[Antibody-drug conjugates combined with immunotherapy: a potential game changer in the treatment of upper tract urothelial carcinoma].

Currently, treatment strategies for upper tract urothelial carcinoma (UTUC) are changing rapidly. However, there are many limitations in the implementation of new surgical methods and systemic treatment options, which cannot reverse the current status quo of UTUC treatment. In recent years, antibody-drug conjugates have shown great potential in the field of cancer treatment, which can activate the immune system and enhance the effect of immunotherapy while accurately killing targeted tumor cells. The results of multiple clinical trials, including the EV-302 study, have confirmed that combination therapy can improve the survival rate of patients with advanced urothelial cancer, and may replace chemotherapy as the first-line treatment for advanced urothelial cancer. However, there are still a series of challenges in the application of combination therapy in UTUC, such as low level of evidence, adverse reactions, and drug resistance. In the future, it is necessary to focus on clinical trials of UTUC combination therapy, further optimize antibody drug conjugates and immunotherapy drugs to adapt to the disease characteristics of UTUC, and further study the molecular biology characteristics of UTUC to meet this series of challenges.

[Effectiveness of 13-valent pneumococcal conjugate vaccine against invasive disease caused by serotype 19A in children: a meta-analysis].

Objective: Using Meta-analysis to evaluate the vaccine effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against invasive Streptococcus pneumoniae disease (IPD) caused by serotype 19A in children <5 years old. Methods: "Streptococcus pneumoniae infection""invasive pneumococcal disease""13-valent pneumococcal polysaccharide conjugate vaccine""PCV13""effectiveness""infant""child" and related terms were searched from China National Knowledge Infrastructure (CNKI), WANFANG DATA, PubMed, SCOPUS and Web of science with no limited on language, region and research institution. The retrieval time was limited from January 2010 to February 2023 and cohort study, case-control study and randomized controlled trial were included. Data were extracted from eligible studies by two independent reviewers, and after study quality assessment by NOS scale, Meta-analysis was completed using Stata 16.0 software. Results: A total of 2 340 related literatures were searched, and 10 literatures were finally included, including 5 case-control studies and 5 indirect cohort studies, which showed good literature quality. The vaccine effectiveness against serotype 19A IPD of PCV13 in children was 83.91% (95%CI: 78.92%-88.89%), and the subgroup analysis (P=0.240) showed there was no significant difference among the case-control study (VE=87.34%, 95%CI:79.74%-94.94%) and the indirect cohort study (VE=81.30%, 95%CI:74.69%-87.92%). The funnel plot and Egger test suggested that the possibility of publication bias was small. Conclusion: The present evidence indicates that PCV13 has a good vaccine effectiveness against serotype 19A IPD in children, and it is recommended to further increase the vaccination rate of PCV13 to reduce the disease burden of IPD in children <5 years old.

[Clinical and pathological features of 20 cases of congenital hepatic fibrosis].

Objective: To investigate the clinical and pathological features of congenital hepatic fibrosis (CHF). Methods: The clinical and pathological findings of 20 patients diagnosed with CHF from 2017 to 2023 were retrospectively analyzed. Results: Among the 20 patients, 8 were males and 12 were females with a median age of 21.5 years. Mostly patients were admitted to the hospital with cirrhosis, portal hypertension and upper gastrointestinal bleeding. Pathological features were diffuse fibrosis in the portal area, formation of fibrous septa of varying width, segmentation of the liver parenchyma, with hyperplasia of small bile ducts. Among them, 1 case (5%) was complicated with Caroli's disease, and 1 case (5%) was HNF1α hepatocellular adenoma. IHC GS showed that was positively expressed in acinar region 3 in 75% cases. Conclusion: CHF is mainly manifested by portal hypertension and its complications. Histopathology is the gold standard for diagnosis. The possibility of CHF should be considered first in children and adolescents with portal hypertension but no history of hepatitis, and complicated kidney disease. The positive pattern of acinus-3 region of GS in IHC is helpful for the diagnosis of CHF.

