Outcomes for Organ Preservation with Chemoradiation Therapy for T4 Larynx and Hypopharynx Cancer.

OBJECTIVE: Limited data is available to guide non-surgical management of Stage T4 larynx and hypopharynx cancer patients who have inoperable disease or refuse surgery. We aim to review the nonoperative management of T4 laryngeal and hypopharyngeal cancer and report the long-term therapeutic and functional outcomes. METHODS: We reviewed the nonoperative management of T4 laryngeal (n = 44) and hypopharyngeal (n = 53) cancer from 1997 to 2015 and performed a univariate analysis (UVA). RESULTS: The 2-/5-year OS rates were 73%/38% for larynx patients and 52%/29% for hypopharynx patients. Locoregional failure (LRF) occurred in 25% and 19% of larynx and hypopharynx patients, respectively. On UVA of the larynx subset, N3 nodal status and non-intensity-modulated radiation therapy were negatively associated with OS; treatment with radiation therapy alone impacted disease-free survival; and age >70 was associated with LRF. On UVA of the hypopharynx subset, only T4b status significantly impacted OS. In the larynx and hypopharynx groups, 68% and 85% received a percutaneous endoscopic gastrostomy (PEG) tube and 32% and 40% received a tracheostomy tube, respectively. At the last follow-up visit, 66% of our larynx cohort had neither tracheostomy or PEG placed and 40% of our hypopharynx cohort had neither. CONCLUSION: We report better than previously noted outcomes among T4 larynx and hypopharynx patients who have unresectable disease or refuse surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1138-1145, 2023.

Application value of CT plain scan and dynamic enhanced scan in the diagnosis of solitary pulmonary nodules / 中国医师杂志

Objective:To explore the application value of computed tomography (CT) plain scan and dynamic enhanced scan in the diagnosis of solitary pulmonary nodules.Methods:The clinical data of 120 patients with solitary pulmonary nodules detected by physical examination in Baoding First Central Hospital from January 2018 to December 2020 were retrospectively reviewed. All patients were confirmed by surgery and pathology, including 77 benign lesions and 43 malignant lesions; All patients underwent CT plain scan and dynamic enhanced scan before operation. The accuracy of the two examination methods in the diagnosis of benign and malignant lesions of solitary pulmonary nodules was analyzed and compared. The detection rate of CT dynamic enhanced scan imaging characteristics (vacuole sign, ground glass sign, spinous sign, lobulation sign, hair prick sign, blood vessel cluster, pleural depression) of benign and malignant lesions of solitary pulmonary nodules was compared, and the diagnostic value of CT plain scan and dynamic enhanced scan in the differential diagnosis of benign and malignant solitary pulmonary nodules was evaluated based on the results of surgical pathological diagnosis. The manifestations and characteristic curves of CT dynamic enhanced scan of solitary pulmonary nodules was analyzed.Results:The diagnostic accuracy of CT dynamic enhanced scan for solitary pulmonary nodules was 80.00% (96/120), which was higher than that of CT plain scan (63.33%) (76/120) ( P<0.05). The sensitivity, specificity, and negative predictive value of CT dynamic enhanced scan for the diagnosis of benign and malignant lesions of solitary pulmonary nodules were higher than those of CT plain scan (all P<0.05). Among the imaging characteristics of CT dynamic enhanced scans of malignant lesions, the ground glass sign, spinous process sign, lobulation sign, spiculation sign, vascular clustering and pleural indentation were detected more frequently than those of benign lesions (all P<0.05). Benign lesions usually showed homogeneous enhancement, and a few showed heterogeneous enhancement; Malignant nodules often showed uneven enhancement, and a few had even enhancement. The time density curves of dynamic enhanced CT values in the regions of interest of benign and malignant solitary pulmonary nodules were different. Conclusions:The value of dynamic enhanced CT scan in the differential diagnosis of benign and malignant lesions of solitary pulmonary nodules is higher than that of CT plain scan, and the imaging features are obvious, with higher sensitivity and specificity, which is worthy of application.

Current situation and reflections on art therapy guidelines / 中华行为医学与脑科学杂志

Art therapy plays an important role in enhancing the emotional expression of patients, treating mental and psychological diseases, and promoting the recovery of cancer patients.Due to its extensive meaning and various intervention measures, strengthening the guidance and monitoring of art therapy are important in improving the medical quality of related fields.Clinical practice guidelines are important tools to guide and standardize medical behavior, and also are important guarantees for the implementation effect of medical behavior.Therefore, this article will summarize the current situation of art therapy guidelines, and on this basis, reflect on the formulation and implementation of relevant guidelines and recommendations.

