Single-cell sequencing reveals the impact of endothelial cell PIEZO1 expression on thoracic aortic aneurysm.

INTRODUCTION: Thoracic aortic aneurysm (TAA) is a severe vascular disease that threatens human life, characterized by focal dilatation of the entire aortic wall, with a diameter 1.5 times larger than normal. PIEZO1, a mechanosensitive cationic channel, monitors mechanical stimulations in the environment, transduces mechanical signals into electrical signals, and converts them into biological signals to activate intracellular signaling pathways. However, the role of PIEZO1 in TAA is still unclear. METHODS: We analyzed a single-cell database to investigate the expression level of PIEZO1 in TAA. We constructed a conditional knockout mouse model of Piezo1 and used the PIEZO1 agonist Yoda1 to intervene in the TAA model mice established by co-administration of BAPN and ANG-II. Finally, we explored the effect of Yoda1 on TAA in vitro. RESULTS AND DISCUSSION: We observed decreased PIEZO1 expression in TAA at both RNA and protein levels. Single-cell sequencing identified a specific reduction in Piezo1 expression in endothelial cells. Administration of PIEZO1 agonist Yoda1 prevented the formation of TAA. In PIEZO1 endothelial cell conditional knockout mice, Yoda1 inhibited TAA formation by interfering with PIEZO1. In vivo and in vitro experiments demonstrated that the effect of Yoda1 on endothelial cells involved macrophage infiltration, extracellular matrix degradation, and neovascularization. This study highlights the role of PIEZO1 in TAA and its potential as a therapeutic target, providing opportunities for clinical translation.

Potential Risk Factors of Disorders of Gut-Brain Interaction in Undergraduates and Postgraduates: Partially Mediated by Life Stress and Lifestyle.

INTRODUCTION: This study aimed to investigate the prevalence of disorders of gut-brain interaction (DGBI) and life stress in college students, and explore risk factors of DGBI in college students and the role of life stress. METHODS: A total of 2,578 college students filled up validated questionnaires assessing GI symptoms, lifestyle, and life stress. Participants were diagnosed as DGBI based on the Rome III criteria. Multivariate ordinal logistic regression analysis and mediation effect model were employed to explore potential risk factors of DGBI and the mediating role of life stress and lifestyle in DGBI. RESULTS: A total of 437 of 2,578 (17.0%) college students were diagnosed with DGBI. College students with DGBI had higher levels of life stress, including eight specific categories. Females (1.709 [1.437, 2.033]), staying up late (1.519 [1.300, 1.776]), and life stress (1.008 [1.006, 1.010]) were risk factors for DGBI, while postgraduates (0.751 [0.578, 0.976]) and regular diet (0.751 [0.685, 0.947]) were protective factors. Males and poor family economic were associated with a higher risk of DGBI after controlling stress, while an association between grade and DGBI was mediated by stress, regular diet, and sleep habits. CONCLUSION: DGBI was common among college students. Life stress and lifestyle were associated with DGBI and mediated partial association between grade and DGBI in college students. More attention should be paid to undergraduates.

The Short-Term Efficacy of Bifidobacterium Quadruple Viable Tablet in Patients With Diarrhea-Predominant Irritable Bowel Syndrome: Potentially Mediated by Metabolism Rather Than Diversity Regulation.

INTRODUCTION: The therapeutic effect of probiotics for irritable bowel syndrome (IBS) was controversial. This study aims to evaluate the short-term efficacy of Bifidobacterium quadruple viable tablet in patients with diarrhea-predominant IBS and explore factors associated with response to probiotics. METHODS: A randomized, double-blind, placebo-controlled, multicenter trial was performed in 15 hospitals. A total of 290 patients who fulfilled the eligibility criteria were assigned to the probiotics or placebo group randomly with a ratio of 1:1 for a 4-week treatment and a 2-week follow-up. The primary outcome was the response rate. It was regarded as the proportion of patients with composite responses of improvement in both abdominal pain and diarrhea simultaneously. RESULTS: After 4-week continuous administration, the response rates of the probiotics and the placebo were 67.59% and 36.55%, respectively ( P < 0.001). In the probiotics, those with higher abdominal pain scores (2.674 [1.139-6.279]) were more likely to respond, but responders in placebo had lower Hamilton Depression Scale score (0.162 [0.060-0.439]), lower Hamilton Anxiety Scale score (0.335 [0.148-0.755]), and higher degree of bloating (2.718 [1.217-6.074]). Although the diversity of the microbiota was not significantly changed by probiotics, the abundance of bacteria producing short-chain fatty acids (SCFAs), including Butyricimonas ( P = 0.048), Pseudobutyrivibrio ( P = 0.005), Barnesiella ( P = 0.020), and Sutterella ( P = 0.020), and the concentration of SCFAs including butyric acid ( P = 0.010), valeric acid ( P = 0.019), and caproic acid ( P = 0.046) in feces increased. DISCUSSION: A Bifidobacterium quadruple viable tablet had a significant short-term efficacy for the treatment of diarrhea-predominant IBS and was more effective in patients with higher abdominal pain scores. This kind of probiotics could improve the abundance of several bacteria producing SCFAs and the concentration of fecal SCFAs compared with placebos.