[Epidemiological characteristics and spatiotemporal clustering of hepatitis A in Zhejiang Province from 2010 to 2019].

Objective: To analyze the epidemiological characteristics and spatiotemporal clustering of hepatitis A in Zhejiang Province from 2010 to 2019. Methods: The data of hepatitis A incidence in Zhejiang Province from 2010 to 2019 were collected from the infectious disease surveillance system of China Information System for Disease Control and Prevention. ArcGIS 10.7 software was used for spatial autocorrelation analysis. SaTScan 9.6 software was used for spatiotemporal scanning analysis. SPSS 25.0 software was used for additional analysis. Results: Zhejiang Province has reported 5 465 cases of hepatitis A in 2010-2019 years, with an average annual incidence rate of 1.00/100 000, and periodicity and seasonality are not obvious. The incidence of male was higher than that of female (P=0.023), and the highest incidence rate was 50-59 years old. Spatial autocorrelation analysis showed that there was a positive spatial correlation between the incidence of hepatitis A in Zhejiang Province from 2010 to 2017, with the weakest correlation in 2010 (Moran's I =0.103, Z=1.769, P=0.049), and the strongest correlation in 2016 (Moran's I=0.328, Z=4.979, P=0.001). Spatiotemporal scanning analysis showed that there was spatial aggregation of hepatitis A in Zhejiang Province from 2010 to 2019, with a total of three aggregation areas identified. Among them, the mostly aggregation area was concentrated in Xiangshan county of Ningbo city, which covered 10 counties (cities and districts), including Ninghai county and Yinzhou district, and appeared from January 1 to June 30, 2012. Conclusion: The incidence level of hepatitis A in Zhejiang Province shows a stable fluctuation trend from 2010 to 2019, and the seasonal regularity is not obvious. The population group aged 50-59 years old is the key population. There is spatial aggregation in the epidemic situation of hepatitis A. Targeted prevention and control measures of hepatitis A should be done based on the law of spatiotemporal aggregation and local incidence.

Isolation and identification of bioactive substance 1-hydroxyphenazine from Pseudomonas aeruginosa and its antimicrobial activity.

A strain named as Pseudomonas aeruginosa 2016NX1, which could produce phenazine and cereusitin, was isolated from the root of Millettia specisoa. Phenazines were extracted, isolated and purified by chloroform, thin-layer chromatography, column chromatography and high-performance liquid chromatography. Then the purified materials were identified by analysis of nuclear magnetic resonance. The major yellow component is 1-hydroxyphenazine and the minor blue component is cereusitin A. The tests of antimicrobial activity of yellow component showed that the growth of several common plant pathogenic fungi and bacteria (such as Cochliobolus miyabeanus, Diaporthe citri, Salmonella sp., Klebsiella oxytoca) could be strongly inhibited. This study suggested that Pseudomonas aeruginosa strain 2016NX1 had a significant potential for biological control of phytopathogenic fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, one bioactive substance from Pseudomonas aeruginosa 2016NX1 was identified and its antimicrobial activity was verified. This study demonstrated that one bioactive substance from P. aeruginosa can strongly inhibit the growth of plant pathogenic fungi and bacteria. This study suggested that P. aeruginosa strain 2016NX1 has a significant potential for biological control of phytopathogenic fungi.

Insulin Control of Blood Glucose and GLUT4 Expression in the Skeletal Muscle of Septic Rats.