Vps34 Inhibits Hepatocellular Carcinoma Invasion by Regulating Endosome-Lysosome Trafficking via Rab7-RILP and Rab11 / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The role of vacuolar protein sorting 34 (Vps34), an indispensable protein required for cell vesicular trafficking, in the biological behavior of hepatocellular carcinoma (HCC) has yet to be studied. @*Materials and Methods@#In the present study, the expression of Vps34 in HCC and the effect of Vps34 on HCC cell invasion was detected both in vivo and in vitro. Furthermore, by modulating the RILP and Rab11, which regulate juxtanuclear lysosome aggregation and recycling endosome respectively, the underlying mechanism was investigated. @*Results@#Vps34 was significantly decreased in HCC and negatively correlated with the HCC invasiveness both in vivo and in vitro. Moreover, Vps34 could promote lysosomal juxtanuclear accumulation, reduce the invasive ability of HCC cells via the Rab7-RILP pathway. In addition, the deficiency of Vps34 in HCC cells affected the endosome-lysosome system, resulting in enhanced Rab11 mediated endocytic recycling of cell surface receptor and increased invasion of HCC cells. @*Conclusion@#Our study reveals that Vps34 acts as an invasion suppressor in HCC cells, and more importantly, the endosome-lysosome trafficking regulated by Vps34 has the potential to become a target pathway in HCC treatment.

Evolution of ACE2 and SARS-CoV-2 Interplay Across 247 Vertebrates

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause the most serious pandemics of Coronavirus Disease 2019 (COVID-19), which threatens human health and public safety. SARS-CoV-2 spike (S) protein uses angiotensin-converting enzyme 2 (ACE2) as recognized receptor for its entry into host cell that contributes to the infection of SARS-CoV-2 to hosts. Using computational modeling approach, this study resolved the evolutionary pattern of bonding affinity of ACE2 in 247 jawed vertebrates to the spike (S) protein of SARS-CoV-2. First, high-or-low binding affinity phenotype divergence of ACE2 to the S protein of SARS-CoV-2 has appeared in two ancient species of jawed vertebrates, Scyliorhinus torazame (low-affinity, Chondrichthyes) and Latimeria chalumnae (high-affinity, Coelacanthimorpha). Second, multiple independent affinity divergence events recur in fishes, amphibians-reptiles, birds, and mammals. Third, high affinity phenotypes go up in mammals, possibly implying the rapid expansion of mammals might accelerate the evolution of coronaviruses. Fourth, we found natural mutations at eight amino acid sites of ACE2 can determine most of phenotype divergences of bonding affinity in 247 vertebrates and resolved their related structural basis. Moreover, we also identified high-affinity or low-affinity-associated concomitant mutation group.The group linked to extremely high affinity may provide novel potentials for the development of human recombinant soluble ACE2 (hrsACE2) in treating patients with COVID-19 or for constructing genetically modified SARS-CoV-2 infection models promoting vaccines studies. These findings would offer potential benefits for the treatment and prevention of SARS-CoV-2.

Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice / 神经科学通报·英文版

A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whether DISC1 mouse models have an impairment in avoiding potential risks. In the present study, we used DISC1-N terminal truncation (DISC1-N

Importance of zinc in human immune system / 中华微生物学和免疫学杂志

Zinc is one of the essential trace elements for human. It is essential for human health. In recent decades, the distribution and transport of zinc in human body have gradually become more evident. The immunomodulatory effects of zinc on the immune system have also been elucidated. Zinc is involved in regulating the cellular signaling pathways of immune cells and affecting the development of immune organs, the physiological state and function of immune cells and the secretion of cytokines. It is an indispensable element in the immune system and plays an important role in maintaining the integrity and stability of the immune system. This article briefly introduced the distribution and transportation of zinc in the human body, with the emphasis on the relationship between zinc and the development and function of immune cells.

