[Research progress in emergency assessment of acute poisoning].

Acute poisoning represents a prevalent critical illness jeopardizing patient survival. Early, precise assessment of the condition and subsequent appropriate therapeutic intervention are pivotal in enhancing treatment success rates. Currently, a standardized approach to evaluating the severity of acute poisoning is lacking. Various scoring systems, including Poisoning Severity Score (PSS) , Modified Early Warning Score (MEWS) , and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) , offer valuable insights into acute poisoning assessment. Nevertheless, the distinct attributes of each scoring system constrain their broad clinical utility. Confronted with the intricate clinical demands of acute poisoning, the adoption of staged and dynamic assessment strategies is imperative to ascertain the condition of acute poisoning patients with greater accuracy.

Altered hippocampal functional connectivity in primary Sjögren syndrome: a resting-state fMRI study.

Structural and metabolic abnormalities in the hippocampus have been associated with the pathophysiological mechanism of central nervous system involvement in primary Sjögren syndrome (pSS). Nevertheless, how hippocampal function is altered in pSS remains unknown. The purpose of our study is to investigate the alterations in hippocampal functional connectivity (FC) in pSS by using resting-state functional magnetic resonance imaging (rs-fMRI). Thirty-eight patients with pSS and 38 age- and education level-matched healthy controls (HCs) underwent magnetic resonance imaging examination. Prior to each MRI examination, neuropsychological tests were performed. Left and right hippocampal FCs were analyzed by using seed-based whole-brain correlation and compared between pSS and HCs. Spearman correlation analysis was performed between the z-value of hippocampal FC in brain regions with significant difference between the two groups and neuropsychological tests/clinical data in pSS. Compared with the controls, the patients with pSS showed decreased hippocampal FC between the left hippocampus and the right inferior occipital gray (IOG)/inferior temporal gray (ITG), as well as between the right hippocampus and right IOG/middle occipital gray (MOG), left MOG, and left middle temporal gray. In addition, increased hippocampal FCs were detected between the left hippocampus and left putamen, as well as between the right hippocampus and right cerebellum posterior lobe. Moreover, the visual reproduction score positively correlated with the FC between right hippocampus and right IOG/MOG. The white matter hyperintensity score negatively correlated with the FC between left hippocampus and right IOG/ITG. In conclusion, patients with pSS suffered decreased hippocampal FC mainly sited in the occipital and temporal cortex with right hippocampal laterality. Altered hippocampal FC might be a potential biomarker in detecting brain function changes and guiding neuroprotection in pSS.

MiR-15b is a key regulator of proliferation and apoptosis of chondrocytes from patients with condylar hyperplasia by targeting IGF1, IGF1R and BCL2.

OBJECTIVE: This study aimed to explore potential microRNAs (miRNAs), which participate in the pathological process of condylar hyperplasia (CH) through targeting specific proliferation- and apoptosis- related genes of chondrocytes. METHODS: Insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R) and B-cell CLL/lymphoma 2 (BCL2) in CH cartilage were detected by real-time polymerase chain reaction (PCR), Western blot, immunohistochemistry and immunofluorescence. MiRanda and TargetScanS algorithms were used to predict certain miRNAs in CH chondrocytes concurrently modulating the above three genes. MiR-15b was screened and identified using real-time PCR. After transfection of miR-15b mimics or inhibitor into CH chondrocytes, expression of the above three genes was detected by real-time PCR and western blot, meanwhile, cell proliferation and apoptosis was examined by CCK8, cell cycle assays, flow cytometry and Hoechst staining. Dual luciferase activity was performed to identify the direct regulation of miR-15b on IGF1, IGF1R and BCL2. RESULTS: Expression of IGF1, IGF1R and BCL2 increased in CH cartilage. Seven microRNAs concurrently correlated with IGF1, IGF1R and BCL2. Among them, only miR-15b significantly changed in CH chondrocytes. Overexpression of miR-15b in CH chondrocytes suppressed the expression of IGF1, IGF1R and BCL2, while it increased when miR-15b was knockdown. Furthermore, miR-15b suppressed their expression by directly binding to its 3'-UTR in these cells. Besides, miR-15b hampered chondrocytes proliferation through targeting IGF1 and IGF1R and accelerated chondrocytes apoptosis through targeting BCL2. CONCLUSION: Suppressed miR-15b contributed to enhanced proliferation capacity and weakened apoptosis of chondrocytes through augmentation of IGF1, IGF1R and BCL2, thereby resulting in development of CH.

