Relationship Between Peripheral Blood T Lymphocyte Subsets and Prognosis of Patients with Advanced Non-small Cell Lung Cancer Treated with Camrelizumab / 肿瘤防治研究

Objective To explore the relationship between peripheral blood T lymphocyte subsets and prognosis of patients with advanced non-small cell lung cancer (NSCLC) who received treatment with camrelizumab. Methods We retrospectively collected data from 88 patients with advanced NSCLC who underwent camrelizumab treatment. Peripheral blood lymphocyte subsets were collected from patients before and two months after treatment. Kaplan-Meier curves and Cox regression analysis were employed to investigate the relationship between peripheral blood T lymphocyte subsets and PFS and OS. Results Compared with non-responder group, the baseline peripheral blood CD4+/CD8+ ratio was higher (P=0.038), while the CD8+T lymphocyte percentage was lower (P=0.036) in the responder group. Kaplan-Meier curves showed that a high baseline CD4+/CD8+ ratio was associated with long PFS and OS (P=0.001, P=0.023). Multivariate Cox analysis revealed that the baseline CD4+/CD8+ ratio was a significant predictor for PFS and OS. Additionally, a high post-treatment CD4+/CD8+ ratio and high CD4+T lymphocyte percentage were associated with long PFS (P=0.005, P=0.015), whereas a low post-treatment CD8+T lymphocyte percentage was associated with long PFS and OS (P=0.001, P=0.016). Conclusion The peripheral blood CD4+/CD8+ ratio can serve as a predictive factor for survival of patients with NSCLC treated with camrelizumab.

Mechanism of Yi-xin-yin oral liquid according to homotherapy for heteropathy theory based on UHPLC-Q-TOF/MS combined with network pharmacology and molecular docking techniques / 中国临床药理学与治疗学

AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.

Mechanism of Qingfei Huatan Zhuyu Decoction in Treatment of COPD Based on "Lung and Intestinal Co-treatment" / 中国实验方剂学杂志

ObjectiveTo observe the effect of Qingfei Huatan Zhuyu decoction on the lung and intestinal function of rats with chronic obstructive pulmonary diseases （COPD） and explore the deep-seated mechanism of its embodiment of lung and intestinal co-treatment. MethodA total of 60 Wistar rats were randomly divided into six groups， with 10 rats in each group， and the groups were control group， model group， acute syrup group （10 g·kg-1·d-1）， and low， medium， and high-dose groups （10， 15， 20 g·kg-1·d-1） of Qingfei Huatan Zhuyu decoction. The COPD rat model was established by lipopolysaccharide tracheal drip combined with the smoke inhalation method， and the acute syrup group and the Qingfei Huatan Zhuyu decoction group were administered by gavage with corresponding dose concentrations respectively， while the rest groups were controlled by saline gavage， and the lung function and blood gas indexes of rats were monitored after the last administration. The histopathological changes in the lung and intestine were observed microscopically. The expression of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （IgA） in colon tissue were measured by enzyme-linked immunosorbent assay （ELISA）. The biochemical indexes such as serum diamine oxidase （DAO）， D-lactic acid， and malondialdehyde （MDA） were measured. Immunohistochemistry was used to detect the expression of tight junction protein （Occludin） in rat colon tissue. The expression of F4/80 positive alveolar macrophages in rat lung tissue， and the expression of α-actin （α-SMA） and colonic atresia small band protein-1 （ZO-1） were determined by immunofluorescence. The protein expression of p-NF-κB p65， NF-κB p65， p-p38 MAPK， and p-p38 MAPK and the expression of Occludin and ZO-1 in colon tissue were detected in rat lung tissue by Western blot. ResultCompared with the normal group， the model group had pulmonary dysfunction， reduced forced vital capacity （FVC）， arterial partial oxygen pressure （PaO2）， arterial oxygen saturation （SaO2）， and dynamic lung compliance （Cdyn） （P<0.01）， and the pathological changes in the lung and intestine were obvious. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were increased （P<0.05，P<0.01）， and the protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue was increased. The expression of F4/80 positive macrophages in lung tissue was enhanced. The expression of IgA， Occludin， and ZO-1 in colon tissue decreased （P<0.05，P<0.01）. Compared with the model group， the pulmonary function of the rats in the acute syrup group and groups of Qingfei Huatan Zhuyu decoction was significantly improved， and the FVC， PaO2， SaO2， and Cdyn were increased （P<0.05， P<0.01）. The pathological changes in the lung and intestine were significant. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were decreased （P<0.05，P<0.01）， and the expressions of F4/80 positive macrophages in lung tissue were decreased （P<0.01）. The protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue decreased （P<0.01）， and the expression of IgA， Occludin， and ZO-1 in colon tissue increased （P<0.01）. ConclusionQingfei Huatan Zhuyu decoction can effectively reduce the symptoms of COPD rats， and its mechanism of action is related to inhibiting the inflammatory response of lung tissue and improving the barrier function of the intestinal mucosa.