Human coronavirus OC43 and its correlation with SARS-CoV-2 / 中华微生物学和免疫学杂志

Human coronavirus OC43 (HCoV-OC43) and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) belong to the β-coronavirus genus. Since the discovery in 1967, HCoV-OC43 has been continuously circulating in human population and has become one of the common seasonal respiratory viruses. SARS-CoV-2, which has a higher morbidity and fatality rate, appeared at the end of 2019, followed by the emergence of a variety of variants, and the transmission and infection capacity of SARS-CoV-2 has been enhanced. HCoV-OC43 may be similar to SARS-CoV-2 in terms of genomic structure and function, species evolution, epidemic characteristics and clinical manifestations. In this review, the epidemiology, genomics, phylogenetic evolution and other aspects of HCoV-OC43 and SARS-CoV-2 were analyzed. Such an analysis would be helpful to understand the association and differences between the two viruses, and provide reference for understanding the potential threats of HCoV-OC43.

The Chinese version of the Chelsea Critical Care Physical Assessment Tool applied in critically ill patients / 中国实用护理杂志

Objective:To explore the threshold and diagnostic value of Chinese version of the Chelsea Physical Function Assessment Tool (CPAx-Chi) for ICU acquired weakness(ICU-AW).Methods:To learn the details and precautions of the CPAx-Chi scale, and then two researchers used the CPAx-Chi scale and MRC-Score scale to independently evaluate 200 patients who come from a comprehensive ICU in a top first-class hospital in Gansu Province simultaneously. The best cut-off point and value of the CPAx-Chi scale in the diagnosis of ICU-AW were determined by calculating the Receiver Operating Characteristic (ROC) curve, the Youden index(YI) and the consistency test that are all based on the MRC-Score≤48.Results:The ROC Area Under Curve(AUC) of the CPAx-Chi scale diagnosis ICU-AW which based on the MRC-Score≤48 were as follows: ROC AUC of group A was 0.899 (95% CI 0.862-1.025); ROC AUC of group B was 0.874 (95% CI 0.824-0.925). When the best cut-off point of CPAx-Chi scale for diagnosis ICU-AW was 31.5, the maximum YI=0.643, the sensitivity was 87%, and the specificity was 77% in group A; and the maximum YI= 0.62, the sensitivity was 75%, and the specificity was 87% in group B. Meanwhile, when the best cut-off point of CPAx-Chi scale for diagnosis ICU-AW was 30.5, the maximum YI=0.62, the sensitivity was 79%, and the specificity was 83% in group B. Taking the CPAx -Chi≤31 as the best cut-off point, the score differences in ICU-AW group and the non-ICU-AW group were not detected, A group ( F value was 4.53, P=0.035) or B group ( F value was 6.51, P=0.011). The consistency of CPAx -Chi≤31 and MRC-Score≤48 in the diagnosis of ICU-AW was high, and the Kappa=0.845 ( P=0.02) in the group A; the Kappa=0.839( P=0.04) in the group B, and the group differences were detected. Conclusions:CPAx-Chi≤31 is the best cut-off point for diagnosing ICU-AW, and has good sensitivity and specificity. CPAx-Chi scale can be popularized and applied in the critical care medicine in China.

Effects of broad-spectrum antibiotics on the efficacy of 5-fluorouracil treatment of CT26 tumor-bearing mice / 中华微生物学和免疫学杂志

