Clinical Observation of Shengmaisan Combined with Polymyxin B in Treatment of Sepsis Complicated with Severe Acute Respiratory Distress Syndrome / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Shengmaisan combined with polymyxin B in the treatment of carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome. MethodA total of 90 patients suffering from carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome were randomly divided into a control group and an observation group， with 45 cases in each group. The control group was treated with polymyxin B， and the observation group was treated with Shengmaisan combined with polymyxin B. The treatment course of both groups was seven days. The infection-related indicators ［white blood cell （WBC） count， procalcitonin （PCT）， neutrophil apolipoprotein （HNL）］， inflammatory factors ［interleukin-6 （IL-6）， serum chemokine ligand 2 （CXCL2）］， and T lymphocyte subpopulations （CD3+， CD4+， CD8+， and CD4+/ CD8+ value）， acute physiological and chronic health Ⅱ （APACHE Ⅱ） score before and after treatment， as well as bacterial clearance rate and 28-day survival rate after treatment were observed. Result① The experiment was completed， and 81 cases were included， including 41 cases in the observation group and 40 cases in the control group. The general data of the two groups were comparable. ② The bacterial clearance rate of the observation group and the control group was 75.6% （31/41） and 52.5% （21/40）， respectively， and the observation group was higher than the control group （χ2=4.7， P<0.05）. ③ The WBC count， PCT， HNL， IL-6， CXCL2， and APACHE Ⅱ scores of the observation group and the control group all decreased after treatment （P<0.05）. Except for the WBC count， the PCT， HNL， IL-6， CXCL2， and APACHE Ⅱ scores of the observation group were lower than those of the control group （P<0.05）. ④ The values of CD3+， CD4+， and CD4+/CD8+ in the observation group were increased after treatment （P<0.05）， and CD8+ was decreased （P<0.05）. In the control group， only CD3+ value was increased （P<0.05）. The values of CD3+， CD4+， and CD4+/CD8+ in the observation group were higher than those in the control group， and the value of CD8+ was lower than that in the control group （P<0.05）. ⑤ The 28-day survival rate in the observation group was higher than that in the control group （χ2=4.3， P<0.05）. ConclusionShengmaisan combined with polymyxin B in the treatment of carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome can better clear bacteria， control infection， reduce the level of inflammatory factors， regulate the immune state of the body， and improve the short-term prognosis.

Andrographolide regulates SLC7A11/GPX4 axis in ferroptosis to attenuate intestinal injury in sepsis / 安徽医科大学学报

Objective To investigate whether Andrographolide(AG)can alleviate intestinal injury in sepsis by ac-tivating the SLC7A11/GPX4 axis in ferroptosis.Methods Forty rats were randomly divided into sham group(sham group),sepsis group(CLP group),AG low,medium and high dose groups(5,10 and 20 mg/kg).HE staining was used to observe the pathological changes of Intestinal tract.ELISA method was used to determine Inter-leukin 6(IL-6),tumour necrosis factor α(TNF-α),intestinal fatty acid binding protein(I-FABP),D-lactate content.The mechanism of ferroptosis was explored with AG high dose group(AG20 group),forty rats were ran-domly divided into sham group,CLP group,ferroptosis inhibitor(Fer-1)group,AG20+Fer-1 group.HE staining and transmission electron microscopy were used to observe the pathological changes of Intestinal tract.The kits were used to determine oxidative stress MDA,GSH levels and Fe3+content.Western blot was used to detect the protein levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and ferritin heavy poly-peptide 1(FTH-1).Results Compared with the sham group,the CLP group showed severe morphological damage to the small intestine,with significantly higher levels of inflammation,I-FABP and D-lactate(all P＜0.05),the AG group reversed these changes in a concentration-dependent manner(all P＜0.05).Compared with the CLP group,the AG20 and Fer-1 groups showed improved pathological damage to the small intestine,with lower levels of MDA and Fe3+and higher levels of GSH,SLC7A11,GPX4 and FTH-1 protein expression increased(all P＜0.05),and pathological injury and oxidative stress were reduced in the AG20+Fer-1 group,and SLC7A11,GPX4 and FTH-1 protein expression increased more significantly(all P＜0.05).Conclusion The mechanism by which AG attenuates intestinal injury in sepsis may be related to SLC7A11/GPX4 axis activation in ferroptosis.

Effect of helicobacter pylori eradication therapy on small intestinal bacterial overgrowth in children / 中国综合临床