[Clinical application of plasma exchange combined with continuous veno-venous hemofiltration dialysis in children with refractory Kawasaki disease shock syndrome]. / 血浆置换联合连续性静脉-é™è„‰è¡€æ¶²æ»¤è¿‡é€æžæ²»ç–—åœ¨å„¿ç«¥å·å´Žç— ä¼‘å ‹ç»¼åˆå¾ä¸­çš„ä¸´åºŠåº”ç”¨.

OBJECTIVES: To study the role of plasma exchange combined with continuous blood purification in the treatment of refractory Kawasaki disease shock syndrome (KDSS). METHODS: A total of 35 children with KDSS who were hospitalized in the Department of Pediatric Intensive Care Unit, Hunan Children's Hospital, from January 2019 to August 2022 were included as subjects. According to whether plasma exchange combined with continuous veno-venous hemofiltration dialysis was performed, they were divided into a purification group with 12 patients and a conventional group with 23 patients. The two groups were compared in terms of clinical data, laboratory markers, and prognosis. RESULTS: Compared with the conventional group, the purification group had significantly shorter time to recovery from shock and length of hospital stay in the pediatric intensive care unit, as well as a significantly lower number of organs involved during the course of the disease (P<0.05). After treatment, the purification group had significant reductions in the levels of interleukin-6, tumor necrosis factor-α, heparin-binding protein, and brain natriuretic peptide (P<0.05), while the conventional group had significant increases in these indices after treatment (P<0.05). After treatment, the children in the purification group tended to have reductions in stroke volume variation, thoracic fluid content, and systemic vascular resistance and an increase in cardiac output over the time of treatment. CONCLUSIONS: Plasma exchange combined with continuous veno-venous hemofiltration dialysis for the treatment of KDSS can alleviate inflammation, maintain fluid balance inside and outside blood vessels, and shorten the course of disease, the duration of shock and the length of hospital stay in the pediatric intensive care unit.

[Application of transport ventilator in the inter-hospital transport of critically ill children]. / è½¬è¿å‘¼å¸æœºåœ¨å±é‡æ‚£å„¿é™¢é™ è½¬è¿ä¸­çš„åº”ç”¨ç ”ç©¶.

OBJECTIVES: To study the application value of transport ventilator in the inter-hospital transport of critically ill children. METHODS: The critically ill children in Hunan Children's Hospital who were transported with or without a transport ventilator were included as the observation group (from January 2019 to January 2020; n=122) and the control group (from January 2018 to January 2019; n=120), respectively. The two groups were compared in terms of general data, the changes in heart rate, respiratory rate, and blood oxygen saturation during transport, the incidence rates of adverse events, and outcomes. RESULTS: There were no significant differences between the two groups in sex, age, oxygenation index, pediatric critical illness score, course of disease, primary disease, heart rate, respiratory rate, and transcutaneous oxygen saturation before transport (P>0.05). During transport, there were no significant differences between the two groups in the changes in heart rate, respiratory rate, and transcutaneous oxygen saturation (P>0.05). The incidence rates of tracheal catheter detachment, indwelling needle detachment, and sudden cardiac arrest in the observation group were lower than those in the control group during transport, but the difference was not statistically significant (P>0.05). Compared with the control group, the observation group had significantly shorter duration of mechanical ventilation and length of stay in the pediatric intensive care unit and significantly higher transport success rate and cure/improvement rate (P<0.05). CONCLUSIONS: The application of transport ventilator in the inter-hospital transport can improve the success rate of inter-hospital transport and the prognosis in critically ill children, and therefore, it holds promise for clinical application in the inter-hospital transport of critically ill children.