Objective:To study the effects of broad-spectrum antibiotics and induced antibiotic-resistant bacteria on the efficacy of 5-fluorouracil (5-FU) chemotherapy for mice with colon cancer and to investigate the underlying mechanisms associated with anti-tumor immune responses.Methods:BALB/c mice were subcutaneously injected with CT26 colon cancer cells and randomized into four groups: tumor-bearing control group, antibiotic group treated with ampicillin, streptomycin and colistin, 5-FU group and anitibiotic+ 5-FU group. Tumor volumes and body weights were measured and recorded. Seven days after the last 5-FU treatment, the percentages of splenic immune cell subpopulations and proliferated CD8 + T cells after co-culturing with CT26 were analyzed by flow cytometry. Gut microbiota composition was detected by 16S rRNA sequencing and the bacteria in mesenteric lymph nodes (mLN) were isolated and cultured. Bone marrow-derive macrophages were stimulated with identified bacteria and the expression of M1 and M2 polarization markers were assessed by quantitative PCR. The proliferation of CD8 + T cells co-cultured with bacteria-treated macrophages was analyzed by flow cytometry. In addition, tumor-bearing mice were treated with 5-FU and oral gavage of bacteria isolated from antibiotic+ 5-FU group or PBS. Tumor volumes, gut microbiota composition and the percentages of proliferated CD8 + T cells co-cultured with CT26 were assessed. Results:Tumor volumes were larger and body weights were lower in the antibiotic+ 5-FU group than in the 5-FU group. The percentages of CD4 + T cells, CD8 + T cells and neutrophils did not varied significantly after using antibiotics, however, the percentage of monocytes was increased in the antibiotic group. The percentage of proliferated tumor-specific CD8 + T cells in the antibiotic+ 5-FU group was decreased compared with that in the 5-FU group. Compared with the control group and 5-FU group, antibiotic usage was associated with the changes in gut microbiota composition with decreased α diversity indexes. Escherichia coli, Klebsiella pneumonia, and Proteus mirabilis were isolated from mLNs of the antibiotic group, 5-FU group and antibiotic+ 5-FU group, respectively. Bone marrow-derived macrophages stimulated with Proteus mirabilis expressed arginase at a high level, which was a M2 polarization marker of macrophage, and associated with the decreased percentage of proliferated CD8 + T cells after co-culturing. Bacteria of the genus Proteus were enriched in the gut microbiota of 5-FU-treated tumor-bearing mice with the oral gavage of Proteus mirabilis. Although no significant inhibitory effect on tumor growth was observed, the oral gavage of Proteus mirabilis was associated with the decreased percentage of proliferated tumor-specific CD8 + T cells in vitro. Conclusions:Broad-spectrum antibiotics inhibited the efficacy of chemotherapy and the proliferation of tumor-specific CD8 + T cells, in which antibiotic-resistant bacteria might be involved.

Meta-analysis of effects of neuromuscular electrical stimulation of lower limbs on patients with mechanical ventilation in intensive care unit / 中华危重病急救医学

Objective:To evaluate the effect of lower limb neuromuscular electrical stimulation (NMES) on mechanical ventilation patients in intensive care unit (ICU).Methods:Databases including the Cochrane Library, PubMed, Web of Science, Embase, SinoMed, CNKI, VIP and Wanfang database were searched from inception to May 2021. Randomized controlled trails (RCT) about the influence of NMES of lower limbs in patients with mechanical ventilation in ICU were collected. Routine rehabilitation measures were implemented in the control group, while the combination of routine rehabilitation and NMES on the lower limbs was implemented in the observation group. The literature screening, data extracting, and bias risk assessment of included studies were conducted independently by two reviewers. RevMan 5.3 software was used to perform Meta-analysis. Funnel plot was used to test publication bias.Results:A total of 8 RCT were eventually enrolled. The literature quality evaluation results showed that 1 study was grade A and 7 studies were grade B, suggesting that the quality of the included literature was relatively high. The Meta-analysis results showed that NMES in the lower extremities could effectively shorten the duration of mechanical ventilation in ICU patients [standardized mean difference ( SMD) = -0.51, 95% confidence interval (95% CI) was -0.72 to -0.31, P < 0.000 01], increase the maximum inspiratory pressure [MIP; mean difference ( MD) = 14.19, 95% CI was 9.30 to 19.09, P < 0.000 01], and improve the functional status of critically ill patients [functional status score for ICU (FSS-ICU); MD = 10.44, 95% CI was 3.12 to 17.77, P = 0.005] with statistically significances. However, there were no significant advantages in increasing the Medical Research Council (MRC) score ( MD = 2.13, 95% CI was -1.38 to 5.63, P = 0.23), reducing ICU mortality [relative risk ( RR) = 0.80, 95% CI was 0.51 to 1.24, P = 0.31], shortening length of ICU stay ( MD = -0.54, 95% CI was -3.67 to 2.59, P = 0.74), and the combined effect was not statistically significant. Funnel plot based on the duration of mechanical ventilation showed that the distribution of included articles was basically symmetrical, and no publication bias was detected. Conclusions:NMES of the lower limbs can not only shorten the ventilation duration effectively, but also improve the MIP and functional status of mechanically ventilated patients in ICU. However, it has no significant effect on the MRC score, ICU mortality and length of ICU stay of patients with mechanical ventilation. In the future, high-quality, large sample size and multi-center RCT are needed to verify the effects of NMES.

