Diagnostic Value of Conventional Polymerase Chain Reaction for Detecting BRAF V595E Mutation in Liquid and Tissue Specimens of Canine Urothelial and Prostate Carcinomas.

Canine urothelial carcinoma (UC) and prostatic carcinoma (PC) often present diagnostic challenges due to their anatomical locations. The BRAF V595E mutation, analogous to the human BRAF V600E mutation, has been identified in UC and PC. Digital PCR of urine is a non-invasive diagnostic method of mutation detection, but the availability of the necessary equipment is limited. This study aimed to develop a conventional PCR to detect the BRAF V595E mutation in urine and prostatic wash specimens from dogs with UC or PC. Specific primers for detecting wild-type and mutant BRAF V595E genes were validated in 34 formalin-fixed paraffin-embedded (FFPE) tissues, 116 urine samples, and 9 prostatic wash specimens. The results showed that the BRAF V595E mutation detection rate for UC and PC in the tissues was 51.6%. The detection rate in liquid specimens from dogs with lower urinary tract or prostate masses was 53.2%. Of the 41 cases with follow-up, 16 were further diagnosed with UC or PC, with 75% of liquid specimens from these dogs showing the BRAF V595E mutation. This conventional PCR method provides a reliable and non-invasive screening tool for UC and PC in dogs, especially in settings without advanced equipment.

Immunotherapeutic allogeneic dendritic cell and autologous tumor cell fusion vaccine alone or combined with radiotherapy in canine oral malignant melanoma is safe and potentially effective.

Introduction: Immunotherapy represents a promising breakthrough in cancer management and is being explored in canine melanomas. Dendritic cells (DCs) play a crucial role in priming T-cell-mediated immune reactions through the antigen-presenting function. Combining immunotherapy and radiation therapy may generate more substantial anti-cancer efficacy through immunomodulation. Objectives: Our research reported a preliminary result of the safety and outcome of a kind of immunotherapy, the allogeneic dendritic cell and autologous tumor cell fusion vaccine, alone or in combination with hypofractionated radiation therapy, in canine oral malignant melanoma. Methods: Two groups of dogs with histopathological diagnoses of oral malignant melanoma were recruited. In group 1 (DCRT), dogs received a combination of DC fusion vaccine and radiotherapy. In group 2 (DC), dogs received DC fusion vaccine alone. DC vaccination was given once every 2 weeks for four doses. Radiotherapy was performed weekly for five fractions. Dogs that received carboplatin were retrospectively collected as a control group (group 3). Results: Five dogs were included in group 1 (two stage II, three stage III), 11 in group 2 (three stage I/II, eight stage III/IV), and eight (two stage I/II, six stage III/IV) in the control group. Both DC and DCRT were well-tolerated, with only mild adverse events reported, including mucositis, gastrointestinal discomfort, and injection site reactions. The median progression-free intervals in groups 1, 2, and 3 were 214 (95% CI, NA, due to insufficient data), 100 (95% CI, 27-237), and 42 days (95% CI, NA-170), respectively, which were not significantly different. The 1-year survival rates were 20, 54.5, and 12.5% in groups 1, 2, and 3. Dogs in the DCRT group exhibited significantly higher TGF-ß signals than the DC group throughout the treatment course, indicating a possible higher degree of immunosuppression. Conclusion: The manuscript demonstrated the safety of dendritic cell/tumor cell fusion vaccine immunotherapy, alone or in combination with radiotherapy. The results support further expansion of this immunotherapy, modification of combination treatment and protocols, and investigation of combining DC vaccine with other treatment modalities. Clinical trial registration: Preclinical Trials, PCTE0000475.

Superb Silk Hydrogels with High Adaptability, Bioactivity, and Versatility Enabled by Photo-Cross-Linking.

