Clathrin Light Chains negatively regulate plant immunity by hijacking the autophagy pathway.

The crosstalk between clathrin-mediated endocytosis (CME) and autophagy pathway has been reported in mammals. However, the interconnection of CME with autophagy has not been established in plants. In this report, we showed that Arabidopsis CLATHRIN LIGHT CHAIN (CLC) subunit 2 and 3 double mutant, clc2-1 clc3-1, phenocopied the Arabidopsis AUTOPHAGY-RELATED GENE (ATG) mutants both in auto-immunity and nutrient sensitivity. Accordingly, the autophagy pathway was significantly compromised in the clc2-1 clc3-1 mutant. Interestingly, we demonstrated with multiple assays that CLC2 directly interacted with ATG8h/ATG8i in a domain-specific manner. As expected, both GFP-ATG8h/GFP-ATG8i and CLC2-GFP were subjected to autophagic degradation and the degradation of GFP-ATG8h was significantly reduced in the clc2-1 clc3-1 mutant. Notably, simultaneously knocking out ATG8h and ATG8i by the CRISPR/CAS9 resulted in an enhanced resistance against Golovinomyces cichoracearum, supporting the functional relevance of the CLC2-ATG8h/8i interactions. In conclusion, our results uncovered a link between the function of CLCs and the autophagy pathway in Arabidopsis.

Partially knocking out NtPDK1a/1b/1c/1d simultaneously in Nicotiana tabacum using CRISPR/CAS9 technology results in auxin-related developmental defects.

The eukaryotic AGC protein kinase subfamily (protein kinase A/ protein kinase G/ protein kinase C-family) is involved in regulating numerous biological processes across kingdoms, including growth and development, and apoptosis. PDK1(3-phosphoinositide-dependent protein kinase 1) is a conserved serine/threonine kinase in eukaryotes, which is both a member of AGC kinase and a major regulator of many other downstream AGC protein kinase family members. Although extensively investigated in model plant Arabidopsis, detailed reports for tobacco PDK1s have been limited. To better understand the functions of PDK1s in tobacco, CRISPR/CAS9 transgenic lines were generated in tetraploid N. tabacum, cv. Samsun (NN) with 5-7 of the 8 copies of 4 homologous PDK1 genes in tobacco genome (NtPDK1a/1b/1c/1d homologs) simultaneously knocked out. Numerous developmental defects were observed in these NtPDK1a/1b/1c/1d CRISPR/CAS9 lines, including cotyledon fusion leaf shrinkage, uneven distribution of leaf veins, convex veins, root growth retardation, and reduced fertility, all of which reminiscence of impaired polar auxin transport. The severity of these defects was correlated with the number of knocked out alleles of NtPDK1a/1b/1c/1d. Consistent with the observation in Arabidopsis, it was found that the polar auxin transport, and not auxin biosynthesis, was significantly compromised in these knockout lines compared with the wild type tobacco plants. The fact that no homozygous plant with all 8 NtPDK1a/1b/1c/1d alleles being knocked out suggested that knocking out 8 alleles of NtPDK1a/1b/1c/1d could be lethal. In conclusion, our results indicated that NtPDK1s are versatile AGC kinases that participate in regulation of tobacco growth and development via modulating polar auxin transport. Our results also indicated that CRISPR/CAS9 technology is a powerful tool in resolving gene redundancy in polyploidy plants.

Knocking out NtSARD1a/1b/1c/1d by CRISPR/CAS9 technology reduces the biosynthesis of salicylic acid (SA) and compromises immunity in tetraploid Nicotiana tabacum.