BACKGROUND: Insulin resistance is common in septic patients. The level at which the serum glucose should be maintained using insulin infusions for optimal utilization by skeletal muscles is not yet established. OBJECTIVE: The objective of the present study was to compare glucose transporter 4 (GLUT4) mRNA and GLUT4 expression and glucose utilization at the recommended glucose levels of 6-8 mmol/L (110-140 mg/dL) and 8-10 mmol/L (140-180 mg/dL) in septic rats. SUBJECTS AND METHODS: This was a prospective randomized study using 44 Sprague-Dawley rats (260-330 g). Rats were anaesthetized with gaseous diethyl ether. Catheters were implanted into the jugular vein and artery. Following a laparotomy, rats in the experimental group (n = 36) were rendered septic by standard caecal ligation and puncture (CLP) and intraperitoneal lipopolysaccharide (LPS) infusion (O111:[B4], 1 mg/kg). Control animals (n = 8) underwent laparotomy, but no caecal ligation or puncture and no LPS injection. Four experimental groups were studied: sham-operated control, sepsis treated with fluid maintenance only, sepsis treated with fluid and insulin infusion controlling blood glucose concentration at 6-8 mmol/L and sepsis treated with fluid and insulin infusion controlling blood glucose concentration at 8-10 mmol/L. Hyperinsulinaemic-euglycaemic clamp experiment was done before fluid maintenance and insulin treatment to calculate average glucose infusion rate. RESULTS: All septic rats were markedly hyperglycaemic compared with sham-operated controls two hours after operation. Glucose infusion rate during hyperinsulinaemic-euglycaemic clamp experiment was slower in septic rats, suggesting that they were insulin resistant. At the 12th and 24th hour, skeletal muscle was taken to observe pathological change and analyse the GLUT4 mRNA and GLUT4 levels. There were more inflammatory cells, less GLUT4 mRNA and GLUT4 expression in the skeletal muscles of septic rats. Insulin increased the expression of GLUT4 mRNA and GLUT4 in the skeletal muscle of septic rats. Among all septic rats, the expression of GLUT4 mRNA and GLUT4 was more in the 8-10 mmol/L group. CONCLUSION: Blood glucose concentration of 8-10 mmol/L results in more glucose utilization than 6-8 mmol/L in the skeletal muscle of septic rats during insulin therapy.

Cost-effectiveness of onabotulinumtoxinA for the treatment of wrist and hand disability due to upper-limb post-stroke spasticity in Scotland.

BACKGROUND AND PURPOSE: The objective was to evaluate the cost-effectiveness of treating upper-limb post-stroke spasticity (ULPSS) with usual care (UC) plus onabotulinumtoxinA versus UC alone in Scotland. METHODS: We developed a model to simulate costs and quality-adjusted life years (QALYs) gained from treating ULPSS. Efficacy data and health utilities were taken from clinical trials. Unit costs were taken from published Scottish sources. We compared UC plus onabotulinumtoxinA and UC alone in three scenarios: (i) a scenario from the National Health Service perspective, which included differences in onabotulinumtoxinA use, specialist visits and day-hospital visits; (ii) a scenario that only included differences in onabotulinumtoxinA use and specialist visits; and (iii) a scenario from a societal perspective that included differences in onabotulinumtoxinA use, specialist visits and caregiver burden. RESULTS: In the first scenario, the model predicted that UC plus onabotulinumtoxinA produced 0.107 QALYs at an additional cost of £1099 compared with UC alone over 5 years, resulting in an incremental cost-effectiveness ratio (ICER) of £10,271/QALY. In the second scenario, the ICER increased to £27,134/QALY. In the third scenario (societal perspective), UC plus onabotulinumtoxinA produced lower total cost and higher QALYs, and therefore was superior to UC alone. CONCLUSIONS: Based on a model, UC plus onabotulinumtoxinA improved disability, which translated into greater QALYs but also increased direct medical costs compared with UC alone; however, the resulting ICER can be considered cost-effective. Moreover, UC plus onabotulinumtoxinA can be cost-saving if reduction in caregiver burden was included. OnabotulinumtoxinA offers value for money in the management of ULPSS in Scotland.

Sevoflurane has no adverse effects on renal function in cirrhotic patients: a comparison with propofol.