Efficacy of plasma exchange in children with severe hemophagocytic syndrome: a prospective randomized controlled trial. / è¡€æµ†ç½®æ¢åœ¨å„¿ç«¥é‡ç—‡å™¬è¡€ç»†èƒžç»¼åˆå¾ä¸­åº”ç”¨çš„ç–—æ•ˆåˆ†æžï¼šå‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the efficacy and application value of plasma exchange as an adjuvant therapy in children with hemophagocytic syndrome (HPS). METHODS: A prospective randomized controlled trial was designed. Forty children with severe HPS were enrolled, who were treated in the pediatric intensive care unit (PICU) of Hunan Children's Hospital from October 2018 to October 2020. The children were randomly divided into a plasma exchange group and a conventional treatment group using a random number table, with 20 children in each group. The children in the conventional treatment group received etiological treatment and conventional symptomatic supportive treatment, and those in the plasma exchange group received plasma exchange in addition to the treatment in the conventional treatment group. The two groups were compared in terms of general information, clinical symptoms and signs before and after treatment, main laboratory markers, treatment outcome, and prognosis. RESULTS: Before treatment, there were no significant differences between the two groups in gender, age, course of the disease before admission, etiological composition, pediatric critical illness score, involvement of organ or system functions, and laboratory markers (P>0.05). After 7 days of treatment, both groups had remission and improvement in clinical symptoms and signs. After treatment, the plasma exchange group had significantly lower levels of C-reactive protein, procalcitonin, and serum protein levels than the conventional treatment group (P<0.05). The plasma exchange group also had significantly lower levels of alanine aminotransferase and total bilirubin than the conventional treatment group (P<0.05). The length of stay in the PICU in the plasma exchange group was significantly shorter than that in the conventional treatment group (P<0.05). The plasma exchange group had a significantly higher treatment response rate than the conventional treatment group (P<0.05). There were no significant differences between the two groups in the total length of hospital stay and 3-month mortality rate (P>0.05). CONCLUSIONS: Plasma exchange as an adjuvant therapy is effective for children with severe HPS. It can improve clinical symptoms and signs and some laboratory markers and shorten the length of stay in the PICU, and therefore, it may become an optional adjuvant therapy for children with severe HPS.

[Impact of continuous blood purification on T cell subsets in children with severe sepsis].

OBJECTIVE: To investigate the impact of continuous blood purification (CBP) on T-cell subsets and prognosis in children with severe sepsis. METHODS: A total of 42 children with severe sepsis were randomly divided into a control group (n=22) and a CBP group (n=20). The patients in the control group received conventional treatment, while those in the CBP group underwent continuous veno-venous hemofiltration daily 12-24 hours for 3 days besides conventional treatment. Changes in clinical variables and in peripheral blood regulatory T cell subsets were assessed 3 and 7 days after treatment. RESULTS: The pediatric intensive care unit length of stay and duration of mechanical ventilation were significantly shortened and the 28-day mortality rate was significantly lower in the CPB treatment group as compared with the control group (P<0.05). In the CBP treatment group, the percentage of CD3(+), CD4(+), CD8(+) T cell populations and PCIS scores were significantly higher at 3 and 7 days after treatment than before treatment (P<0.05). At 7 days after treatment, the percentage of CD3(+), CD4(+), CD8(+) T cell populations, CD4(+)/CD8(+) ratio and PCIS scores were significantly higher in the CBP group than in the control group (P<0.05). CONCLUSIONS: The CBP treatment may counteract the suppression of immune function and thus improve prognosis in children with severe sepsis.

Effect of different thermal processing methods on sensory, nutritional, physicochemical and structural properties of Penaeus vannamei.

The aim of this study was to investigate the effect of different thermal processing methods on the nutritional and physicochemical qualities of Penaeus vannamei. Three different thermal processing methods, namely, drying (DS, 120 °C/40 min), steaming (SS, 100 °C/2 min), and microwaving (MS, 600 W/2 min) were used to treat the shrimps. Low-field nuclear magnetic resonance data indicated that fixed water was the main component of Penaeus vannamei. The ratio of fatty acids in MS and DS samples was more in line with the FAO/WHO recommended health requirements; The myofibrillar protein carbonyl group increased, whereas sulfhydryl content decreased after thermal processing, indicating that the proteins were oxidized by thermal processing. The magnitude of oxidation is: MS > SS > DS. Different thermal processing methods can exert great influence on color texture and nutrition to Penaeus vannamei, which can provide a theoretical knowledge for consumers to choose the appropriate processing method.