Salicylic acid (SA) is a key phyto-hormone that is essential for plant immunity. SARD1 (SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1), a member of the CBP60 (CALMODULIN-BINDING PROTEIN60) gene family, is one of the major transcription factors regulating the expression of the genes in SA biosynthesis. SARD1 has been extensively studied in model plant Arabidopsis. However, the function of SARD1 homologues in SA biosynthesis and immune responses have rarely been investigated in other plant species. In this study, the CRISPR/CAS9 (Clustered Regularly Interspersed Short Palindromic Repeats/CAS9) technology was used in creating transgenic tobacco mutant lines with 6-8 alleles of four NtSARD1 homologous genes (NtSARD1a/1b/1c/1d) knocked out. No significant difference in morphological phenotype was observed between the transgenic knockout lines and the wild type tobacco plants, indicating that knocking out NtSARD1s does not affect the growth and development in tobacco. However, knocking out or partially knocking out of NtSARD1a/b/c/d resulted in a significantly reduced expression of NtICS1, the key gene in SA biosynthesis pathway, and thus the subsequently decreased SA/SAG accumulations in response to Pst DC3000 (Pseudomonas syrangae pv.tomato DC3000) infection, indicating a key role of NtSARD1 genes in SA biosynthesis in tobacco. As a consequence of reduced SA/SAG accumulation, the Pst DC3000-induced expression of NtPR genes as well as the resistance to Pst DC3000 were both significantly reduced in these knockout lines compared with the wild type tobacco plants. Interestingly, the reductions in the SA/SAG level, NtPR gene induction and Pst DC3000 resistance were positively correlated with the number of alleles being knocked out. Furthermore, LUC reporter gene driven by the promoter of NtICS1 containing two G(A/T)AATT(T/G) motifs could be activated by NtSARD1a, suggesting that NtSARD1a could bind to the core G(A/T)AATT(T/G) motifs and thus activate the expression of LUC reporter. Taken together, our results demonstrated that the NtSARD1 proteins play essential roles in SA biosynthesis and immune responses in tobacco. Our results also demonstrated that the CRISPR/CAS9 technology can overcome gene redundancy and is a powerful tool to study gene functions in polyploid plant species.

Silencing GmATG7 Leads to Accelerated Senescence and Enhanced Disease Resistance in Soybean.

Autophagy plays a critical role in nutrient recycling/re-utilizing under nutrient deprivation conditions. However, the role of autophagy in soybeans has not been intensively investigated. In this study, the Autophay-related gene 7 (ATG7) gene in soybeans (referred to as GmATG7) was silenced using a virus-induced gene silencing approach mediated by Bean pod mottle virus (BPMV). Our results showed that ATG8 proteins were highly accumulated in the dark-treated leaves of the GmATG7-silenced plants relative to the vector control leaves (BPMV-0), which is indicative of an impaired autophagy pathway. Consistent with the impaired autophagy, the dark-treated GmATG7-silenced leaves displayed an accelerated senescence phenotype, which was not seen on the dark-treated BPMV-0 leaves. In addition, the accumulation levels of both H2O2 and salicylic acid (SA) were significantly induced in the GmATG7-silenced plants compared with the BPMV-0 plants, indicating an activated immunity. Consistently, the GmATG7-silenced plants were more resistant against both Pseudomonas syringae pv. glycinea (Psg) and Soybean mosaic virus (SMV) compared with the BPMV-0 plants. However, the activated immunity in the GmATG7-silenced plant was not dependent upon the activation of MPK3/MPK6. Collectively, our results demonstrated that the function of GmATG7 is indispensable for autophagy in soybeans, and the activated immunity in the GmATG7-silenced plant is a result of impaired autophagy.

Midday Napping, Nighttime Sleep, and Mortality: Prospective Cohort Evidence in China / 生物医学与环境科学（英文）