Early mobilization on mortality of patients with mechanical ventilation in intensive care unit after discharge: a Meta-analysis / 中华危重病急救医学

Objective:To evaluate the effect of early mobilization on mortality in intensive care unit (ICU) patients with mechanical ventilation after discharge by Meta-analysis.Methods:Databases including SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang data, PubMed, the Cochrane Library, Web of Science, and Embase were searched from inception to September 17th, 2020, to collect randomized controlled trials (RCT) about early mobilization on mortality of patients with mechanical ventilation in ICU after discharge, the references included in the literature were traced. The control group was given routine care, the experimental group was given early mobilization on the basis of the control group, including passive or active mobilization on the bed, sitting on the bed, standing by the bed, transferring to the bedside chair and assisting walking. The literature screening, data extracting, and the bias risk assessment of included studies were conducted independently by two reviewers. Stata 12.0 software was then used to perform Meta-analysis. Funnel plot was used to test publication bias.Results:A total of 10 RCT studies involving 1 323 patients were included, with 660 patients in the control group and 663 patients in the experimental group. The results of literature quality evaluation showed that 7 studies were grade A and 3 studies were grade B, indicating that the overall quality of included literatures was high. The Meta-analysis results showed that early mobilization did not increase the mortality of patients with mechanical ventilation in ICU after discharge [odds ratio ( OR) = 0.92, 95% confidence interval (95% CI) was 0.75-1.13, P = 0.449]. Subgroup analysis results showed that early mobilization had a tendency to reduce the mortality of ICU patients with mechanical ventilation at 3, 6 and 12 months after discharge, but the difference was not statistically significant (3-month mortality: OR = 1.02, 95% CI was 0.74-1.40, P = 0.927; 6-month mortality: OR = 0.95, 95% CI was 0.70-1.27, P = 0.712; 12-month mortality: OR = 0.60, 95% CI was 0.33-1.10, P = 0.101). Funnel plot showed that the distribution of included literatures was not completely symmetrical, suggesting that publication bias might exist. Conclusions:Early mobilization does not increase the mortality of ICU patients with mechanical ventilation after discharge. Although it tends to have a favorable outcome in reducing mortality, and has a trend to reduce the mortality. However, due to the small number of included literatures, small sample size and differences in the specific implementation of early mobilization among various studies, a large number of high-quality RCT studies are still needed for further verification.

Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice / 神经科学通报·英文版

A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whether DISC1 mouse models have an impairment in avoiding potential risks. In the present study, we used DISC1-N terminal truncation (DISC1-N

Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine

A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.

Temporal dynamics of human respiratory and gut microbiomes during the course of COVID-19 in adults

SARS-CoV-2 infects multiple organs including the respiratory tract and gut. Whether regional microbiomes are disturbed significantly to affect the disease progression of COVID-19 is largely unknown. To address this question, we performed cross-sectional and longitudinal analyses of throat and anal swabs from 35 COVID-19 adults and 15 controls by 16S rRNA gene sequencing. The results allowed a partitioning of patients into 3-4 categories (I-IV) with distinct microbial community types in both sites. Lower-diversity community types often appeared in the early phase of COVID-19, and synchronous fast restoration of both the respiratory and gut microbiomes from early dysbiosis towards late near-normal was observed in 6/8 mild COVID-19 adult patients despite they had a relatively slow clinical recovery. The synchronous shift of the community types was associated with significantly positive bacterial interactions between the respiratory tract and gut, possibly along the airway-gut axis. These findings reveal previously unknown interactions between respiratory and gut microbiomes, and suggest that modulations of regional microbiota might help to improve the recovery from COVID-19 in adult patients.

Progressive worsening of the respiratory and gut microbiome in children during the first two months of COVID-19

Children are less susceptible to COVID-19 and manifests lower morbidity and mortality after infection, for which a multitude of mechanisms may be proposed. Whether the normal development of gut-airway microbiome is affected by COVID-19 has not been evaluated. We demonstrate that COVID-19 alters the respiratory and gut microbiome of children. Alteration of the microbiome was divergent between the respiratory tract and gut, albeit the dysbiosis was dominated by genus Pseudomonas and sustained for up to 25-58 days in different individuals. The respiratory microbiome distortion persisted in 7/8 children for at least 19-24 days after discharge from the hospital. The gut microbiota showed early dysbiosis towards later restoration in some children, but not others. Disturbed development of both gut and respiratory microbiomes, and prolonged respiratory dysbiosis in children imply possible long-term complications after clinical recovery from COVID-19, such as predisposition to an increased health risk in the post-COVID-19 era.