BACKGROUND: Cirrhotic patients are prone to developing renal dysfunction after anaesthesia and surgery. However, no consensus has been reached whether sevoflurane could have adverse effects on renal function in cirrhotic patients. We hypothesised that the use of sevoflurane for general anaesthesia would lead to post-operative renal dysfunction in cirrhotic patients undergoing liver resection. METHODS: A total of 200 patients undergoing liver resection were randomly assigned to a propofol or sevoflurane group. The influence of sevoflurane or propofol on renal function was evaluated by the maximal change, the difference between the pre-operative baseline and the highest values of serum creatinine and blood urea nitrogen measured at day 1, 3 and 6 post-operatively. RESULTS: The maximal change in serum creatinine after liver resection was -4.52 (5.78) µmol/l and -3.37 (7.34) µmol/l with P = 0.398, and that in blood urea nitrogen was 0.41 (1.49) mmol/l and 0.93 (1.54) mmol/l with P = 0.098 between the sevoflurane group (n = 52) and the propofol group (n = 50), respectively. CONCLUSIONS: Sevoflurane does not seem to impair post-operative renal function in cirrhotic patients undergoing liver resection.

The efficacy and safety of vildagliptin in patients with type 2 diabetes: a meta-analysis of randomized clinical trials.

WHAT IS KNOWN AND OBJECTIVE: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a relatively new class of drugs for the management of type 2 diabetes (T2DM). Vildagliptin is an oral DPP-4 inhibitor approved in more than 70 countries. The purpose of this meta-analysis is to provide an update on the clinical efficacy and safety of vildagliptin in patients with T2DM. METHODS: A literature search identified 30 randomized controlled trials comparing vildagliptin with comparators (placebo or other hypoglycaemic agents). Meta-analyses were conducted for HbA1c, weight, fasting plasma glucose (FPG), hypoglycaemia and other adverse events. The outcomes of HbA1c, weight and FPG were analysed as weighted mean differences (WMD), and the number of ADRs events as relative risks (RR). RESULTS: Compared with placebo, vildagliptin lowered HbA1c {WMD, -0·77% [95% confidence interval (CI), -0·96% to -0·58%] for 100 mg/day of vildagliptin and -0·58% [95% CI, -0·72% to -0·44%] for 50 mg/day of vildagliptin}. The effect was non-inferior to thiazolidinediones, sulfonylureas and α-glycosidase inhibitors, but inferior to metformin. Compared with placebo, treatment with 50 mg/day of vildagliptin caused neutral weight changes, while 100 mg/day of vildagliptin resulted in slight weight gain [0·95 kg (95% CI, 0·73-1·17 kg)]. In addition, compared to comparators, vildagliptin was not associated with an increase in overall risk for any adverse events [RR, 0·97 (95% CI, 0·94-0·99)]. The incidence of hypoglycaemia was low with vildagliptin, and the risk with vildagliptin was not significantly different from the comparators [0·85 (95% CI, 0·49-1·47)]. The use of vildagliptin did not display any increased risks of infection [1·03 (95% CI, 0·94-1·13) for nasopharyngitis and 1·07 (95% CI, 0·90-1·27) for upper respiratory tract infection]. WHAT IS NEW AND CONCLUSION: Vildagliptin is effective in glycaemic control with a low risk of hypoglycaemia and other adverse reactions. This may have an important impact on patient adherence to this medication.

A comparison of liver function after hepatectomy with inflow occlusion between sevoflurane and propofol anesthesia.

BACKGROUND: In this study, we compared liver function tests after hepatectomy with inflow occlusion as a function of propofol versus sevoflurane anesthesia. METHODS: One hundred patients undergoing elective liver resection with inflow occlusion were randomized into a sevoflurane group or a propofol group. General anesthesia was induced with 3 µg/kg fentanyl, 0.2 mg/kg cisatracurium, and target-controlled infusion of propofol, set at a plasma target concentration of 4 to 6 µg/mL, or sevoflurane initially started at 8%. Anesthesia was maintained with target-controlled infusion of propofol (2-4 µg/mL) or sevoflurane (1.5%-2.5%). The primary end point was postoperative liver injury assessed by peak values of liver transaminases. RESULTS: Transaminase levels peaked between the first and the third postoperative day. Peak alanine aminotransferase was 504 and 571 U/L in the sevoflurane group and the propofol group, respectively. Peak aspartate aminotransferase was 435 U/L after sevoflurane and 581 U/L in the propofol group. There were no significant differences in peak alanine aminotransferase or peak aspartate aminotransferase between groups. Other liver function tests including bilirubin and alkaline phosphatase, and peak values of white blood cell counts and creatinine, were also not different between groups. CONCLUSIONS: Sevoflurane and propofol anesthetics resulted in similar patterns of liver function tests after hepatectomy with inflow occlusion. These data suggest that the 2 anesthetics are equivalent in this clinical context.

