[Expert consensus on the application of critical care ultrasonography in invasive procedures].

The evolution of critical care medicine is inextricably linked to the development of critical care procedures. These procedures not only facilitate diagnosis and treatment of critically ill patients, but also provide valuable insights into disease pathophysiology. While critical care interventions offer undeniable benefits, the potential for iatrogenic complications necessitates careful consideration. The recent surge in critical care ultrasound (US) utilization is a testament to its unique advantages: non-invasiveness, real-time bedside availability, direct visualization of internal structures, elimination of ionizing radiation exposure, repeatability, and relative ease of learning. Recognizing the need to optimize procedures and minimize complications, critical care utrasound study group of Beijing critical care ultrasound research assocition convened a panel of critical care experts to generate this consensus statement. This document serves as a guide for healthcare providers, aiming to ensure patient safety and best practices in critical care.

[Analysis of the change in human resources of centers for disease control and prevention in different regions of China from 2010 to 2020].

Objective: To analyze the change in human resources within China's Centers for Disease Control and Prevention (CDC) from 2010 to 2020. Methods: The self-reported information from provincial, prefectural (city), and county (district) levels of China's CDC, covering employee counts, staff composition, professional qualifications, educational backgrounds, technical titles, and tenure, were extracted from the China Disease Prevention and Control Information System. The demographic context was provided by the annual population figures from the China Statistical Yearbook (2010-2020). The profile of CDC personnel was described, and the average annual percentage rate change (AAPC), average annual percentage rate change (APC), human resource agglomeration degree (HRAD) and the difference between HRAD and population agglomeration degree (PAD) were calculated. The Joinpoint regression model was used to analyze the time trend. Results: The decade under review witnessed a net increase of 17 300 active and 18 300 enrolled personnel in the CDC, surpassing the national population growth rate with AAPCs of 0.93% and 1.03%, respectively. This upward trajectory was statistically significant (P<0.05). The ratio of disease control personnel per 10 000 population escalated from 1.14 to 1.21. An initial decline in active CDC workforce density (from 1.31 to 1.27 per 10 000 population between 2010 and 2017) was followed by an increase (from 1.28 to 1.37 between 2018 and 2020), with APCs of -0.40% and 3.73%, respectively. The proportion of professional and technical staff in 2019 was highest in the eastern region (86.01%), followed by the western (83.75%) and central regions (79.54%). The period also saw an enhancement in the average academic degree (from 1.91 to 2.43 points) and professional title scores (from 1.39 to 1.53 points) of CDC personnel. While the average tenure in the eastern and western regions showed a slight decline, the central region experienced an increase, with HRAD values indicating a higher concentration in the eastern and central regions compared to the western region. The HRAD-PAD discrepancy revealed a negative value in the eastern region, nearing zero in the central and western regions. Conclusion: Between 2010 and 2020, China's CDC experienced notable growth in human resources and underwent structural optimization, albeit with significant regional disparities in concentration.

Recombinant erythropoietin protective and related effects on brain injury in premature infants.