Ultrasonic characterization of multi-layered porous lithium-ion battery structure for state of charge.

A multi-layered porous finite element model of lithium-ion battery is proposed by using Voronoi polygons. The time domain simulation of ultrasonic transmission characteristics with different state of charge (SOC) are carried out, and the variation of acoustic parameters versus SOCs is explored. Then, in the experiment research, the ultrasonic transmission signals are obtained by employing piezoelectric ceramic transducers during the discharging step. By extracting the time domain characteristic parameters, it is discovered that the amplitude and time-of-flight (TOF) have a strong correlation with SOC, the slow pressure-wave (SPW) velocities of the experiments correspond well with the simulation results. In addition, the frequency domain analysis shows a linear link between the amplitude of the frequency spectrum and SOC. Moreover, via repeated experiments, it is found that the ultrasonic transmission method has good repeatability in probing the SOC, and the SPW velocities acquired by experiments can almost be covered by 95% confidence interval formed based on the results of the simulation. Furthermore, according to the results of the experiments, a gray model based on the particle swarm optimization-based-simulated annealing (GM-PSO-SA) is established, which realized the prediction of the SOC under the condition of small sample data. The research results can serve as a reference for creating a comprehensive finite element model of the multi-layered porous structure of lithium-ion battery. Meanwhile, it also provides a detection and evaluation tool for the monitoring of the SOC.

Preparation of inhalable N-acetylcysteine-loaded magnetite chitosan microparticles for nitrate adsorption in particulate matter.

Airborne particulate matter has been designated as a class 1 carcinogen by the World Health Organization. Nitrate is a toxic substance that accounts for a large proportion of particulate matter, and nitrate toxicity has long been reported. In this study, we aimed to optimize the adsorption and removal of particulate matter containing nitrate for effective elimination by the lungs. To this end, particles were designed to optimize the inhalation and removal efficiencies. These particles were prepared as chitosan-based particles containing N-acetylcysteine by using emulsion diffusion methods. Chitosan adsorbs nitrate, while N-acetylcysteine dissolves mucus. This removal mechanism has been found to occur in various in vitro models that mimic respiratory environments and in vivo models. In particular, the removal of exogenous substances, such as particulate matter, by the motility of respiratory cilia through mucolytic effect was investigated. This new approach for the adsorption and elimination of toxic substances entering the lungs represents an alternative defense mechanism against exposure to nitrates from air pollution.

Theoretical derivation and clinical validation of the resolution limit of human eye to spherical lens change: a self-controlled study.

PURPOSE: The aim of this study was to deduce theoretically and verify the resolution limit of human eye to spherical lens change for more reasonable design of the trial lenses. METHODS: A total of 119 normal subjects with different myopia (not more than - 6D) were included. First, the resolution limit of discernible change in spherical power was derived based on the optical model. Then, the subjects were observed to see if they could perceive the changes in spherical power as per the resolution limit and compare the difference in the best-corrected visual acuity obtained with the resolution limit and interval of 0.25D. RESULTS: Assuming that the cone cell diameter is 3 µm and the pupil diameter of 4 mm, the theoretically resolution limit was 0.05D. When the diopter of spherical power was increased, the ratios of ability to perceive 0.05D spherical lens change were 98.3% and 96.7% in right and left eyes. When the diopter of spherical power was decreased, the ratios of ability to perceive 0.05D spherical lens change were 78.9% and 83.2% in right and left eyes. The best-corrected visual acuity obtained with the 0.05 D interval trial lens was significantly better than in the 0.25 D interval on both eyes (Right eye - 0.04 ± 0.07 vs - 0.02 ± 0.06, p < 0.001; Left eye - 0.07 ± 0.06 vs - 0.04 ± 0.06, t = 8.825, p < 0.001). CONCLUSION: The resolution limit of human eye to spherical lens change was about 0.05D and the better corrected visual acuity can be obtained by adjusting the spherical power at an interval of 0.05D. TRIAL REGISTRATION NUMBER: ChiCTR2100047074. Date of registration: 2021/6/7.