The exceptional biocompatibility and adaptability of hydrogels have garnered significant interest in the biomedical field for the fabrication of biomedical devices. However, conventional synthetic hydrogels still exhibit relatively weak and fragile properties. Drawing inspiration from the photosynthesis process, we developed a facile approach to achieve a harmonious combination of superior mechanical properties and efficient preparation of silk fibroin hydrogel through photo-cross-linking technology, accomplished within 60 s. The utilization of riboflavin and H2O2 enabled a sustainable cyclic photo-cross-linking reaction, facilitating the transformation from tyrosine to dityrosine and ultimately contributing to the formation of highly cross-linked hydrogels. These photo-cross-linking hydrogels exhibited excellent elasticity and restorability even after undergoing 1000 cycles of compression. Importantly, our findings presented that hydrogel-encapsulated adipose stem cells possess the ability to stimulate cell proliferation along with stem cell stemness. This was evidenced by the continuous high expression levels of OCT4 and SOX2 over 21 days. Additionally, the utilization of photo-cross-linking hydrogels can be extended to various material molding platforms, including microneedles, microcarriers, and bone screws. Consequently, this study offered a significant approach to fabricating biomedical hydrogels capable of facilitating real-time cell delivery, thereby introducing an innovative avenue for designing silk devices with exceptional machinability and adaptability in biomedical applications.

High biocompatible bone screw enabled by a rapid and robust chitosan/silk fibroin composite material.

Hydrogel has attracted tremendous attentions due to its excellent biocompatibility and adaptability in biomedical field. However, it is challenging by the conflicts between inadequate mechanical properties and service requirements. Herein, a rapid and robust hydrogel was developed by interpenetrating networks between chitosan and silk fibroin macromolecules. Thanks to these unique networks, the chitosan-based hydrogel exhibited superior mechanical performances. The maximum breaking strength, Young's modulus and swelling ratio of the hydrogel were 1187.8 kPa, 383.1 MPa and 4.5 % respectively. The hydrogel also supported the proliferation of human umbilical vein endothelial cells for 7 days. Notably, the hydrogel was easily molded into bone screw, and demonstrated compressive strengths of 45.7 MPa, Young's modulus of 675.6 MPa, respectively. After 49-day biodegradation, the residual rate of the screw in collagenase I solution was up to 89.6 % of the initial weight. In vitro, the screws not only had high resistance to biodegradation, but also had outstanding biocompatibility of osteoblast. This study provided a promising physical-chemical double crosslinking strategy to build orthopedic materials, holding a great potential in biomedical devices.

Preparation and Application of Polypyrrole Conductive Hydrogels in Biomedical Field / 分析化学

Hydrogel is a kind of material with high water content,good biocompatibility and extracellular matrix-like property,among which polypyrrole(PPy)conductive hydrogels have both physical characteristics and excellent conductivity of hydrogels themselves.Its conductivity can be used to detect electrical signals generated in biological systems and provide electrical stimulation to regulate the activities and functions of cells and tissues.These characteristics make it widely used in the biomedical field.The recent progress of PPy conductive hydrogels in biomedical field was reviewed in this paper.In terms of classification,according to the cross-linking mechanism of PPy and hydrogel matrix,the non-covalent cross-linked PPy conductive hydrogels and covalent cross-linked PPy conductive hydrogels were divided.The applications of PPy conductive hydrogels in the biomedical field(Skin damage repair,nerve repair,myocardial repair and flexible sensing,etc.)were mainly introduced,and the development trend and challenges of PPy conductive hydrogels in the biomedical field were discussed.