OBJECTIVE: The aim of this study was to investigate the protective effect of recombinant erythropoietin at different doses on brain injury in premature infants and the related effects on blood routine, liver function, intellectual development, mental development index (MDI), psychomotor development index (PDI), etc. PATIENTS AND METHODS: A total of 120 premature infants were divided into four groups, including experimental group A (n=30), experimental group B (n=30), experimental group C (n=30) and control group (n=30). The experimental group was treated with different doses of recombinant erythropoietin for brain injury protection of premature infants, while the control group with conventional methods. RESULTS: There was no statistical significance in all test indicators of the four groups of patients before the intervention. After the intervention experiment, the S-100B index was p<0.05, and the erythropoietin (EPO) index was p<0.05. In the comparison of IL-6 indicators, the indicators of the experimental group were reduced after the comparison experiment, and there were significant differences, p<0.05. In neonatal behavior evaluation, there was a statistical difference between groups A and B and the control group (p<0.05), and no statistical significance was shown between group C and the control group (p>0.05). In the intelligence test comparison, the F value of the experimental group was 3.113 three months after treatment. After six months, the F value was 3.654. After nine months, the F value was 3.392 with p<0.05. In the comparison of blood routine indicators, the p-values of four indicators between groups were more than 0.05. In the comparison of liver function indexes, the indexes of groups A, B, and C were significantly changed before and after treatment, and the data after treatment were significantly different from those before treatment, p<0.05. In the comparison of development, there were no significant differences observed in the p-values of the two indicators of vigorous exercise and language in the experimental group. CONCLUSIONS: Recombinant erythropoietin has a protective effect on infants with brain injury and can improve the intellectual development of premature infants, but has no significant effect on blood routine indicators. It can effectively improve the MDI, PDI, and related cytokines of premature infants, and has certain significance for the treatment of brain injury.

[Current status and challenges of anticoagulation management in extracorporeal membrane oxygenation].

The anticoagulant management of extracorporeal membrane oxygenation(ECMO) is facing great challenges. Complications related to the coagulation system such as bleeding or embolism are one of the main factors affecting the mortality of patients. How to control the dynamic balance between thrombosis and bleeding complications has become the top priority of ECMO management. This article reviews the coagulation changes during ECMO support, how to choose appropriate anticoagulant drugs and anticoagulation monitoring methods, aiming to explore the best anticoagulation strategy for ECMO patients.

The binding between NPM and H2B proteins signals for the diabetes-associated centrosome amplification.

Diabetes not only increases the risk for cancer but also promotes cancer metastasis. Centrosome amplification (CA) is sufficient to initiate tumorigenesis and can enhance the invasion potential of cancer cells. We have reported that diabetes can induce CA, with diabetic pathophysiological factors as the triggers, which involves the signaling of nucleophosmin (NPM). Thus, CA can serve as a candidate biological link between diabetes and cancer. In the present study, we attempted to identify the NPM binding partners and investigated whether the binding between NPM and its partner mediated the CA. We confirmed that high glucose, insulin, and palmitic acid cancer could elicit CA in the HCT16 colon cancer cells and found that the experimental treatment increased the binding between NPM and H2B, but not between p-NPM and H2B. The molecular docking analysis supported the fact that NPM and H2B could bind to each other through various amino acid residues. The treatment also increased the colocalization of NPM and H2B in the cytosol. Importantly, disruption of the NPM1-H2B complex by individual knockdown of the protein level of NPM or H2B led to the inhibition of the treatment-evoked CA. In conclusion, our results suggest that the binding between NPM and H2B proteins signals for the CA by high glucose, insulin, and palmitic acid.

[Preliminary study on differentially expressed proteins in a mouse model of secondary cystic echinococcosis based on data independent acquisition proteomics].

OBJECTIVE: To identify the differentially expressed proteins in different liver tissues in the mouse model of cystic echinococcosis (CE), so as to provide insights into the research and development of therapeutic drugs targeting CE. METHODS: Female Kunming mice at ages of 6 to 8 weeks were randomly assigned into the CE group and the control group. Mice in the CE group were intraperitoneally infected with 2 000 Echinococcus multilocularis protoscoleces, while mice in the control group were injected with the same volume of physiological saline. All mice in both groups were sacrificed after breeding for 350 d, and the lesions (the lesion group) and peri-lesion specimens (the peri-lesion group) were sampled from the liver of mice in the CE group and the normal liver specimens (the normal group) were sampled from mice in the control group for data independent acquisition (DIA) proteomics analysis, and the differentially expressed proteins were subjected to Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. RESULTS: A total of 26 differentially expressed proteins were identified between the lesion group and the normal group and between the peri-lesion group and the normal group, including 8 up-regulated proteins and 18 down-regulated proteins. GO term enrichment analysis showed that these differentially expressed proteins were predominantly enriched in endoplasmic reticulum membrane (biological components), oxidoreductase activity (molecular function) and oxoacid metabolic process and monocarboxylic acid metabolic process (biological processes). KEGG pathway enrichment analysis revealed that the differentially expressed protein Acyl-CoA oxidase 1 (Acox1), which contributed to primary bile acid biosynthesis during the fatty acid oxidation, was involved in peroxisome signaling pathway, and the differentially expressed protein fatty acid binding protein 1 (Fabp1), which contributed to fatty acid transport, was involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. CONCLUSIONS: Differentially expressed proteins are identified in the liver specimens between mouse models of CE and normal mice, and some differentially expressed proteins may serve as potential drug targets for CE.