Objective:To investigate the effect of helicobacter pylori (HP) infection and eradication treatment on small intestinal bacterial overgrowth (SIBO) in children.Methods:A prospective case-control study was conducted to select 68 children with symptoms of abdominal distension, abdominal pain, diarrhea and suspected digestive system diseases admitted to the Affiliated Hospital of Xuzhou Medical University from June 2021 to June 2022. They were divided into HP negative group and HP positive group according to HP infection. HP positive group received triple standardized HP eradication treatment, 14 days as a course of treatment. The baseline SIBO positive rate and gastrointestinal symptom rating scale (GSRS) score of the two groups were compared. The HP positive group was followed up for 4 and 12 weeks after drug withdrawal for quantitative assessment of gastrointestinal symptoms and LHBT. The SIBO positive rate, GSRS score of the two groups and the change of SIBO positive rate and GSRS score of the HP positive group before and after treatment were compared. The measurement data with normal distribution were expressed, and independent sample t-test was used for comparison between the two groups. M( Q1, Q3) was used to represent the measurement data of non normal distribution, and Mann Whitney U test was used to compare the two groups; Friedman test was used for comparison between multiple time points, and Nemenyi test was used for pairwise comparison. Four grid table or paired χ 2 test was used to compare the counting data between groups. Results:The positive rate of SIBO in HP negative group was lower than that in HP positive group (36.1% (13/36) vs 62.5% (20/32)), the difference was statistically significant (χ 2=4.72, P=0.030). Four weeks after drug withdrawal, the SIBO positive rate in HP positive group was higher than that before treatment (87.5% (28/32) vs 62.5% (20/32)), and 12 weeks after drug withdrawal was lower than that before treatment (21.9% (7/32) vs 62.5% (20/32)), with statistically significant differences (χ 2=8.00, P=0.008; χ 2=13.00, P<0.001). There was no statistically significant difference in GSRS score between HP negative group and HP positive group ( P=0.098). The clinical symptoms of 32 children in HP positive group were improved 4 and 12 weeks after HP eradication was stopped. GSRS scores were lower than those before treatment (8.0 (6.0, 12.8), 7.0 (5.0, 9.0) points vs 15.0 (12.0, 19.0) points) , and the differences were statistically significant ( Z values were -3.91, -4.68, respectively; all P<0.001). Conclusions:HP infection can increase the positive rate of SIBO in children with suspected digestive system diseases. The standardized triple HP eradication therapy may further aggravate the overgrowth of intestinal bacteria while treating HP infection, but this effect can be eliminated after 12 weeks of treatment.

Systematic Review on Safety of Chinese Medicines Combined with Tripterygium wilfordii Preparations in Treatment of Rheumatoid Arthritis and Exploration on Underlying Network Regulatory Mechanisms of Enhancing Efficacy and Reducing Toxicity / 中国实验方剂学杂志

ObjectiveTo systematically evaluate the safety of Chinese medicines combined with Tripterygium wilfordii polyglycoside tablets/Tripterygium wilfordii tablets （TWPT/TWT） in the treatment of rheumatoid arthritis （RA）， and to explore the network regulatory mechanisms of enhancing efficacy and reducing toxicity of commonly used combination regimes. MethodThe literature involving the adverse reactions of TWPT/TWT in treating RA was searched and collected from three Chinese databases （CNKI， Wanfang Data， VIP） and three English databases （PubMed， Cochrane Library， Embase） from the inception of the databases to July 2021. All studies were assessed by the Cochrane risk of bias tool， and the data were extracted and analyzed by Stata 15.0. Furthermore， Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine 2.0 （TCMIP v2.0，http：//www.tcmip.cn/） was used to construct a "drug target-symptom gene of efficacy and toxicity" interaction network， to explore the underlying network regulatory mechanisms of enhancing efficacy and reducing toxicity of common T. wilfordii preparation combinations. ResultA total of 2 132 articles on Chinese medicines combined with TWPT/TWT in the treatment of RA were retrieved， and 18 of them were finally included. The systematic review showed that the adverse reactions of TWPT/TWT against RA mainly occurred in the digestive system， blood system， and reproductive system， of which digestive system had the highest incidence of damages. However， the combination with Chinese medicines effectively alleviated the adverse reactions caused by TWPT/TWT ［RR （95% CI）=0.45 （0.30， 0.66）， P<0.01］. In addition， the subgroup analysis indicated that the age of RA patients， course of disease， combination regimen， medication dosage and duration of treatment all affected the occurrence of adverse reactions of TWPT/TWT. It was found in clinical studies that total glucosides of paeony （TGP） and TWPT/TWT was most widely combined， and the effect of TGP in reducing TWPT/TWT-induced hepatotoxicity was also more significant than that of other Chinese medicines. Moreover， taking this combination regime as an example， this paper explored the "efficacy-toxicity" association mechanisms of TGP-TWPT/TWT against RA. The "drug target-symptom gene of efficacy and toxicity" interaction network revealed that the core network targets of TGP-TWPT/TWT enhanced efficacy and reduced toxicity mainly through regulating immunity-inflammation-related pathways， metabolic pathways and cell signal transduction. Especially， interleukin-4 （IL-4） and interleukin-13 （IL-13）， which were involved in the "immunity-inflammation" module， were the common targets of TGP-TWPT/TWT to enhance efficacy and reduce toxicity. The endogenous sterols， bile acids and bile salts， insulin secretion and other metabolic pathways in the "body metabolism" module were closely associated with the mechanisms of TWPT/TWT inducing hepatotoxicity and TGP reducing hepatotoxicity. While cell function regulation pathways， such as stem cell factor （SCF）/tyrosine kinase receptor （KIT） signaling pathway and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）signaling pathway were involved in both anti-RA effects and hepatotoxicity of TWPT/TWT. ConclusionClinical application of suitable Chinese medicines combined with TWPT/TWT in the treatment of RA can effectively improve the rheumatism and reduce the adverse reactions of TWPT/TWT， and TGP-TWPT/TWT has the most significant toxicity-reducing effect. Further biological network-based investigation indicates that the toxicity-reducing mechanism of TGP-TWPT/TWT may be related to the regulation of interleukin signaling pathway and bile acid metabolism pathway， and the synergistic efficacy-enhancing effect of the combination may be achieved by acting on interleukin signaling pathway and cell function regulation pathway.

