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Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA., 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 © 2024 Zhang, Zhang, Li, Yin, Jin, Xun, Xue, Yang, Zhang, Qu, Xing and Wang.)

Background: Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear., Objective: The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance., Methods: The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses., Results: PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-β signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed., Conclusion: PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1., (© 2024. The Author(s).)

Visceral leishmaniasis (VL), a parasitic, poverty-linked, neglected disease, is endemic across multiple regions of the world and fatal if untreated. There is an urgent need for a better and more affordable treatment for VL. DNDI-6148 is a promising drug candidate being evaluated for the treatment of VL; however, the current process for producing the key intermediate of DNDI-6148, 6-amino-1-hydroxy-2,1-benzoxaborolane, is expensive and difficult to scale up. Herein, we describe two practical approaches to synthesizing 6-amino-1-hydroxy-2,1-benzoxaborolane from inexpensive and readily available raw materials. Starting with 4-tolunitrile, the first approach is a five-step sequence involving a Hofmann rearrangement, resulting in an overall yield of 40%. The second approach utilizes 2-methyl-5-nitroaniline as the starting material and features borylation of aniline and continuous flow hydrogenation as the key steps, with an overall yield of 46%. Both routes bypass the nitration of 1-hydroxy-2,1-benzoxaborolane, which is challenging and expensive to scale. In particular, the second approach is more practical and scalable because of the mild operating conditions and facile isolation process., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Several observational studies have reported an association between obesity and primary liver cancer (PLC), while the causality behind this association and the comparison of the risk effects of different obesity indicators on PLC remain unclear. In this study, we performed two-sample Mendelian randomization (MR) analyses to assess the associations of genetically determined liver fat, visceral adipose tissue (VAT), and body mass index (BMI) with the risk of PLC. The summary statistics of exposures were obtained from two genome-wide association studies (GWASs) based on the UK Biobank (UKB) imaging cohort and the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. GWAS summary statistics for PLC were obtained from FinnGen consortium R7 release data, including 304 PLC cases and 218 488 controls. Inverse-variance weighted (IVW) was used as the primary analysis, and a series of sensitivity analyses were performed to further verify the robustness of these findings. IVW analysis highlighted a significant association of genetically determined liver fat (OR per SD increase: 7.14; 95% CI: 5.10-9.99; P = 2.35E-30) and VAT (OR per SD increase: 5.70; 95% CI: 1.32-24.72; P = .020) with PLC but not of BMI with PLC. The findings were further confirmed by a series of MR methods. No evidence of horizontal pleiotropy between these associations existed. Our study suggested that genetically determined liver fat and VAT rather than BMI were associated with an increased risk of PLC, which suggested that visceral fat distribution is more predictive of the clinical risk of PLC than common in vitro measures., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Objectives: To observe the effect of acupuncture on the expressions of neuropeptides and related inflammatory factors in rats with diarrhea-predominant irritable bowel syndrome(IBS-D), so as to explore the mechanism of acupuncture in the treatment of IBS-D., Methods: Male Wistar rats were randomly divided into blank group, model group, medication group, and acupuncture group, with 6 rats in each group. Except for the blank group, the other groups were subjected to 14-day "acetic acid enema + restraint stress" to establish the IBS-D rat model. After successful modeling, the medication group received gavage of pinaverium bromide(15 mg/kg) once a day, and the acupuncture group received acupuncture at "Baihui"(GV20) and bilateral "Tianshu"(ST25), "Shangjuxu"(ST37), "Zusanli"(ST36), and "Taichong"(LR3) for 20 min every day, both groups were treated continuously for 14 days. The general state of the rats in each group was observed, and the body weight of the rats was measured. The open-field experiment was conducted to measure the horizontal and vertical movements, and the number of fecal pellets of rats. The histopathological morphology of hypothalamus and colon of rats was observed by HE staining. Toluidine blue staining was used to observe and count the mast cells(MCs) in the colon tissue of rats. ELISA was used to detect the serum contents of tumor necrosis factor-α(TNF-α) and interleukin(IL)-10. Real-time fluorescence quantitative PCR was performed to detect the mRNA expressions of calcitonin gene-related peptide(CGRP) in the hypothalamus and colon tissue. Western blot was used to detect the expressions of corticotropin-releasing factor(CRF) in the hypothalamus and colon tissue., Results: HE staining showed that there was inflammatory cell infiltration in the lamina propria of colon in the model group, and it was reduced in the other groups. Compared with the blank group, the model group showed significantly decreased body weight, decreased walking distance and upright times in open field experiment, decreased serum IL-10 contents( P <0.05, P <0.01), increased fecal pellet number ( P <0.01), increased MC number in the colon tissue, serum TNF-α contents, and CGRP mRNA expressions and CRF expressions in the hypothalamus and colon tissue( P <0.01). Compared with the model group, both medication and acupuncture groups showed significantly increased body weight, walking distance and upright times in the open-field experiment, and serum IL-10 contents( P <0.01, P <0.05), significantly decreased fecal pellet number ( P <0.05), significantly decreased MC number in the colon tissue, serum TNF-α contents, and CGRP mRNA expressions in the hypothalamus and colon tissue( P <0.01)；at the same time, the acupuncture group showed significantly decreased CRF expressions in the hypothalamus and colon tissue( P <0.01, P <0.05). There was no significant difference in the above indicators between the medication group and the acupuncture group., Conclusions: Acupuncture can improve the general and emotional state, inflammatory response, and neuropeptide expression in rats with IBS-D, and alleviate the symptoms of IBS-D, which may be related to the regulation of neuropeptides and inflammatory factors levels.