OBJECTIVE@#In developed countries, midday napping and nighttime sleep duration have been linked to long-term survival; however, little is known about such effects in less developed regions. Therefore, this study aimed to assess the associations of midday napping and nocturnal sleep with mortality in middle-aged and older Chinese adults.@*METHODS@#A nationwide cohort of 15,524 adults aged ≥ 45 years was enrolled from 28 provincial regions across mainland China and followed up from 2011 to 2018, using data from the Chinese Health and Retirement Longitudinal Study. Midday napping and nighttime sleep duration were assessed using standardized questionnaires. Cox proportional hazards models with random intercepts for the surveyed provinces were used to estimate hazard ratios ( HRs) of all-cause mortality, adjusting for sociodemographic characteristics, behavioral factors, and health status.@*RESULTS@#A total of 1,745 deaths occurred during a median follow-up of 7.1 years, and the mean (standard deviation) age was 59 (10.1) years at baseline. Compared with non-nappers, over 60 min nappers had a higher risk of all-cause mortality [ HR: 1.35, 95% confidence interval ( CI): 1.17-1.56], while no significant associations were observed among < 30 min nappers. Compared with sleep duration of 6-8 h/night, both short (< 6 h) and long (≥ 8 h) sleep duration were significantly associated with increased mortality, with corresponding HR (95% CI) estimates of 1.21 (1.05-1.38) and 1.26 (1.10-1.44), respectively. We observed significant patterns for greater risks associated with longer nap duration, with a P trend value < 0.001 for all-cause mortality. No significant evidence of an additive interaction was identified between midday napping and nighttime sleep.@*CONCLUSION@#Long midday napping and inappropriate nighttime sleep were independently associated with an increased risk of all-cause mortality in middle-aged and older Chinese populations. Biological studies are needed to validate our findings and clarify the mechanisms underlying this association.

Advances in the fluid management strategies of pediatric acute respiratory distress syndrome / 国际儿科学杂志

Pediatric acute respiratory distress syndrome(PARDS)is a pulmonary inflammation syndrome caused by a variety of proinflammatory factors induced by many causes, which is mainly characterized by noncardiogenic pulmonary edema.The main pathophysiological feature is the destruction of the integrity of the alveolar capillary membrane, and the loss of the alveolar epithelial-endothelial barrier function.In the PARDS′s clinical practice, the mainstay of the treatment is supportive.Although there is still no clear definition and general consensus or guidelines, appropriate liquid therapy is an important part of non-ventilatory treatment measures.Proper fluid management strategy is helpful to improve pulmonary edema, maintain normal circulatory perfusion, prevent functional failure of important organs and improve the prognosis of patients.According to volume status, implementing the goal-oriented and phased differentiated fluid management strategy is significant for the therapy of PARDS patients.However, the effects of fluid strategy management according to PARDS phenotypes remain to be evaluated.

Monte Carlo design and preliminary test of X-ray protective rubber / 中国辐射卫生

@#<b>Objective</b> To complete the Monte Carlo design and preliminary test of X-ray protective rubber. <b>Methods</b> According to the characteristics of X-ray energy spectrum for interventional therapy, the shielding effects of lead rubber, tungsten and bismuth composite rubber, and gadolinium and bismuth composite rubber samples were calculated by Monte Carlo simulation. The variation law of lead equivalent of lead-free rubber and lead rubber with X-ray peak tube voltage was obtained through actual measurement. <b>Results</b> Within the peak tube voltage range of 60-110 kV, lead-free rubber effectively replaced lead rubber. <b>Conclusion</b> The shielding and attenuation effect of the existing lead-free protective rubber on low-energy stray X-rays is better than that of lead rubber. Considering the inherent defects of lead rubber, flexible X-ray protective materials with thermoplastic elastomer as filler will have broad development prospects.