Effect of the route of foot-and-mouth disease virus infection of piglets on the course of disease.

Three different routes of Foot-and-mouth disease virus (FMDV) infection of piglets, namely intranasal (i.n.) through drops, intradermal (i.d.) into the foot, and intramuscular (i.m.) were compared regarding the onset and severity of the disease. The results showed that the i.d. injection of the virus resulted in the fastest onset of the disease. The i.m. injection led to a delayed onset, but the final effect was identical with i.d. injection. Moreover, the i.m. injection was simpler to perform and easier to evaluate. Therefore, the i.m. injection of piglets is recommended as the optimal infection route for evaluation of the FMDV vaccine potency.

Disruption of cytoskeletal integrity impairs Gi-mediated signaling due to displacement of Gi proteins.

beta1 integrins play a crucial role as cytoskeletal anchorage proteins. In this study, the coupling of the cytoskeleton and intracellular signaling pathways was investigated in beta1 integrin deficient (-/-) embryonic stem cells. Muscarinic inhibition of the L-type Ca2+ current (ICa) and activation of the acetylcholine-activated K+ current (IK,ACh) was found to be absent in beta1 integrin-/- cardiomyocytes. Conversely, beta adrenoceptor-mediated modulation of ICa was unaffected by the absence of beta1 integrins. This defect in muscarinic signaling was due to defective G protein coupling. This was supported by deconvolution microscopy, which demonstrated that Gi exhibited an atypical subcellular distribution in the beta1 integrin-/- cardiomyocytes. A critical role of the cytoskeleton was further demonstrated using cytochalasin D, which displaced Gi and impaired muscarinic signaling. We conclude that cytoskeletal integrity is required for correct localization and function of Gi-associated signaling microdomains.

The effects of obstructive jaundice on the pharmacodynamics of propofol: does the sensitivity of intravenous anesthetics change among icteric patients?

BACKGROUND: Some studies suggest that certain clinical symptoms of cholestasis, such as fatigue and pruritus, result from altered neurotransmission. Patients with obstructive jaundice also have labile blood pressure and heart rate. In the present study, the authors investigated whether obstructive jaundice affects a patient's sensitivity to hypnotics and the haemodynamic profile of propofol. METHODS: Thirty-six ASA physical status I/II/III patients with serum total bilirubin (TBL) from 7.8 to 362.7 micromol/l scheduled for bile duct surgery were recruited. A computer-controlled propofol infusion programmed for effect site target was used to rapidly attain and maintain sequential increase of the compartment concentration (from 1 to 3 microg/ml). Each target-controlled concentration was maintained for about 12 min, and arterial blood samples were drawn for propofol concentration determination. The bispectral index (BIS) and mean arterial pressures (MAP) were used as indices of the propofol effect. The relation between the concentration and the effects was described by the Hill equation. The pharmacodynamic parameters were optimized using a nonlinear mixed-effect model. RESULTS: TBL was not a significant covariate of EC(50) for the pharmacodynamic model. For BIS and MAP, the parameters of the pharmacodynamic model were E(max)=75.77%, EC(50)=2.34 microg/ml, and gamma=1.82, and E(max)=47.83%, EC(50)=1.49 microg/ml, and gamma=1.88, respectively. CONCLUSIONS: We demonstrated that obstructive jaundice with serum TBL from 7.8 to 362.7 micromol/l had no effect on propofol pharmacodynamics observed by BIS and MAP.

Anaplastic lymphoma kinase expression and prognosis in inflammatory myofibroblastic tumours of the maxillary sinus.