Background: Pseudomonas aeruginosa ( P. aeruginosa ) is an important cause of nosocomial infections, and contributes to high morbidity and mortality, especially in intensive care units. P. aeruginosa is considered a 'critical' category bacterial pathogen by the World Health Organization to encourage an urgent need for research and development of new antibiotics against its infections., Aim: To investigate the effectiveness of baicalin combined with tobramycin therapy as a potential treatment method for carbapenem-resistant P. aeruginosa (CRPA) infections., Methods: Polymerase chain reaction (PCR) and RT-PCR were used to detect the expression levels of drug-resistant genes (including VIM , IMP and OprD2 ) and biofilm-related genes (including algD , pslA and lasR ) in CRPA that confer resistance to tobramycin, baicalin and tobramycin combined with baicalin (0, 1/8, 1/4, 1/2 and 1MIC)., Results: There was a correlation between biofilm formation and the expression of biofilm-related genes. In addition, VIM , IMP , OprD2 , algD , pslA and lasR that confer biofilm production under different concentrations in CRPA were significantly correlated. The synergistic effect of baicalin combined with tobramycin was a significant down-regulation of VIM , IMP , algD , pslA and lasR ., Conclusion: Baicalin combined with tobramycin therapy can be an effective treatment method for patients with CRPA infection., Competing Interests: Conflict-of-interest statement: There is no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: Positive lymph node (LN) is a key prognostic factor in radically resected gallbladder cancer (GBCA). However, only a few underwent an adequate lymphadenectomy, and the number and extent of lymph node dissection (LND) have not been standardized. This study aims to develop an en bloc and standardized surgical procedure of LND for GBCA under laparoscopy., Methods: Data of patients with GBCA underwent laparoscopic radical resection using a standardized and en bloc technique for LND were collected. Perioperative and long-term outcomes were retrospectively analyzed., Results: A total of 39 patients underwent laparoscopic radical resection using standardized and en bloc technique for LND except one case (open conversion rate: 2.6%). Patients with stage T1b had significantly lower LNs involved rate than patients with stage T3 (P = 0.04), whereas median LN count in stage T1b was significantly higher than that in stage T2 (P = 0.04), which was significantly higher than that in stage T3 (P = 0.02). Lymphadenectomy with ≥ 6 LNs accounted for 87.5% in stage T1b, up to 93.3% in T2 and 81.3% in T3, respectively. All the patients in stage T1b were alive without recurrence at this writing. The 2-year recurrence-free survival rate was 80% for T2 and 25% for T3, and the 3-year overall survival rate was 73.3% for T2 and 37.5% for T3., Conclusion: The standardized and en bloc LND permits complete and radical removal of lymph stations for patients with GBCA. This technique is safe and feasible with low complication rates and good prognosis. Further studies are required to explore its value and long-term outcomes compared to conventional approaches., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Phthalic acid esters (PAEs), a class of typical endocrine disruptors, have received considerable attention due to their widespread applications and adverse effects on biological health. In this study, 30 water samples, along the mainstream of the Yangtze River (YR), were collected from Chongqing (upper stream) to Shanghai (estuary) from May to June in 2019. The total concentrations of 16 targeted PAEs ranged from 0.437 to 20.5 μg/L, with an average of 1.93 μg/L, where dibutyl phthalate (DBP, 0.222-20.2 μg/L), bis (2-ethylhexyl) phthalate (DEHP, 0.254-7.03 μg/L), and diisobutyl phthalate (DIBP, 0.0645-0.621 μg/L) were the most abundant PAEs. According to the pollution level in the YR to assess the ecological risk posed by PAEs, the results showed medium risk level of PAEs in the YR, among which DBP and DEHP posed a high ecological risk to aquatic organisms. The optimal solution for DBP and DEHP is found in ten fitting curves. The PNEC SSD of them is 2.50 μg/L and 0.34 μg/L, respectively., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The second leading cause of preventable battlefield death involves airway management. Tactical combat casualty care (TCCC) guidelines emphasize combat casualty airway, breathing and respiratory evaluation, including respiratory rate (RR) measurement. The current standard of practice for the US Army medics is to measure the RR by manual counting. Manual counting methods are operator-dependent, and medics face situational stressors limiting accurate measurement of RR in combat settings. To date, no published studies evaluate alternate methods of RR measurement by medics. The purpose of this study is to compare RR assessment by medics against waveform capnography and commercial finger pulse oximeters with continuous plethysmography., Materials and Methods: We conducted a prospective, observational study to compare Army medic RR assessments against plethysmography and waveform capnography RR. Assessments were performed prior to and following exertion at 30 and 60 seconds with both the pulse oximeter (NSN 6515-01-655-9412) and defibrillator monitor (NSN 6515-01-607-8629), followed by end-user surveys., Results: Of the 40 medics enrolled over a 4-month period, most were male (85%), and reported between less than 5 years of military and medical experience. The mean manual RR reported by medics at rest did not significantly differ from waveform capnography (14.05 versus 13.98, p is equal to 0.523); however, mean manual RR reported by medics on post-exertional subjects was significantly lower than waveform capnography (25.62 versus 29.77, p is less than 0.001). Time to medic-obtained RR was slower than the pulse oximeter (NSN 6515-01-655-9412) both at rest (-7.37 seconds, p is less than 0.001) and at exertion (-6.50 seconds, p is less than 0.001). While the mean difference in RR between the pulse oximeter (NSN 6515-01-655-9412) and waveform capnography in models at rest at 30 seconds was statistically significant (-1.38, p is less than 0.001). There was no overall statistically significant differences in RR between the pulse oximeter (NSN 6515-01-655-9412) and waveform capnography in models at exertion at 30 seconds and at rest and exertion at 60 seconds., Conclusion: Resting RR measurement did not differ significantly; however, medic-obtained RR considerably deviated from both pulse oximeters and waveform capnography at elevated rates. Existing commercial pulse oximeters with RR plethysmography do not differ significantly from waveform capnography and should be investigated further for consideration in fielding across the force for RR assessment.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most commonly identified cause of autoimmune encephalitis. Therapeutic plasma exchange has been increasingly employed to treat this disease. This expansion is a consequence of improved techniques and apheresis instruments, as well as the recognition of its applicability in neurological diseases. However, several aspects of treatment remain incompletely clarified, and treatment strategies are still heterogeneous, especially with regard to therapeutic plasma exchange in anti-NMDAR encephalitis. This review provides an overview of the use of therapeutic plasma exchange including the principle and mechanisms, the evidence, initial time, efficiency and complications in anti-NMDAR encephalitis., (© 2022 International Society for Apheresis and Japanese Society for Apheresis.)

The innate immune response and inflammation contribute to hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). Dectin-1 is a pathogen recognition receptor in innate immunity. In this study, we investigated the role of Dectin-1 in the pathogenesis of NAFLD. We first showed that Dectin-1 expression was significantly elevated in liver tissues of patients with NASH. NAFLD was induced in mice by feeding high fat diet (HFD) for 24 weeks. At the end of treatment, mice were sacrificed, and their blood and liver tissues were collected for analyses. We showed HFD feeding also increased liver Dectin-1 levels in mice, associated with macrophage infiltration. Either gene knockout or co-administration of a Dectin-1 antagonist laminarin (150 mg/kg twice a day, ip, from 16 th week to 24 th week) largely protected the livers from HFD-induced lipid accumulation, fibrosis, and elaboration of inflammatory responses. In primary mouse peritoneal macrophages (MPMs), challenge with palmitate (PA, 200 μM), an abundant saturated fatty acid found in NAFLD, significantly activated Dectin-1 signaling pathway, followed by transcriptionally regulated production of pro-inflammatory cytokines. Dectin-1 was required for hepatic macrophage activation and inflammatory factor induction. Condition media generated from Dectin-1 deficient macrophages failed to cause hepatocyte lipid accumulation and hepatic stellate activation. In conclusion, this study provides the primary evidence supporting a deleterious role for Dectin-1 in NAFLD through enhancing macrophage pro-inflammatory responses and suggests that it can be targeted to prevent inflammatory NAFLD., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: We aimed to assess the efficacy of the artificial liver support system (ALSS) in pediatric acute liver failure (PALF) patients and to examine the risk factors associated with the effect of ALSS. Similar data are limited in PALF., Methods: All patients diagnosed with PALF who received ALSS from June 2011 to June 2021 in the pediatric intensive care unit of the First Hospital of Jilin University were included in this retrospective cohort analysis. The effect of ALSS was measured using difference tests before and after treatments. The risk factors associated with the effect of ALSS were evaluated according to whether the total bilirubin (TBIL) and serum ammonia decreased after ALSS (TBIL-unresponsive group vs. TBIL-responsive group, serum ammonia-unresponsive group vs. serum ammonia-responsive group)., Results: Thirty-nine patients who received ALSS during the study period were eligible for inclusion. The most common cause of PALF was undetermined causes ( n  = 14, 35.9%) followed by infection ( n  = 11, 28.2%). Four patients received pediatric liver transplantation. The overall survival rate was 76.9% (30/39). Fifteen (38.4%) patients received only one modality, whereas 61.6% patients received hybrid treatments. The most commonly used modality of ALSS was plasma exchange combined with continuous renal replacement therapy ( n  = 14, 35.9%). Alanine aminotransferase, TBIL, the international normalized ratio, and serum ammonia were significantly decreased after ALSS ( P  < 0.001). Compared with other causes, more patients with infection and toxication were observed in the TBIL-unresponsive group. A longer ALSS duration was significantly related to blood ammonia reduction., Conclusions: ALSS can effectively reduce serum alanine aminotransferase, TBIL, international normalized ratio, and serum ammonia and may reduce mortality. The reduction in TBIL levels after ALSS is dependent on etiology. A longer ALSS duration was associated with blood ammonia reduction. Prospective multicenter studies are needed for further validation., 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., (© 2022 Yang, Liu, Jin and Li.)