Efficacy of 0.01% atropine in myopic children of different ages / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To valuate the efficacy of 0.01% atropine for controlling myopia in children of different ages.METHOD: A randomized, double-blind, placebo control and single-center study was conducted. A total of 295 myopic children, aged 6～13 years, with myopia of -0.5D～-6.00D and astigmatism ≤2.0D, who admitted to our hospital from May 2019 to May 2020 were randomly assigned to experimental group(197 cases)and control group(98 cases)in a 2:1 ratio. Two groups were further divided into three subgroups according to age, 6～8 years old group(40/26 cases), 9～10 years group(84/34 cases), and 11～13 years group(73/38 cases). 0.01% atropine was administrated in the experimental group and placebo was administrated in the control group once before sleep. The changes of parameters were compared before and at 2wk, 3, 6, 9 and 12mo after treatment. Intraocular pressure, accommodation amplitude, best corrected distance and near visual acuity, pupil diameter and tear film were tested at 2wk. Cycloplegic refraction was assessed before treatment, and at 6 and 12mo after treatment.RESULTS: The spherical equivalent and axial length progression at 12mo after administration was -0.37±0.69D and 0.29±0.24mm in the experimental group, and -0.59±0.65D and 0.37±0.23mm in the control group(P=0.008, 0.006). In 6～8 years group, spherical equivalent and axial length progression between experimental and control group were not statistically significant(t=0.054, P=0.957; t=-0.623, P=0.536). In 9～10 years group, spherical equivalent and axial length progression between groups were statistically significant(t=2.056, P=0.042; t=-2.057 P=0.042). In 11～13 years group, spherical equivalent and axial length progression between groups were statistically significant(t=2.33, P=0.022; t=-2.424, P=0.017). The pupil was slightly dilated and the accommodation amplitude was decreased in experimental group, and the mean pupil diameter of the two groups was 3.94±0.79 and 3.16±0.48 mm respectively at 12mo after treatment(P<0.001). Other parameters and adverse event noted between groups were not statistically significant.CONCLUSIONS: 0.01% atropine is helpful to control the progression of myopia in children, which is well tolerated by adolescents. However, the effect of 0.01% atropine on the control of myopia for children aged 6～8 years is not enough. The findings suggest that increased concentration of atropine can be tried for 6～8 years old.

GmCBP60b Plays Both Positive and Negative Roles in Plant Immunity.

CBP60b (CALMODULIN-BINDING PROTEIN 60b) is a member of the CBP60 transcription factor family. In Arabidopsis, AtCBP60b not only regulates growth and development but also activates the transcriptions in immune responses. So far, CBP60b has only been studied extensively in the model plant Arabidopsis and rarely in crops. In this study, Bean pod mottle virus (BPMV)-mediated gene silencing (BPMV-VIGS) was used to silence GmCBP60b.1/2 in soybean plants. The silencing of GmCBP60b.1/2 resulted in typical autoimmunity, such as dwarfism and enhanced resistance to both Soybean mosaic virus (SMV) and Pseudomonas syringae pv. glycinea (Psg). To further understand the roles of GmCBP60b in immunity and circumvent the recalcitrance of soybean transformation, we generated transgenic tobacco lines that overexpress GmCBP60b.1. The overexpression of GmCBP60b.1 also resulted in autoimmunity, including spontaneous cell death on the leaves, highly induced expression of PATHOGENESIS-RELATED (PR) genes, significantly elevated accumulation of defense hormone salicylic acid (SA), and significantly enhanced resistance to Pst DC3000 (Pseudomonas syrangae pv. tomato DC3000). The transient coexpression of a luciferase reporter gene driven by the promoter of soybean SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (GmSARD1) (ProGmSARD1::LUC), together with GmCBP60b.1 driven by the 35S promoter, led to the activation of the LUC reporter gene, suggesting that GmCBP60b.1 could bind to the core (A/T)AATT motifs within the promoter region of GmSARD1 and, thus, activate the expression of the LUC reporter. Taken together, our results indicate that GmCBP60b.1/2 play both positive and negative regulatory roles in immune responses. These results also suggest that the function of CBP60b is conserved across plant species.

Silencing GmBIR1 in Soybean Results in Activated Defense Responses.

Receptor-like kinases (RLKs) are a large group of pattern recognition receptors (PRRs) and play a critical role in recognizing pathogens, transducing defense signals, and mediating the activation of immune defense responses. Although extensively studied in the model plant Arabidopsis, studies of RLKs in crops, including soybean, are limited. When a BAK1-interacting receptor-like kinase (BIR1) homolog (referred to as GmBIR1 hereafter) was silenced by the BPMV (Bean pod mottle virus)-induced gene silencing (BPMV-VIGS), it resulted in phenotypes that were reminiscent of constitutively activated defense responses, including a significantly stunted stature with observable cell death on the leaves of the silenced plants. In addition, both SA and H2O2 were over-accumulated in the leaves of the GmBIR1-silenced plants. Consistent with this autoimmune phenotype, GmBIR1-silenced plants exhibited significantly enhanced resistance to both Pseudomonas syringae pv. glycinea (Psg) and Soybean mosaic virus (SMV), two different types of pathogens, compared to the vector control plants. Together, our results indicated that GmBIR1 is a negative regulator of immunity in soybean and the function of BIR1 homologs is conserved in different plant species.