Exploration on "Efficacy-toxicity" Association Mechanisms of Tripterygium wilfordii Polyglycoside Tablets Against Rheumatoid Arthritis Based on Multi-omics Integrated Regulatory Network / 中国实验方剂学杂志

ObjectiveTo explore the "efficacy-toxicity" association mechanisms of Tripterygium wilfordii polyglycoside tablets （TWPT） by establishing and analyzing an interaction network associated with the clinical efficacy of TWPT in the treatment of rheumatoid arthritis （RA） and TWPT-induced liver injury. MethodOn the basis of the TWPT efficacy-related gene expression profile and TWPT-induced liver injury-related protein expression profile which were both obtained from our clinical cohorts， the "efficacy-toxicity" association network of TWPT was constructed， and the key network targets were identified by calculating the topological values of the nodes， including the degree， closeness and betweenness. After that， the biological functions and pathways of the key network targets were investigated by enrichment analysis. ResultA total of 119 differentially expressed genes （58 up-regulated and 61 down-regulated） between RA patients with TWPT well and weak response were identified as TWPT efficacy-related genes by clinical transcriptomics， and 49 differentially expressed proteins （36 up-regulated and 13 down-regulated） were demonstrated to be TWPT-induced liver injury-related proteins by clinical proteomics. In addition， the clinical symptom enrichment analysis indicated that the TWPT efficacy-related genes were significantly associated with various clinical symptoms of arthralgia in traditional Chinese medicine and clinical phenotypes of modern medicine， and most of the TWPT-induced liver injury-related proteins were involved in digestive system abnormalities. Therefore， the aforementioned multi-omics data represented the main clinical symptoms of TWPT treating RA and inducing liver injury. Mechanically， the "efficacy-toxicity" association network revealed that both TWPT efficacy-related genes and TWPT-induced liver injury-related core proteins were involved in the "immune-inflammatory" imbalance， especially playing an important role in neutrophil degranulation， complement cascade reaction， and immune-inflammatory response mediated by protein post-translational modification. Notably， the above genes and proteins were also enriched in various signaling pathways related to cell proliferation and cell cycle regulation， such as RAS and mitogen-activated protein kinase （MAPK） signaling pathway， and in several liver functional processes， such as glycogen metabolism and redox reaction. ConclusionThis study systematically explained the "efficacy-toxicity" association characteristics and molecular mechanisms of TWPT by applying a research strategy integrating clinical phenomics， transcriptomics and proteomics， laying a good data foundation for exploring the "efficacy enhancing and toxicity-reducing" mechanisms of TWPT.

Cornelia de Lange syndrome with recurrent seizures and SMC1A gene c. 2923C > T mutation: a case report and literature review / 中华实用儿科临床杂志

Objective:To explore the characteristics, clinical manifestations and gene mutation types of Cornelia de Lange syndrome (CdLs), and to improve the understanding of the disease.Methods:Clinical data and gene test results of a pediatric case of CdLs diagnosed in the First Affiliated Hospital of Xinxiang Medical University in August 2019 were analyzed retrospectively.Results:A female patient with 2 years and 8 months old presented a special appearance with a low and flat nose, a wide eye distance, audition ears, a downward inclination of the mouth corner, a high arch of the jaw and a small jaw deformity, who had recurrent seizures, speech and mental retardation.The result of gene test showed the mutation of SMC1A gene c. 2923C > T, and thus the patient was diagnosed as type 2 CdLs. Conclusions:CdLs is a rare genetic metabolic disease with special facial features and physical signs.There is only one case of CdLs with gene mutation of SMC1A in China through literature review.The mutation of SMC1A gene c. 2923C>T in CdLs cases has not been reported at home and abroad, which expands the variation spectrum of the SMC1A gene.

Human mobility and COVID-19 transmission: a systematic review and future directions

Without a widely distributed vaccine, controlling human mobility has been identified and promoted as the primary strategy to mitigate the transmission of COVID-19. Many studies have reported the relationship between human mobility and COVID-19 transmission by utilizing the spatial-temporal information of mobility data from various sources. To better understand the role of human mobility in the pandemic, we conducted a systematic review of articles that measure the relationship between human mobility and COVID-19 in terms of their data sources, statistical models, and key findings. Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we selected 47 articles from Web of Science Core Collection up to September 2020. Restricting human mobility reduced the transmission of COVID-19 spatially, although the effectiveness and stringency of policy implementation vary temporally and spatially across different stages of the pandemic. We call for prompt and sustainable measures to control the pandemic. We also recommend researchers 1) to enhance multi-disciplinary collaboration; 2) to adjust the implementation and stringency of mobility-control policies in corresponding to the rapid change of the pandemic; 3) to improve statistical models used in analyzing, simulating, and predicting the transmission of the disease; and 4) to enrich the source of mobility data to ensure data accuracy and suability.

Distribution of pathogenic bacteria and immune status in patients with pulmonary infection after lung cancer treatment / 公共卫生与预防医学

Objective To explore distribution of pathogenic bacteria and immune status in patients with pulmonary infection after lung cancer treatment. Methods A total of 102 patients with pulmonary infection after lung cancer treatment (infection group) who were admitted to our hospital from September 2015 to October 2019 were selected, and 120 patients without pulmonary infection after lung cancer treatment were enrolled in the same period (control group). The species, distribution, drug resistance rate of pathogenic bacteria of the infected group were analyzed. The immune status, serum neuron-specific enolase (NSE), squamous cell carcinoma associated antigen (SCC) and carcinoembryonic antigen (CEA) levels of the two groups were compared. Results A total of 174 strains of pathogenic bacteria were isolated and cultured from 102 patients in the infected group, of which 94 strains were gram-negative (accounting for 54.02%), mainly Klebsiella pneumoniae and Pseudomonas aeruginosa, and 46 strains were gram-positive bacteria (26.44%), mainly Staphylococcus aureus and Coagulase-negative staphylococcus. In addition, there were 34 strains of fungus (19.54%). Gram-negative bacteria were resistant to aztreonam and cefotaxime, while gram-positive bacteria were resistant to penicillin and erythromycin. The serum levels of NSE, SCC and CEA in the infected group were higher than those in the control group (P<0.05). The levels of CD3+, CD4+ and CD4+/CD8+ in peripheral blood of the infected group were lower than those in the control group (P<0.05). Conclusion After lung cancer treatment, the pathogenic bacteria of patients with pulmonary infection were mainly gram-negative bacteria. The immune function of patients with pulmonary infection decreased, and the tumor markers such as serum NSE and SCC increased.