[Preliminary study on differentially expressed proteins in a mouse model of secondary alveolar echinococcosis based on data independent acquisition proteomics].

OBJECTIVE: To identify the differentially expressed proteins in different liver tissues in the mouse model of alveolar echinococcosis using high-resolution mass spectrometry with data independent acquisition (DIA), and to identify the key proteins contributing to the pathogenesis of alveolar echinococcosis. METHODS: Protoscoleces were isolated from Microtus fuscus with alveolar echinococcosis and the experimental model of alveolar echinococcosis was established in female Kunming mice aged 6 to 8 weeks by infection with Echinococcus multilocularis protoscoleces. Mice were divided into the experimental and control groups, and animals in the experimental group was injected with approximately 3 000 protoscoleces, while mice in the control group were injected with the same volume of physiological saline. Mouse liver specimens were sampled from both groups one year post-infection and subjected to pathological examinations. In addition, the lesions (the lesion group) and peri-lesion specimens (the peri-lesion group) were sampled from the liver of mice in the experimental group and the normal liver specimens (the normal group) were sampled from mice in the control group for DIA proteomics analysis, and the differentially expressed proteins were subjected to bioinformatics analysis. RESULTS: A total of 1 020 differentially expressed proteins were identified between the lesion group and the normal group, including 671 up-regulated proteins and 349 down-regulated proteins, and 495 differentially expressed proteins were identified between the peri-lesion group and the normal group, including 327 up-regulated proteins and 168 down-regulated proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these differentially expressed proteins were involved in peroxisome, peroxisome proliferator-activated receptor (PPAR) and fatty acid degradation pathways, and the peroxisome and PPAR signaling pathways were found to correlate with liver injury. Several differentially expressed proteins that may contribute to the pathogenesis of alveolar echinococcosis were identified in these two pathways, including fatty acid binding protein 1 (Fabp1), Acyl-CoA synthetase long chain family member 1 (Acsl1), Acyl-CoA oxidase 1 (Acox1), Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (Ehhadh) and Acetyl-Coenzyme A acyltransferase 1B (Acaa1b), which were down-regulated in mice in the experimental group. CONCLUSIONS: A large number of differentially expressed proteins are identified in the liver of the mouse model of alveolar echinococcosis, and Fabp1, Acsl1, Acox1, Ehhadh and Acaa1b may contribute to the pathogenesis of alveolar echinococcosis.

Hexavalent chromium induces centrosome amplification through ROS-ATF6-PLK4 pathway in colon cancer cells.

