The plant AT-rich sequence and zinc-binding protein (PLATZ) family is composed of plant-specific zinc finger-like transcription factors, which play important roles in plant growth, development, and stress tolerance. In this study, to gain a better understanding of the PLATZ gene in C. sinensis and elucidate its response under drought and high temperature conditions, the PLATZ gene family of the C. sinensis cultivar 'Tieguanyin' was systematically identified, and a total of 12 CsPLATZ family members were identified. Expasy online and other bioinformatics tools were used to analyze the members of the PLATZ gene family in terms of protein physicochemical properties, phylogenetic relationships, cis-acting elements, gene structures, and intra- and inter-species collinearity. The results of phylogenetic analysis classified the CsPLATZ family members into 2 subfamilies. The conserved domains and gene structures of PLATZ family members within the same subfamily had a high degree of consistency, whereas a certain degree of diversity was observed among the subfamilies. Twelve PLATZ genes were unevenly distributed across 7 chromosomes of C. sinensis and the promoter regions of these genes had multiple cis-acting elements related to hormone and stress responses. The collinearity analysis showed that there were 4 pairs of duplication events in the CsPLATZ gene family, all of which were segmental duplications. Based on this gene family, C. sinensis had a closer evolutionary relationship with A. thaliana than with O. sativa. The transcriptome analysis showed that the expression levels of CsPLATZ family members varied in different tissue samples of C. sinensis. 6 genes (CsPLATZ-1, CsPLATZ-2, CsPLATZ-3, CsPLATZ-4, CsPLATZ-6, and CsPLATZ-8) with high expression in shoots, young leaves, and roots were selected for high temperature and drought stress treatments, and their expression was quantified by qRT-PCR. The results indicated that the six genes might play important roles in the response to drought stress. In addition, CsPLATZ-2 and CsPLATZ-8 might have important functions in the response to high temperature stress. The results of this study will contribute to a better understanding of the biological functions of PLATZ genes and their possible roles in the growth, development, and stress responses of C. sinensis.
Droughts ; Camellia sinensis/physiology* ; Phylogeny ; Gene Expression Regulation, Plant ; Plant Proteins/genetics* ; Stress, Physiological/genetics* ; Multigene Family ; Transcription Factors/genetics* ; Hot Temperature ; Genes, Plant

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 epitranscriptomic mark N⁶-methyladenosine (m⁶A), which is the predominant internal modification in RNA, is important for plant responses to diverse stresses. Multiple environmental stresses caused by the tea-withering process can greatly influence the accumulation of specialized metabolites and the formation of tea flavor. However, the effects of the m⁶A-mediated regulatory mechanism on flavor-related metabolic pathways in tea leaves remain relatively uncharacterized. We performed an integrated RNA methylome and transcriptome analysis to explore the m⁶A-mediated regulatory mechanism and its effects on flavonoid and terpenoid metabolism in tea (Camellia sinensis) leaves under solar-withering conditions. Dynamic changes in global m⁶A level in tea leaves were mainly controlled by two m⁶A erasers (CsALKBH4A and CsALKBH4B) during solar-withering treatments. Differentially methylated peak-associated genes following solar-withering treatments with different shading rates were assigned to terpenoid biosynthesis and spliceosome pathways. Further analyses indicated that CsALKBH4-driven RNA demethylation can directly affect the accumulation of volatile terpenoids by mediating the stability and abundance of terpenoid biosynthesis-related transcripts and also indirectly influence the flavonoid, catechin, and theaflavin contents by triggering alternative splicing-mediated regulation. Our findings revealed a novel layer of epitranscriptomic gene regulation in tea flavor-related metabolic pathways and established a link between the m⁶A-mediated regulatory mechanism and the formation of tea flavor under solar-withering conditions.
RNA/metabolism* ; Epigenome ; Plant Proteins/metabolism* ; Plant Leaves/metabolism* ; Camellia sinensis/metabolism* ; Flavonoids ; Terpenes/metabolism* ; Tea/metabolism* ; Gene Expression Regulation, Plant

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.