Diagnostic efficacy of serum NT-proBNP and D-dimer for cardiogenic cerebral embolism based on population in southern Sichuan / 中国医师杂志

Objective:To investigate the diagnostic efficacy of serum N-terminal B-type brain natriuretic peptide (NT-proBNP) and D-dimer for cardiogenic cerebral embolism (CE) based on population in southern Sichuan.Methods:We selected the clinical data of 313 patients with acute cerebral infarction (ACI) for the first time, 34 patients with simple atrial fibrillation (AF) and 30 healthy people who were admitted to the Affiliated Hospital of Southwest Medical University from June 2019 to April 2021. The patients with ACI were divided into four subgroups according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) typing: large artery atherosclerosis (LAA), CE, small artery occlusion (SAO), and indeterminate subtype (UT). The differences in clinical data in the groups were compared. At the same time, the differences of NT-proBNP and D-dimer in serum in CE group, AF group and healthy group were compared; The risk factors of CE were analyzed by binary logistic regression, and the diagnostic efficacy of serum NT-proBNP and D-dimer for CE was evaluated by receiver operating characteristic (ROC) curve.Results:The prevalence of hypertension, diabetes, systolic blood pressure (SBP) and diastolic blood pressure (DBP) at admission, prothrombin time (PT), international normalized ratio (INR), fibrinogen (FIB), D-dimer, fibrinogen degradation products (FDP), National Institutes of Health Stroke Scale (NIHSS) score at admission, NT-proBNP and AF rate were significantly different among ACI subgroups (all P<0.05); There was no significant difference in PT and NIHSS score at admission between LAA group and CE group (all P>0.05). The prevalence of D-dimer, NT-proBNP and AF rate in CE group was significantly higher than those in other three groups (all P<0.05). The D-dimer, NT-proBNP, FDP and SBP level in CE group were significantly higher than those in AF group and healthy group (all P<0.05). Binary logistic regression analysis showed that D-dimer and NT-proBNP were independent risk factors for CE (both P<0.05). When the optimal cut-off value of serum D-dimer was 1.015 mg/L, the area under the ROC curve (AUC) was 0.896 (95% CI: 0.856-0.935, P<0.01); the sensitivity and specificity were 0.878 and 0.833, respectively; the positive predictive value and the negative predictive value were 0.705 and 0.953, respectively. When the best cut-off value of serum NT-proBNP was 657.145 ng/L, the AUC was 0.987 (95% CI: 0.977-0.998, P<0.01); the sensitivity and specificity were 0.959 and 0.963, respectively; the positive predictive value and the negative predictive value were 0.922 and 0.981, respectively. The accuracy of the combined detection of serum D-dimer and NT-proBNP in the diagnosis of CE was higher, and the AUC was 0.988 (95% CI: 0.978-0.998, P<0.01), sensitivity of 0.960, specificity of 0.977, positive predictive value of 0.950, negative predictive value of 0.982. Conclusions:The serum levels of NT-proBNP and D-dimer in CE patients increased significantly; NT-proBNP and D-dimer are important predictors of CE and have higher diagnostic efficacy for CE. The combination of them has a higher specificity for diagnosis.

One case of Creutzfeldt-Jakob disease with restless leg syndrome as the first symptom and literature analysis / 中国基层医药