[Analysis and Modeling of Risk Factors for Children with Intestinal Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To analyze factors associated with intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT) in children and to develop a prediction model for intestinal aGVHD after allo-HSCT in children. METHODS: The clinical data of 62 children who underwent allo-HSCT at the Department of Hematology of the People's Hospital of Xinjiang Uygur Autonomous Region from February 2018 to September 2021 were retrospectively analyzed. Intestinal aGVHD was evaluated according to the Mount Sinai Acute GVHD International Consortium (MAGIC) grading criteria, the variables were screened by LASSO (least absolute shrinkage and selection operator) regression analysis with 10-fold cross-validation, and developed a model for predicting intestinal aGVHD after allo-HSCT in children. RESULTS: A total of 33 (53.2%) of the 62 children developed intestinal aGVHD, of which 25 were degree II and 8 were degree III-IV. The results of screening variables by 10-fold cross-validated LASSO regression showed that the significant variables included ethnic minorities (OR =7.229; 95%CI: 2.337-22.354), platelet (PLT) (OR =0.971; 95%CI: 0.932-0.993), uric acid (UA) (OR =0.971; 95%CI: 0.935-0.988), C-reactive protein (CRP) (OR =1.217; 95%CI: 1.053-1.545), and viral infection (OR =10; 95%CI: 3.021-32.668), and these variables were independently associated with intestinal aGVHD in children (all P <0.05). A prediction model was constructed based on above variables. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was calculated, and the AUC value was 0.985 (0.966-1), the Brier score was 0.055. The evaluation showed that the model has a high degree of discrimination and calibration. CONCLUSION: Ethnic minorities, low PLT, low UA, high CRP, and viral infections are independently associated with intestinal aGVHD in children, and early attention should be paid to these high-risk children.

Changes in corneal endothelial cell density after trabeculectomy.

BACKGROUND: Glaucoma is a leading cause of blindness worldwide for which trabeculectomy is the most effective surgical intervention for advanced disease. However, trabeculectomy has been associated with alterations to corneal endothelium, including a decrease in corneal endothelial cell density (CECD). The purpose of this study was to investigate changes in CECD after trabeculectomy, and identify factors contributing to cell loss, such as pre-operative biometry and lens status. METHODS: This retrospective study included 72 eyes of 60 patients who underwent trabeculectomy between January 2018 and June 2021 at two private hospitals. Demographic and clinical data were obtained at baseline. Corneal specular microscopy was performed pre-operatively and at 6 months after surgery. CECD was evaluated and compared between groups to quantify changes to corneal endothelium and identify significant factors affecting decreases in cell density. RESULTS: Mean CECD was 2284.66 ± 375.59 pre-operatively and 2129.52 ± 401.96 after 6 months (p < 0.001). A greater decrease in CECD (p = 0.005) was observed in phakic eyes (235.45 ± 118.32) compared to pseudophakic eyes (137.82 ± 107.30). The amount of cell loss was negatively correlated with pre-operative central corneal thickness (p = 0.009) and anterior chamber (AC) depth (p = 0.033). There were no significant correlations between changes to CECD and patient age, gender, number of pre-operative glaucoma medications and number of post-operative antifibrotic agents. CONCLUSIONS: Significant decreases in CECD occurred after trabeculectomy. Less corneal endothelial cell loss occurred in pseudophakic eyes. Hence, if patients need trabeculectomy and cataract surgery, it may be better to perform cataract surgery first. Longer term studies should derive more information.

Recent progress in silk-based biosensors.

The applications of biosensors, in both medical and non-medical fields, have expanded enormously over the last few years. For conventional sensing applications, petrochemical materials, conducting polymers, metals and carbon-based materials are used. However, biosensing, especially in the medical field, places stringent material requirements of biocompatibility, biodegradability and other performance. Silk, an ancient natural organic material, is endowed with excellent biocompatibility, adjustable biodegradability, high strength and outstanding processability due to its unique physical and chemical structure. Owing to these exceptional properties, silk and its derivatives are of interest to researchers as biosensor matrices (supports). Herein, we review the representative research results of silk-based biosensors in medical and non-medical fields and highlight the applications and challenges of silk and its derivatives in medical biosensing applications. We envision that silk-based biosensors will become an integral part of the healthcare monitoring system in future.