Background: Neuroblastoma (NB) is the most frequent solid tumor in pediatrics, which accounts for roughly 15% of cancer-related mortality in children. NB exhibited genetic, morphologic, and clinical heterogeneity, which limited the efficacy of available therapeutic approaches. Recently, a new term 'cuproptosis' has been used to denote a unique biological process triggered by the action of copper. In this instance, selectively inducing copper death is likely to successfully overcome the limitations of conventional anticancer drugs. However, there is still a gap regarding the role of cuproptosis in cancer, especially in pediatric neuroblastoma., Methods: We characterized the specific expression of cuproptosis-related genes (CRGs) in NB samples based on publicly available mRNA expression profile data. Consensus clustering and Lasso-Cox regression analysis were applied for CRGs in three independent cohorts. ESTIMATE and Xcell algorithm was utilized to visualize TME score and immune cell subpopulations' relative abundances. Tumor Immune Dysfunction and Exclusion (TIDE) score was used to predict tumor response to immune checkpoint inhibitors. To decipher the underlying mechanism, GSVA was applied to explore enriched pathways associated with cuproptosis signature and Connectivity map (CMap) analysis for drug exploration. Finally, qPCR verified the expression levels of risk-genes in NB cell lines. In addition, PDHA1 was screened and further validated by immunofluorescence in human clinical samples and loss-of-function assays., Results: We initially classified NB patients according to CRGs and identified two cuproptosis-related subtypes that were associated with prognosis and immunophenotype. After this, a cuproptosis-related prognostic model was constructed and validated by LASSO regression in three independent cohorts. This model can accurately predict prognosis, immune infiltration, and immunotherapy responses. These genes also showed differential expression in various characteristic groups of all three datasets and NB cell lines. Loss-of-function experiments indicated that PDHA1 silencing significantly suppressed the proliferation, migration, and invasion, in turn, promoted cell cycle arrest at the S phase and apoptosis of NB cells., Conclusions: Taken together, this study may shed light on new research areas for NB patients from the cuproptosis perspective., 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 Tian, Xiang, Yu, Li, Zhang, Zhanghuang, Jin, Wang, Mi, Chen, Liu and Wei.)

Anaphylaxis is a severe allergic reaction that requires immediate recognition and intervention. This study investigated the factors related to the timely administration of epinephrine in cases of pediatric anaphylaxis. We performed a retrospective chart review of 107 patients who visited a pediatric emergency center with anaphylaxis between 2015 and 2017. In total, 76 patients received epinephrine injections. We analyzed factors including allergy history, anaphylaxis signs and symptoms, allergen sensitization, anaphylaxis triggers, and time of epinephrine injection. Anaphylactic patients who received epinephrine took a median of 50 min to arrive at the hospital, and patients who did not receive epinephrine took a median of 94 min. Epinephrine administration was significantly delayed by more than 60 min from symptom onset in patients <2 years old. Patients presenting with wheezing symptoms or history of bronchial asthma were significantly more likely to receive epinephrine within 60 min of symptoms onset, while patients with food allergen sensitization were significantly more likely to receive epinephrine within 30 min of hospital arrival. Wheezing, history of asthma, age (≥2 years old), food triggers, and food allergen sensitivity were significant factors for the rapid administration of epinephrine. An immediate diagnosis of anaphylaxis and a rapid administration of epinephrine are essential.

Wilms tumour (WT) is the most common kidney malignancy in children. Chemoresistance is the leading cause of tumour recurrence and poses a substantial therapeutic challenge. Increasing evidence has underscored the role of the tumour immune microenvironment (TIM) in cancers and the potential for immunotherapy to improve prognosis. There remain no reliable molecular markers for reflecting the immune landscape and predicting patient survival in WT. Here, we examine differences in gene expression by high-throughput RNA sequencing, focused on differentially expressed immune-related genes (IRGs) based on the ImmPort database. Via univariate Cox regression analysis and Lasso-penalized Cox regression analysis, IRGs were screened out to establish an immune signature. Kaplan-Meier curves, time-related ROC analysis, univariate and multivariate Cox regression studies, and nomograms were used to evaluate the accuracy and prognostic significance of this signature. Furthermore, we found that the immune signature could reflect the immune status and the immune cell infiltration character played in the tumour microenvironment (TME) and showed significant association with immune checkpoint molecules, suggesting that the poor outcome may be partially explained by its immunosuppressive TME. Remarkably, TIDE, a computational method to model tumour immune evasion mechanisms, showed that this signature holds great potential for predicting immunotherapy responses in the TARGET-wt cohort. To decipher the underlying mechanism, GSEA was applied to explore enriched pathways and biological processes associated with immunophenotyping and Connectivity map (CMap) along with DeSigN analysis for drug exploration. Finally, four candidate immune genes were selected, and their expression levels in WT cell lines were monitored via qRT-PCR. Meanwhile, we validated the function of a critical gene, NRP2. Taken together, we established a novel immune signature that may serve as an effective prognostic signature and predictive biomarker for immunotherapy response in WT patients. This study may give light on therapeutic strategies for WT patients from an immunological viewpoint., 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 Tian, Xiang, Jin, Mi, Wang, Zhanghuang, Zhang, Chen, Shi, Liu, Lin and Wei.)