Objective:To analyze the clinical features and auxiliary examination results of sporadic Creutzfeldt-Jakob disease (sCJD) with restless leg syndrome (RLS) as the first symptom.Methods:The clinical features and auxiliary examination results of one case of sCJD who received treatment in Sichuan Mianyang 404 Hospital were analyzed based on relevant literature.Results:A 59-year-old woman of Han nationality who had sCJD with restless leg-like manifestation of the left lower limb for 18 days was included in this study. The patient was first treated in orthopedic department, but her symptom did not improve after treatment. Twenty days later, she was transferred to neurology department for further treatment. Her daily life and activities were not affected. Head magnetic resonance imaging, electroencephalography, cerebrospinal fluid routine examination and biochemical test results were normal. Five days later, the patient had mild left-sided ataxia, which then progressed rapidly, followed by right-sided ataxia, left-leg spasticity and adduction, involuntary movement, myoclonia, cognitive decline, akinetic mutism, repeated hyperthermia, repeated complex partial seizures. Two weeks later, head magnetic resonance imaging examination revealed hyperintense signal of the cingulate gyrus, frontal cortex and right island cortex on DWI, with cerebellar atrophy and three-phase electroencephalography wave. Four weeks later, CSF14-3-3 protein was positive, and no related genetic mutation in the prion protein gene was found. The duration from onset to death was about 8 months.Conclusion:sCJD is a common subtype of prion protein disease, and the condition can be stabilized for more than 1 month after the onset of RLS. There is no specificity in early clinical and auxiliary examinations, and neither dobutazine treatment nor neurotrophic treatment is effective. The disease progresses rapidly after 1 month, head MRI and EEG reexamination can reveal clues, and CSF14-3-3 protein can assist clinical diagnosis.

China guideline for the screening, early detection and early treatment of gastric cancer (2022, Beijing) / 中华肿瘤杂志

Gastric cancer (GC) is a major digestive tract malignancy in China, which seriously threatens the health of Chinese population. A large number of researches have demons-trated that screening, early detection and early treatment are effective in reducing the incidence and mortality of GC. The development of the guideline for GC screening, early detection and early treatment in line with epidemic characteristics of GC in China will greatly promote the homogeneity and standardization, and improve the effect of GC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. Following the World Health Organization Handbook for Guideline Development, this guideline combined the most up-to-date evidence of GC screening, China's national conditions, and practical experience in cancer screening. This guideline provided evidence-based recommendations with respect to the screening population, technology and procedure management, aiming to improve the effect of GC screening and provide scientific evidence for the GC prevention and control in China.

Influence of ADOPT mode nursing intervention on airway self-care ability in patients after total laryngectomy / 中国实用护理杂志

Objective:To explore the effect of ADOPT mode nursing intervention on airway self-care ability in patients with total laryngectomy.Methods:50 patients who received total laryngectomy were randomly divided into control group (25 cases) and observation group (25 cases). The control group received routine nursing, while the observation group received ADOPT mode nursing intervention on the basis of routine nursing. The Exercise of Self-Care Agency Scale and self-made airway self-care knowledge questionnaire were used to evaluate the airway self-care ability and the incidence of airway related complications was also evaluated.Results:On discharge and 3 months after discharge, total scores about self-care knowledge of airway were 83.80 ± 5.06 and 89.40 ± 4.86 in the experimental group, which were significantly higher than those in the control group (68.75 ± 5.57, 72.50 ± 6.76), the differences were statistically significant ( t = -9.91, -10.09, both P<0.05). On discharge and 3 months after discharge, total scores in ESCA were 126.88 ± 9.77 and 133.60 ± 8.10 in the experimental group, which were significantly higher than those in the control group (113.29 ± 17.06 and 119.13 ± 15.30). The differences were significant ( t = -3.42, -4.12, both P<0.05). The incidence of airway complications was 41.67% (10/24) in the control group and 12.00%(3/25) in the observation group, which was statistically significant ( χ2 = 5.53, P<0.05). Conclusions:ADOPT mode nursing intervention can significantly improve the airway self-care ability of patients with total laryngectomy, reduce the incidence of airway complications, and is beneficial to patients′ physical and mental recovery.

Fluid overload in critically ill children and advances in its treatment / 国际儿科学杂志

Fluid overload(FO)is significantly associated with survival in critically ill children.Excessive fluid accumulation in the body causes tissue oedema, which may lead to heart failure, acute kidney injury(AKI)and acute pulmonary oedema, affecting length of hospital stay, readmission rates and prognosis.According to the cause of the FO, the main treatments are fluid restriction, diuretics, and ultrafiltration.Diuretics are often used clinically to treat patients with FO.International guidelines recommend ultrafiltration to remove excess water when diuretic therapy is not effective or when diuretic resistance occurs, or when life-threatening complications arise.However, there is no conclusion on the setting for the net ultrafiltration intensity in ultrafiltration, particularly in critically ill children.With the development of ultrafiltration technology, the application of ultrafiltration in the treatment of FO patients will be further carried out.This article provides a review of the FO and its treatment in critically ill children.