Psychological factors may affect the quality of life in irritable bowel syndrome patients more than the gut itself? A multicenter cross-sectional study.

Background and Aim: Both intestinal symptoms and comorbidities exist in irritable bowel syndrome (IBS) patients and influence their quality of life (QOL). More research is needed to determine how these variables impact the QOL of IBS patients. This study aimed to determine which specific factors had a higher influence on QOL and to further compare the effects of intestinal symptoms and comorbidities on QOL. Methods: IBS patients were recruited from six tertiary hospitals in different regions of China. QOL, gastrointestinal symptoms, and comorbidities were assessed by different scales. Correlation analysis, multiple linear regression, and mediation model were used for statistics. Results: Four hundred fifty-three IBS patients (39.7% women, mean age 45 years) were included and no significant differences in QOL were found across demographic characteristics. Abnormal defecation (r = -0.398), fatigue (r = -0.266), and weakness (r = -0.286) were found to show higher correlation with QOL. More than 40% of IBS patients were found to suffer from varying degrees of anxiety or depression, and anxiety (r = -0.564) and depression (r = -0.411) were significantly negatively correlated with QOL (P < 0.001). Psychological factors showed the strongest impact (ß' = -0.451) and play a strong mediating role in the impact of physiological symptoms on QOL. Anxiety was found to be the strongest factor (ß' = -0.421). Conclusion: Compared with other symptoms, psychological symptoms, particularly anxiety, are more common and have a more negative influence on QOL. The QOL of IBS patients is also significantly impacted by abnormal defecation, abdominal distension, and systemic extraintestinal somatic symptoms. In the treatment of IBS patients with unhealthy mental status, psychotherapy might be prioritized.

[Clinical risk factors for capillary leak syndrome in children with sepsis].

OBJECTIVE: To investigate the clinical features of capillary leak syndrome (CLS) in children with sepsis, and to analyze its risk factors. METHODS: Clinical data of 384 children with sepsis was studied retrospectively. They included 304 cases of general sepsis, 54 cases of severe sepsis and 26 cases of septic shock, and were divided into non-CLS (n=356) and CLS groups (n=28). Univariate analysis was performed for each of the following variables: sex, age, malnutrition, anemia, coagulation disorders, white blood cell count, C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, blood glucose, lactic acid, Pediatric Risk of Mortality (PRISM) III score, pediatric critical illness score (PICS), severe sepsis and number of failed organs≥3. The statistically significant variables (as independent variables) were subjected to multivariate logistic regression analysis. RESULTS: The incidence rate of CLS in children with septic shock, severe sepsis and general sepsis were 42.3%, 20.1% and 1.3%, respectively, with significant differences among them (P<0.01). There were significant differences in anemia, coagulation disorders, CRP, PCT>2 ng/mL, TNF, IL-1, IL-6, blood glucose, lactic acid, PRISM III score, PICS and number of failed organs≥3 between the non-CLS and CLS groups (P<0.05). Severe sepsis/shock and PRISM III score were the independent risk factors for CLS in children with sepsis. CONCLUSIONS: The severity of sepsis and PRISM III score are positively correlated with the incidence of CLS in children with sepsis. Early monitoring of such factors as infection markers and blood glucose in children with severe sepsis and high PRISM III score may contribute to early diagnosis and effective intervention, thus reducing the mortality from CLS in children with sepsis.

[Changes in T cell subsets in children with sepsis, and their clinical significance].

OBJECTIVE: To observe changes in T cell subsets in children with sepsis and their prognosis, and to investigate the clinical significance of these changes in the occurrence and development of sepsis. METHODS: Fifty children with severe sepsis and 150 children with general sepsis were enrolled as subjects, and 50 age-matched healthy children were included as controls. The percentages of CD3(+), CD4(+) and CD8(+) T cells in peripheral blood and CD4(+)/CD8(+) ratio were measured by flow cytometry. The pediatric critical illness score (PCIS) was calculated within 24 hours of admission. RESULTS: The children with severe sepsis showed significantly lower percentages of CD3(+), CD4(+) and CD8(+) T cells CD4(+)/CD8(+) ratio and PCIS than the controls and children with general sepsis (P<0.01). Among the 200 cases of sepsis, the percentages of CD3(+), CD4(+) and CD8(+) T cells, CD4(+)/CD8(+) ratio and PCIS were significantly lower in the cured group than in the deceased group. CONCLUSIONS: Children with sepsis have different degrees of cellular immunosuppression, and the degree of cellular immunosuppression is significantly correlated with the severity of the disease. Detection of T cell subsets in peripheral blood is of great significance for evaluating immune function and judging disease severity in children with sepsis.