Inflammatory myofibroblastic tumours (IMT) of the nasal cavity and nasal sinus are rare and, although over 50 cases have been reported in the English-language literature, their precise aetiology and biological behaviour have not been elucidated. Recent studies suggest that anaplastic lymphoma kinase (ALK)-positive tumours have a very low risk of metastasis, but ALK reactivity does not appear to correlate with recurrence. Between March 2002 and December 2008, we encountered three cases of maxillary sinus IMT and investigated them to determine the clinicopathological course, prognosis and immunohistochemical expression of ALK. Two of the patients died < 13 months after the initial diagnosis and the third had multiple recurrences. All three cases were immunohisto chemically negative for ALK expression. IMT of the sino-nasal tract is rare and may undergo malignant transformation in a minority of cases. The three cases manifested progressive extension with bone destruction and multiple recurrences, and two cases had a fatal outcome and one case had high recurrence.

[Effects and mechanisms of high-volume hemofiltration on endotoxin-induced acute lung injury of piglets].

Objective: To compare the effects of high-volume hemofiltration (HVHF) and continuous veno-venous hemofiltration (CVVH) on cardiopulmonary functions, lung fluid balance, lung damage and cytokine expression in endotoxin-induced acute lung injury piglet model, and to further evaluate the value of high-volume hemofiltration in acute lung injury. Method: Eighteen piglets were randomly divided into the control group (6 piglets), the CVVH group (6 piglets) and the HVHF group (6 piglets). By general anesthesia, the intravenous infusion of 0.15 mg/kg endotoxin were received in all the animals and induced acute lung injury.High-volume hemofiltration and continuous veno-venous hemofiltration were addressed to different groups.Subsequently, hemodynamic parameters (heart rate, mean arterial blood pressure, central venous pressure, pulse contour cardiac index, systemic venous resistance index and extravascular lung water index) as well as gas exchange and lung mechanics parameters (respiratory rate, partial pressure of carbon dioxide, partial pressure of oxygen/fraction of inspired oxygen, dynamic lung compliance and airway resistance) were intermittently measured.Lung tissues were collected for further analysis (the lung wet-to-dry weight ratio, lung injury scoring). The plasma protein levels of cytokines (interleukin(IL) -6, 10 and tumor necrosis factors alpha(TNF-α)) were also assessed.Two-way analysis of variance (ANOVA) and Bonferroni post-test were conducted to identify significant differences among the control, CVVH and HVHF group. Result: Compared with CVVH, HVHF had the capacity to improve significantly the index of Cdyn(HVHF (2.3±0.5) vs. CVVH (1.5±0.5) ml/(cmH(2)O·kg), 1 cmH(2)O=0.098 kPa, P<0.05)and Rrs(HVHF (22.0±1.9) vs.CVVH (29.5±1.5) cmH(2)O/(L·s), P<0.05)at the time of 6 h, and decreased lung water accumulation(index of EVLWI in HVHF (22.7±2.1) vs.CVVH (39.5±2.6) ml/m(2,) P<0.01) at the time of 6 h, and the plasma concentration of cytokines(IL-6, IL-10, TNF-α)in the HVHF group had an obvious decline compared with those in the CVVH group at the time of 6 h( (200±55) vs. (280±61), (74±17) vs. (102±21), (54±13) vs. (73±21) pg/ml, all P<0.05). The lung injury scoring of HVHF group was significantly lower than those of CVVH group((7.8±1.9) vs. (11.3±2.2) scores, P<0.05). Although the plasma concentration of cytokines(IL-6, IL-10, TNF-α) in the CVVH group were lower than those in the control group at the time of 6 h((374±55), (137±25), (98±17) pg/ml, all P<0.05), the indexes of respiratory function were not improved (all P<0.05). Conclusion: Different doses hemofiltration can reduce plasma inflammatory mediators indicators in piglets.Early high volume hemofiltration can improve respiratory function of piglets with endotoxin-induced acute lung injury and reduce lung injury pathological score.

Reliability and validity of a patient self-administered daily questionnaire to assess impact of oral mucositis (OM) on pain and daily functioning in patients undergoing autologous hematopoietic stem cell transplantation (HSCT).