A polymorphic MYC response element in KBTBD11 influences colorectal cancer risk, especially in interaction with an MYC-regulated SNP rs6983267.

Background: MYC is a well-established cancer driver gene regulating the expression of numerous genes, indicating that polymorphisms in MYC response elements could affect tumorigenesis through altering MYC regulation. We performed integrative multistage study to evaluate the effects of variants in MYC response elements and colorectal cancer (CRC) risk. Patients and methods: We systematically integrated ChIP-Seq, DNase-Seq and transcription factor motif data to screen variants with potential ability to affect the MYC binding affinity. Then, we conducted a two-stage case-control study, totally consisting of 4830 CRC cases and 4759 controls in Chinese population to identify risk polymorphisms and interactions. The effects of risk variants were confirmed by functional assays in CRC LoVo, SW480 and HCT15 cells. Results: We identified a novel polymorphism rs11777210 in KBTBD11 significantly associated with CRC susceptibility (P = 2.43 × 10-12). Notably, we observed a significant interaction between rs11777210 and MYC nearby rs6983267 (P-multi = 0.003, P-add = 0.005), subjects carrying rs6983267 GG and rs11777210 CC genotypes showing higher susceptibility to CRC (2.83-fold) than those carrying rs6983267 TT and rs11777210 TT genotypes. We further demonstrated that rs6983267 T > G increased MYC expression, and MYC bound to and negatively regulated KBTBD11 expression when the rs11777210 C risk allele was present. KBTBD11 was downregulated in tumor tissues, and KBTBD11 knockdown promoted cell proliferation and inhibited cell apoptosis. Conclusion: The rs11777210 is a potential predictive biomarker of CRC susceptibility, and KBTBD11 functions as a putative tumor suppressor in tumorigenesis. Our study highlighted the high CRC risk of people carrying rs6983267 G and rs11777210 C alleles, and provided possible biological mechanism of the interaction.

Integrated network analysis to identify the key genes, transcription factors, and microRNAs involved in hepatocellular carcinoma.

HCC (hepatocellular carcinoma), which can be induced by cirrhosis and viral hepatitis infection, is the most frequent form of liver cancer. This study is performed to investigate the mechanisms of HCC. GSE57957 was obtained from Gene Expression Omnibus database, including 39 HCC samples and 39 adjacent non-tumorous samples. The DEGs (differentially expressed genes) were screened using the limma package in R, and then were conducted with enrichment analysis using "BioCloud" platform. Using STRING database, WebGestalt tool, as well as ITFP and TRANSFAC databases, PPI (protein-protein interaction) pairs, miRNA (microRNA)-target pairs, and TF (transcription factor)-target pairs separately were predicted. Followed by integrated network was constructed by Cytoscape software and module analysis was performed using the MCODE plugin of Cytoscape software. There were 518 DEGs identified from the HCC samples, among which 17 up-regulated genes (including MCM2, MCM6, and CDC20) and 5 down-regulated genes could also function as TFs. In the integrated network for the down-regulated genes, FOS and ESR1 had higher degrees, and both of them were targeted by miR-221 and miR-222. Additionally, MCM2 had interaction with MCM6 in the up-regulated module with the highest score. MCM2, MCM6, CDC20, FOS, ESR1, miR-221 and miR-222 might affect the pathogenesis of HCC.

Iron overload induces apoptosis of murine preosteoblast cells via ROS and inhibition of AKT pathway.