Finite element analysis of 14-year-old adolescent after spinal foraminoplasty at L / 解剖学报

Objective To establish the three-dimensional finite element model of lumbar spine(L) 3-5 segments of the normal spine of 14-year-old adolescents to analyze the biomechanical changes of the lumbar spine after different degrees of lumbar foraminal plasty, and to provide reference for improvement of adolescent foraminoplasty. Methods A14-year-old female volunteer with no previous history of lumbar spine was selected to collect lumbar CT image data and we imported it into Mimics 16.0 software for modeling. ABAQUS software was used to conduct finite element model force analysis. Models M

Erythrocyte membrane-associated protein inhibiting Th17 cell differentiation via IL-6 / STAT3 / ROR-γt signaling pathway in experimental autoimmune encephalomyelitis mice / 解剖学报

Objective To explore the effect of exogenous and endogenous erythrocyte membrane-associated protein (ERMAP) on helper T cell 17 (Th17) cell differentiation through interleukin 6 / signal transducers and activators of transcription 3 / retionoid-related orphan nuclear receptor-γt(IL-6 / STAT3 / ROR-γt) signal pathway in the mouse model of experimental autoimmune encephalomyelitis (EAE) . Methods Using flow cytometry to verify the function of ERMAP-Ig fusion protein at different concentrations; Agarose gel electrophoresis was performed to identify ERMAP knockout mice. Flow cytometry was performed to detect the effect of ERMAP-Ig fusion protein on Th17 cell differentiation in vitro. Forty 6-week-old normal C57BL / 6 mice were randomly divided into 2 groups to establish EAE models, control-Ig and ERMAP-Ig groups, with 20 mice in each group; Clinical scores were recorded; Flow cytometry was performed to detect Th17 cell differentiation in EAE mice in vivo. Forty 6-week-old identified wild-type and ERMAP knockout mice were divided into 2 groups to establish EAE models. Identified wild-type and ERMAP knockout mice were divided into 2 groups to establish EAE models, ERMAP

Effect of a novel phosphodiesterase type 5 inhibitor, CPD1, on paraquat-induced lung fibrosis in rats / 中国药理学通报

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on lung pathological phenotype and epithelial-mesenchymal transition of alveolar epithelial cells in lung fibrosis model rats caused by paraquat (PQ). Methods Lung fibrosis model was constructed by a single intraperitoneal injection of PQ (30 mg·kg

Health-related quality of life in patients with type 2 diabetes based on the European 5-Dimensional Health Scale / 公共卫生与预防医学

Objective To evaluate the quality of life of patients with type 2 diabetes mellitus in Weifang City, Shandong Province and to explore its influencing factors. Methods A multistage stratified random sampling method was used to investigate patients in endocrine outpatient clinics in four medical institutions in Weifang from July to September 2022. The survey included general information, multi-dimensional evaluation of quality of life with the EQ-5D-5L scale, calculation of health utility values, and analysis of influencing factors using Tobit regression models. Results A total of 397 patients with type 2 diabetes were included in the present investigation, with health utility value of 0.82±0.21 points and visual analogue scale (VAS) score of 79.47±12.81 points. Pain or discomfort, anxiety or depression were more prominent in the study population. Age, diabetic complications, BMI, daily need for care, social support, and daily level of glycemic control were factors influencing health-related quality of life in patients with type 2 diabetes. Conclusion In the actual treatment of type 2 diabetes patients, an emphasis should be placed on protecting elderly type 2 diabetic patients, preventing and controlling the occurrence and development of diabetic complications, and improving daily blood glucose control to further improve the health-related quality of life of the population.

Exploring the common mechanism of Yindan Xinnaotong soft capsule in the treatment of stroke and coronary heart disease through HIF1α-MMP9-mediated HIF1α signaling pathway / 药学学报

Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1α (HIF1α)-matrix metalloproteinase-9 (MMP9)-mediated HIF1α signaling pathway serves as one of the common mechanisms. YDXNT could reduce the increase of mitochondrial fluorescence intensity and the protein expression of HIF1α and MMP9 in HL-1 and HA induced by oxygen and glucose deprivation/reperfusion (OGD/R) in a dose-dependent manner. Baicalin may be the material basis for treating stroke and CHD with YDXNT. In conclusion, the HIF1α signaling pathway is one of the common key mechanisms of YDXNT in the co-treatment of stroke and CHD. The study provides support and basis for the in-depth scientific connotation of the traditional Chinese medicine theory of "same treatment to different diseases".