Analysis and Modeling of Risk Factors for Children with Intestinal Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To analyze factors associated with intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT) in children and to develop a prediction model for intestinal aGVHD after allo-HSCT in children.@*METHODS@#The clinical data of 62 children who underwent allo-HSCT at the Department of Hematology of the People's Hospital of Xinjiang Uygur Autonomous Region from February 2018 to September 2021 were retrospectively analyzed. Intestinal aGVHD was evaluated according to the Mount Sinai Acute GVHD International Consortium (MAGIC) grading criteria, the variables were screened by LASSO (least absolute shrinkage and selection operator) regression analysis with 10-fold cross-validation, and developed a model for predicting intestinal aGVHD after allo-HSCT in children.@*RESULTS@#A total of 33 (53.2%) of the 62 children developed intestinal aGVHD, of which 25 were degree II and 8 were degree III-IV. The results of screening variables by 10-fold cross-validated LASSO regression showed that the significant variables included ethnic minorities (OR =7.229; 95%CI: 2.337-22.354), platelet (PLT) (OR =0.971; 95%CI: 0.932-0.993), uric acid (UA) (OR =0.971; 95%CI: 0.935-0.988), C-reactive protein (CRP) (OR =1.217; 95%CI: 1.053-1.545), and viral infection (OR =10; 95%CI: 3.021-32.668), and these variables were independently associated with intestinal aGVHD in children (all P <0.05). A prediction model was constructed based on above variables. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was calculated, and the AUC value was 0.985 (0.966-1), the Brier score was 0.055. The evaluation showed that the model has a high degree of discrimination and calibration.@*CONCLUSION@#Ethnic minorities, low PLT, low UA, high CRP, and viral infections are independently associated with intestinal aGVHD in children, and early attention should be paid to these high-risk children.

Etiology detection and epidemiological analysis of influenza in Hainan Province,2013-2021 / 中国人兽共患病学报

The purpose of this study was to investigate the epidemiological characteristics and risk factors of influenza in Hainan province,to provide evidence to support influenza prevention and control efforts.Pathogen monitoring data of influenza-like illness(ILI)in six national sentinel hospitals in Hainan province from 2013 to 2021 were analyzed in SPSS 20.0 software.A total of 50 415 ILI cases were detected during the 2013-2021 season,of which 5 581 were positive for influenza viruses,with a positivity rate of 11.07％.The dominant strains were type B,type A(H1N1)pdm09 and type A(H3N2).The positivi-ty rate of influenza virus was highest in people 5-14 years of age(17.56％)and lowest in people 0-4 years of age(7.32％).Influenza activity showed both a summer peak and a winter-spring peak in the 2014-2016,2017-2018 and 2019-2020 sea-sons,and was concentrated in April to September,with a maximum peak of 53.64％,and in November to March of the next year,with a peak of 47.30％.The 2013-2014,2016-2017 and 2018-2019 seasons showed only a winter-spring peak concen-trated between October and March of the next year,with a maximum peak of 54.17％,but no obvious summer peak.The pre-dominant influenza viruses during the eight surveillance seasons varied among H1N1,H3N2 and type B.The positive detection rate of influenza virus steeply declined during the 2020-2021 season:the positive detection rate was only 0.25％,and no obvi-ous epidemic period was observed.The intensity of influenza epidemic varied among monitoring years,and the dominant strains changed rapidly in Hainan Province.People 5-14 years of age were the key population affected.Summer,winter and spring were the key periods for influenza prevention and control.Etiological surveillance of influenza should continue to be strength-ened,the roles of health education and publicity should be emphasized,and the dual measures of influenza vaccination and non-drug intervention should be actively promoted to decrease the occurrence of influenza.

Continuous Glucose Monitoring for the Diagnosis of Gestational Diabetes Mellitus: A Pilot Study.