Oral mucositis (OM) is a frequent complication of myeloablative therapy and HSCT. We evaluated the feasibility, reliability, and validity of a new patient self-reported daily questionnaire on OM and its impact on daily functions. This OM Daily Questionnaire (OMDQ), containing 10 items, was developed for use in palifermin clinical trials. In a phase 3 study, 212 patients received palifermin or placebo for three consecutive days before conditioning and three consecutive days after HSCT. Compliance rates were consistently >80% for most patients. Mouth and throat soreness (MTS) and MTS-Activity Limitations (MTS-AL) (swallowing, drinking, eating, talking, and sleeping) scores on consecutive days were highly correlated (days 7,8 = 0.70-0.86; test-retest reliability). Correlations among items measuring the same construct ranged between 0.5 and 0.8 (internal consistency reliability). The WHO Oral Toxicity scale was the clinical comparator to assess the criterion, discriminative, and evaluative validities of MTS-related questions. Most correlation coefficients between the WHO and MTS ranged between 0.45 and 0.55. Patients with more severe WHO OM grades had higher MTS mean scores. Changes in MTS scores were similar, but patients detected changes 1-3 days earlier than clinicians. In conclusion, the OMDQ is a feasible, reliable, valid, and responsive patient-reported measure of OM severity.

[Application of right jugular vessels to build extracorporeal membrane oxygenation for treating the critically ill children].

OBJECTIVE: To summarize the experience in applying a technique of inserting a cannula through right internal jugular vein and common carotid artery to build extracorporeal membrane oxygenation (ECMO) for critically ill children. METHOD: The data of critically ill patients received ECMO support through right internal jugular vein and common carotid artery between December 2011 and December 2015 from Children's Hospital of Fudan University were analyzed retrospectively.The data included diagnosis, age, body weight, time of cannula and ECMO running, complication and prognosis. RESULT: In total 28 patients received ECMO support, 3 patients of post-cardiac surgery with transthoracic cannula were excluded.Twenty-five patients inserted cannula through neck vessels were enrolled, 15 boys and 10 girls, the median age was 1.8 years (range, 1 d-13 years), the median weight was 12.0 (2.8-50.0) kg.All the cannula sites were right internal jugular vein and right common carotid artery, before cannula use 5 patients had been inserted central vein tube and 3 patients with blood filter tube in right internal jugular vein, in one case cannula was applied during cardiopulmonary resuscitation.V-A ECMO had been built for all the cases successfully, the median operation time was (45±26) min.The pump flow was 80-150 ml/(kg·min), the median duration of ECMO support was 153(14-567) h. Sixteen (64%) patients weaned off ECMO successfully, 15(60%) survived to hospital discharge.About the complication of cannula, six patients developed cannula site bleeding, and two patients required re-fixation of cannula, one patient's external jugular vein had been hurt and sutured for bleeding. CONCLUSION: Application of right jugular vessels to build ECMO is easy and safe for treating the sick children. The skill should be proficient to assure ECMO run and reduce the complications.

[Follow-up of survived children supported by extracorporeal membrane oxygenation].

Objective: To summarize the follow-up of children treated with venoarterial extracorporeal membrane oxygenation (ECMO) by incision of internal carotid artery-vein. Method: This was a retrospective study, 10 children in whom the conventional therapy failed, but survived after treatment with ECMO technique through right internal jugular artery-venous incision and ligation after ECMO in pediatric intensive care unit (PICU) of Fudan University were followed up from December 2011 to December 2015. Primary disease situation, neurological development, growth and development, quality of life and personality development were included. All children were followed up once every six months after discharge, and once a year after 2 years. The longest follow-up period was 2 years. Result: Of the 10 children 6 were boys and 4 girls, and ranged in age of onset from 1 day to 12 years . Five children had neurological problems, including abnormal brain CT (n=3), abnormal electroence phalogram (EEG) (n=3), and mental retardation (n=2). Three of those children had a history of hypoxia, 2 of whom accepted cardiopulmonary resuscitation. Eight children had normal brainstem evoked potential (BEAP) examinations. Primary diseases were all well controlled except for 6 children who had different degrees of sequelae, including mild arrhythmia (n=1), heart structure abnormality (n=2) and abnormal pulmonary function (n=3). The sequelae caused by the primary diseases were just embodied in examination. Their head circumference measurement and physical examination showed no obvious abnormalities, and blood biochemical tests, hemoglobin and blood gas analysis were also normal. One child's height was less than P3. The one who accepted cardiopulmonary resuscitation (CPR) at early stage of primary disease had trouble in daily life, presenting uncoordinated and unstable walking. One child was slightly bad tempered and asocial, and the rest were normal. Conclusion: The rest could take care of themselves. The ECMO sequelae of those survived children were mostly caused by primary diseases. ECMO treatment is safe and has less adverse consequences.