Centrosome amplification (CA) refers to a numerical increase in centrosomes resulting in cells with more than two centrosomes. CA has been shown to initiate tumorigenesis and increase the invasive potential of cancer cells in genetically modified experimental models. Hexavalent chromium is a recognized carcinogen that causes CA and tumorigenesis as well as promotes cancer metastasis. Thus, CA appears to be a biological link between chromium and cancer. In the present study, we investigated how chromium triggers CA. Our results showed that a subtoxic concentration of chromium-induced CA in HCT116 colon cancer cells, resulted in the production of reactive oxygen species (ROS), activated ATF6 without causing endoplasmic reticulum stress, and upregulated the protein level of PLK4. Inhibition of ROS production, ATF6 activation, or PLK4 upregulation attenuated CA. Inhibition of ROS using N-acetyl-l-cysteine (NAC) inhibited chromium-induced activation of ATF6 and upregulation of PLK4. ATF6-specific siRNA knocked down the protein level and activation of ATF6, and upregulated PLK4, with no effect on ROS production. Knockdown of PLK4 protein had no effect on chromium-induced ROS production or activation of ATF6. In conclusion, our results suggest that hexavalent chromium induces CA via the ROS-ATF6-PLK4 pathway and provides molecular targets for inhibiting chromium-mediated CA, which may be useful for the assessment of CA in chromium-promoted tumorigenesis and cancer cell metastasis.

Acute heat stress alters the expression of genes and proteins associated with the unfolded protein response pathway in the liver of broilers.

1. The aim of this study was to explore the effects of acute heat stress on serum hormone levels and the expression of genes and proteins related to the unfolded protein response (UPR) pathway and apoptotic process in the liver of broilers.2. A total of 144 Arbor Acres broilers (35-d-old) were randomly allocated to 4 different environmental-controlled chambers for acute heat exposure. The temperature of the 4 environmental chambers was adjusted to 26°C (control), 29°C, 32°C, and 35°C within 1 h, respectively. The blood and liver samples were collected after 6 h of constant heat exposure at set temperatures.3. The results showed that 6 h of acute heat stress increased serum hormone levels and up-regulated the expression of heat shock protein. The endoplasmic reticulum (ER) stress markers, GRP78 and GRP94, in the liver of broilers were significantly upregulated at the mRNA and protein levels. The PERK, IRE1, and XBP1 genes, which are involved in the unfolded protein response signalling, were significantly up-regulated at the mRNA levels. However, other pro-apoptotic genes showed no significant changes in the liver of broiler chickens in all groups except for upregulation of the anti-apoptotic gene BCL-xl.4. The results suggested that broilers have tolerance to acute heat stress to a certain extent. The UPR activation can alleviate ER stress and further prevent apoptosis in the liver of broilers under short-term exposure to high ambient temperatures.

Epidemiological characteristics of COVID-19 patients in convalescence period.

This study aimed to investigate the clinical characteristics and to analyse the epidemiological features of coronavirus disease 2019 (COVID-19) patients during convalescence. In this study, we enrolled 71 confirmed cases of COVID-19 who were discharged from hospital and transferred to isolation wards from 6 February to 26 March 2020. They were all employees of Zhongnan Hospital of Wuhan University or their family members of which three cases were <18 years of age. Clinical data were collected and analysed statistically. Forty-one cases (41/71, 57.7%) comprised medical faculty, young and middle-aged patients (aged ⩽60 years) accounted for 81.7% (58/71). The average isolation time period for all adult patients was 13.8 ± 6.1 days. During convalescence, RNA detection results of 35.2% patients (25/71) turned from negative to positive. The longest RNA reversed phase time was 7 days. In all, 52.9% of adult patients (36/68) had no obvious clinical symptoms, and the remaining ones had mild and non-specific clinical symptoms (e.g. cough, sputum, sore throat, disorders of the gastrointestinal tract etc.). Chest CT signs in 89.7% of adult patients (61/68) gradually improved, and in the others, the lesions were eventually absorbed and improved after short-term repeated progression. The main chest CT manifestations of adult patients were normal, GGO or fibre streak shadow, and six patients (8.8%) had extrapulmonary manifestations, but there was no significant correlation with RNA detection results (r = -0.008, P > 0.05). The drug treatment was mainly symptomatic support therapy, and antibiotics and antiviral drugs were ineffective. It is necessary to re-evaluate the isolation time and standard to terminate isolation for discharged COVID-19 patients.

[Validity and reliability of physical activity questionnaires in children and adolescents: a Meta-analysis].