Background: Non-alcoholic fatty liver disease (NAFLD) is the most predominant form of liver diseases worldwide. Recent evidence shows that myeloid differentiation factor 2 (MD2), a protein in innate immunity and inflammation, regulates liver injury in models of NAFLD. Here, we investigated a new mechanism by which MD2 participates in the pathogenesis of experimental NAFLD., Methods: Wild-type, Md2 -/- and bone marrow reconstitution mice fed with high-fat diet (HFD) were used to identify the role of hepatocyte MD2 in NAFLD. Transcriptomic RNA-seq and pathway enrich analysis were performed to explore the potential mechanisms of MD2. In vitro, primary hepatocytes and macrophages were cultured for mechanistic studies., Results: Transcriptome analysis and bone marrow reconstitution studies showed that hepatocyte MD2 may participate in regulating lipid metabolism in models with NAFLD. We then discovered that Md2 deficiency in mice prevents HFD-mediated suppression of AMP-activated protein kinase (AMPK). This preservation of AMPK in Md2-deficient mice was associated with normalized sterol regulatory element binding protein 1 (SREBP1) transcriptional program and a lack of lipid accumulation in both hepatocytes and liver. We then showed that hepatocyte MD2 links HFD to AMPK/SREBP1 through TANK binding kinase 1 (TBK1). In addition, MD2-increased inflammatory factor from macrophages induces hepatic TBK1 activation and AMPK suppression., Conclusion: Hepatocyte MD2 plays a pathogenic role in NAFLD through TBK1-AMPK/SREBP1 and lipid metabolism pathway. These studies provide new insight into a non-inflammatory function of MD2 and evidence for the important role of MD2 in NALFD., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Microglial inflammation plays an essential role in neurodegenerative disease. Our previous studies had shown that κ-carrageenan oligosaccharides (KOS) could inhibit the excessive activation of microglia that induced by LPS, while the interrelated mechanisms were still indistinct. Therefore, we detected the inflammatory signaling pathway on LPS-activated microglia that pretreat by different content of KOS to reveal the mechanism on KOS's inhibition of microglia inflammatory response. ELISA was used to detect the effects of KOS on the secretion of interleukin-1 (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and prostaglandin E2 (PG-2) by LPS-activated microglia, respectively. The production of reactive oxygen species (ROS) and nitric oxide (NO) in microglia cells was detected by flow cytometry, and the protein expression of immunoinflammation-related signaling pathways were detected by Western Blot. The results showed that KOS could significantly protected the microglia from the over-activated inflammatory by inhibiting the release of inflammatory cytokines and the oxidative stress response. And KOS could reduce the expression of the protein that related to the TLR4/NF-κB and p38/JNK MAPKs pathways activated by LPS in microglia. However, there may be no specific target of KOS in cells. Therefore, KOS, a natural algal source oligosaccharide, has immunomodulatory effects and can be used as a potential intervention therapy for inflammatory related neurodegenerative diseases., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To compare the short-term efficacy and long-term prognosis of laparoscopic and laparotomy radical resection for gallbladder cancer(GBC). Methods: From January 2010 to December 2020,the clinical data and survival information for 133 patients who underwent radical resection of GBC at the Department of Hepatopancreatobiliary Surgery,Zhejiang Provincial People's Hospital,were retrospectively collected. Eighty patients(23 males and 57 females) underwent laparoscopic radical resection and had a median age( M (IQR)) of 66.0(12.8)years(range:28.0 to 82.0 years). Fifty-three patients(45 males and 8 females) who received laparotomy were 63.0(6.0)years old(range:45.0 to 80.0 years old). There were no significant differences in age,gender,body mass index,preoperative albumin,preoperative total bilirubin,N stages,vascular invasion,peri-neural invasion or tumor differentiation between the laparoscopic and laparotomy group(all P >0.05). But there were significant differences in preoperative CA19-9( Z =-2.955, P =0.003), preoperative ALT level( Z =-2.801, P =0.031) and T stage (χ 2 =19.110, P =0.007) between the two groups. A non-parametric test was used for quantitative data. χ 2 test or Fisher exact probability method was used for count data. Results: Patients in the laparoscopic group did not differ from those in the laparotomy group in terms of length of operation,number of lymph node yield,number of positive lymph nodes,the incidence of intraoperative gallbladder rupture,incidence of postoperative bile leakage,abdominal bleeding or abdominal infection,30-day mortality,90-day mortality, the incidence of incision implantation or peritoneal cavity metastasis(all P >0.05). Patients in the laparoscopic group showed less intraoperative bleeding(100.0(200.0)ml vs. 400.0(250.0)ml)( Z =-5.260, P <0.01),fewer days with drainage tube indwelling(6.0(3.8)days vs. 7.0(4.0)days)( Z =-3.351, P =0.001), and fewer postoperative days in hospital(8.0(5.0)days vs. 14.0(7.5)days)( Z =-6.079, P <0.01) than those in the laparotomy group. Patients in the laparoscopic group displayed better overall survival ( P <0.01) and progression-free survival ( P <0.01). Subgroup analysis for GBC of T1b-T2 and T3 stages revealed comparable overall survival and progression-free survival between the laparoscopic and laparotomy groups ( P >0.05). Conclusions: Laparoscopic radical resection can achieve long-term survival for GBC comparable to that with open surgery. Laparoscopic radical resection has advantages over open surgery regarding surgical trauma and postoperative recovery.

This paper aims to explore the impact of social medical insurance (SMI) on poverty reduction (PR) in China. Considering the time-varying characteristics of factors, this paper uses the bootstrap Granger full sample causality and subsample rolling window model to find the relationship between SMI and PR. The results highlight that in some periods, there is a bidirectional causal link between SMI and PR. Influenced by the medical insurance reform and medication measures. Social medical insurance does not have a positive impact on poverty reduction in some periods. These results are supported by the Utility Maximization Model of Insurance Consumption, which highlights that individuals make utility maximization choices when choosing insurance. The effect of medical insurance on poverty alleviation depends on whether an individual's investment in medical insurance can maximize its utility. If the proportion of social medical insurance reimbursement is too low, individuals will give up buying social medical insurance. Thus, the anti-poverty effect of social medical insurance is difficult to achieve. Therefore, authorities need to pay attention to specific contexts and social medical insurance policies and further improve the social medical insurance system to promote the realization of the anti-poverty of social medical insurance., 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 Sun, Tao, Wang and Jin.)

Microglia are the main effector cells of immune response in central nervous system and are important targets for disease prevention and treatment. Κ-carrageenan Oligosaccharide (KOS), obtained by enzymatic hydrolysis from carrageenan of marine red algae, can inhibit the release of inflammatory factors from the over-activated microglia. The mechanism of microglia autophagy induced by KOS and its relationship with inflammation were studied to explore the development prospect of KOS in the research and treatment of inflammatory related diseases. The effect of KOS on inducing autophagy was detected by the secretion of cytokines by lipopolysaccharide (LPS)-activated microglia, respectively. The protein expression of autophagy-related signaling pathways were detected by Western Blot. The results showed that KOS could significantly protect the microglia from over-activated inflammatory by inducing the autophagy and inhibiting the release of inflammatory cytokines. And KOS could reduce the expression of the protein that related to the AMPK/ULK1 pathways in microglia, so as to regulate the autophagy pathway, and inhibit the inflammatory response of over-activated microglia. The study on the effect of KOS on microglia autophagy and excessive inflammatory response will provide a theoretical basis for further studies on the inhibition of nerve injury by regulating microglia autophagy and inflammatory response., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Study Objective: The goal of the study was to assess a low-dose versus a high-dose of intramuscular (IM) ketorolac for non-inferiority in adults with acute MSK pain in an emergency department (ED)., Methods: This was a single-blinded, randomized controlled, non-inferiority trial of adults presenting to an ED with a chief complaint of acute MSK pain. Patients were randomized to either a 15 mg or a 60 mg IM ketorolac dose. The primary outcome was the mean difference of change in pain from baseline to 60-min between the two groups as reported on a 100-mm (mm) visual analog scale (VAS). Secondary outcomes included the mean difference of change in VAS scores at 30-min and the incidence of reported adverse effects associated with the administration of ketorolac., Results: One hundred ten patients were randomized with 55 in each group. The mean difference in pain between groups at 60-min (0.2 mm [95% CI -8.5-8.7]; p = .98) and 30 min (-1.7 mm [95% CI -8.5-5.1; p = .63) was less than the predetermined non-inferiority margin of 13 mm. There were no major adverse effects reported. Minor adverse effects were more frequent in the 60 mg group (n = 9; 16.4% vs. n = 1; 1.8%; p = .016) with burning at the injection site being the most commonly reported., Conclusions: A 15 mg dose of IM ketorolac was found to be non-inferior to a 60 mg dose for acute MSK pain in adults presenting to the ED. Discontinuing the practice of ordering 60 mg doses of IM ketorolac in place of a lower dose for acute MSK pain should be considered., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier Inc.)