OBJECTIVE: This study investigates the inhibitory effect of iron overload on MC3T3-E1 cells and its molecular mechanism. METHODS: MC3T3-E1 cells were grown under different concentrations of FAC (ferric ammonium citrate), and the WST-8 assay was used to investigate the proliferation of cells following FAC with or without deferasirox. DCFH-DA fluorescence probe was applied to detect the cellular reactive oxygen species (ROS) level. The apoptotic cells were analyzed with Annexin V-FITC/PI and the Hoechst 33258 nuclear staining assay. The JC-1 staining assay was applied to observe the change in the mitochondrial transmembrane potential. The expression levels of caspase-3, PARP, Bcl-2 family proteins, and AKT kinase were detected with the Western blot assay. RESULTS: Iron overload had a cytotoxic effect on MC3T3-E1 cells in a dosage-dependent way and resulted in increasing level of intracellular ROS. Iron overload induced apoptosis in MC3T3-E1 cells via a caspase-dependent mechanism that is accompanied by mitochondria dysfunction and decreased expression of anti-apoptotic proteins. The expression levels of cleaved-caspase-3 and cleaved-PARP were upregulated, while the expression levels of caspase-9, caspase-7, caspase-3, and PARP were downregulated. Phosphorylation of AKT kinase decreased. CONCLUSION: Iron overload can generate ROS in cells, inhibit AKT kinase and its downstream proteins activity, and subsequently initiate apoptotic events.

[The altered topology of brain structural network in patients with acute stress response after traffic accident].

Objective: To explore the changes of brain activities in traffic accident survivors with acute stress response (ASR) within a week by using complex networks analysis method based on graph-theory, and to find out the alteration of topological properties in structural brain network. Method: From January, 2013 to February, 2016, twenty traffic accidents survivors with acute stress disorders (Acute Stress Disorder Interview, ASDI>3)and twenty healthy controls underwent the 3T diffusion tensor imaging (DTI) magnetic resonance imaging scan in Nanjing General Hospital.The graph-theory analysis method was used to compare the structural brain network properties and nodal features between ASR survivors and controls.Statistical analyses were also performed by including anxiety and depression as covariates to evaluate their effect.In additional, Pearson correlation was performed between abnormal parametric values and clinical indices. Results: (1) The brain structural networks had small-world properties in both groups; (2) while compared with healthy controls, patients with ASR showed increased weighted connectivity strength (Si, 1.36±0.47 vs 0.92±0.38, P=0.008) and nodal betweenness centrality (BCi, 20±15 vs 7±6, P=0.002) in left triangular part of inferior frontal (IFG triang_L), increased Si in orbital part of inferior frontal gyrus (1.10±0.31 vs 0.77±0.30, P=0.004) and obviously decreased Si in left caudate (0.75±0.24 vs 1.04±0.35, P=0.004); (3) furthermore, the inclusion of anxiety and depression as covariates abolished nodal parameters differences in IFG triang_L, left caudate, thalamus and inferior temporal gyrus. Conclusions: The brain structure network in ASR patients has small world properties.But nodal parameters change obviously in some nodes compared with healthy controls and mainly locate in prefrontal lobe and striatum. High levels of anxiety and depression in ASR patients may partly account for these alterations.

Selective Sensitization of Zinc Finger Protein Oxidation by Reactive Oxygen Species through Arsenic Binding.

Cysteine oxidation induced by reactive oxygen species (ROS) on redox-sensitive targets such as zinc finger proteins plays a critical role in redox signaling and subsequent biological outcomes. We found that arsenic exposure led to oxidation of certain zinc finger proteins based on arsenic interaction with zinc finger motifs. Analysis of zinc finger proteins isolated from arsenic-exposed cells and zinc finger peptides by mass spectrometry demonstrated preferential oxidation of C3H1 and C4 zinc finger configurations. C2H2 zinc finger proteins that do not bind arsenic were not oxidized by arsenic-generated ROS in the cellular environment. The findings suggest that selectivity in arsenic binding to zinc fingers with three or more cysteines defines the target proteins for oxidation by ROS. This represents a novel mechanism of selective protein oxidation and demonstrates how an environmental factor may sensitize certain target proteins for oxidation, thus altering the oxidation profile and redox regulation.