Objective: This review is to systematically summarize the studies examining physical activity questionnaires in children and adolescents and assess the overall validity and reliability, providing evidence on epidemiology research of physical activity in youth. Methods: A meta-analysis was performed using Stata 14.0 software. PubMed/Medline and EMBASE databases using the following terms:'Physical Activity'AND (' Questionnaire'OR'Self-report'OR'Recall') AND'Valid*'AND (' Reliab*'OR'Reproducib*'OR'Sensitiv*'OR'Responsiv*') AND (' Child*' OR'Adolescen*'OR'Youth') were searched from January 2008 to December 2018. Articles meeting the inclusion criteria were screened and adopting 'COnsensusbased Standards for the selection of health status Measurement Instruments' to evaluate the quality of the included studies. Results: This review yielded 17 articles on 20 different physical activity questionnaires, the total number of 2 778 participants for validity study and 2 137 participants for reliability study. The combined values of correlation coefficients in validity study were 0.27 (95%CI: 0.23-0.31) for moderate-to-vigorous intensity physical activity, 0.24 (95%CI: 0.18-0.30) for moderate intensity physical activity, 0.33 (95%CI: 0.24-0.42) for vigorous intensity physical activity. The combined values of intraclass correlation coefficients in reliability study were 0.75 (95%CI: 0.68-0.83) for moderate-to-vigorous intensity physical activity, 0.56 (95%CI: 0.46-0.65) for moderate intensity physical activity, 0.68 (95%CI: 0.61-0.75) for vigorous intensity physical activity. Conclusion: Until now, no questionnaires were identified for good validity and reliability to assess the physical activity level in young population.

[Emerging of Japanese encephalitis virus and Getah virus from specimen of mosquitoes in Inner Mongolia Autonomous Region].

Objective: To investigate the types and distribution of blood-sucking insects and arboviruses in Inner Mongolia autonomous region, and provide basic data for the prevention of arbovirus transmitted disease. Methods: Blood-sucking insects were collected by lamp trapping method in nature. Mosquito samples were classified according to morphologic characteristics and then stored at liquid nitrogen. Viruses were isolated in cell culture and characterized, using molecular biological methods. Results: A total of 24 240 mosquitoes and 17 110 aphids were collected from 2 sites of 5 counties (Flags) in Inner Mongolia in 2014 and during 2017-2018. Among them, Japanese encephalitis virus gene was detected in Culex pipiens pallens, and 4 virus strains isolates which could be stably passaged. The isolates were identified as Getah virus and densonucleosis virus by molecular biology identification. Phylogenetic analysis on the E2 gene of the Getah virus (NMDK1813-1) showed that it belonged to the same evolutionary branch of the Gansu isolates (GS10-2) and having six common amino acid variation sites. Conclusions: The emergence of Japanese encephalitis virus and Getah virus from specimen of mosquitoes in Inner Mongolia indicated the new challenges on the prevention and control of arbovirus and related diseases. The results pf this study provided basic data for the prevention and control stretagies of arbovirus transmitted diseases in Inner Mongolia.

Beneficial effect of Rhodopseudomonas palustris on in vitro rumen digestion and fermentation.