Objective: To explore the effects of Eriodictyol to the growth, apoptosis and oxidative stress of Burkitt lymphoma (BL) cells and phosphorylation of protein kinase B (AKT) in children., Methods: The effects of Eriodictyol (0, 1.25, 2.5, 5, 10, 20, 40, 80, 160, 320 μmol/L) to viability of BL cell line DG-75 cells were detected by CCK-8. The effects of Eriodictyol (0, 10, 20, 40 μmol/L) to the proliferation activity of DG-75, apoptosis rate, levels of apoptosis-related proteins, oxidative stress indexes ［superoxide dismutase (SOD), malondialdehyde (MDA)］, mitochondrial membrane potential (MMP) and phosphorylation level of phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycinm (mTOR) were detected by clony formation assay and Wester blot., Results: When the treatment concentration of Eriodictyol was 20 μmol/L, the proliferation activity of the cells was decreased (P<0.05). The concentrations at 10, 20, 40 μmol/L were selected for subsequent experiments. Compared with 0 μmol/L Eriodictyol, the proliferation activity of DG-75, SOD activity, MMP, phosphorylation levels of PI3K, AKT and mTOR in 20 and 40 μmol/L Eriodictyol treatment groups were significantly decreased (P<0.05), while cells apoptosis rate, Cleaved-Caspase-3/Caspase-3, Bax/Bcl-2 and MDA level were significantly increased (P<0.05)., Conclusion: Eriodictyol may promote the mitochondrial apoptosis pathway by inhibiting the abnormal activation of PI3K/AKT/mTOR to reduce the proliferation activity of DG-75, and inhibit oxidative stress response to increase the apoptosis rate and play anti-tumor roles.

Objective: To establish an animal model of reflux renal damage through bladder outlet obstruction., Methods: Sixty male C57BL/6 mice aged 6-8 weeks were randomly assigned to a control group, a sham operation group, and a partial bladder outlet obstruction (PBOO) group, with 20 mice in each group. Laparotomy were performed on the PBOO mice under anesthesia in order to separate the bladder necks and to perform guided partial ligation of the bladder neck with a metal rod of 0.3 mm diameter. Mice in the sham operation group had laparotomy and had their bladder necks separated without ligation. The control group did not receive any treatment. 7 days after the surgery, 12 surviving mice were randomly selected from each group to observe the general changes of the bladder, ureter, renal pelvis and kidney. Retrograde urography was performed through the bladder. Kidney tissues were extracted for histopathological analysis. The expression levels of Vimentin, proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were examined with Western blot, immunohistochemistry and immunofluorescence staining tests, respectively., Results: Compared with the control and sham operation group, the bladder, ureter, and renal pelvis of the mice in the PBOO group were significantly enlarged, vesicoureteral reflux was more obvious, the kidney volume and mass increased ( P <0.001), and renal parenchyma became thinner ( P <0.000 1). Histopathological staining showed glomerular atrophy, renal tubule expansion, tubulointerstitial inflammatory cell infiltration, glomerular basement membrane hyperplasia and obvious interstitial fibrosis. Western blot, immunofluorescence and immunohistochemistry staining showed that the expression levels of Vimentin, PCNA and α-SMA in kidney tissue were elevated ( P <0.000 1)., Conclusion: After PBOO, the bladder, ureter, and kidney of the mice showed obvious morphological alteration and presented reflux renal fibrosis-like damage. This can be used as an animal model to study the pathological alteration mechanism and therapeutic measures of renal fibrosis caused by bladder outlet obstruction., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Background and Objectives: Anaphylaxis, a severe allergic disease, can be triggered by various causes. This study investigated the association between allergic sensitization and anaphylactic symptoms and the severity of anaphylaxis in children. Patients and Methods: A retrospective review of 107 pediatric patients with anaphylaxis was performed between January 1, 2015, and December 31, 2017; 74 patients underwent allergen testing for specific immunoglobulin E. Allergic sensitizations and associations with anaphylactic symptoms and severity were investigated. Results: Overall, 64 (86.5%) patients were sensitized to food or inhalant allergens. In children under 2 years of age, 90.5% were sensitized to food ( P = 0.001); in those over 6 years of age, 84.6% were sensitized to inhalant allergens ( P = 0.001). Milk sensitization was significantly associated with severe anaphylaxis ( P = 0.036). The following symptoms showed significant associations with certain allergen sensitizations: facial edema with food; wheezing with milk; dyspnea with mite, etc. Certain allergen sensitizations presenting as risk factors for anaphylactic symptoms: wheat (adjusted odds ratio [aOR] = 4.644, P = 0.044) and nuts (aOR=3.614, P = 0.041) for wheezing, nuts (aOR=5.201, P = 0.026) for dyspnea, and milk (aOR=4.712, P = 0.048) for vomiting. Conclusion: The allergen sensitization status differed according to the age of the children experiencing anaphylaxis. The severity, symptoms, and signs of anaphylaxis differed depending on the allergen sensitization status., 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 Lee, Cha, Han and Lee.)

Organic azides have been increasingly employed as nitrogen sources for catalytic olefine aziridination due to their ease of preparation and generation of benign N 2 as the only byproduct. Among common organic azides, carbonyl azides have not been previously demonstrated as effective nitrogen sources for intermolecular olefin aziridination despite the synthetic utilities of N-carbonyl aziridines. As a new application of metalloradical catalysis, we have developed a catalytic system that can effectively employ the carbonyl azide TrocN 3 for highly asymmetric aziridination of alkenes at room temperature. The resulting enantioenriched N -Trocaziridines have been shown as valuable chiral synthons for stereoselective synthesis of other chiral aziridines and various chiral amines. The Co(II)-based metalloradical system, which proceeds with distinctive stepwise radical mechanism, may provide a general method for asymmetric synthesis of chiral aziridines from alkenes with organic azides.

Objective: To observe the effect of proximal and distal acupoint catgut-embedding on the contents of prostaglandin E 2 (PGE 2 ) and prostaglandin F 2α (PGF 2α ) in the uterus, serum Interleukin-2 (IL-2) contents and splenic natural killer (NK) cell activity in primary dysmenorrhea (PD) rats，so as to explore the different effects of proximal and distal acupoint catgut-embedding on PD rats., Methods: Female Wistar rats were randomly divided into control, model, proximal catgut-embedding and distal catgut-embedding groups, with 8 rats in each group. The PD model was established by subcutaneous injection of estradiol ben-zoate (0.5 mg/rat on the first day and 10th day, and 0.2 mg/rat from the 2nd to the 9th day) and intraperitoneal injection of oxytocin (2 U/rat, on the 11th day). Catgut-embedding was applied at bilateral "Guanyuan"(CV4) and "Ciliao"(BL32) in the proximal catgut-embedding group, and bilateral "Sanyinjiao" (SP6) and "Diji"(SP8) in the distal catgut-embedding group. After the treatment, the body writhing times in 30 min and uterine mass were recorded, PGE2 and PGF2αin uterus and IL-2 in serum were assayed by using ELISA, the activity of NK cell in the spleen was detected using MTT colorimetry., Results: Following modeling, the body writhing times of the model group was increased than that of the control group ( P <0.01); After interventions, the body writhing times were decreased in the proximal and distal catgut-embedding groups than those of the model group ( P <0.01). Compared with the control group, the uterine mass and uterus PGF 2α content were increased ( P <0.01), while uterus PGE 2 , serum IL-2 and splenic NK cell activity were decreased ( P <0.01) in the model group. After interventions, the uterine mass and uterus PGF 2α were down-regulated ( P <0.01, P <0.05), while the contents of uterus PGE 2 , serum IL-2 and splenic NK cell activity up-regulated ( P <0.01) in the proximal and distal catgut-embedding groups in contrast to the model group. The content of uterus PGF 2α was down-regulated ( P <0.05) and splenic NK cell activity was up-regulated ( P <0.01) in the proximal catgut-embedding group than those of the distal catgut-embedding group., Conclusion: Both proximal and distal acupoint catgut-embeding can increase PGE 2 and decrease PGF 2α in the uterus, increase the level of serum IL-2 and the activity of NK cells in the spleen in PD model rats, thereby achieving analgesic effect. The effect of proximal catgut-embedding is better than that of distal catgut-embedding.