Analysis of predictors of systemic lupus erythematosus with intestinal symptoms as the first manifestation / 中华消化杂志

Objective:To analyze the predictors of systemic lupus erythematosus (SLE) with intestinal symptoms as the first manifestation, and to provide evidence for the diagnosis and differential diagnosis of the disease.Methods:From January 2013 to June 2020, the clinical data of 165 patients diagnosed with SLE and treated at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. According to whether the intestinal symptoms were the first manifestations, they were divided into intestinal symptoms as the first manifestations group ( n=50) and intestinal symptoms not as the first manifestations group ( n=115). The baseline data, imaging findings, orgen involvement and laboratory indicators of the two groups were compared and analyzed. Independent sample t test, non-parametric test and chi-square test were used for statistical analysis. Logistic regression analysis was used to establish a prediction model of SLE with intestinal symptoms as the first manifestation. Receiver operating characteristic curve (ROC) and Hosmer-Lemeshow test were used to evaluate the predictive value of the model. From July 2020 to May 2021, the data of 72 SLE patients treated at the First Affiliated Hospital of Zhengzhou University were collected (22 patients with intestinal symptoms as the first manifestation and 50 patients with intestinal symptoms not the first manifestation), and the predictive power of the model was validated. Results:Compared with intestinal symptoms not as the first manifestation group, the proportions of patients with fever, muscle involvement and joint involvement in intestinal symptoms as the first manifestation group were lower, while the proportions of patients with polyserositis, ascites, edema and dilatation or thickening of intestines, hydronephrosis or dilatation of the ureter, kidney involvement, blood system involvement were higher, and the level of complement C3, level of complement C4, absolute lymphocyte value and albumin level were lower (67.8%, 78/115 vs. 32.0%, 16/50; 24.3%, 28/115 vs. 4.0%, 2/50; 68.7%, 79/115 vs. 14.0%, 7/50; 27.8%, 32/115 vs. 86.0%, 43/50; 16.5%, 19/115 vs. 78.0%, 39/50; 13.9%, 16/115 vs. 86.0%, 43/50; 4.3%, 5/115 vs. 62.0%, 31/50; 29.6%, 34/115 vs. 48.0%, 24/50; 30.4%, 35/115 vs. 52.0%, 26/50; 0.76 g/L, 0.43 to 0.97 g/L vs. 0.48 g/L, 0.40 to 0.57 g/L; 0.14 g/L, 0.08 to 0.23 g/L vs. 0.09 g/L, 0.06 to 0.15 g/L; 0.90×10 9/L, 0.51×10 9 to 1.28×10 9/L vs. 0.64×10 9/L, 0.44×10 9 to 1.08×10 9/L; (34.07±7.30) g/L vs. (28.77±5.43) g/L), and the differences were statistically significant ( χ2=18.246, 9.699, 41.776, 47.567, 57.781, 78.833, 67.903, 5.195 and 6.955, Z=-4.053, -3.295 and -2.204, t=-4.606; all P<0.05). The results of multivariate logistic regression analysis showed that low level of complement C3 and low albumin level were risk factors of SLE with intestinal symptoms as the first manifestation (odds ratio 0.136, 95% confidence interval 0.031 to 0.590; odds ratio 0.923, 95% confidence interval 0.871 to 0.977; P=0.008 and 0.006). The established prediction model for SLE with intestinal symptoms as the first manifestation was p=1/(1+ e - Y), in which Y=2.906-1.994×complement C3 (g/L) -0.08×albumin (g/L). The area under the ROC was 0.761 (95% confidence interval 0.687 to 0.834, P<0.01). The result of Hosmer-Lemeshow test showed the model had good calibration ability ( χ2=13.024, P=0.111). The result of validation analysis showed that when p≥0.255 to predict SLE with intestinal symptoms as the first symptoms, the sensitivity of the model was 72.7% (16/22), the specificity was 76.0% (38/50), and the accuracy was 75.0% (54/72). Conclusions:The symptoms of SLE with intestinal symptoms as the first manifestations are obscure and easily misdiagnosed. When the imaging examination of patients with intestinal symptoms as the first manifestations shows edema and dilatation or thickening of intestines, hydronephrosis or dilatation of the ureter, or laboratory examination indicates low level of complement C3 and low albumin level, be wary of the possibility of SLE. Early diagnosis and intervention can greatly improve the prognosis of patients.