Characterization of the SARS-CoV-2 Spike in an Early Prefusion Conformation

Pandemic coronavirus disease 2019 (COVID-19) is caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there are no efficacious vaccines or therapeutics that are urgently needed. We expressed three versions of spike (S) proteins--receptor binding domain (RBD), S1 subunit and S ectodomain--in insect cells. RBD appears monomer in solutions, whereas S1 and S associate into homotrimer with substantial glycosylation. The three proteins confer excellent antigenicity with six convalescent COVID-19 patient sera. Cryo-electron microscopy (cryo-EM) analyses indicate that the SARS-CoV-2 S trimer dominate in a unique conformation distinguished from the classic prefusion conformation of coronaviruses by the upper S1 region at lower position ~15 [A] proximal to viral membrane. Such conformation is proposed as an early prefusion state for the SARS-CoV-2 spike that may broaden the knowledge of coronavirus and facilitate vaccine development.

Pangolin homology associated with 2019-nCoV

To explore potential intermediate host of a novel coronavirus is vital to rapidly control continuous COVID-19 spread. We found genomic and evolutionary evidences of the occurrence of 2019-nCoV-like coronavirus (named as Pangolin-CoV) from dead Malayan Pangolins. Pangolin-CoV is 91.02% and 90.55% identical at the whole genome level to 2019-nCoV and BatCoV RaTG13, respectively. Pangolin-CoV is the lowest common ancestor of 2019-nCoV and RaTG13. The S1 protein of Pangolin-CoV is much more closely related to 2019-nCoV than RaTG13. Five key amino-acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and 2019-nCoV but four amino-acid mutations occur in RaTG13. It indicates Pangolin-CoV has similar pathogenic potential to 2019-nCoV, and would be helpful to trace the origin and probable intermediate host of 2019-nCoV.

Current practice and obstacle factors of intensive care unit-acquired weakness assessment / 中华危重病急救医学

Objective:To investigate the current status of intensive care unit-acquired weakness (ICU-AW) assessment, analyze the assessment barriers, and to provide reference to improve ICU-AW assessment.Methods:A convenient sampling cross-sectional survey was conducted. First, an interview outline which based on related domestic and international literatures and combining with the research purpose of this study were designed. Thirteen medical personnel (8 ICU nurses, 3 ICU doctors, 1 respiratory therapist and 1 physiotherapist) who worked in the intensive care unit (ICU) of the First Hospital of Lanzhou University were enrolled with convenience sampling method to interview. Second, the topics were comprehensively analyzed and extracted, and then a questionnaire was constructed, and the reliability and validity was assessed. Finally, the questionnaire survey including the general situation of ICU medical staffs, the current practices of ICU-AW and influencing factors was implemented in China.Results:The retest reliability was 0.92 and expert validity was 0.96 of the questionnaire. There were 3 563 respondents in 31 provinces, municipalities and autonomous regions which eliminated 357 unqualified questionnaires, including 173 respondents from neonatal or pediatric ICU, 89 respondents whose working time was less than 6 months, and 95 invalid respondents, and then there were finally 3 206 valid questionnaires and the response rate were 90.0%. Those 3 206 respondents included 616 doctors (19.2%), 2 371 nurses (74.0%), 129 respiratory therapists (4.0%), 51 physiotherapist (1.6%) and 39 dietitians (1.2%). The mean age was (30.7±6.3) years old. Most of them had bachelor's degree (65.9%), master and above was 14.1%. Associate senior physician and above was 8.0%; ICU working time was (5.94±4.50) years. In clinical practice, only 26.5% of the ICU medical staffs confirmed that they had treated or taken care for ICU-AW patients; 52.9% of medical staffs evaluated ICU-AW only based on clinical experience, and only 12.3% used ICU-AW assessment tools. The majority of respondents believed that ICU-AW knowledge training should be performed (81.8%), ICU-AW assessment should be as important as other complications (pressure sore, infected ventilator associated pneumonia, etc., 75.1%), and ICU-AW assessment should be part of daily treatment and care activities (61.2%). However, only 10.2% of respondents had received ICU-AW related knowledge training, and 42.7% respondents believed that their ICU-AW related knowledge could not meet clinical needs. Only 18.7% respondents would actively assess whether patients suffered from ICU-AW or not, and 42.3% respondents thought that ICU-AW should be assessed every day, and the assessment tools were also inconsistent. There were 44.0% respondents considered the Medical Research Council Muscle score (MRC-score) scale was the optimal tool for diagnosing ICU-AW, the following were neuro-electrophysiological examination (17.2%) and manual muscle strength (MMT, 11.1%). The main cause of the ICU-AW assessment barriers was the lack of ICU-AW related knowledge (88.1%), and the following were lack of ICU-AW assessment guidelines (76.5%), patients' cognitive impairment or limited understanding ability (84.6%), unable to cooperate with the assessment due to critical illness (83.0%), and inadequate attention to ICU-AW assessment by the department (77.5%).Conclusion:The current status of ICU-AW assessment were unsatisfying in China, and the main barriers were lack of skills and knowledge.