Prevalence and Associated Factors of Cancer-Related Fatigue Among Cancer Patients in Eastern China.

BACKGROUND: Cancer-related fatigue (CRF) is a subjective and distressing symptom, and its associated factors in developing countries remain ambiguous. The goal of this study was to determine the prevalence of and factors associated with CRF among cancer patients in China. METHODS: This study was designed as a cross-sectional study to determine the prevalence of and factors associated with CRF among cancer patients in eastern China, regardless of their diagnoses. Data were collected by using a questionnaire survey (including demographic information and brief fatigue inventory) after informed written consent was obtained. A chi-square test was used to analyze the correlations between single categorical factors and CRF, and multiple logistic regression analysis was used to evaluate the associations of potential risk factors with the presence of CRF. RESULTS: Out of a total population of 1,938 cancer patients, 1,749 had completed the study questionnaire; 52.07% (n = 904) reported clinically significant fatigue (score ≥4 on Brief Fatigue Inventory). Four hundred twenty-seven (48.47%) patients younger than age 58 years (the median age) and 475 (55.69%) patients age 58 years or older reported clinically significant fatigue. In multivariate analysis, higher sleep quality (p < .01) was negatively associated with CRF, whereas never engaging in physical exercise (p < .01) and higher clinical stage of cancer (p < .01) were positively associated factors that could increase the odds of CRF. CONCLUSION: The results of this study suggest that effective management of the two changeable contributing factors of CRF may reduce CRF and thus could be used as references for CRF management. IMPLICATIONS FOR PRACTICE: The two modifiable factors of cancer-related fatigue (CRF)-sleep disturbance and physical exercise-should be specifically assessed and managed to mitigate CRF.

MicroRNA221-3p modulates Ets-1 expression in synovial fibroblasts from patients with osteoarthritis of temporomandibular joint.

OBJECTIVE: This study aimed to screen differential expression of microRNAs (miRNAs), and investigate function of the specifically selected miRNA in synovial fibroblasts from patients suffering osteoarthritis of temporomandibular joint (TMJOA). METHODS: MiRNA microarray was used to select differentially expressed miRNAs between TMJOA and normal synovial fibroblasts. The expression of screened miRNA221-3p was quantified using real-time PCR, and its specific target gene was predicted by bioinformatics. After transfection of miRNA221-3p mimics or inhibitor into synovial fibroblasts, the expression of v-Ets avian erythroblastosis virus E26 oncogene homolog 1 (Ets-1) was detected by immunohistochemistry, real-time PCR and Western blot, respectively. Dual luciferase activity was performed to identify the direct regulation of miRNA221-3p on Ets-1. Interlukin-1ß (IL-1ß) mimics an inflammatory situation. RESULTS: In TMJOA synovial fibroblasts, eight miRNAs were up-regulated and six miRNAs were down-regulated. MiRNA221-3p was the most down-expressed. A sequence in the 3'-untranslated (3'-UTR) of Ets-1 complementary to the seed sequence of miRNA221-3p. Elevated expression of Ets-1 associated with attenuation of miRNA221-3p. Over-expression of miRNA221-3p suppressed the activity of a reporter construct containing the 3'-UTR of Ets-1 transcript and inhibited the expression of Ets-1 as well as its downstream molecules, matrix metalloproteinase 1 (MMP1) and MMP9 in TMJOA synovial fibroblasts. IL-1ß suppressed the expression of miRNA221-3p in both a dose-dependent and time-dependent manner. CONCLUSION: The reduction of miRNA221-3p in synovial fibroblasts, attributed from abundance of IL-1ß in inflamed circumstance, induces Ets-1 up-regulation and then, initiates MMP1 and MMP9 secretion, thereby leading to continuously pathological development in TMJOA.

Maximizing the security of chaotic optical communications.