Abnormalities of efficiency in resting state functional brain network in first-episode paranoid schizophrenia / 中华行为医学与脑科学杂志

Objective:To explore the abnormalities of efficiency in resting state functional brain network in patients with paranoid schizophrenia and the correlations between efficiencies and clinical symptoms.Methods:A total of 73 patients with schizophrenia (SZ group) met with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-Ⅳ) criteria for schizophrenia and 70 healthy controls (HC group) were included .All subjects were checked by using functional magnetic resonance imaging (fMRI), and positive and negative syndrome scale(PANSS) were used to assess the symptoms.Abnormalities of global and local efficiency of brain regions in brain functional network were analyzed by graph theory.Pearson correlation was used to analyze the correlation between the abnormal global efficiency and local efficiency of brain regions of SZ group and PANSS.SPSS 20.0 software was used for dependent-sample t-test, ANOVA test and Pearson correlation analysis. Results:Compared with the HC group, SZ group showed increased global efficiency in bilateral thalamus(left: 0.26±0.06, 0.28±0.04, t=2.03, P=0.044.right: 0.26±0.06, 0.28±0.05, t=2.08, P=0.040), right orbital part of middle frontal gyrus(0.21±0.04, 0.23±0.05, t=2.25, P=0.026), cerebellar lobule Ⅸ(0.19±0.06, 0.21±0.05, t=2.56, P=0.011) and vermis Ⅲ(0.15±0.08, 0.19±0.07, t=3.27, P=0.001), while decreased global efficiency in bilateral parahippocampal gyrus(left: 0.25±0.05, 0.22±0.05, t=-3.34, P=0.001.right: 0.27±0.04, 0.23±0.05, t=-4.96, P=0.000), superior occipital gyrus(left: 0.27±0.03, 0.26±0.03, t=-2.70, P=0.008.right: 0.27±0.02, 0.26±0.03, t=-2.73, P=0.007), superior parietal gyrus(left: 0.27±0.03, 0.26±0.05, t=-2.63, P=0.010.right: 0.27±0.03, 0.25±0.05, t=-2.76, P=0.007), paracentral lobule(left: 0.28±0.03, 0.26±0.07, t=-2.47, P=0.015.right: 0.28±0.04, 0.25±0.07, t=-3.06, P=0.003), left precental gyrus(0.28±0.04, 0.27±0.04, t=-1.98, P=0.049), left cuneus(0.26±0.04, 0.25±0.04, t=-2.08, P=0.039), left lingual gyrus(0.29±0.03, 0.28±0.03, t=-2.28, P=0.024), left middle occipital gyrus(0.29±0.03, 0.28±0.03; t=-2.74, P=0.007), left middle temporal gyrus(0.28±0.03, 0.26±0.03, t=-2.73, P=0.007), temporal pole in left middle temporal gyrus(0.20±0.06, 0.18±0.06, t=-2.59, P=0.011) and right hippocampus(0.27±0.04, 0.26±0.06, t=-2.05, P=0.042).Compared with the HC group, SZ group showed increased local efficiency in bilateral caudate nucleus(left: 0.33±0.06, 0.35±0.05, t=2.54, P=0.012.right: 0.33±0.07, 0.35±0.04, t=2.77, P=0.007) and left superior occipital gyrus(0.39±0.03, 0.40±0.02, t=2.17, P=0.031), while decreased local efficiency in bilateral parahippocampal gyrus(left: 0.35±0.04, 0.32±0.07, t=-3.16, P=0.002.right: 0.34±0.04, 0.32±0.07, t=-2.91, P=0.004), left supplementary motor area(0.36±0.02, 0.35±0.05, t=-2.01, P=0.047), left inferior parietal but supramarginal and angular gyrus(0.35±0.03, 0.34±0.05, t=-2.65, P=0.009), left cerebellar crus Ⅱ(0.37±0.03, 0.36±0.04, t=-2.01, P=0.046), lobule ⅦB(0.37±0.03, 0.35±0.07, t=-1.98, P=0.049), right posterior cingulate gyrus(0.36±0.04, 0.34±0.07, t=-2.07, P=0.041), right superior parietal gyrus(0.37±0.03, 0.36±0.05, t=-2.19, P=0.031), right precuneus(0.36±0.02, 0.35±0.04, t=-2.36, P=0.020), right paracentral lobule(0.37±0.02, 0.36±0.06, t=-2.07, P=0.041) and right temporal pole in middle temporal gyrus(0.33±0.08, 0.30±0.09, t=-2.09, P=0.038).The global efficiency of bilateral paracentral lobule and left temporal pole in middle temporal gyrus in SZ group were negatively correlated with the negative scale scores( r=-0.25, -0.25, -0.26, all P<0.05).The global efficiency of right hippocampus in SZ group was positively correlated with total scores of PANSS( r=0.23, P=0.049).The global efficiency of left middle temporal gyrus in SZ group was negatively correlated with total scores of PANSS( r=-0.23, P=0.049).The local efficiency of right paracentral lobule in SZ group was negatively correlated with the positive scale scores( r=-0.24, P=0.038). Conclusion:The brain networks of patients with first-episode paranoid schizophrenia may have regional dysfunction in the transmission efficiency and fault-tolerant ability of resting state brain functional network, and the abnormalities of efficiency may be associated with the severity of psychiatric symptoms in several brain regions.

Recapitulation of SARS-CoV-2 Infection and Cholangiocyte Damage with Human Liver Organoids

The newly emerged pandemic coronavirus, SARS-CoV-2, has posed a significant public health threat worldwide. However, the mode of virus transmission and tissue tropism is not well established yet. Recent findings of substantial liver damage in patients and ACE2+ cholangiocytes in healthy liver tissues prompted us to hypothesize that human liver ductal organoids could serve as a model to determine the susceptibility and mechanisms underlining the liver damage upon SARS-CoV-2 infection. By single-cell RNA sequencing, we found that long-term liver ductal organoid culture preserved the human specific ACE2+ population of cholangiocytes. Moreover, human liver ductal organoids were permissive to SARS-CoV-2 infection and support robust replication. Notably, virus infection impaired the barrier and bile acid transporting functions of cholangiocytes through dysregulation of genes involved in tight junction formation and bile acid transportation, which could explain the bile acid accumulation and consequent liver damage in patients. These results indicate that control of liver damage caused directly by viral infection should be valued in treating COVID-19 patients. Our findings also provide an application of human organoids in investigating the tropism and pathogenesis of SARS-CoV-2, which would facilitate novel drug discovery.

