ObjectiveTo observe the effect of Chonglian oral liquid on inflammatory and immune markers as well as the clinical outcomes of patients with mild-to-moderate corona virus disease 2019（COVID-19） and comprehensively evaluate its efficacy and safety. MethodA clinical randomized controlled trial （RCT） was conducted， involving 120 confirmed cases of mild-to-moderate COVID-19. The patients were randomly divided into two groups， with 55 cases in the observation group and 56 cases in the control group. According to the updated diagnosis and treatment protocol， the control group received standard western medical treatment， while the observation group received Chonglian oral liquid in addition to standard western medical treatment. Both groups were treated continuously for 10 days. The traditional Chinese medicine （TCM） syndrome scores， syndrome efficacy， fever abatement time， nucleic acid negative conversion time， inflammatory and immune markers， improvement in imaging findings， clinical outcomes， and occurrence of adverse events were compared between the two groups. ResultBoth groups showed a significant decrease in TCM syndrome scores after treatment （P<0.01）. Compared with the control group after treatment， the observation group exhibited a more significant improvement in cough， dry throat， sore throat， fatigue， and muscle pain （P<0.05）. The total effective rate in the observation group was 100% （55/55）， significantly higher than 98.21% （55/56） in the control group （Z=3.707， P<0.01）. The observation group also showed a significantly shorter duration of fever abatement and nucleic acid negative conversion compared with the control group after treatment （P<0.05）. Both groups had a significant increase in lymphocyte count （LYM）， lymphocyte percentage （LYM%）， mature T lymphocytes （CD3⁺）， and helper/inducer T lymphocytes （CD4⁺） after treatment （P<0.01）. Compared with the control group after treatment， the observation group showed greater improvement in these markers （P<0.05）. In terms of inflammatory markers， both groups had a significant decrease compared with those before treatment （P<0.01）. The observation group exhibited lower levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-6 （IL-6）， and procalcitonin （PCT） than the control group after treatment （P<0.05）. There was no statistically significant difference in imaging efficacy evaluation and clinical outcomes between the two groups. No adverse events were reported in either group during the treatment period. ConclusionChonglian oral liquid combined with standard western medical treatment significantly improves clinical symptoms， shortens fever abatement and nucleic acid negative conversion time， regulates immune function， and inhibits inflammatory responses in patients with mild-to-moderate COVID-19， leading to improved clinical efficacy.

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.
Animals ; Cell Differentiation ; Disease Models, Animal ; Ischemic Stroke ; Proteomics ; Rats ; Stem Cell Transplantation/methods* ; Stroke/therapy*

Hepatogenous diabetes (HD) is a common complication of end-stage liver disease, and many studies have confirmed its adverse effect on prognosis. In recent ten years, a great number of studies have been conducted on the pathogenesis of HD and some progress has been made. This article reviews the research advances in the pathogenesis of HD, in order to provide a reference for the diagnosis and treatment of HD by clinicians.

Both diabetes mellitus and liver cirrhosis have high incidence rate and mortality rate around the world, and in recent ten years, scholars in China and globally have conducted many studies on the association between diabetes mellitus and liver cirrhosis. This article systematically reviews the advances in the basic and clinical research on the influence of diabetes mellitus on liver cirrhosis and its complications and summarizes possible mechanisms. The results show that diabetes mellitus can accelerate the process of liver fibrosis, increase the risk of complications and progression to liver cancer in patients with liver cirrhosis, and reduce their survival rate.

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.