Different dosages of vonoprazan for gastroesophageal reflux disease: study protocol for a pragmatic, crossover-cluster, randomized controlled trial with patient preference arms.

BACKGROUND: Vonoprazan results in more potent acid suppression for gastroesophageal reflux disease (GERD) than proton pump inhibitors. It has only been approved for treating erosive esophagitis in China, but 30-40% of GERD patients cannot achieve the goal of treatment with vonoprazan 20 mg daily. This study aims to investigate whether vonoprazan could relieve the symptoms of Chinese patients with non-erosive reflux disease (NERD) and whether increased dosage or different times of dosing could increase the response rate of GERD. METHODS: This study is a pragmatic, open-label, crossover-cluster, randomized controlled trial with patient preference arms. Two thousand eight hundred eighty patients with GERD from 48 hospitals in China will be enrolled. These hospitals will be divided into a compulsory randomization cluster (24 hospitals) and a patient preference cluster (24 hospitals). Patients in the compulsory randomization cluster will be randomized to three regimens according to the crossover-cluster randomization. Patients in the patient preference cluster may choose to receive any regimen if they have a preference; otherwise, patients will be randomly assigned. The three treatment regimens will last 4 weeks, including (1) vonoprazan 20 mg p.o. after breakfast, (2) vonoprazan 20 mg p.o. after dinner, and (3) vonoprazan 20 mg p.o. after breakfast and after dinner. Patients will attend a baseline visit, a 4-week e-diary, a fourth-week visit, and a sixth-month visit online. The primary outcome is the symptom relief rate of all patients after 4-week therapy. Secondary outcomes include the healing rate of EE patients, the severity of symptoms, compliance with the therapy at the fourth-week follow-up visit, recurrent symptoms, and the frequency of self-conscious doctor visits at the sixth-month follow-up visit. DISCUSSION: This trial will explore the effectiveness of different regimens of vonoprazan that will be implemented with GERD patients in China. The randomization with patient preferences considered and the crossover-cluster component may improve the robustness and extrapolation of study conclusions. TRIAL REGISTRATION: https://www.chictr.org.cn ChiCTR2300069857. Registered on 28 March 2023. PROTOCOL VERSION: February 18, 2023, Version 2.

[Relationship between blood lactate level and disease severity in critically ill children].

OBJECTIVE: To study the relationship between blood lactate level and disease severity in critically ill children. METHODS: The clinical data of 232 children who were critically ill between September and December, 2010 were retrospectively studied. According to blood lactate levels within 24 hrs of admission, the 232 patients were classified into three groups: normal (n=146), high lacticemia (n=72) and lactic acidosis (n=14). The circulation functions, pediatric critical illness scores and prognosis were compared among the three groups. RESULTS: The degree of sepsis among the three groups was different (χ2 = 13.592, P<0.01). The occurrence of septic shock in the lactic acidosis group (42.9%) was significant compared with that in the normal (7.5%) and the high lacticemia groups (11.1%). The pediatric critical illness scores were different among the three groups (χ2 = 12.854, P<0.05). The blood lactate level was significantly negatively correlated with the pediatric critical illness scores (r=-0.405, P=0.002). The prognosis among the three groups was also varied (χ2 = 25.599, P<0.01). The curative rate (7.1% vs 23.3%; P<0.05) and the improvement rate (28.6% vs 58.2%; P<0.05) in the lactic acidosis group were significantly lower than in the normal group, and the mortality (28.6%) was significantly higher than in the normal (5.5%) and the high lacticemia groups (6.9%). CONCLUSIONS: A higher blood lactic acid level is associated with a more severe illness state and a worse prognosis.

Association between multiple sleep dimensions and functional bowel disorders among Chinese college freshmen.