Manifestations of acute regional occult outer retinopathy in full-field electroretinogram / 中华眼底病杂志

Objective:To observe the full-field ERG (ff-ERG) characteristics of patients with acute regional occult outer retinopathy (AZOOR).Methods:A retrospective observational study. From June 2017 to June 2019, 62 eyes of 42 patients (AZOOR group) who were diagnosed with AZOOR in the Department of Ophthalmology of West China Hospital of Sichuan University were included in the study. All patients had no obvious localized disease on the fundus. Among 62 eyes, BCVA of 16 eyes were <0.1, BCVA of 27 eyes were ≤0.5, and BCVA of 19 eyes were> 0.5. From June 2018 to January 2019, 40 normal volunteers (80 eyes) who attended the outpatient clinic of West China Hospital of Sichuan University and passed detailed ophthalmological examination to exclude all eye diseases including refractive errors were selected as the normal control group. All the examined eyes were tested with ff-ERG using the German Roland visual electrophysiological inspection system. The peak times and amplitudes of the waveforms induced by each response of dark adaptation 0.01 ERG, dark adaptation 3.0 ERG, dark adaptation 3.0 ERG, light adaptation 3.0 ERG, and light adaptation 30 Hz flicker ERG were recorded, respectively. The peak time and amplitude of each ff-ERG response between the two groups were compared by independent sample t test. The peak time and amplitude of each ff-ERG response between different BCVA eyes in the AZOOR group were compared by variance test. Results:Compared with the normal control group, 0.01 ERG b wave of the dark adaptation of AZOOR group ( t=3.601, -6.120), 3.0 ERG a wave and b wave of dark adaptation ( t=2.627, -4.263, 3.719,-5.866), 3.0 Oscillation potential P2 wave of dark adaptation ( t=-6.625), 3.0 ERG a wave and b wave of bright adaptation ( t=3.762, -3.612, 3.648, -3.739) and 30 Hz flicker ERG P wave of bright adaptation ( t=-3.832), all peak time of those were significantly delayed, the amplitude decreased, and the difference was statistically significant ( P<0.05). Comparison of different BCVA eyes in the AZOOR group showed that 0.01 ERG b wave amplitude of dark adaptation ( F=3.950), 3.0 ERG a peak and b wave amplitude of dark adaptation ( F=4.408, 4.876), oscillation potential P2 wave amplitude of dark adaptation ( F=4.295), 3.0 ERG b wave amplitude of bright adaptation ( F=4.344) and 30 Hz flicker ERG P wave amplitude of bright adaptation ( F=4.483) of differences were statistically significant ( P<0.05). There was no statistically significant difference in waveform peak time and amplitude of the other reactions ( P>0.05). Pairwise comparison results showed that, compared with those with 0.1≤BCVA≤0.5 and BCVA> 0.5, those with BCVA <0.1 dark adaptation to 0.01 ERG b wave, dark adaptation 3.0 ERG b wave, dark adaptation oscillation potential P2 wave, and light adaptation 3.0 ERG b wave and light adaptation 30 Hz scintillation ERG P wave amplitude were significantly reduced, and dark adaptation to 3.0 ERG a peak was significantly delayed, the difference was statistically significant ( P<0.05). Conclusions:The ff-ERG of patients with AZOOR show delayed peak time and decreased amplitude of each response. The worse BCVA are accompanied by the more obvious decrease of each response amplitude of ff-ERG.

Study on the variation of visual evoked potential and its diagnostic value in children with optic neuritis / 中国小儿急救医学

Objective@#To investigate the characteristics and clinical value of visual evoked potentials(VEP) in children with optic neuritis.@*Methods@#The VEP of 33 children with optic neuritis were tested by NICOLET evoked potential instrument.The results were compared with those of cranial and/or orbital MRI and fundus examination, and the consistency with visual performance was analyzed.The correlation between visual sensitivity and VEP results was analyzed.@*Results@#Among 33 children with optic neuritis, the abnormal rate of VEP in 52 abnormal eyes was 88.5%; the abnormal rate of cranial and/or orbital MRI was 38.5%; the abnormal rate of fundus examination was 62.2%; the abnormal rate of VEP examination was significantly higher than that of cranial and/or orbital MRI and fundus examination (P<0.05); the consistency rate between VEP examination and visual acuity was 84.8%.The consistency rate between pattern reversal visual evoked potential (P-VEP) and visual acuity was 86.8%, and that between flash visual evoked potential (F-VEP) and visual acuity was 82.1%.With the increase of visual impairment, the percentage of P100 wave loss increased gradually.There was no correlation between visual acuity and the prolongation of P100 wave latency.@*Conclusion@#There are significant differences between VEP and fundus examination and MRI, the sensitivity of VEP is superior to both.P-VEP is more consistent with visual acuity than F-VEP.VEP has certain value in evaluating the degree of visual impairment in children with optic neuritis.It can not be used to evaluate the level of optic sensitivity when the latency of P100 wave is prolonging.