China guideline for the screening, early detection and early treatment of esophageal cancer (2022, Beijing) / 中华肿瘤杂志

Esophageal cancer (EC) is a major digestive tract malignancy in China, which seriously threatens the health of Chinese population. A large number of researches have demonstrated that screening and early detection are effective in reducing the incidence and mortality of EC. The development of the guideline for EC screening and early detection in line with epidemic characteristics of EC in China will greatly promote the homogeneity and standardization, and improve the effect of EC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. Following the World Health Organization Handbook for Guideline Development, this guideline combined the most up-to-date evidence of EC screening, China's national conditions, and practical experience in cancer screening. This guideline provided evidence-based recommendations with respect to the screening population, technology and procedure management, aiming to improve the effect of EC screening and provide scientific evidence for the EC prevention and control in China.

Clinical Characteristics of Recurrent-positive Coronavirus Disease 2019 after Curative Discharge: a retrospective analysis of 15 cases in Wuhan China

In China, the patients with previously negative RT-PCR results again test positive during the post-discharge isolation period. We aimed to determine the clinical characteristics of these "recurrent-positive" patients. We retrospectively reviewed the data of 15 recurrent-positive patients and 107 control patients with non-recurrent, moderate COVID-19 treated in Wuhan, China. Clinical data and laboratory results were comparatively analyzed. We found that recurrent-positive patients had moderate disease. The rate of recurrent-positive disease in our hospital was 1.87%. Recurrent-positive patients were significantly younger (43(35-54) years) than control patients (60(43-69) years) (P=0.011). The early LOS (length of stay in hospital before recurrence) was significantly longer in recurrent-positive patients (36(34-45) days) than in control patients (15(7-30) days) (P =0.001). The time required for the first conversion of RT-PCR results from positive to negative was significantly longer in recurrent-positive patients (14(10-17) days) than in control patients (6(3-9) days) (P =0.011). Serum COVID-19 antibody levels were significantly lower in recurrent-positive patients than in control patients (IgM: 13.69 {+/-} 4.38 vs. 68.10 {+/-} 20.85 AU/mL, P = 0.015; IgG: 78.53 {+/-} 9.30 vs. 147.85 {+/-} 13.33 AU/mL, P < 0.0001). Recurrent-positive patients were younger than control patients. The early LOS (length of stay in hospital before recurrence) was significantly longer in recurrent-positive group than that in control group. COVID-19 IgM/IgG antibody levels were significantly lower in recurrent-positive group than those in control group, which might explain why the virus RNA RT-PCR was positive after the initial "clinical cure"(with three times of virus RNA RT-PCR negative). The virus might not be fully eliminated because of the lower IgG level and their later replicating might result in recurrent-positive virus RNA RT-PCR.

Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study

The outbreak of novel coronavirus disease 2019 (COVID-19) has become a pandemic. Drug repurposing may represent a rapid way to fill the urgent need for effective treatment. We evaluated the clinical utility of chloroquine and hydroxychloroquine in treating COVID-19. Forty-eight patients with moderate COVID-19 were randomized to oral treatment with chloroquine (1000 mg QD on Day 1, then 500 mg QD for 9 days; n=18), hydroxychloroquine (200 mg BID for 10 days; n=18), or control treatment (n=12). Adverse events were mild, except for one case of Grade 2 ALT elevation. Adverse events were more commonly observed in the chloroquine group (44.44%) and the hydroxychloroquine group (50.00%) than in the control group (16.67%). The chloroquine group achieved shorter time to clinical recovery (TTCR) than the control group (P=0.019). There was a trend toward reduced TTCR in the hydroxychloroquine group (P=0.049). The time to reach viral RNA negativity was significantly faster in the chloroquine group and the hydroxychloroquine group than in the control group (P=0.006 and P=0.010, respectively). The median numbers of days to reach RNA negativity in the chloroquine, hydroxychloroquine, and control groups was 2.5 (IQR: 2.0-3.8) days, 2.0 (IQR: 2.0-3.5) days, and 7.0 (IQR: 3.0-10.0) days, respectively. The chloroquine and hydroxychloroquine groups also showed trends toward improvement in the duration of hospitalization and findings on lung computerized tomography (CT). This study provides evidence that (hydroxy)chloroquine may be used effectively in treating moderate COVID-19 and supports larger trials.