BACKGROUND: Although sleep disorder is thought as a risk factor for functional bowel disorders, its impact role in adolescents remains unknown and the contribution of different sleep dimensions may deserve further attention. This study aimed to evaluate the relationship between multiple sleep dimensions and functional bowel disorders among Chinese college freshmen. METHODS: A cross-sectional survey was conducted in college freshmen from Huazhong University of Science and Technology in Wuhan, China in September 2019 with random cluster sampling method. All participants completed questionnaires about living habits, sleep and digestive symptoms. Diagnosis of irritable bowel syndrome and functional constipation were based on the Rome IV criteria. Univariate and multivariate logistic regression models were applied to assess the association of sleep dimensions with irritable bowel syndrome or functional constipation. RESULTS: Based on the 3335 individuals who completed the questionnaire, the overall prevalence of irritable bowel syndrome and functional constipation in college freshmen were 2.5% and 1.7%, respectively. Multivariate analysis revealed that compared with individuals reporting good sleep quality, those reporting poor (OR = 7.269, 95%CI: 2.876-18.370) were associated with increased risk of irritable bowel syndrome. Similarly, those reporting fair (OR = 2.068, 95%CI: 1.010-4.236) and poor (OR = 5.664, 95%CI: 1.864-17.205) were associated with increased risk of functional constipation. There was no statistically significant association between other sleep dimensions (sleep duration, sleep timing, or sleep latency) and irritable bowel syndrome or functional constipation. CONCLUSION: Self-reported poor sleep quality was a stronger independent predictor of functional bowel disorders than other sleep dimensions among Chinese college freshmen. Future intervention studies should consider the role of sleep quality for the prevention of FBDs in adolescents.

Association Between Different Obesity Patterns and the Risk of Developing Type 2 Diabetes Mellitus Among Adults in Eastern China: A Cross-Sectional Study.

PURPOSE: Obesity has become a public health challenge worldwide and can lead to the development of diabetes. However, studies examining the associations between different obesity patterns and the development of type 2 diabetes mellitus (T2DM) in China are limited. Therefore, this study aimed to explore the associations between three obesity patterns and the risk of T2DM development in Eastern China. METHODS: A cross-sectional study was conducted at our health examination center, involving 5860 adults, from June to December 2019. Data, including sociodemographic information, lifestyle, and biochemical measurements, were collected, and obesity was classified into three patterns: overweight and general obesity, abdominal obesity, and compound obesity. Multivariate logistic regression was used to assess the associations between different obesity patterns and T2DM risk after adjustment for confounding factors. Subgroup analysis was used to further explore the associations between obesity patterns and T2DM risk. RESULTS: A total of 5860 subjects were enrolled in this study. A significant difference in the T2DM incidence was observed between men and women with normal weight or overweight and general obesity (p < 0.05); however, no significant differences were observed between men and women with abdominal obesity and compound obesity. After multivariable adjustment, multivariate logistic regression analysis showed that the odds ratios (ORs) [95% confidence interval (CI)] for T2DM in individuals with abdominal and compound obesity were 1.55 [1.08-2.24] and 1.85 [1.25-2.73], respectively, compared with the normal-weight group. Subgroup analysis showed that different obesity patterns were not independent risk factors for T2DM development among adults aged ≥ 60 years, whereas abdominal and compound obesity were highly associated with the risk of T2DM development among individuals who report current smoking or alcohol drinking. CONCLUSION: Abdominal obesity and compound obesity are risk factors for T2DM. More attention should be paid to obesity prevention among individuals younger than 60 years and improving control of cigarette and alcohol abuse.

Intravenous Dexmedetomidine Administration Prior Anesthesia Induction With Propofol at 4°C Attenuates Propofol Injection Pain: A Double-Blind, Randomized, Placebo-Controlled Trial.