Background: Gestational diabetes mellitus (GDM) is diabetes first diagnosed in pregnancy. GDM, together with its short- and long-term negative outcomes, is increasing in incidence all over the world. The current diagnostic method for GDM, the oral glucose tolerance test (OGTT), is dated and has been reported as inconvenient for women as well as poorly reproducible and reliable. Aims: We aimed at assessing the acceptability, feasibility, and accuracy of continuous glucose monitoring (CGM) as a diagnostic test for GDM and explore its correlation with the OGTT and risk factors for GDM. Methods: In this prospective cohort study, pregnant women due for or having completed OGTT underwent CGM for seven days, performing daily finger-prick blood glucose levels before completing an acceptability questionnaire. Data on GDM risk factors and CGM variability were analyzed and compared with OGTT results. Results: Seventy-three women completed CGM (40 GDM, 33 normal glucose tolerances); 34 concurrently underwent OGTT. CGM was acceptable and generally well-tolerated, with skin irritation/itchiness the only adverse event (11 mild, one severe). CGM and OGTT strongly correlated for fasting glucose values (r = 0.86, p < 0.05) only. Triangulating GDM risk factors, OGTT results and CGM variability parameters with the application of machine learning highlighted the possibility of unmasking false positive (11 showed low CGM variability and demographic risks but positive OGTT) and false-negative OGTT diagnoses (1 showed high CGM variability and demographic risks but negative OGTT). Conclusions: CGM was well-tolerated, showing poorer glycaemic control in GDM, and revealing potential misdiagnosis of the OGTT when combined with GDM risk factors. Future research is needed to determine cut-off values for CGM-defined and OGTT-independent screening criteria for GDM.

Investigation of Toxoplasma infection in zoo animals using multispecies ELISA and GRA7 nested PCR.

BACKGROUND: Toxoplasma is an obligate intracellular protozoan that causes an important zoonotic disease with a worldwide distribution. Felids are the definitive hosts of this parasite, while virtually all warm-blooded animals, including birds, serve as intermediate hosts. Four ring-tailed lemurs (Lemur catta) in the Taipei Zoo died of acute Toxoplasma infection in June 2019. Since then, Toxoplasma has occasionally been identified in this Zoo during necropsy of dead animals and PCR of animal blood samples. Therefore, a general survey of Toxoplasma infection in animals in the Zoo seems to be needed. METHODS AND RESULTS: An indirect multispecies ELISA was used for the first time to screen for Toxoplasma infection in 326 serum samples collected from 75 species of animals. The infection rate of Toxoplasma was 27% (88/326). A commercial latex agglutination (LAT) assay was used to re-examine the samples with doubtful and uncertain ELISA results (151 samples from 42 species). The infection rate increased to 36.2% (118/326), and the indirect multispecies ELISA appeared to be applicable to 31 of 75 species animals included in this study. Nested PCR assays targeting the dense granule protein 7 (GRA7) gene and B1 gene were also used to detect Toxoplasma in DNA samples extracted from 10 liver or blood specimens from 8 animals. GRA7 gene fragments were amplified from 8 samples from 7 animals, while B1 gene fragments were amplified from only 4 samples from 4 animals. From the B1 nested PCR and the sequence data of GRA7 fragments amplified from infectious specimens, the animals in the Zoo were speculated to have been infected by at least three different Toxoplasma variants. CONCLUSIONS: According to the serological investigation, we speculated that over one-third (36.2%) of animals in Taipei Zoo presented the infection of Toxoplasma, and the indirect multispecies ELISA we used can be applied to detect Toxoplasma infection in 31 animal species included in this study. Sequence analysis revealed that at least three Toxoplasma variants were infecting the animals of Taipei Zoo.

Ureteroscopic Lithotripsy in Reverse Trendelenburg Position and Intraoperative Furosemide.