As a member of photosynthetic bacteria, Rhodopseudomonas palustris, which has extraordinary metabolic versatility, has been applied as one of potential probiotics in feed industry. To explore whether R. palustris can increase rumen microbial viability and thus improve microbial fermentation, a 2×5 factorial experiment was conducted to evaluate the effect of R. palustris at dose rates of 0, 1.3, 2.6, 3.9, 5.2×106 cfu/ml on ruminal fermentation of two representative total mixed rations (HY, a ration for high-yield (>32 kg/d) lactating cows; LY, a ration for low-yield (<25 kg/d) lactating cows). After a 48 h in vitro rumen incubation, both rations resulted in different fermentation characteristics. The HY in comparison with LY group presented greater in vitro dry matter disappearance (IVDMD), cumulative gas production (GP48) and total volatile fatty acids (VFA, P<0.01). Increasing R. palustris addition linearly increased IVDMD (P<0.01) and GP48 (P<0.05), and the IVDMD increment in response to R. palustris addition was greater in LY than HY group (6.4% vs 1.4%). Meanwhile, increasing R. palustris addition also linearly enhanced microbial protein synthesis and increased total VFA production (P<0.01), especially in LY group (up to 21.5% and 24.5% respectively). Unchanged acetate and declined propionate in molar percentage were observed in response to the R. palustris addition. Furthermore, increasing R. palustris addition altered fermentation gas composition in which molar O2 proportion in headspace of fermentation system was linearly reduced by 46.1% in LY and 32.9% in HY group, respectively (P<0.01), and methane production in both ration groups was enhanced by 1.9-4.1% (P=0.02). In summary, the R. palustris addition exhibited high potential for promoting the growth of rumen microorganism and enhancing microbial fermentation towards non-glucogenic energy supply by maintaining an anaerobic environment to microbe equilibrium.

[The changing trend of capacity on policy implementation related to the prevention and control of chronic non-communicable disease at the provincial level, from 2011 to 2017].

Objective: To assess the follow-up situstion and changes of policies related to the prevention and control on chronic non-communicable diseases (NCDs), in various provinces from 2011 to 2017. Methods: Three national assessment programs on the prevention and control capacity of NCDs were carried out from September 2012 to March 2013, September 2014 to March 2015, and July to November 2018 respectively. Data related to the capacity on policy implementation among the 31 provinces, autonomous regions, municipality directly under the central government and Xinjiang Production and Construction Corps, were collected through online surveys. Results: The rate of data collection in all the provinces reached 100%, for all three surveys. In 2011, 2013, and 2017, the capacity for policy development special funding was distributed for prevention and control NCDs under the provincial fiscal revenue by 27 provinces (84.4%), 26 provinces (81.3%) and 25 provinces (78.1%), and the numbers of provincial governments leaders attended the local activities related to prevention and control NCDs was 15 (46.9%), 13 (40.6%) and 19(59.4%), respectively. From 2009 to 2011, 14 (43.8%) proposals related to the topics on prevention and control of NCDs, were raised at the provincial People's Congress and Political Consultative Conference, while from 2011 to 2013 and2014 to 2017, 13 (40.6%) and 12 (37.5%) were respectively raised. In terms of capacity for policy development, numbers of provincial comprehensive plan which targeting prevention and control of NCDs reached 6 (18.8%), 20 (62.5%) and 27 (84.4%) in 2011, 2013, and 2017 respectively. In 2011, 2013 and 2017, numbers of provincial special plans that targeting on NCDs or the risk factors of NCDs prevention and control were 0, 1, and 3, respectively. Conclusions: Under the continuous introduction of international and national policies related to prevention and control on NCDs, capacity for policy formulation in various provinces has been greatly improved. However, a slight progress has been made in the capacity for policy making. The increase of capacity building on policy making regarding prevention and control of NCDs, at the provincial government level, has become a key issue.

[Assessment on the capacity for prevention and control programs for chronic non-communicable diseases in China, in 2014].

