistar rats were divided randomly into two groups:(1) burn model group (n =40) undergoing burning and made into model of acute gastric mucosal lesion; and then subdivided into 5 equal subgroups: 3, 6, 12, 24, and 48 h after burning; (2) normal control group (n = 8); (3) HS preconditioning + burn group (n = 40), undergoing burning 24 h after HS preconditioning; and (4) HS preconditioning group (n = 8), without burn as experimental control A number of rats were sacrificed and laparotomized before and 3, 6, 12, 24, and 48 h after the burning. Specimens were obtained from the gastric antrum, bodies if stomach and gastric lesion to undergo microscopy and determination of the ulcer index ( UI ). Streptavidin-peroxidase immunohistochemistry was used to detect the protein expression of heat shock protein (HSP)-60 and HSP-70. Mitochondria were isolated and the activities of CCO and SOD in mitochondria were measured. The dynamic postburn changes in micro and ultra structure of gastric mucosal cells of scalded rats were observed., Results: The rats of the burn group showed conspicuous gastric mucosal lesions. The UI levels at every time point of the HS group were all the lowest in comparison with other groups. The expression levels of HSP70 and HSP60 of the HS group, especially those at the time points 3, 6, 12, and 24 h were significantly higher than those of the burn group (P <0.05 or P <0.01). The activities of mCCO and mSOD of the HS group did not decrease remarkably at any time point in comparison with the control groups, and the activities of mCCO and mSOD at the time points 6, 12, and 24 h of the HS group were all significantly higher than those of the burn group (P <0.05 of P <0.01). Electron microscopy showed that the ultrastructural lesion was mild and alteration of gastric mucosal mitochondria was not significant in the HS group compared with those of the burn group. A positive correlation was shown between SOD and HSP70 (r = 0.436, P <0.05) and also between CCO and HSP60 (r =0.679, P <0.05)., Conclusion: HS preconditioning ameliorates the burn-induced acute gastric mucosal lesion and has a protective role to gastric mucosal mitochondria. The role of HS preconditioning on mitochondria is associated with the protection of the activity of antioxidase and CCO by HSP60 and 70.

Objective: To observe the modulation effect of a concoction of Chinese herb drugs on immune dysfunction in severely burned rats., Methods: One hundred healthy Wistar rats were randomly divided into A group (n = 30, with Chinese herb drug feeding after burns), B group (n = 30, with bouillon feeding after burns), C group (n = 30, with ordinary feeding after burns), and D group (n = 10, with sham burns as normal controls). The rats in A, B and C groups were subjected to 30% TBSA full-thickness burns and received conventional treatment. The rats in A group received 2 ml of Chinese herbal drug at 37 degrees C by gavage two times a day beginning from 2 postburn-hours(PBH). The rats in B group received 2 ml bouillon by gavage instead, and otherwise treatment was the same as A group, while the rats in C group were not fed by gavage. The activity of natural killer cell and T lymphocyte, and the levels of IgA, IgG, IgM, C3, C4 in A, B, C groups were examined on 3, 7, 14 PBD, and these indices were also determined in D group., Results: Compared with D group, the amount of the CD3+, CD4+ lymphocyte, the ratio of the CD4+/CD8+, the level of IgA, IgG, IgM, C3, C4, the activity of NK cells, and the density of the sIgA in A, B, C groups were obviously decreased, but the amount of the CD8+ were obviously increased (P < 0.05 or P < 0.01). Furthermore, the above indices in A group improved more quickly when compared with B and C groups., Conclusion: The concoction of Chinese herb drugs can improve the distribution of T lymphocyte subsets, increase the activity of NK cells, promote the secretion of sIgA in intestinal mucous membrane and promote recovery of IgM, IgG, C3, C4 levels, thereby improves the immune function of the body.