Glucuronic acid metabolites of phenolic acids target AKT-PH domain to improve glucose metabolism / 中草药·英文版

OBJECTIVE@#Phenolic acids widely exist in the human diet and exert beneficial effects such as improving glucose metabolism. It is not clear whether phenolic acids or their metabolites play a major role in vivo. In this study, caffeic acid (CA) and ferulic acid (FA), the two most ingested phenolic acids, and their glucuronic acid metabolites, caffeic-4'-O-glucuronide (CA4G) and ferulic-4'-O-glucuronide (FA4G), were investigated.@*METHODS@#Three insulin resistance models in vitro were established by using TNF-α, insulin and palmitic acid (PA) in HepG2 cells, respectively. We compared the effects of FA, FA4G, CA and CA4G on glucose metabolism in these models by measuring the glucose consumption levels. The potential targets and related pathways were predicted by network pharmacology. Fluorescence quenching measurement was used to analyze the binding between the compounds and the predicted target. To investigate the binding mode, molecular docking was performed. Then, we performed membrane recruitment assays of the AKT pleckstrin homology (PH) domain with the help of the PH-GFP plasmid. AKT enzymatic activity was determined to compare the effects between the metabolites with their parent compounds. Finally, the downstream signaling pathway of AKT was investigated by Western blot analysis.@*RESULTS@#The results showed that CA4G and FA4G were more potent than their parent compounds in increasing glucose consumption. AKT was predicted to be the key target of CA4G and FA4G by network pharmacology analysis. The fluorescence quenching test confirmed the more potent binding to AKT of the two metabolites compared to their parent compounds. The molecular docking results indicated that the carbonyl group in the glucuronic acid structure of CA4G and FA4G might bind to the PH domain of AKT at the key Arg-25 site. CA4G and FA4G inhibited the translocation of the AKT PH domain to the membrane, while increasing the activity of AKT. Western blot analysis demonstrated that the metabolites could increase the phosphorylation of AKT and downstream glycogen synthase kinase 3β in the AKT signaling pathway to increase glucose consumption.@*CONCLUSION@#In conclusion, our results suggested that the metabolites of phenolic acids, which contain glucuronic acid, are the key active substances and that they activate AKT by targeting the PH domain, thus improving glucose metabolism.

Iodine nutrition status of pregnant women in Ningxia Hui Autonomous Region from 2017 to 2020 / 中华地方病学杂志

Objective:To analyze and compare the salt iodine content and iodine nutrition status of pregnant women in Ningxia Hui Autonomous Region (Ningxia for short), and to provide basis for formulation of prevention and control measures.Methods:From 2017 to 2020, 100 pregnant women were surveyed each year in 22 counties (cities, districts) in Yinchuan, Shizuishan, Wuzhong, Guyuan and Zhongwei of Ningxia, salt samples and urine samples were collected for salt iodine and urinary iodine detection.Results:Totally 8 807 salt samples were collected, the median salt iodine was 24.6 mg/kg. The qualified rate of iodized salt was 91.59% (7 838/8 558), the coverage rate of iodized salt was 97.17% (8 558/8 807), and the consumption rate of qualified iodized salt was 89.00% (7 838/8 807). The consumption rate of qualified iodized salt increased year by year (χ 2trend = 248.47, P < 0.001). There were statistical differences in salt iodine levels in different years and regions ( H = 259.14, 37.09, P < 0.001). Totally 8 107 urine samples were collected, the median urinary iodine of pregnant women was 165.00 μg/L, which reached the appropriate level. The median and composition of urinary iodine were statistically different in different regions and pregnancies ( H = 28.87, 17.91, P < 0.001; χ 2 = 85.89, 20.59, P < 0.05). Conclusions:The coverage rate of iodized salt among pregnant women in Ningxia is high, and the urinary iodine level is generally in a suitable state. However, for pregnant women at risk of iodine deficiency, special attention should be paid and targeted iodine supplementation measures should be taken.

Analysis of research hotspots of iodine nutrition in pregnant women based on CiteSpace bibliometric method / 中华地方病学杂志