Objective: To assess the capacity of prevention and control on chronic non- communicable diseases (NCDs) in China. Methods: On-line questionnaire survey was adopted by 3 395 CDCs at provincial, municipal and county (district) levels and 3 000 primary health care units, and assess on capacity of policy, infrastructure, capacity of training and guidance, cooperation, surveillance, intervention and management, assessment and scientific research from September 2014 to March 2015. Results: (1) Capacity of policy: 23 (71.9%) provincial, 139 (40.6%) municipal and 919 (31.2%) county (district) governments or health administrative departments had existing plans for prevention and control of NCDs. (2) Capacity of infrastructure: 25 (78.1%) provincial, 136 (39.8%) municipal and 529 (18.0%) county (district) CDCs had set up departments dedicated to the prevention and control of NCDs, with 9 787 staff members, accounting for 5.0% of the total CDC personnel, working on NCDs prevention and control programs. 68.1% of the CDCs had special funding set for NCDs prevention and control. (3) Capacity of training and guidance: 2 485 CDCs (74.9%) held all kinds of training on prevention and control of NCDs. 2 571 (87.3%) CDCs at the county (district) level provided technical guidance for primary health care units. (4) Capacity of cooperation: 42.0% of the CDCs had experiences collaborating with the mass media. (5) Capacity of surveillance: 73.8% of the CDCs had set up programs for death registration while less than 50.0% of the CDCs had implemented surveillance programs on major NCDs and related risk factors. In terms of primary health care units, 32.4% of them had set up reporting system for newly developed stroke case and 29.9% of them having programs on myocardial infarction case reporting. (6) Capacity of intervention and management: 69.1% and 68.2% of the CDCs conducted individualized intervention programs on hypertension and diabetes, while less than 40.0% CDCs conducting intervention programs on other NCDs and risk factors. More than 90.0% of the primary health care units carried out follow-up surveys on hypertension and diabetes. However, only 17.4% and 13.7% of the CDCs working on hypertension and diabetes patient management programs while 83.7% and 80.4%, of them following the standardized guidelines for management, with successful rates of control as 59.2% and 55.2%, respectively. (7) Capacity of assessment: 32.4% of the CDCs or health administrations carried out evaluation programs related to the responses on NCDs. (8) Capacity of scientific research: the capacity on scientific research among provincial CDCs was apparently higher than that at the municipal or county (district) CDCs. Conclusions: Compared with the results of previous two surveys, the capacity on policies set for the prevention and control programs improved continuously, at all level NCDs, but remained relatively weak, especially at both county (district) and primary health care units.

[Efficacy and safety of anlotinib in 16 patients with advanced non-small cell lung cancer].

Objective: To evaluate the efficacy and safety of anlotinib in patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients with stage ⅢB/Ⅳ NSCLC who progressed after two lines or more regimens were randomized into anlotinib group (12 mg daily from day 1 to 14 of a 21-day cycle) or placebo group with ratio of 2∶1. Study drugs or placebo were given until disease progression or intolerable toxicity. The primary endpoint was overall survival (OS), and the second endpoints were progression free survival (PFS), objective response rate, and disease control rate. Results: Between April 2015 and December 2015, twenty-four patients were assigned at Peking Union Medical College Hospital. The baseline characteristics of the anlotinib group (n=16) and placebo group (n=8) were fairly comparable. The median OS was 12.7 months in anlotinib group and 11.1 months in placebo group (P=0.460).The median PFS was 4.0 months in anlotinib group and 1.4 months in placebo group (P=0.065).The common adverse events were manageable such as hypertension, hand-foot syndrome, thyroiddy sfunction. No drug-related mortality occurred. Conclusions: Anlotinib had a trend of improvement in OS and PFS as third-line treatment or beyond in advanced NSCLC compared with placebo with manageable toxicity. ClinicalTrials:: NCT02388919.

[Technical specification for clinical application of critical ultrasonography].

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound, the examiner and interpreter of the image are critical care medicine physicians. The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes. With the idea of critical care medicine as the soul, it can integrate the above information and clinical information, bedside real-time diagnosis and titration treatment, and evaluate the therapeutic effect so as to improve the outcome. CUS is a traditional technique which is applied as a new application method. The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept, implementation and application of CUS. It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure. At the same time, the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications, and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS. Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group, based on the rich experience of clinical practice in critical care and research, combined with the essence of CUS, to learn the traditional ultrasonic essence, established the clinical application technical specifications of CUS, including in five parts: basic view and relevant indicators to obtain in CUS; basic norms for viscera organ assessment and special assessment; standardized processes and systematic inspection programs; examples of CUS applications; CUS training and the application of qualification certification. The establishment of applied technology standard is helpful for standardized training and clinical correct implementation. It is helpful for clinical evaluation and correct guidance treatment, and is also helpful for quality control and continuous improvement of CUS application.