The practical application of chaotic optical communications has been limited by two aspects: the difficulty in concealing the time delay - a critical security parameter in feedback chaotic systems, and the difficulty of significantly enlarging the key space without complicating the implementation. Here we propose an architecture to break the above limits. By introducing a frequency-dependent group delay module with frequency tuning resolution of 1 MHz into the chaotic feedback loop, we demonstrate excellent time delay concealment effect, and an additional huge key space of 1048 can be achieved at the same time. The effectiveness is proved by both numerical simulation and experiment. Besides, the proposed scheme is compatible with the existing commercial optical communication systems, thus pave the way for high-speed secure optical communications.

[Study of functional connectivity density mapping in patients with acute stress response by using resting-state functional MRI after traffic accident].

Objective: To explore the changes of brain activity in traffic accident survivors with acute stress response within a week by using functional connectivity density (FCD) method. Method: A total of 20 traffic accidents survivors with acute stress disorders (acute stress disorder interview >3) and twenty healthy controls from Nanjing Jinling Hospital underwent the 3.0 T resting-state functional magnetic resonance imaging scan from January 2013 to February 2016. Functional connectivity density mapping was used to compare the brain functional connective networks between acute stress response survivors and controls. In additional, Pearson correlation was performed between abnormal short, long-range FCD values and clinical indices. Results: (1) Compared with controls, patients with acute stress response showed decreased short-range FCD in left ventromedial prefrontal cortex (-0.815±0.264 vs-0.468±0.615, t=-2.198, P<0.05), left hippocampal and parahippocampal gyri (-1.212±0.135 vs-0.887±0.234), t=-5.070, all P<0.05), and increased short-range FCD in right precentral gyrus(0.428±0.256 vs 0.016±0.298, t=4.456, P<0.05), left inferior parietal and superior parietal lobes (0.623±0.290 vs 0.143±0.300, t=4.878, allP<0.05); (2)compared with normal controls, ASR patients showed increased long-range FCD in left precuneus (0.502±0.400 vs-0.042±0.253, t=4.879, P<0.05); (3)the HAMA score of patients positively correlated with short-range FCD value of the left vmPFC (r=0.50, P<0.05). Conclusion: The long-and short-range functional connectivity in frontal-limbic system is widely changed in survivors with acute stress response, especially the short-range FCD change more significantly, and partly correlated with the severity of their stress symptoms.

Thalassemia major is a major risk factor for pediatric melioidosis in Kota Kinabalu, Sabah, Malaysia.

BACKGROUND: Melioidosis is an important cause of community-acquired infection in Southeast Asia and northern Australia. Studies from endemic countries have demonstrated differences in the epidemiology and clinical features among children diagnosed with melioidosis. This suggests that local data are needed to determine the risk factors and outcome in specific areas. METHODS: This was a retrospective study of all children admitted to Likas Women's and Children Hospital, Kota Kinabalu, Sabah, Malaysia, with a blood or clinical sample positive for Burkholderia pseudomallei from 2001 to 2012. RESULTS: Of 28 children with confirmed melioidosis, 27 records were reviewed including 11 (41%) children with thalassemia major. Twenty of the children had bacteremia, and 16 (59%) had a fatal outcome. Six children had chronic disease, and none died. Empiric use of antibiotics not specific for B. pseudomallei was associated with increased risk of death (P < .001). The annual incidence of melioidosis in children with thalassemia major from 2001 to 2010 was 140 per 100 000/year vs 0.33 per 100 000/year for other children (P < .001). After institution of iron chelation therapy in 2010, no child with thalassemia major was diagnosed with melioidosis in 2011 or 2012. CONCLUSIONS: Pediatric melioidosis in Sabah is associated with a high proportion of bacteremia and death. Thalassemia major was a major risk factor for melioidosis among children from 2001 to 2010, but infections decreased markedly from 2011 to 2012 after universal availability of iron chelation therapy. Inappropriate empiric therapy was associated with an increased risk of death.

ALDH1 is an independent prognostic factor for patients with stages II-III rectal cancer after receiving radiochemotherapy.