Peritoneal dialysis improves lung function in rats with lung injury induced by shock wave / 中华肾脏病杂志

Objective To prove the efficacy of peritoneal dialysis on shock wave-induced acute lung injury of rats, and analyze its mechanisms. Methods Forty-five adult Sprague-Dawley rats were randomly divided into three groups: control group, sham operation (Sham) group and peritoneal dialysis (PD) group. Sham group and PD group did abdominal catheterization before blast injury. The 55 kg shock wave (bst-I) was used to induce lung blast injury. After one hour of blast injury, PD group was given 2.5％ peritoneal dialysate 20 ml to stay abdomen, which was released 30 min posted, repeated 12 cycles. After 6 hours of peritoneal dialysis, all of the rats were sacrificed. Partial damaged tissues in lung were used to evaluate the pathomorphologic changes by HE staining, and the remnants were used to measure the lung water content. Lung function was detected by blood gas analyzer and small animal detector from the arterial blood gas. The levels of serum inflammatory factors, such as tumor necrosis factor - α (TNF - α), interleukin (IL) - 1β, IL - 6 and monocyte chemoattractant protein-1 (MCP-1) were tested by ELISA. Results The relative integrity of alveolar structure, interstitial edema and inflammatory cell infiltration in PD group were significantly improved than those in control group. The lung water content of PD group was significantly lower than that of control group (P<0.05). The levels of TNF-α, IL-1β, IL-6 and MCP-1 in serum of PD group were significantly lower than those in control group (all P<0.05). The blood oxygen saturation, oxygen partial pressure, oxygenation index, vital capacity, functional residual volume and maximum mid-expiratory flow rate in PD group were significantly higher than those in control group (all P<0.05). Conclusions Through reducing pulmonary edema and inflammatory factors, peritoneal dialysis can improve lung function in shock wave-induced acute lung injury of rats.

Resting-state functional magnetic resonance imaging of supramarginal gyrus-cerebellum circuit in obsessive-compulsive disorder / 中华行为医学与脑科学杂志

Objective Regional homogeneity (ReHo) and functional connectivity (FC) were used to study obsessive-compulsive disorder(OCD),and to explore the mechanism of OCD in resting state.Method Resting-state functional magnetic resonance imaging (RS-fMRI) was performed in 55 patients with OCD (OCD group) and 50 normal controls (control group) matched by sex,age,nationality and education.The data and screening abnormal brain areas were analyzed and compared by DPARSFA2.3 and Rest software in OCD group.Whole brain FC analysis was performed with abnormal brain areas as seed points.Result Compared with the control group,ReHo in right thalamus (MNI:x=9,y=-24,z=6,t=4.3217) and left superior marginal gyrus (MNI:x =-45,y =-30,z =27,t =3.6320) increased and ReHo in right caudate nucleus (MNI:x=3,y=15,z=9,t=-3.1687) decreased in obsessive-compulsive disorder group,and the difference was statistically significant(P＜0.05).Using left superior marginal gyrus,fight thalamus and right caudate nucleus as seed voxels,the whole brain FC analysis showed that there were abnormal functional connections between bilateral cerebellar foot 1/2 area and left supramarginal gyrus,right thalamus and right caudate nucleus (P＜0.05) and the left supramarginal gyrus-bilateral cerebellum feet 1 area-right thalamic circuit and left supramarginal gyrus-bilateral cerebellum feet 1,2-right caudate nucleus-right thalamic circuit existed in 0CD group.Conclusion The left supramarginal gyrus-bilateral cerebellum feet 1 area-right thalamic circuit and left supramarginal gyrus-bilateral cerebellum feet 1,2-right caudate nucleus-right thalamic circuit may play an important role in the mechanism of OCD.

Peritoneal dialysis improves lung function in rats with lung injury induced by shock wave / 中华肾脏病杂志

Objective@#To prove the efficacy of peritoneal dialysis on shock wave-induced acute lung injury of rats, and analyze its mechanisms.@*Methods@#Forty-five adult Sprague-Dawley rats were randomly divided into three groups: control group, sham operation (Sham) group and peritoneal dialysis (PD) group. Sham group and PD group did abdominal catheterization before blast injury. The 55 kg shock wave (bst-I) was used to induce lung blast injury. After one hour of blast injury, PD group was given 2.5% peritoneal dialysate 20 ml to stay abdomen, which was released 30 min posted, repeated 12 cycles. After 6 hours of peritoneal dialysis, all of the rats were sacrificed. Partial damaged tissues in lung were used to evaluate the pathomorphologic changes by HE staining, and the remnants were used to measure the lung water content. Lung function was detected by blood gas analyzer and small animal detector from the arterial blood gas. The levels of serum inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and monocyte chemoattractant protein-1 (MCP-1) were tested by ELISA.@*Results@#The relative integrity of alveolar structure, interstitial edema and inflammatory cell infiltration in PD group were significantly improved than those in control group. The lung water content of PD group was significantly lower than that of control group (P<0.05). The levels of TNF-α, IL-1β, IL-6 and MCP-1 in serum of PD group were significantly lower than those in control group (all P<0.05). The blood oxygen saturation, oxygen partial pressure, oxygenation index, vital capacity, functional residual volume and maximum mid-expiratory flow rate in PD group were significantly higher than those in control group (all P<0.05).@*Conclusions@#Through reducing pulmonary edema and inflammatory factors, peritoneal dialysis can improve lung function in shock wave -induced acute lung injury of rats.