[A meta-analysis of randomized controlled trials of bismuth-containing quadruple therapy combined with probiotic supplement for eradication of Helicobacter pylori].

Objective: The bismuth containing quadruple therapy (BCQT) acts as first-line therapy in China. Probiotics supplement also shows Helicobacter pylori eradication effects. Adding probiotics along with BCQT may improve eradication rate of Helicobacter pylori. Methods: Electronic databases including Medline, Embase, Wanfang Database, etc. were searched by the established searching strategy. After that, a funnel plot was adopted to evaluate publication bias. The meta-analysis was supplemented in fixed effect model for low heterogeneity and randomized effect model for high heterogeneity conversely. Results: A total of 16 RCTs with 2 466 subjects finally met the inclusion criteria. There was no significant heterogeneity among the trials. Compared with control group (BCQT only), the probiotic group (combined supplement of probiotics and BCQT) underwent higher eradication rate[90.76%(1 130/1 245) vs 80.43%(982/1 221)]with statistical significance (P=0.000). The probiotics might improve the eradication rate in patients not receiving previous eradication therapy [89.00%(445/500) vs 84.73%(416/491), P=0.04]. Probiotics might also improve the eradication rate[91.06%(326/358) vs 73.83%(268/363)]in patients relapsed from triple therapy (P=0.000). The patients who underwent the combination of BCQT and single Lactobacillus genus showed higher eradiation rate than those with two or more genera. Moreover, fewer adverse reactions were reported in probiotics group than that in control group[13.59%(104/765) vs 28.90%(213/737), P=0.000]. Conclusions: The combination of BCQT and probiotics may improve the eradication rate of Helicobacter pylori especially in patients receiving front-line eradication regimen or failed from triple therapy. Probiotics may reduce the adverse reactions when combined with other eradication agents.

[The therapeutic value and safety of icotinib as first-line therapy for advanced non-small cell lung cancer patients].

Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%. The median PFS was 14.9 months (95%CI 13.5-16.3) and the OS was 37.0 weeks (95%CI 27.9-46.1). Patients with brain metastases showed higher ORR(P=0.049). Patients with stage ⅢB had longer PFS than those with stage Ⅳ(P=0.007). The most common adverse events were grade 1-2 skin rash (38 patients, 40.9%). Other adverse events included dry skin, oral mucositis, diarrhea and liver function injury. Three patients withdrew because of severe liver injury or skin rash. No treatment related mortality occurred. Conclusions: Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.

The impact of CVB3 infection on host cell biology.

CVB3 myocarditis can lead to dilated cardiomyopath (DCM). DCM is one of the leading causes of the need for heart transplantation, so it is important to understand the life cycle of CVB3 and its interactions with the host cell. Infection causes rapid death of host cardiomyocytes by altering normal cellular homeostasis for the efficient release of progeny virion. In this chapter, we will examine the impact that CVB3 replication has on host cell biology, from events that take place at receptor ligation to progeny virus release. The primary focus will be on the myriad of signalling pathways that are activated at all stages of virus replication and their downstream effects. We will also discuss some of the extracellular effects of infection as well as immune and matrixmetalloprotease activation. Interactions of host cell proteins with the 5' untranslated region (UTR) are required for translation and replication of CVB3. These interactions do not always benefit the virus since the interactions of a 28-kDa host protein with the 5' UTR are thought to be responsible for inhibitory activity against CVB3. Finally, we will discuss how the elucidation of the different stages of replication has provided the opportunity to develop novel strategies for combating CVB3 infection.