Objective:To evaluate the effect of preventing and treatment of pharmaceuticals on intensive care unit-acquired weakness (ICU-AW) by systematic review.Methods:The randomized controlled trials (RCTs) concerning pharmaceutical prevention and treatment about ICU-AW in SinoMed, CNKI, Wanfang data, PubMed, Cochrane Library, Web of Science, EMbase, and other sources were searched from their foundation to May 30th, 2019. The patients in the intervention group were treated with drugs to prevent or treat ICU-AW; and those in control group were treated with other rehabilitation methods. Data searching, extracting and quality evaluation were assessed by two reviewers independently. Stata 12.0 software was then used for Meta-analysis. Only descriptive analysis was conducted when only one study was enrolled.Results:A total of 11 RCTs were enrolled with 1 865 patients in the intervention group and 1 894 in the control group. The results of quality evaluation showed that 4 studies were A-level and 7 studies were B-level, indicating that the overall quality of the enrolled literature was high. Meta-analysis showed that intensive insulin therapy could prevent ICU-AW [relative risk ( RR) = 0.761, 95% confidence interval (95% CI) was 0.662-0.876, P = 0.000], but reduced phenylalanine loss (nmol·100 mL -1·min -1: -3±3 vs. -11±3, P < 0.05) and glutamine intake (nmol·100 mL -1·min -1: -97±22 vs. -51±13, P < 0.05). There was no significant difference in the prevention and treatment of ICU-AW between other drugs (including growth hormone, glutamine, dexmedetomidine, neostigmine, oxandrolone, and intravenous immunoglobulin) and control group. Conclusions:Intensive insulin therapy can prevent ICU-AW, but the risk of hypoglycemia will increase. Other drugs including growth hormone, glutamine, dexmedetomidine, neostigmine, oxandrolone, and intravenous immunoglobulin have no obvious advantages in the prevention and treatment of ICU-AW, so no drug has been recommended to prevent and treat ICU-AW.

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.

Objective To determine the safety criteria for early goal-oriented rehabilition exercise in patients undergoing mechanical ventilation in intensive care unit (ICU) by systematic review.Methods Randomized controlled trails (RCTs) and cohort studies about early goal-oriented rehabilition exercise in patients undergoing mechanical ventilation in ICU were retrieved in CBM,CNKI,Wanfang Data,PubMed,Cochrane Library and Web of Science from their foundation to March 2018,and other sources as supplement was also retrieved.The intervention program of RCT study was ICU routine nursing in control group,early activity in observation group,and early activity in cohort study without control group.Early activities included active and passive activities on the bed,sitting upright,bed-chair transfer,standing and walking.Literature screening and data extraction were performed independently by two researchers.Variables or parameters.related to cardiovascular,respiratory,nervous,orthopedic and other systems were collected for safety criteria.Variables or parameters used in at least three literatures were collected for each system.Cochrane 5.1.0 was used to evaluate the quality of RCT study,and Newcastle-Ottawa scale (NOS) was used to evaluate the quality of cohort study.Results A total of 24 articles about early activity of patients undergoing mechanical ventilation in ICU were enrolled,involving 4647 patients,including 11 RCT studies involving 1 031 patients,509 in control group and 522 in observation group;13 cohort studies including 3616 patients.It was shown by systematic review that safety criteria for early activity in patients undergoing mechanical ventilation in ICU involved five systems,20 variables or parameters.The cardiovascular system included 8 variables or parameters,such as 40 bpm ＜ heart rate (HR) ＜ 130 bpm (n =4),hemodynamic stability (n =5),no myocardial infarction (n =3),no arrhythmia (n =4),no vascular active drugs (n =4),90 mmHg ＜ systolic blood pressure (SBP) ＜ 200 mmHg (1 mmHg =0.133 kPa,n =4),65 mmHg ≤ mean arterial pressure (MAP) ≤ 110 mmHg (n =3),no history of cardiopulmonary resuscitation (CPR,n =5).The respiratory system included 4 variables or parameters,involving 5 times/min ＜ respiratory rate (RR) ＜ 40 times/min (n =5),fraction of inspired oxygen (FiO2) ≤ 0.60 and positive end-expiratory pressure (PEEP) ≤ 10 cmH2O (1 cmH2O =0.098 kPa,n =4),FiO2 ＜ 0.60 or PEEP ＜ 10 cmH2O (n =3),pulse blood oxygenation (SpO2) ＞ 0.88 (n =5).The nervous system included 4 variables,including no neuromuscular disease (n =7),no increase in intracranial pressure (n =7),no coma (n =4),understand and do the right thing (n =4).The orthopedic system included 2 variables,including no fracture (n =3),no unstable fracture (n =8).Other factors included 2 variables,including no open abdomen wound (n =4),and no palliative care (n =3).Conclusions This study identified safety criteria for early goal-directed rehabilition exercise in patients undergoing mechanical ventilation in ICU included five systems of cardiovascular,respiratory,neurological,orthopedic,and other systems,in which cardiovascular and respiratory systems were the most frequently cited variables or parameters.The consistency of each system security criteria or variables reported by different literatures was high,but the parameters need to be further verified by high-quality study.