Background: Propofol injection pain, despite various interventions, still occurs during the anesthesia induction and causes intense discomfort and anxiety in patients. This study aimed to explore the effect of intravenous dexmedetomidine on propofol injection pain prior to anesthesia induction with propofol at 4°C. Methods: A total of 251 patients (American Society of Anesthesiologists I-II) who underwent oral and maxillofacial surgery were randomly assigned to a combination group (n = 63), lidocaine group (n = 62), dexmedetomidine group (n = 63), and placebo-control group (n = 63); they received 0.5 ug/kg dexmedetomidine prior to anesthesia induction with propofol at 4°C, 40 mg lidocaine, 0.5 ug/kg dexmedetomidine prior to anesthesia induction, and normal saline, respectively. Incidence of pain, pain intensity, and reaction to the pain stimulus were evaluated by using verbal categorial scoring (VCS), a numerical rating scale (NRS), and the Surgical Pleth Index (SPI), respectively. In addition, hemodynamic parameters such as heart rate (HR) and mean arterial pressure (MAP) were also measured. The VCS and NRS were evaluated at 5 s after propofol injection. In addition, SPI, HR, and MAP were evaluated at three time points (before anesthesia induction and 5 and 30 s after propofol injection). Results: The incidence of pain in the combination group (51%) was significantly lower than that in the lidocaine group (71%), dexmedetomidine group (67%), or placebo-control group (94%) (p < 0.001). VCS and NRS scores in the combination group were also lower compared with the other three groups (p < 0.001), with no statistically significant differences between the lidocaine group and dexmedetomidine group (p > 0.05). The SPI of the combination group decreased significantly in comparison with the other three groups at 5 s after propofol injection (F = 96.23, p < 0.001) and 30 s after propofol injection (F = 4.46, p = 0.005). Further comparisons between HR and MAP revealed no significant differences across the groups (p > 0.05). Conclusion: Because of the sedative nature of dexmedetomidine and analgesic effect of low temperature, this study showed that intravenous dexmedetomidine prior to anesthesia induction with propofol at 4°C is highly effective in attenuating the incidence and severity of pain during injection compared with lidocaine (40 mg), dexmedetomidine 0.5 ug/kg) and placebo. This approach was not associated with any anesthesia complications. Clinical Trial Registration: ClinicalTrials.gov, identifier: ChiCTR-2000034663.

Heparin impairs skeletal muscle glucose uptake by inhibiting insulin binding to insulin receptor.

AIM: Heparin, a widely used antithrombotic drug has many other anticoagulant-independent physiological functions. Here, we elucidate a novel role of heparin in glucose homeostasis, suggesting an approach for developing heparin-targeted therapies for diabetes. METHODS: For serum heparin levels and correlation analysis, 122 volunteer's plasma, DIO (4 weeks HFD) and db/db mice serums were collected and used for spectrophotometric determination. OGTT, ITT, 2-NBDG uptake and muscle GLUT4 immunofluorescence were detected in chronic intraperitoneal injection of heparin or heparinase (16 days) and muscle-specific loss-of-function mice. In 293T cells, the binding of insulin to its receptor was detected by fluorescence resonance energy transfer (FRET), Myc-GLUT4-mCherry plasmid was used in GLUT4 translocation. In vitro, C2C12 cells as mouse myoblast cells were further verified the effects of heparin on glucose homeostasis through 2-NBDG uptake, Western blot and co-immunoprecipitation. RESULTS: Serum concentrations of heparin are positively associated with blood glucose levels in humans and are significantly increased in diet-induced and db/db obesity mouse models. Consistently, a chronic intraperitoneal injection of heparin results in hyperglycaemia, glucose intolerance and insulin resistance. These effects are independent of heparin's anticoagulant function and associated with decreases in glucose uptake and translocation of glucose transporter type 4 (GLUT4) in skeletal muscle. By using a muscle-specific loss-of-function mouse model, we further demonstrated that muscle GLUT4 is required for the detrimental effects of heparin on glucose homeostasis. CONCLUSIONS: Heparin reduced insulin binding to its receptor by interacting with insulin and inhibited insulin-mediated activation of the PI3K/Akt signalling pathway in skeletal muscle, which leads to impaired glucose uptake and hyperglycaemia.

Neurological complications and risk factors of cardiopulmonary failure of EV-A71-related hand, foot and mouth disease.

From 2010 to 2012, large outbreaks of EV-A71-related- hand foot and mouth disease (HFMD) occurred annually in China. Some cases had neurological complications and were closely associated with fatal cardiopulmonary collapse, but not all children with central nervous system (CNS) involvement demonstrated a poor prognosis. To identify which patients and which neurological complications are more likely to progress to cardiopulmonary failure, we retrospectively studied 1,125 paediatric inpatients diagnosed with EV-A71-related HFMD in Hunan province, including 1,017 cases with CNS involvement. These patients were divided into cardiopulmonary failure (976 people) group and group without cardiopulmonary failure (149 people). A logistic regression analysis was used to compare the clinical symptoms, laboratory test results, and neurological complications between these two groups. The most significant risk factors included young age, fever duration ≥3 days, coma, limb weakness, drowsiness and ANS involvement. Patients with brainstem encephalitis and more CNS-involved regions were more likely to progress to cardiopulmonary failure. These findings can help front-line clinicians rapidly and accurately determine patient prognosis, thus rationally distributing the limited medical resources and implementing interventions as early as possible.