[Complications of critically ill children supported by venoarterial extracorporeal membrane oxygenation].

OBJECTIVE: To study the complications occurred in the process of venoarterial extracorporeal membrane oxygenation (VA-EMCO) in critically ill children. METHOD: To analyze retrospectively 25 children who were admitted to PICU of Children's Hospital of Fudan University from December 2011 to December 2015. They were all treated with VA-ECMO with incision and catheterization in right internal carotid artery and jugular vein. Complications were recorded during ECMO process. RESULT: The duration of ECMO treatment was 14 to 567 h (153 (112, 204) h). Seventeen cases (68%) withdrew from ECMO successfully and 15 cases (60%) survived to discharge. Thirty-three complications occurred during ECMO treatment. Of which, mechanical complications occurred 9 times, including oxygenator leakage (n=3), hemolysis (n=2), water tank failure (n=2), pump head rupture (n=1) and piping thrombosis (n=1). Somatic complications appeared 24 times, including neurological complications (n=8) which included cerebral infarction (n=2), convulsions (n=2), intracranial hemorrhage (n=2), thrombosis after ligation of internal jugular vein (n=1) and cerebral atrophy (n=1); bleeding complications (n=8) which included bleeding at puncture sites (n=4), ECMO canalized site bleeding (n=3), and spontaneous (n=1), intracranial hemorrhage or hematoma cases(n=2) in mechanical complications; acute kidney injury (n=5) and microcirculation thrombosis (n=3). CONCLUSION: ECMO technique may cause complications, which mainly include neurological, mechanical and clotting complications. Advanced equipments and materials and well-managed teamwork are helpful in decreasing complications.

Acute experimental allergic encephalomyelitis in SJL/J mice induced by a synthetic peptide of myelin proteolipid protein.

Clinical, histologic, and ultrastructural characteristics of acute experimental allergic encephalomyelitis (EAE) induced by sensitization with a synthetic peptide corresponding to mouse myelin proteolipid protein (PLP) residues 139-151 HCLGKWLGHPDKF were studied in SJL/J mice. Groups of mice were immunized with 20, 50, or 100 nmol of the peptide and were killed from seven to 28 days after sensitization or when they were moribund. Beginning on Day 9, the mice showed signs of EAE and the disease progressed rapidly to paralysis. Central nervous system (CNS) inflammation, edema, gliosis, and demyelination were found in all mice killed between Days 10 and 28 and white matter lesion areas correlated with clinical score at the time the mice were killed. Peripheral nerve roots and the cauda equina did not have lesions. Within the range studied, the severity of clinical or histologic disease was the same regardless of the PLP peptide dose. Two of ten mice immunized with 100 nmol and none of 14 mice given smaller doses of a synthetic peptide of mouse myelin basic protein (MBP) showed clinical EAE. These mice had small numbers of CNS lesions that were indistinguishable from those in PLP peptide-sensitized mice. These findings demonstrate that immunization of SJL/J mice with PLP peptide 139-151 produces a disease with the clinical and morphologic features of CNS tissue-, whole PLP-, whole MBP-, and MBP peptide-induced acute EAE. Thus, PLP is a major encephalitogen and immune reactions to epitopes of different myelin proteins may induce identical patterns of injury in the CNS.