PURPOSE: Upward stone migration is a significant problem during ureteroscopic lithotripsy (URSL) for upper ureteral stone, especially in absence of a ureteral occlusion device. In this study, we evaluated the novel strategy of reverse Trendelenburg position (RTP) and intraoperative diuresis for URSL without ureteral occlusion devices to avoid upward migration. MATERIALS AND METHODS: From March 2018 to May 2020, a total of 119 URSLs were performed for upper ureteral stone (6-15 mm) with 67 procedures in RTP and 52 procedures in conventional lithotomy position (CLP). 20 mg of intravenous furosemide was administered prior to stone fragmentation with holmium laser only in RTP group. Patient demographics, stone side, stone size and operative characteristics were recorded and compared between the two groups. RESULTS: Patient data, stone side and size were similar in the two groups. All procedures were complete without conversion to open surgery and major complications. There was no significant difference in the mean operative time (47.9 ± 7.7 min vs 45.3 ± 7.0 min, P = .062) and mean hospital stay (3.9 ± 0.9 d vs 4.0 ± 1.0 d, P = .336) between the RTP and CLP group. Stone upward migration was significantly less in RTP group (3.0%, 2/67) than in CLP group (19.2%, 10/52) (P = .005). Stone-free rate at one month after initial treatment was 92.5% in RTP group and 73.1% in CLP group (P = .004). CONCLUSION: The strategy of placing the patient in RTP and intraoperative administration of intravenous furosemide is simple, feasible and cost-effective in preventing stone upward migration during URSL with holmium laser in absence of a ureteral occlusion device for upper ureteral stone.

Tropism and transduction of oncolytic adenovirus vectors in prostate cancer therapy.

Oncolytic adenovirus has been applied in cancer therapy because of several advantages such as cost-effective production, high transduction efficiency and low toxicity. Recent efforts have been focused on the modification of oncolytic adenovirus by encoding transgenes within the viral genome to efficiently and selectively replicate within cancer cells, destroy cancerous cells, induce tumor cell apoptosis, and stimulate the recruitment of immune cells to the tumor site. Nevertheless, there are still big challenges for translational research of oncolytic virotherapy in clinical cancer management. Therefore, here we summarize current status on the design and application of oncolytic adenovirus vectors for prostate cancer therapy. In particular, we describe the main receptors associated with the tropism and transduction of oncolytic adenovirus vectors, and propose new directions in future studies for prostate cancer virotherapy.

Molecular cloning and functional studies on magang goose toll-like receptor 5.

Disease outbreaks heavily impact the economic viability of animal industries. Little is known about the mechanisms of immune system-related diseases in geese. Toll-like receptors (TLRs) play a major role in the anti-inflammatory immunity process in most animal species, but they have not been studied in the Magang goose. To elucidate the role of TLRs, reverse transcription polymerase chain reaction (RT-PCR) and PCR amplification of cDNA ends (Smart RACE) were used to clone the Magang goose TLR5 gene (mgTLR5). The full-length cDNA of mgTLR5 was 2967 bp in length, including a 5'-terminal untranslated region (UTR) of 215 bp, a 3'-terminal UTR of 384 bp, and an open reading frame of 2583 bp that encodes a protein of 860 amino acids. Structurally, mgTLR5 has a toll/interleukin-receptor (TIR) domain, a transmembrane domain, and seven leucine-rich repeats (LRRs) domains. Homology alignment of TLR5 and its TIR domains with other species revealed that mgTLR5 shared 98 % and 81.3 % of sequence similarity with white goose TLR5 and chicken TLR5, respectively. Quantitative RT-PCR showed that the mgTLR5 gene of the goose is widely expressed in all tested tissues, with the highest expression in the kidney and spleen. The increase in NF-κB promoter activity stimulated by flagellin was dependent on mgTLR5 expression in 293 T cells. Salmonella pullorum and flagellin significantly upregulated the expression of TLR5, IL-8, and IL-1 mRNA in peripheral blood mononucleotide cells of Magang goose cultured in vitro. Stimulation by S. pullorum for 24 h upregulated mgTLR5 expression in the cecum and kidney. We conclude that Magang goose TLR5 is a functional TLR5 homologue of the protein in other species and plays an important role in bacterial recognition.

D-dimer levels is associated with severe COVID-19 infections: A meta-analysis.