[Clinical study of variation and significance of the high insulin levels in critically ill children].

OBJECTIVE: To analyze the variation of serum insulin levels in critically ill children and investigate the underlying mechanism and clinical significance to provide the basis for treatment. METHOD: Totally 332 critically ill children admitted in pediatric intensive care unit (PICU) of Hunan Children's Hospital from Nov., 2011 to April, 2012 were studied. The high insulin group (n = 332) was defined as insulin levels within 24 h > 11.1 mU/L and was divided into 2 groups: mildly elevated group (n = 194): 11.10 - 33.30 mU/L, increased three times group (n = 138): > 33.3 mU/L. Insulin, C-peptide and blood glucose were measured within 24 hours after admission, on day 3 and 7. Other results of inflammatory markers, lactate, cardiac enzymes, amylase, pancreatic ultrasound, hepatic and renal function as well as indicators related to severity and prognosis were recorded after admission. RESULT: The peak of insulin level was seen on day 1, then presented a downward trend and reached the normal level on day 7. The peaks of blood glucose and C-peptide level were seen on day 1 then declined, the levels on day 7 were still slightly higher than normal level. The insulin level on admission (41.47 ± 30.85) mU/L were positively correlated with lactic acid (2.29 ± 1.81) mmol/L and procalcitonin level (5.08 ± 6.70) ng/ml (r = 0.370, P = 0.000; r = 0.168, P = 0.002) (P < 0.01). The insulin level on admission in children with 1 organ failure (41.24 ± 22.60) mU/L or 2 or multiple organ failure (48.98 ± 22.17) mU/L was higher than that in children with non-organ failure (34.11 ± 29.84) mU/L (U = 1621.001, P = 0.000;U = 1300.000, P = 0.000) (P < 0.01). The insulin level on admission in death group (52.99 ± 32.34) mU/L was higher than that in survival group (32.85 ± 24.10) mU/L (U = 1585.000, P = 0.000) (P < 0.01). Ten cases in death group were complicated with pancreatic damage and the average insulin level on admission was (65.29 ± 50.53) mU/L. CONCLUSION: The high insulin level was correlated with the degree of inflammatory response, ischemia and hypoxia. The high insulin level in critically ill children was relevant to the pancreatic damage, the severity of the disease, organ dysfunction, and evaluation of prognosis.

Clinical and pathologic characteristics of pancreatic necrosis in critically ill children.

BACKGROUND: Pancreatic damage in critically ill patients is associated with the progressive failure of multiple organs, but little is known about its clinical characteristics. At present, no guidelines are available for the diagnosis and management of pancreatic damage. This study was undertaken to analyze the clinical and pathologic characteristics of pancreatic necrosis in critically ill children, and to find some biological markers of pancreatic damage or pancreatic necrosis. METHODS: We retrospectively reviewed the clinical data, laboratory results, and autopsy findings of 25 children, who were admitted to Hunan Children's Hospital, China from 2003 to 2009, and died of multiple organ failure. The autopsy revealed pancreatic necrosis in 5 children, in whom sectional or gross autopsy was performed. RESULTS: The 5 children had acute onset and a fever. Two children had abdominal pain and 2 had abdominal bulging, flatulence and gastrointestinal bleeding. Four children had abnormal liver function, characterized by decreased albumin and 3 children had elevated level of C-reactive protein (CRP). B-ultrasonography revealed abnormal acoustic image of the pancreas in all children, and autopsy confirmed pancreatic necrosis, which may be associated with the damage of the adrenal gland, liver, lung, heart, spleen, kidney, intestine, thymus, mediastinal and mesenteric lymph nodes and other organs. Children 1 and 2 died of acute hemorrhagic necrotizing pancreatitis (AHNP); children 3-5 died of multiple organ dysfunction syndrome (MODS) due to pancreatic necrosis. CONCLUSION: Pancreatic damage or pancreatic necrosis in critically ill children is characterized by acute onset, severity, short course, multiple organ damage or failure. It may be asymptomatic in early stage, and easy to be ignored.