BACKGROUND: About one in five patients with locally advanced rectal cancer (RC) suffers recurrence or distant metastasis after neoadjuvant therapy. We investigated how cancer stem cell markers change after neoadjuvant therapy and how these markers relate to recurrence. METHODS: Pretreatment biopsies and postoperative specimens were taken from 64 patients with locally advanced rectal adenocarcinoma who received preoperative radiochemotherapy (RCT) between sampling. Samples were tested immunohistochemically for CD44, LGR5, ALDH1 and CD166; scores were dichotomised as high or low. The median follow-up period was 36 months. RESULTS: High expression of CD44, LGR5, ALDH and CD166 was found in 38%, 5%, 48% and 10%, respectively, before RCT and 86%, 33%, 71% and 52%, respectively, after RCT. CD44 (P=0.001), LGR5 (P=0.049) and CD166 (P=0.003) were significantly upregulated after RCT. Whereas no recurrence was seen during the follow-up in the low ALDH group, 40% of the high ALDH group suffered recurrence. In multivariate COX analysis, postoperative ALDH1 independently predicted poor prognosis in patients with RC who received RCT (P=0.0095). CONCLUSION: Preoperative RCT upregulates expression of stem cell markers in patients with RC. High post-treatment ALDH1 expression predicts poor prognosis for these patients after neoadjuvant therapy.

A comparative study of Sr-incorporated mesoporous bioactive glass scaffolds for regeneration of osteopenic bone defects.

UNLABELLED: Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis. While much investigation is focused on preventing disease progression, here we fabricate strontium-containing scaffolds and show that they enhance bone defect healing in the femurs of rats induced by ovariectomy. INTRODUCTION: Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis due to its ability to prevent bone loss in osteoporotic patients. Although much emphasis has been placed on using pharmacological agents for the prevention of disease, much less attention has been placed on the construction of biomaterials following osteoporotic-related fracture. The aim of the present study was to incorporate bioactive strontium (Sr) trace element into mesoporous bioactive glass (MBG) scaffolds and to investigate their in vivo efficacy for bone defect healing in the femurs of rats induced by ovariectomy. METHODS: In total, 30 animals were divided into five groups as follows: (1) empty defect (control), (2) empty defects with estrogen replacement therapy, (3) defects filled with MBG scaffolds alone, (4) defects filled with MBG + estrogen replacement therapy, and (5) defects filled with strontium-incorporated mesopore-bioglass (Sr-MBG) scaffolds. RESULTS: The two groups demonstrating the highest levels of new bone formation were the defects treated with MBG + estrogen replacement therapy and the defects receiving Sr-MBG scaffolds as assessed by µ-CT and histological analysis. Furthermore, Sr scaffolds had a reduced number of tartrate-resistant acid phosphatase-positive cells when compared to other modalities. CONCLUSION: The results from the present study demonstrate that the local release of Sr from bone scaffolds may improve fracture repair. Future large animal models are necessary to investigate the future relationship of Sr incorporation into biomaterials.

Activation of glucagon-like peptide-1 receptor inhibits tumourigenicity and metastasis of human pancreatic cancer cells via PI3K/Akt pathway.