Background: Emergency Operations Center (EOC) is a place to provide response to public health emergencies. Chinese Center for Disease Control and Prevention (China CDC)'s EOC was officially established in 2016, which has been the core department for the public health emergencies and risk response. In recent years, we have been continuously improving the function of EOC through many incidents. In the study, we hope to share the construction status, operation management experience of China CDC's EOC and the response process in the human avian influenza A (H7N9) outbreak., Main Text: The China CDC's EOC mainly focus on building the five core elements including sites/places and facilities, information and data, plans and procedures, training and exercises, and logistics. Based on summarizing previous emergency response, the China CDC's EOC established its own incident management and the standardized response procedures. The event-specific data, context-specific data and event management data could be obtained through various source. The logistics department of the EOC also provides comprehensive support. The well-trained staff is another necessary conditions for its operation. Through sharing the response process of H7N9 outbreak, it further explains the EOC's functions in the five phases of outbreak response, such as the formulation of the incident response framework, monitoring, personnel dispatch and resource mobilization., Conclusions: The EOC contributes to faster and more efficient responses during emergencies which enable a greater reduction in morbidity and mortality. Compared with the traditional incident response process, under the command and coordination of China CDC's EOC, each group involved in the response has a clearer goal, responsibilities and tasks at each stage. Meanwhile, each group also gave full play to its own expertise and advantages. As a whole, incident response tended to be more specialized and precise, which generally improves the efficiency of incident response. However, different countries and regions have different response processes to the events. We still suggested that appropriate emergency operation plan should be made according to the complexity of incident response in the region when constructing response mechanism, through our experience. And the China CDC's EOC is still at growing and groping phase.

Radical reactions hold a number of inherent advantages in organic synthesis that may potentially impact the planning and practice for construction of organic molecules. However, the control of enantioselectivity in radical processes remains one of the longstanding challenges. While significant advances have recently been achieved in intramolecular radical reactions, the governing of asymmetric induction in intermolecular radical reactions still poses challenging issues. We herein report a catalytic approach that is highly effective for controlling enantioselectivity as well as reactivity of the intermolecular radical C-H amination of carboxylic acid esters with organic azides via Co(II)-based metalloradical catalysis (MRC). The key to the success lies in the catalyst development to maximize noncovalent attractive interactions through fine-tuning of the remote substituents of the D 2 -symmetric chiral amidoporphyrin ligand. This noncovalent interaction strategy presents a solution that may be generally applicable in controlling reactivity and enantioselectivity in intermolecular radical reactions. The Co(II)-catalyzed intermolecular C-H amination, which operates under mild conditions with the C-H substrate as the limiting reagent, exhibits a broad substrate scope with high chemoselectivity, providing effective access to valuable chiral amino acid derivatives with high enantioselectivities. Systematic mechanistic studies shed light into the working details of the underlying stepwise radical pathway for the Co(II)-based C-H amination.

Objective: To investigate the role of adenovirus-mediated short hairpin RNA (shRNA) in down-regulating the expression of phosphatase and tensin homologue deleted on chromosome ten (PTEN) on p130Crk-related substrates(p130Cas) and paxillin signal transduction to activate hepatic stellate cell (HSC) in vitro. Methods: The rat hepatic stellate cell line, HSC-T6 was cultured and activated in vitro. The adenovirus was used as a vector to transiently transfect shRNA targeting PTEN to activate HSC in vitro, and then PTEN low expression model of activated HSC in vitro was established. Western blot and real-time fluorescence quantitative PCR were used to detect the protein and mRNA expression of PTEN, p130cas and paxillin in activated HSC. The experiment was divided into control group (HSC were transfected with DMEM medium instead of adenovirus), Ad-GFP group (HSC were infected with empty the adenovirus expressing green fluorescent protein (GFP) alone), and Ad-shRNA/PTEN group (HSC were infected with the recombinant adenovirus containing both shRNA targeting PTEN and GFP gene). One-way analysis of variance was used for comparison of multiple groups, and LSD test was used for inter-group comparison. Results: shRNA targeting PTEN was successfully transfected and significantly down-regulated the PTEN protein and mRNA expression of HSC in vitro ( P < 0.05), and the PTEN low expression model of HSC in vitro was successfully constructed. Compared with the expression of p130cas mRNA in the three groups of HSC, the expression fold of p130cas mRNA in the Ad-GFP group and the Ad-shRNA / PTEN group was 1.01 times and 1.52 times, respectively. The expression of p130cas mRNA in HSC of the Ad-shRNA / PTEN group was significantly higher than control group and Ad-GFP group ( P < 0.05), but there was no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05). The expression of p130cas protein in the three groups was higher than that in the control group (0.74 ± 0.07) and the Ad-GFP group (0.72 ± 0.02); P < 0.05, but there was no statistically significant difference between the Ad-GFP group and the control group ( P > 0.05). The expression of paxillin mRNA in the three groups of HSCs was compared with the expression of paxillin mRNA in the control group of HSC being 1, the expression folds of paxillin mRNA in the Ad-GFP group and Ad-shRNA / PTEN group were 0.97 times and 1.58 times, respectively. The expression of paxillin mRNA in the Ad-shRNA / PTEN group was higher than that in the control group and the Ad-GFP group ( P < 0.05), and there was no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05). The expression of paxillin protein in the three groups of HSCs was higher in the Ad-shRNA / PTEN group (0.91 ± 0.05) than control group (0.46 ± 0.03) and Ad-GFP group (0.50 ± 0.04), P < 0.05, and there was no statistically significant difference between the Ad-GFP group and the control group ( P > 0.05). Conclusion: Down-regulation of PTEN expression can significantly boost p130cas and signal transduction activity of paxillin protein in activated HSC in vitro.

Systemic air embolism is a rare but potentially fatal complication related to many factors. The purpose of this article is to alert clinicians once patients occurs an abnormal neurological and cardiovascular status, following minor traumatic treatment, air embolism should be considered. A 20-year-old man who presented with fungal pneumonia with lung cavities formation was admitted to an intensive care unit (ICU) and received positive airway pressure ventilation. Four days later, the fungal pneumonia was improved, but the patient's blood pressure and arterial oxygen saturation deteriorated, so computed tomography (CT) scans were preformed to reevaluate him. The scans detected air embolism in the left atrium and ventricle, ascending aorta, aortic arch and its branches (right brachiocephalic, bilateral common carotid and right subclavian arteries), descending aorta and right coronary artery. A CT scan of the abdomen revealed air in the spleen, cauda pancreatic, superior mesenteric artery and right external iliac artery. The patient died two days later from multiple organ dysfunction. We suggest that vascular air embolism should be considered under mechanical ventilation when patients' neurologic and cardiovascular status deteriorates, and hyperbaric oxygen therapy should be conducted immediately., (Copyright © 2019. Production and hosting by Elsevier B.V.)