Objective:To investigate the effects of mindfulness based stress reduction on irritable bowel syndrome.Methods:PubMed,EMBASE,Cochrane Library,Web of Science,CNKI,Wanfang Data was searched and randomized clinical trials of MBSR treatment in irritable bowel disease were involved.At last two reviewers extracted the data independently.According to Cochrane Handbook5.1.0 handbook,a quality assessment was made.All the data would be analyzed with meta-analysis by the software of Stata.Results:Totally 5 randomized controlled trials were eligible,including 461 participants.Meta-analysis showed that MBSR would be better therapy method to improve the symptom severity of irritable bowel syndrome in 3 months,[SMD =-0.60,95％ CI:-0.86 ～-0.34,P ＜0.01],and the pain index at the 3 months and 6 months was relieved compared to the baseline [SMD =-1.11,95％ CI:-1.45 ～-0.76,P ＜ 0.01,SMD =-0.14,95％ CI:-0.43 ～ 0.14,P ＜ 0.05].Conclusion:Mindfulness based stress reduction therapy could be a adjunctive therapy method in treatment of irritable bowel syndrome.

Objective To systematically evaluate the efficacy of high-flow nasal cannulae oxygen (HFNC) in patients with respiratory failure.Methods Computerized PubMed, Embase, Web of Science, the Cochrane Library, CNKI, CBM, VIP, Wanfang Database up to March 31st, 2017, all published available randomized controlled trials (RCTs) or cohort studies about HFNC therapy for patients with respiratory failure were searched. The control group was treated with face mask oxygen therapy (FM) or non-invasive positive pressure ventilation (NIPPV), while the experimental group was treated with HFNC. The main outcomemeasurements included endotracheal intubation rate, patient comfort, and the secondary outcome was in-hospital mortality. The quality of the literature was completed by two professionally trained evidence-based medical students, and meta-analysis was performed on quality-compliant literature. Funnel plot was used to analyze the publication bias.Results A total of 17 articles were enrolled including 15 RCTs and 2 cohort studies. There were 3909 patients enrolled, 1907 patients in HFNC group, and 2002 in control group (1068 patients with FM, and 934 with NIPPV). Meta-analysis showed that HFNC had a significant advantage over FM in reducing the tracheal intubation rate of patients with respiratory failure [odds ratio (OR) = 0.51, 95% confidence interval (95%CI) = 0.29-0.89,P = 0.02], but there was no significant difference as compared with that of NIPPV (OR = 0.80, 95%CI = 0.54-1.17,P = 0.25). It was shown by pooled analysis of two subgroups that compared with FM/NIPPV, HFNC had a significant advantage in reducing tracheal intubation rate in patients with respiratory failure (pooledOR = 0.66, 95%CI = 0.47-0.94, P = 0.02). Compared with FM, patients with respiratory failure were more likely to receive HFNC for comfort [standardized mean difference (SMD) = -0.41, 95%CI = -0.56 to -0.26,P < 0.00001]. There was no significant difference in hospital mortality between HFNC and FM (OR = 0.82, 95%CI = 0.55-1.24,P = 0.35) or NIPPV (OR = 0.66, 95%CI = 0.37-1.17, P = 0.16). The results of pooled analysis of two subgroups were still unchanged (pooledOR = 0.75, 95%CI = 0.54-1.05, P = 0.09). It was shown by the funnel analysis that there was a bias in the study of tracheal intubation rate in the literature, while the bias of patient comfort and hospital mortality was low.Conclusions Compared with FM, HFNC could reduce the rate of tracheal intubation in patients with respiratory failure, but no difference was found as compared with NIPPV. Compared with FM, HFNC made patients more comfortable, and it was easier to be accepted and tolerated. However, there was no difference in hospital mortality among FM, NIPPV, and HFNC.