Anti-Platelet Therapy in Mild Cerebral Infarction Patients on the Basis of CYP2C19 Metabolizer Status.

This study aimed to investigate the effects of CYP2C19 metabolizer status on the clinical therapeutic efficacy of cerebral infarction. Patients with cerebral infarction (n = 180; NIHSS score ≤ 5) were recruited and divided into Group A and Group B according to CYP2C19 metabolizer status. In Group A, patients received routine clopidogrel therapy for 1 year; in Group B, the patients with extensive metabolizer (EM) were treated with clopidogrel, and patients with intermediate metabolizer (IM) and poor metabolizer (PM) were treated with aspirin for 1 year. On admission, National Institutes of Health Stroke Scale score was determined, and the therapeutic efficacy was evaluated with Modified Rankin Scale score after 1 year of treatment. The outcomes and adverse effects were recorded during the treatment. After routine clopidogrel treatment, the efficacy in EM patients was significantly better than in PM and IM patients. After adjustment of therapeutic protocol, the therapeutic efficacy in PM and IM patients was markedly improved, which was accompanied by significant reduction in recurrence rate of cerebral infarction. Although the adverse effects increased in patients receiving aspirin treatment, they resolved after symptomatic therapy. CYP2C19 metabolizer status is closely related to the clinical efficacy of clopidogrel. Thus, it is necessary to adjust the anti-platelet treatment according to the CYP2C19 metabolizer status to maximize therapeutic efficacy without increasing recurrence and adverse effects.

Effects of salidroside on the secretion of inflammatory mediators induced by lipopolysaccharide in the co-culture of rat alveolar macrophages and type II alveolar epithelial cells / 生理学报

The aim of the present study was to investigate the effect of salidroside (Sal) on inflammatory activation induced by lipopolysaccharide (LPS) in the co-culture of rat alveolar macrophages (AM) NR 8383 and type II alveolar epithelial cells (AEC II) RLE-6TN. CCK-8 colorimetric method was used to detect cell proliferation percentage. The enzyme-linked immunosorbent assay (ELISA) was used to determine the content of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein-2 (MIP-2) and interleukin-10 (IL-10) in the supernatant. Western blot was used to examine the expression levels of phosphorylated AKT (p-AKT) and total AKT protein. The results showed that pretreatment of RLE-6TN cells or co-culture of RLE-6TN and NR 8383 cells with 32 and 128 µg/mL Sal for 1 h, followed by continuous culture for 24 h, significantly increased the cell proliferation (P < 0.05). Compared with control group, 32 and 128 µg/mL Sal pretreatment significantly increased the ratio of p-AKT/AKT in RLE-6TN cells (P < 0.05). Pretreatment of 32 µg/mL Sal not only inhibited the secretion of TNF-α and MIP-2 by NR 8383 cells induced by LPS (P < 0.05), but also enhanced the inhibitory effect of RLE-6TN and NR 8383 cells co-culture on the secretion of TNF-α and MIP-2 by NR 8383 cells induced by LPS (P < 0.05). In addition, 32 µg/mL Sal pretreatment promoted LPS-induced IL-10 secretion by NR 8383 cells (P < 0.05), and enhanced the promoting effect of co-culture of RLE-6TN and NR 8383 cells on the IL-10 secretion by LPS-induced NR 8383 cells (P < 0.05). In conclusion, Sal may directly inhibit LPS-induced inflammatory activation of AM (NR 8383), promote the proliferation of AEC II (RLE-6TN) through PI3K/AKT signaling pathway, and enhance the regulatory effect of AEC II on LPS-induced inflammatory activation of AM.