Introduction: This study was completed to determine if guidewire catheters improve first-pass success and time of placement for peripheral intravenous access. In the military, 21% of casualties from the battlefield arrive to a medical facility in hemorrhagic shock. The importance of successful and timely intravenous placement is crucial in the initial steps of preventing this condition. Multiple studies and reviews have shown that initial first-pass success rates for pre-hospital intravenous placement have been as low as 40%, and an average success rate of 81% when completed by paramedics or similarly skilled personnel. In an attempt to replicate or improve these rates, we proposed to study placement success rates by active duty military combat medics. We hypothesized that there would be no difference in first-pass success rates when using either a standard or guidewire catheter., Materials and Methods: This study was a prospective, randomized, controlled trial with a crossover study design comparing the Accucath 18-gauge guidewire catheter to the standard 18-gauge peripheral intravenous catheter. The study included 93 1st Cavalry Division Army Combat Medics. Participants were voluntarily enrolled and consented on an individual basis. Each participant paired with a partner of their choice and acted as their own control. All supplies were laid out for the participants with the catheters randomly selected for either arm of the patient. The subjects were allowed to choose which catheter they would be tested on first. Times were recorded for only successful attempts., Results: The guidewire catheter was not proven to have a higher cannulation rate, achieving only a 44% success rate versus 66% in the standard catheter group, as well as averaging 42 seconds longer to obtain successful cannulation versus the standard catheter. Interestingly, it was observed that the greater the time in service, there was an increased success rate with the guidewire catheter that was not noted with the standard catheter., Conclusions: There was not a statistically significant improvement in the first-pass success rate of intravenous placement with the use of the guidewire catheter when compared with the standard-issue catheter. With these results, we cannot recommend the guidewire catheter to be used in leu of the standard catheter. Further studies might show improvement if subjects are allotted increased practice and familiarity with the new guidewire device.

This study investigates the effectiveness of information technology-based 2-way referral in the diagnosis and management of cervical lesions in Minhang District, Shanghai, China. Women who underwent screening for cervical lesions in 4 community health centers constituted the intervention group, whereas women from the other 9 community health centers were included as controls. The diagnosis rate of cervical lesions was higher in the intervention group (7.61%) than in the control group (0.36%; P = .000). The diagnosis rate of early cervical lesion was 97.11% in the intervention group and 85.71% in the control group, showing no statistically significant differences ( P = .080). However, early diagnosis rate of precancerous lesion was much higher in the intervention group (95.45%) compared with the control group (64.29%; P = .001). In conclusion, higher effectiveness of early diagnosis and management of cervical lesions was observed in the intervention group compared with the control group.

Objective: To explore the associations between maternal and prenatal depressive symptoms and children's behavioral problems at 2 years old. Methods: In the present study, a total of 491 mother-child pairs were selected from the Shanghai-Minhang Birth Cohort Study (S-MBCS) which was conducted in Maternal and Child Health Hospital of Minhang District in Shanghai between April and December, 2012. Data from the Center for Epidemiologic Studies on Depression was gathered to assess the maternal depressive symptoms in the second and third trimester of pregnancy, as well as at 6 months and 12 months postpartum. Neurodevelopment at 2 years was assessed, using the Child Behavior Checklist. We used generalized linear models with a log-link function and a Binomial distribution to estimate the risk ratios ( RR s) and 95% CI s, on children's behavioral problems at 2 years of age. Sensitivity analyses were performed among participants without postpartum depressive symptoms. Results: After adjustment on factors as maternal age, gestation week, average monthly income per person, parental education and children's gender etc ., maternal depression in second trimester of pregnancy was found associated with higher risk of both developing emotional ( RR =2.61, 95% CI : 1.36-4.99) and internalizing problems ( RR =1.94, 95% CI : 1.22-3.08). However, maternal depression in third trimester was found to be associated with higher risks of developing emotional ( RR =6.46, 95% CI : 3.09-13.53), withdrawn ( RR =2.42, 95% CI : 1.16-5.02), aggressive ( RR =2.93, 95% CI : 1.45-5.94), internalizing ( RR =1.79, 95% CI : 1.01-3.16) or externalizing problems ( RR =2.56, 95% CI :1.49-4.42). In sensitivity analysis, antenatal maternal depression was found positively associated with children's emotional, internalizing and externalizing problems and the differences all statistically significant. Conclusions: Maternal depression during pregnancy might increase the risks of children's behavioral problems. In order to decrease the incidence of children's behavioral problems and promoting both maternal and child health status, monitoring program regarding maternal mental health care should be strengthened.

Silver nanowires with high yield, uniform size and high aspect ratio were successfully synthesized by a simple and effective polyol method under low temperature and quiescent conditions, adopting CuCl2·2H2O as the nucleation control agent for the first time. The synthesized silver nanowires were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and UV-Vis diffuse reflectance spectroscopy (DRS). The results indicate that the silver nanowires were composed of face-centered cubic structure of pure metallic silver with high crystallinity. And the silver nanowires have an average length of 80~100 μm and an average diameter of 40~80 nm. Thus, the aspect ratio of the nanowires was greater than 1000. In addition, the influence on the morphology and structure of the silver nanowires were investigated for reaction temperature, mole ratio of PVP:AgNO3, molecular weight of PVP and mole ratio of control agent CuCl2 · 2H2O:AgNO3. Finally, the optimum reaction condition were obtained for the preparation of the silver nanowires with high aspect ratio.

Background: We hypothesized that a high ticagrelor loading dose (LD) may improve platelet inhibition in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI)., Methods: This interventional multicentre open-label trial randomized 278 patients with NSTE-ACS to a high (360 mg) or conventional (180 mg) ticagrelor LD. The primary outcome was the platelet reactivity index (PRI) 1 hour after administration of the LD. Secondary outcomes included PRI at 0.5 hour, 1 hour, 8 hours, and 24 hours; periprocedural myocardial infarction (PMI); major cardiac adverse events; and bleeding events., Results: Two hundred sixty-two patients completed the major end points. PRI was lower in the high-LD group than in the conventional-LD group at any time point (all, P < 0.05), including at 1 hour (12.2% vs 16.7%; P = 0.023). At 0.5 hour, the high-LD group showed a lower high-platelet reactivity rate (49.6% vs 60.2%; P = 0.013) and a higher low-platelet reactivity rate (24.8% vs 12.8%; P = 0.017) than did the conventional LD group. No significant differences in the bleeding rates were found between the 2 groups (14% vs 14.3%). Four cases of PMI and 1 death in each group, as well as 1 acute myocardial infarction in the conventional LD group, occurred. There was no stroke, target lesion revascularization, or target vessel revascularization., Conclusions: Doubling the ticagrelor LD achieved faster onset and greater platelet inhibition without an increase in adverse events in patients with NSTE-ACS undergoing PCI., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Pancreatic cancer is one of the most aggressive malignancies and chemotherapy is an effective strategy for advanced pancreatic cancer. Gemcitabine (GEM) is one of first-line agents. However, GEM-based combination therapy has shown promising efficacy in patients with advanced pancreatic cancer. This meta-analysis aimed to compare the efficacy and safety of GEM-based combination therapy versus GEM alone in the treatment of advanced pancreatic cancer., Data Sources: A comprehensive search of literature was performed using PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials. A quantitative meta-analysis was performed based on the inclusion criteria from all eligible randomized controlled trials. The outcome indicators included overall survival (OS), 6-month survival, 1-year survival, progression-free survival/time-to-progression (PFS/TTP), and toxicities., Results: A total of nine randomized controlled trials involving 1661 patients were included in this meta-analysis. There was significant improvement in the GEM-based combination therapy with regard to the OS (HR=0.85, 95% CI: 0.76-0.95, P=0.003), PFS (HR=0.76, 95% CI: 0.65-0.90, P=0.002), 6-month survival (RR=1.09, 95% CI: 1.01-1.17, P=0.03), and the overall toxicity (RR=1.68, 95% CI: 1.52-1.86, P<0.01). However, there was no significant difference in the 1-year survival., Conclusions: GEM-based combination chemotherapy might improve the OS, 6-month survival, and PFS in advanced pancreatic cancer. However, combined therapy also added toxicity.