Cognitive impairment after intensive care unit discharge: a Meta-analysis / 中华危重病急救医学

Objective:To investigate the cognitive impairment after intensive care unit (ICU) discharge and provide theoretical basis for prevention and intervention.Methods:Studies about cognitive impairment after ICU discharge were retrieved in PubMed, Embase, Cochrane Library, Web of Science, Wanfang data, CNKI and SinoMed from their foundation to December 2019. The literature screening and data extraction were performed by two researchers independently, and the quality of different types of researches was evaluated using Cochrane Handbook 5.1.0, Newcastle-Ottawa scale (NOS) and agency for healthcare research and quality criteria (AHRQ). The Meta-analysis was performed by Stata 13.0 software. Sensitivity analysis was used to determine the reliability of the combined effect values. Funnel plot and Egger test were used to analyze publication bias. The non-parametric clipping was used to evaluate the impact of publication bias on the results.Results:A total of 35 studies were enrolled, including 27 prospective cohort studies, 4 retrospective cohort studies, 2 randomized controlled trial (RCT) studies, 1 case-control study, and 1 cross-sectional study. Three literatures were published in Chinese and 32 were in English, which covered 13 countries, and a total of 102 504 ICU survivors were followed up successfully. Literature quality evaluation results showed that the NOS scores of 31 cohort studies were between 6 and 9, of which the case-control study scored 9. The quality grade of 2 RCT studies were both B. According to the AHRQ criteria, 1 cross-sectional study's design was scientifically rigorous and of high quality. Thirty-five studies reported that the overall incidence of cognitive impairment after ICU discharge ranged from 2.47% to 66.07%. For the multiple follow-ups studies, the first survey data was selected for Meta-analysis, and the results showed that the pooled incidence was 38.44% [95% confidence interval (95% CI) was 29.32-47.55]. Each study was removed for sensitivity analysis and the pooled results did not change much, which indicated that the results were reliable. The sub-group analysis was performed on different evaluation methods for cognitive impairment after ICU discharge, different types of ICU patients, and different follow-up time. The results showed that the pooled incidence of studies using neuropsychological test to evaluate cognitive impairment after ICU discharge was 31.42% (95% CI was 21.82-41.02), the pooled incidence of studies using questionnaires or scales was 38.75% (95% CI was 29.54-47.96), and the difference between the two groups was statistically significant ( P < 0.01). The pooled incidence of cognitive impairment after ICU discharge in general ICU patients was 43.42% (95% CI was 30.88-55.95), acute respiratory distress syndrome (ARDS) patients' pooled incidence was 34.40% (95% CI was 23.02-45.79), and the pooled incidence of elderly ICU patients was 12.93% (95% CI was 8.48-17.37), the difference among the three groups was statistically significant ( P < 0.01). The incidences of cognitive impairment < 1 year, 1 to 4 years, ≥ 5 years after ICU discharge were 43.30% (95% CI was 29.47-57.13), 34.21% (95% CI was 26.70-41.72), and 20.22% (95% CI was 4.89-35.55), respectively, and the differences among the three groups were statistically significant ( P < 0.01). The funnel plot showed that the distribution of all studies was asymmetric, and the Egger test result also suggested that there might be publication bias ( P < 0.05). The non-parametric clipping was used to estimate the impact of publication bias on the results, and the result showed that the difference in the incidence of cognitive impairment after ICU discharge before and after non-parametric clipping was large, suggesting that publication bias might influence the stability of the research results. Conclusions:The incidence of cognitive impairment after ICU discharge is relatively high and persistent for a long time, but diagnostic criteria of cognitive impairment and follow-up time are quite different. It is necessary to develop consistent evaluation criteria and rigorous designed research in the further.