OBJECTIVE: The ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Excluded typical manifestation of pneumonia and acute respiratory symptoms, COVID-19 patients also have abnormal D-dimer concentration in the serum, but the results are controversial. METHOD: A meta-analysis first aims to explored the connection between D-dimer concentration and COVID-19 patients. RESULTS: Our results found a significant relationship between D-dimer and COVID-19, with a pooled OR of 1.90 (95% CI: 1.32-2.48; P < .001). The pooled data were calculated with the REM as a high heterogeneity within the studies. The sensitivity analysis results showed that the WMD ranged from 1.69 (95% CI: 1.15 to 2.23) to 2.06 (95% CI: 1.51 to 2.62) and there was no publication bias. CONCLUSIONS: Our meta-analysis showed that the severity of patients with COVID-19 significance related to D-dimer concentrations. Meanwhile, the severe COVID-19 patients tend to have a higher concentration of D-dimer when compared with non-severe patients. REVIEW CRITERIA: We used MASH word and searched the online database and followed the inclusion and exclusion standard. The detailed information can be found in the text. MESSAGE FOR THE CLINIC: Our meta-analysis showed that the severity of patients with COVID-19 significance related to D-dimer concentrations. This may be helpful for the clinic COVID-19 patients.

Association of Ang-2, vWF, and EVLWI with risk of mortality in sepsis patients with concomitant ARDS: A retrospective study.

BACKGROUND/PURPOSE: This study aimed to determine the potential effects of angiopoietin-2 (Ang-2), von Willebrand factor (vWF), and extravascular lung water index (EVLWI) on the risk of mortality in sepsis patients with concomitant acute respiratory distress syndrome (ARDS). METHODS: This retrospective study recruited 41 sepsis patients with concomitant ARDS from January 2015 to June 2018. Data of Ang-2 and vWF levels, EVLWI, and sequential organ failure assessment scores were collected at 0, 24, and 48 h after admission to the hospital. RESULTS: The length of intensive care unit stay (P = 0.041) and Acute Physiology and Chronic Health Evaluation-2 (APACHE II) score (P = 0.003) were associated with the risk of mortality. Furthermore, increased Ang-2 levels and EVLWI at 24 h and 48 h were associated with an increased risk of mortality. Moreover, the APACHE II score at hospital admission significantly predicted the risk of mortality (area under the curve [AUC], 0.834; 95% confidence interval [CI], 0.665-0.983). Finally, the models containing a combination of Ang-2 level and EVLWI at 24 h (AUC, 0.908; 95% CI, 0.774-0.996) and Ang-2 level and EVLWI at 48 h (AUC, 0.981; 95% CI, 0.817-1.000) had high diagnostic values for predicting risk of mortality. CONCLUSION: The study findings indicate that Ang-2 levels and EVLWI at 24 h and 48 h after admission are significantly associated with the risk of mortality.

SOCS3 control the activity of NF-κB induced by HSP70 via degradation of MyD88-adapter-like protein (Mal) in IPEC-J2 cells.

Hyperthermia in pigs induces suppressor of cytokine signaling (SOCS) 3 and SOCS4 expression in intestinal gut and causes disruption of inflammation cytokine production. These changes may affect the development of inflammatory bowel disease in heat-stressed pigs. However, the mechanisms are not well understood. Accordingly, in this study, we examined the roles of SOCS members in regulation of the nuclear factor (NF)-κB pathway and heat shock protein (HSP) 70-mediated cytokine induction in 293T human embryonic kidney cells and IPEC-J2 porcine small intestinal epithelial cells. Ectopic expression of HSP70 significantly modulated NF-κB activity (p ≤ .05). Moreover, co-expression of SOCS3 or SOCS4 with HSP70 reduced NF-κB activity, which was abolished by SOCS3 or SOCS4 knockdown with short hairpin RNA. Interestingly, MyD88-adaptor-like (Mal) protein was downregulated in cells expressing SOCS3 but not in cells expressing SOCS4. In addition, SOCS3 but not SOCS4 negatively regulated the activity of NF-κB induced by HSP70 overexpression via degradation of Mal. These findings may facilitate the development of novel SOCS3-based therapeutic strategies to control heat stress-related disorders in pigs.