We discover that emission efficiency of Tm 3+ -doped upconversion nanoparticles can be enhanced through the use of a laser cavity. With suitable control of the lasing conditions, the population of the intermediate excited states of the Tm 3+ can be clamped at a required value above the excitation threshold. As a result, upconversion efficiency for the 300-620 nm emission band of the Tm 3+ -doped nanoparticles under 976 nm excitation can be enhanced by an order of magnitude over the case without a laser cavity. This is because the intrinsic recombination process of the intermediate excited states is suppressed and the surplus of excitation power directly contributes to the enhancement of multiphoton upconversion. Furthermore, our theoretical investigation has shown that the improvement of upconversion emission efficiency is mainly dependent on the cavity loss, so that this strategy can also be extended to other lanthanide-doped systems.

Objective: To investigate the effect of overexpression of wild-type phosphatase and tensin homolog (PTEN) deleted on chromosome 10 and its mutant G129E (exhibiting the activity of protein phosphatase and losing the activity of lipid phosphatase) on F-actin in activated hepatic stellate cells (HSCs) cultured in vitro. Methods: The activated hepatic stellate cell-T6 (HSC-T6) cells were cultured in vitro, and activated HSCs were transfected with adenovirus that carried wild-type PTEN gene and G129E gene using transient transfection. The HSCs were divided into the following groups: control group, which was transfected with DMEM medium instead of virus solution; Ad-GFP group, which was transfected with the empty adenovirus vector with the expression of green fluorescent protein (GFP); Ad-PTEN group, which was transfected with the recombinant adenovirus with wild-type PTEN gene and GFP expression; Ad-G129E group, which was transfected with the recombinant adenovirus with G129E gene and GFP expression. Western blot and quantitative real-time PCR were used to measure the protein and mRNA expression of PTEN in activated HSCs; under a laser scanning confocal microscope (LSCM), phalloidine labeled with the fluorescein tetramethylrhodamine isothiocyanate (TRITC) was used to observe the morphology of HSCs, distribution and fluorescence intensity of F-actin, and changes in pseudopodia and stress fibers, and a calcium fluorescence probe (Rhod-2/AM) was used to measure the changes in Ca(2+) concentration in HSCs. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference test was used for comparison between two groups. Results: Wild-type PTEN and G129E genes were highly expressed in activated HSCs. In the control group and the Ad-GFP group, HSCs had a starlike or polygonal shape, F-actin was reconfigured and formed a large number of stress fibers which stretched across the whole cell, and layered pseudopodia were seen around the cell. In the Ad-PTEN group and the Ad-G129E group, the HSCs had a fusiform shape, F-actin was mainly seen around the cell, a small number of stress fibers were seen inside the cell, and layered pseudopodia around the cell disappeared. The Ad-PTEN group and the Ad-G129E group had significant reductions in the fluorescence intensity of F-actin compared with the control group and the Ad-GFP group (357.67±13.39/377.25±14.55 vs 961.87±27.33/954.68±20.71, F = 1783.486, P < 0.05), while there were no significant differences between the Ad-PTEN group and the Ad-G129E group, as well as between the control group and the Ad-GFP group ( P > 0.05). The Ad-PTEN group and the Ad-G129E group had significant reductions in the relative concentration of Ca(2+) compared with the control group and the Ad-GFP group (251.60±90.88/352.18±146.01 vs 1953.95±132.99/1937.57±115.17, F = 834.988, P < 0.05), while there were no significant differences between the Ad-PTEN group and the Ad-G129E group, as well as between the control group and the Ad-GFP group ( P > 0.05). Conclusion: The overexpressed wild-type PTEN and its mutant G129E can significantly inhibit the formation and reconfiguration of cytoskeletal protein F-actin and reduce the concentration of Ca2+ in activated HSCs in vitro. In addition, there are no significant differences in the above effects between wild-type PTEN and G129E.

Our study aimed to investigate the isoform-specific distribution of 14-3-3 in tongue squamous cell carcinoma (TSCC) and their association with cancer progression, and to further discuss their roles in cancer cell survival. In this study, 42 TSCC specimens and their matched normal para-carcinoma sections were collected. The immunohistochemistry analysis identified that 14-3-3σ and ζ isoforms presented significantly higher expression in cancerous tissues compared with the matched normal tongue tissue sections. 14-3-3ζ expression was associated with tumor T stage, lymph node metastasis and poor prognosis of TSCC. In vitro study revealed that 14-3-3ζ silencing alleviated the proliferation and migration of TSCC cells while promoted cancer cell apoptosis. 14-3-3ζ could bind to and inactivate FOXO3a transcription factor, in turn leading to the movement of the 14-3-3ζ-FOXO3a complex from nucleus to cytoplasm, which was inhibited after 14-3-3ζ silencing. Both 14-3-3ζ and FOXO3a silencing increased caspase 3 and 9 activation, while reduced inner mitochondrial membrane potential. Collectively, 14-3-3ζ may serve as a hallmark and prognostic marker of TSCC. 14-3-3ζ can bind to the FOXO3a transcription factor to promote the export of the complex to the cytoplasm, leading to enhanced proliferation and migration of tongue cancer cells.

Aryloxysulfonyl azides can be effectively activated by commercially available cobalt(II) complex of meso -tetraphenylporphyrin ([Co(TPP)]) at room temperature under neutral and nonoxidative conditions for selective radical aziridination of alkenes via metalloradical catalysis. The [Co(TPP)]-catalyzed radical aziridination system is suitable for different combinations of olefin substrates and aryloxysulfonyl azides, producing various N -aryloxysulfonyl aziridine derivatives in good to excellent yields. In addition to generating the environmentally benign N 2 as the only byproduct, this Co(II)-based metalloradical aziridination process features mild reaction conditions and operational simplicity.

In this work, we examined the effects of the surface charge of stem cell membranes and DNA/polyethyleneimine (PEI) nanocomplexes on gene transfection efficiency, because PEI was one of the most reliable and efficient carriers, and rat bone marrow mesenchymal stem cells (rBMSCs) and rat muscle-derived stem cells (rMDSCs) were one of the readily accessible and plentiful sources of stem cells. Thus, we compared the efficiency of DNA transfection in rBMSCs and rMDSCs using the PEI as a gene carrier. Transfection efficiency was evaluated on the basis of electrostatic interaction between negatively charged stem cell membranes and positively charged DNA/PEI nanocomplexes. DNA was fully complexed with PEI at negative-to-positive (NIP) charge ratios greater than 2, as confirmed by gel electrophoresis and fluorescence measurements. DNA and PEI formed spherical nanocomplexes ranging in diameter from 150 nm to 500 nm. The positive surface charge of DNA/PEI nanocomplexes increased with an increasing N/P charge ratio, as measured using dynamic light scattering and a single-walled carbon nanotube-based field-effect transistor device. rBMSCs and rMDSCs both carried a negative surface charge, with rBMSCs being more negatively charged. The transfection efficiency of rMDSCs measured using DNA/PEI nanocomplexes was very low (1%-5%) at most of the N/P charge ratios tested, whereas better efficiencies were observed with rBMSCs (1%-17%). Nanocomplexes with high NIP charge ratios were cytotoxic to both rBMSCs and rMDSCs. Collectively, the results indicate that rBMSCs were more effectively transfected with DNA/PEI nanocomplexes than were rMDSCs, reflecting the higher negative charge of rBMSC membranes that facilitate the interaction with positively charged DNA/PEI nanocomplexes.