Mechanism of Sodium arsenite by Wnt signaling pathway inhibits the proliferation of oral squamous cell carcinoma and promote apoptosis / 中国生化药物杂志

Objective To investigate the effect of sodium arsenite by Wnt signaling pathway on proliferation and apoptosis of oral squamous cell carcinoma.Methods Cell proliferation was detected after 1.25,2.5,5,10,20μmol/L sodium arsenite treatment human oral squamous cell carcinoma cell line Tca8113 for 24,48,72 hours by CCK8 experiment.0 and 14μmol/L sodium arsenite was used to treatment Tca8113 cells with 48h,cell apoptosis were detected by flow cytometry,Cleaved Caspase3,β-catenin,Cyclin D1 protein expression were detected by Western blot.Tca8113 cells were divided into control group,sodium arsenite group,activating agent+sodium arsenite group,all treated for 48hour,cell proliferation,apoptosis and Cleaved Caspase3,β-catenin,Cyclin D1 protein expression were detected by CCK8 assay,flow cytometry and Western blot.Results Tca8113 cell proliferation was inhibited significantly with the increase of treatment time and sodium arsenite concentration,and has a time and concentration dependent manner(P<0.05 or P<0.01).10μmol/L sodium arsenite as a follow-up study according to the IC50.Cell inhibition rate,apoptosis rate and Cleaved Caspase3 protein expression in 10μmol/L group were significantly higher than that of 0 mol/L group,the expression of β-catenin,Cyclin D1 protein was significantly lower than that of 0 mol/L group(P<0.01).Apoptosis rate,cell inhibition rate and Cleaved Caspase 3 protein expression in sodium arsenite group and activating agent+sodium arsenite group were significantly higher than control group,the expression of β-catenin and Cyclin D1 protein were significantly lower than control group(P<0.01).Apoptosis rate,cell inhibition rate and Cleaved Caspase 3 protein expression in activating agent + sodium arsenite group were significantly lower than that of sodium arsenite group,the expression of β-catenin and Cyclin D1 protein were significantly higher than that of sodium arsenite group(P<0.01).Conclusion Sodium arsenite can inhibit the proliferation of oral squamous cell carcinoma and promote apoptosis,and the mechanism was related to regulation of Wnt signaling pathway.

Identification of genes associated with gastric cancer prognosis from TCGA datasets / 基础医学与临床

Objective To identify genes associated with prognosis or differentiated type in gastric cancer from fre quently mutated genes or highly-expressed genes,using large-scale genomic data from The Cancer Genome Atlas.Methods The somatic mutation data,RNAseqV2 data and clinical information were downloaded from the TCGA website.The frequency of deleterious somatic mutations for each gene was counted to select the frequently mutated genes.DESeq2 was used to analyze the gene expression data.Then survival analysis was performed on genes highlyexpressed in the tumor tissue.Kaplan-Meier curves were generated by R-survival package,and significance was evaluated by log-rank test.Results The frequency for pathogenic mutations in PIK3CA and APC was significantly discordant between different grades of gastric cancer.2 040 genes were up-regulated in tumor tissue,while 2 357 genes were down-regulated.Among the up-regulated genes,7 genes were associated with poor prognosis of gastric cancer and one was associated with better prognosis.Conclusions Genes associated with differentiation types or prognosis in gastric cancer are identified.The result may clue us future research on potential prognostic markers in clinical treatment.

Screening and identification of cardiac-specific peptides / 国际生物医学工程杂志

Objective To screen cardiac-specific short-acting peptides on live myocardial slices using phage display technology,so as to improve the targeted delivery efficiency of drugs in myocardium and provide effective candidates for the targeted therapy of Duchenne muscular dystrophy (DMD) and other cardiomyopathies.Methods Myocardial tissue slices were prepared and cultured in vitro.The protein activities of the tissues were examined by immunohistochemistry.The in vitro cultured myocardial tissue slices were co-incubated with phage library (1×1012 pfu),and the phages that bound to the myocardium were recovered and amplified.The cardiac-specific targeting phages were identified by five rounds of in vitro phage biopanning.The candidate phage-related insertion sequence was sequenced,and the in vivo tissue distribution of the highly enriched phages was verified.Results A platform for in vitro culturing of live myocardial slices was established.Myocardial slices with good biological activity were obtained.After 48 hours of culturing,the normal expression and localization of Dystrophin protein were detected.Using phage library,candidate phages were screened after five rounds of phage biopanning.The results of the sequencing analyses and in vivo tissue distribution verification indicated that the selected candidate phages showed significant enrichment in myocardium and skeletal muscle,and showed low levels in liver and kidney tissues.Conclusions The candidate phages showed higher binding efficiency in both myocardium and skeletal muscle,indicating that the candidate peptides had myocardial targeting property,and that can provide a new method for myocardial targeting therapy of DMD.

The inspection of sitagliptin to metabolic index and carotid artery IMT in metabolic syndrome patients with type 2 diabetes / 中国医师杂志

Objective To evaluate the effects of sitagliptin on blood glucose,blood pressure,blood lip and carotid artery intima media thickness (IMT) in metabolic syndrome patients with type 2 diabetes.Methods The clinical data were collected for 64 cases of inpatient and outpatient patients with metabolic syndrome with type 2 diabetes.Those patients included anti-diabetes native patients and patients only used the stable metformin dose.After signed off the informed consent form,those patients were randomized to the sitagliptin treatment group or original treatment group,and the metabolic index and carotid artery intima-media thickness were evaluated after 24 weeks treatment.Results The body mass index (BMI),waist circumference (WC),fasting plasma glucose (FPG),triglycerides (TG),high density lipoprotein cholesterol (HDL-C),systolic blood pressure (SBP),diastolic blood pressure (DBP),glycated hemoglobin a1c (HbA1c),and carotid artery IMT in two groups were comparable at baseline.After 12 weeks treatment,the FPG,TG,DBP,and HbA1c in the sitagliptin group were significantly better than original treatment group and the baseline,while there was no different between two groups in other index.After 24 weeks treatment,the FPG,TG,HDL-C,DBP,HbA1c,and carotid artery IMT in the sitagliptin group were significantly better than original treatment group and the baseline.Conclusions Sitagliptin presents the functions of lowering blood pressure,adjusting blood lipid,and protecting vascular endothelial in addition to lowering blood glucose.