Objective: To observe the influence of heat shock preconditioning on the expressions of heat shock protein (HSP) 60 and HSP 70 and on the activities of cytochrome oxidase (CCO) and superoxide dismutase (SOD) in mitochondria in gastric mucosa of severely scalded rats, and to investigate its protective mechanism on acute gastric mucosal lesion in rats with severe scald., Methods: One hundred and forty-four Wistar rats were randomized into three groups, i. e. scald group ( n = 40, acute gastric mucosal lesion was made after scald, other 8 normal rats without scald were employed as blank control); HS group ( n =40, with heat shock preconditioning 20 h before scald), and other 8 rats preconditioned with heat shock but without scald were employed as experimental control I; actinomycin D group ( n = 40, with intraperitoneal injection of 0. 1 mg/kg actinomycin D 30 min before heat shock preconditioning and other treatment as HS group), and other 8 rats with merely actinomycin D injection were employed as experimental control II. Eight rats in each group were sacrificed and laparotomized at 3, 6, 12, 24 and 48 post-scald hours (PSH) , respectively to determine the index of gastric mucosal lesions (UI ) , the mRNA expressions of HSP70 and protein expression of HSP60 and HSP70, and the changes in the activities of SOD and CCO., Results: UI of the scalded rats increased as the time elapses, reaching the peak (12. 8 +/- 1.9) at 24 PSH. In addition, UI in HS group was significantly lower than that in scald group at each time-point except that at 3 PSH ( P < 0. 05 or 0. 01). The extent of gastric mucosal lesion in rats in actinomycin D group was obviously aggravated compared with that in scald and HS groups ( P <0. 05). The HSP70 mRNA expression in both scald and HS groups was increased at each time-points except for 48PBH, while that in actinomycin D group was increased at 24 PBH and 48PBH. The expressions of HSP70 and HSP60 were greatly increased in HS group compared with those in scald group ( P < 0. 05 or 0. 01) , while those in actinomycin D group were significantly inhibited ( P < 0. 05). The activities of CCO and SOD were gradually decreased in gastric mucosa in scald group, but it was greatly improved by HS preconditioning at 6, 12, 24 PSH ( P < 0. 05 or 0. 01)., Conclusion: Heat shock preconditioning is beneficial for the protection of acute gastric mucosal lesion of rats after severe scald, due to increase of HPS60 and HSP70 expression, and increase of CCO and SOD activities in mitochondria.

Objective: To analyze the correlation factors affecting the incidence of burn shock, so as to provide guidance for the clinical treatment of shock after burns., Methods: Retrospective analysis of clinical data of 15 624 patients hospitalized in our department from 1973 to 2005 was undertaken . The incidence of shock during every 10 years, as well as the relationship between shock incidence and age, burn area, interval between injury and hospitalization, and complications were analyzed statistically., Results: The incidence of shock during 1973-1980, 1981-1990, 1991-2000 and 2001-2005 periods was 14.69%, 13.50%, 9.38% and 7.88%, respectively, and there was significant difference of shock incidence between each 10 years and its succeeding period (P < 0.01). The occurrence of shock was closely related to age, length of time between injury and hospitalization, and burn area. The shock incidence of children under 7 years old or elderly more than 60 years old was obviously higher than other age groups, and there was positive relationship between burn area and shock incidence. Moreover, the shock incidence of the patients hospitalized later than 4 to 12 hours after burn shock was also markedly higher than those hospitalized earlier (P < 0.01). In addition, the incidence of sepsis, alimentary tract hemorrhage, acute renal failure, pulmonary failure, and cardiac failure in patients with shock was obviously higher than those without shock (P < 0.01)., Conclusion: For the children and aged people, special attention should be paid in the prevention and resuscitation of burn shock. Early fluid resuscitation is vital for the prevention of organ complication, and it is beneficial to promote wound healing.

Background: Choledochal cyst, an isolated defect unrestricted to the bile duct, is more appropriately regarded as the sentinel feature of a constellation of anomalies affecting the pancreatobiliary system. This study was to assess the relationship between the expression of inducible nitric oxide synthase (iNOS) and the p53 gene as well as the pathogenesis of choledochal cysts., Methods: iNOS and p53 were detected by immunohistochemistry staining in 26 patients with congenital choledochal cysts. Histopathologically, hyperplasia of the mucosa of the cysts and the amylase level in the bile were also investigated., Results: Patients with a high level of amylase in the bile had higher expression of iNOS than those with a low level of amylase. p53 protein was expressed neither in fusiform type nor in cystic type. The incidence of mucosal hyperplasia was significantly higher in the fusiform type than that in the cystic type., Conclusions: Higher expression of iNOS may participate in hyperplasia and carcinogenesis of the mucosa of choledochal cysts. The regurgitation of pancreatic juice into the biliary system might induce mucosal hyperplasia of the biliary tract and inflammatory reaction. In preventing regurgitation-caused hyperplasia and malignancy of the bi-liary tract, early surgery is important for children with congenital choledochal cysts.