AIMS: It has been reported that glucagon-like peptide-1 (GLP-1) agents are associated with an increased risk of pancreatic cancer in patients with type 2 diabetes. Reports have indicated that GLP-1 promotes pancreatic metaplasia and premalignant lesions. The aims of this study were to determine the effects of GLP-1-based therapy on pancreatic cancer cells. METHODS: Immunohistochemistry was used to investigate GLP-1 receptor (GLP-1R) expression in 30 human pancreatic cancer tissues. We also analysed associated clinicopathological data and each patient's prognosis. Two human pancreatic cancer cell lines were used to evaluate the in vitro effects of the GLP-1R agonist liraglutide on cell growth, migration and invasion. Mouse xenograft models of human pancreatic cancer were established to evaluate the effects of liraglutide in vivo. RESULTS: Human pancreatic cancer tissues showed lower levels or a lack of GLP-1R expression when compared with levels in the tumour-adjacent pancreatic tissues. Negative GLP-1R expression occurred more frequently in advanced tumours with larger diameters and lymphatic metastasis, and was associated with a poor prognosis. GLP-1R activation with liraglutide inhibited tumourigenicity and metastasis of human pancreatic cancer cells in vitro and in vivo. Akt activation was dose-dependently inhibited by liraglutide, and the PI3K inhibitors, LY294002 and wortmannin, displayed similar suppressive effects to liraglutide in human pancreatic cancer cells. CONCLUSIONS: GLP-1R activation has an antitumour effect on human pancreatic cancers via inhibition of the PI3K/Akt pathway. This finding suggests that GLP-1-based therapies may be beneficial, rather than harmful, in treating type 2 diabetic patients with pancreatic cancer.

Electrodeposition from supercritical fluids.

Recent studies have shown that it is possible to electrodeposit a range of materials, such as Cu, Ag and Ge, from various supercritical fluids, including hydrofluorocarbons and mixtures of CO2 with suitable co-solvents. In this perspective we discuss the relatively new field of electrodeposition from supercritical fluids. The perspective focuses on some of the underlying physical chemistry and covers both practical and scientific aspects of electrodeposition from supercritical fluids. We also discuss possible applications for supercritical fluid electrodeposition and suggest some key developments that are required to take the field to the next stage.

[Nutritional support treatment for short bowel syndrome related intestinal failure].

Intestinal failure is a syndrome characterized by a diminished intestinal function that is inadequate to maintain normal digestion and absorption, leading to systemic metabolic disorder and requiring long-term nutritional supplementation to sustain health and growth. Short bowel syndrome (SBS) is one of the primary causes of intestinal failure. Given the significant differences among SBS patients, nutritional treatment strategies should emphasize individualization. This review focuses on SBS, combining its anatomical and pathological characteristics, to introduce nutritional support treatment plans and experiences for patients with intestinal failure.

Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood-brain barrier damage in early ischemic stroke stage.

Blood-brain barrier (BBB) disruption occurs early enough to be within the thrombolytic time window, and this early ischemic BBB damage is closely associated with hemorrhagic transformation and thus emerging as a promising target for reducing the hemorrhagic complications of thrombolytic stroke therapy. However, the mechanisms underlying early ischemic BBB damage remain poorly understood. Here, we investigated the early molecular events of ischemic BBB damage using in vitro oxygen-glucose deprivation (OGD) and in vivo rat middle cerebral artery occlusion (MCAO) models. Exposure of bEND3 monolayer to OGD for 2 h significantly increased its permeability to FITC-labeled dextran and promoted the secretion of metalloproteinase-2 and -9 (MMP-2/9) and cytosolic translocation of caveolin-1 (Cav-1). This same OGD treatment also led to rapid degradation of tight junction protein occludin and dissociation of claudin-5 from the cytoskeleton, which contributed to OGD-induced endothelial barrier disruption. Using selective MMP-2/9 inhibitor SB-3CT (2-[[(4-phenoxyphenyl)sulfonyl]methyl]-thiirane) or their neutralizing antibodies or Cav-1 siRNA, we found that MMP-2 was the major enzyme mediating OGD-induced occludin degradation, while Cav-1 was responsible for claudin-5 redistribution. The interaction between Cav-1 and claudin-5 was further confirmed by coimmunoprecipitation. Consistent with these in vitro findings, we observed fluorescence tracer extravasation, increased gelatinolytic activity, and elevated interstitial MMP-2 levels in ischemic subcortical tissue after 2 h MCAO. Moreover, occludin protein loss and claudin-5 redistribution were detected in ischemic cerebromicrovessels. These data indicate that cerebral ischemia initiates two rapid parallel processes, MMP-2-mediated occludin degradation and Cav-1-mediated claudin-5 redistribution, to cause BBB disruption at early stroke stages relevant to acute thrombolysis.