Objective:To study the current status of research in the field of iodine nutrition for pregnant women and to detect the hot spots and future trends in the field of iodine nutrition for pregnant women.Methods:Using "pregnant women" and "iodine" as search terms, we searched the literature related to iodine nutrition in pregnant women from January 2000 to December 2021 in China Knowledge Network (CNKI) database, Wanfang database and Chinese Medical Journal Full Text Database. CiteSpace 6.2.2.0 software was used to sort out the publication status, core authors and research hotspots of the papers.Results:A total of 879 valid papers were included, with an overall number of publications increasing trend from 2000 - 2021 and a decline after 2017. Among the 879 papers, 29 first authors were core authors (M≈3), and 109 papers were published, accounting for 12.40% of the total literature; several research groups with relatively stable collaborative relationships had been formed, with the larger collaborative team of Chen Zupei and Zhang Wanqi at Tianjin Medical University. Keyword co-occurrence analysis showed that pregnant women, urinary iodine, and iodine nutrition were high-frequency keywords; keywords with mediated centrality > 0.07 were pregnant women (0.48), pregnancy (0.40), urinary iodine (0.37), iodine deficiency disorders (0.25), iodine nutrition (0.20), thyroid (0.12), thyroxine (0.10), infants and children (0.09). The analysis of the emergent words showed that the evolution of iodine nutrition research themes in pregnant women was broadly based on studies of iodine nutrition monitoring results in key populations such as newborns and infants from 2000 - 2011, studies such as the range of thyroxine reference values during pregnancy from 2012 - 2016, and changes in iodine nutrition status of pregnant women and children after adjustment of iodized salt concentration from 2017 - 2021. The clustering results showed that a total of 355 keywords were aggregated to yield 10 clusters, and the average profile value of clusters (Silhouette) > 0.8, which was a reasonable clustering result; the study topics can be divided into three major categories, iodine nutrition and goiter monitoring results in key populations, thyroid hormones and pregnancy outcomes during pregnancy, and studies on thyroid-related diseases.Conclusions:Iodine plays an important role in the health of pregnant women and their offspring, and changes in the iodine nutrition status of pregnant women should be closely monitored. In response to the new trends of change that are currently present, multidisciplinary cooperation should be developed to respond to social concerns and jointly promote the maintenance of iodine nutrition in pregnant women at appropriate levels.

Effect of homogeneous management combined with staged teaching on physicians receiving standardized training of hepatobiliary surgery / 中华医学教育探索杂志

Objective:To investigate the effect of homogeneous management combined with staged teaching on physicians receiving standardized training of hepatobiliary surgery.Methods:A total of 46 physicians who received standardized training in Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, from January to March 2020 were selected as control group and were given conventional teaching, and 50 physicians who received standardized training from April to June 2020 were selected as observation group and were given homogeneous management combined with staged teaching. The two groups were compared in terms of professional level, clinical ability, and the degree of satisfaction with teaching before and after teaching. SPSS 24.0 was used to perform the independent samples t-test, the paired t-test, the chi-square test, and the rank sum test. Results:After teaching, both groups had significant increases in the scores of theoretical examination and operation skill examination, and compared with the control group, the observation group had significantly higher scores of theoretical examination (94.57±3.28 vs. 90.32±2.12) and operation skill examination (94.37±4.18 vs. 91.25±3.46). After teaching, both groups had significant increases in the scores of clinical consultation, physical examination, humanistic concern, clinical diagnosis, communication ability, organizational ability, and overall evaluation, and the observation group had significantly higher scores of the above seven aspects than the control group (6.98±0.94/6.45±0.14/6.95±0.88/6.65±0.93/6.53±0.26/6.84±0.92/6.58±0.35 vs. 6.13±0.31/6.21±0.76/6.21±0.42/6.18±0.35/6.32±0.61/6.33±0.24/6.25±0.71). The observation group had a significantly higher overall satisfaction rate than the control group [94.00% (47/50) vs. 78.26% (36/46)].Conclusion:In the standardized training and teaching of hepatobiliary surgery, homogeneous management combined with staged teaching can improve the professional level and clinical ability of physicians and enhance the degree of satisfaction with teaching.

Eosinophil-to-neutrophil ratio predicts outcomes in patients with acute ischemic stroke receiving intravenous thrombolysis / 国际脑血管病杂志

Objective:To investigate the predicting value of eosinophil-to-neutrophil ratio (ENR) for outcomes at 3 months after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods:Patients with AIS received intravenous thrombolysis in the Department of Neurology, Huai'an First People's Hospital from July 2019 to July 2022 were included retrospectively. Multivariate logistic regression model was used to determine the independent correlation between ENR and outcomes at 3 months after intravenous thrombolysis. The receiver operating characteristics (ROC) curve was used to evaluate the predictive value of ENR levels for poor outcomes at 3 months after intravenous thrombolysis. Results:A total of 352 patients with AIS receiving intravenous thrombolysis were enrolled, including 240 men (68.1%), age 66.46±12.00 years old. The median National Institutes of Health Stroke Scale score was 8 (interquartile range, 5-13). At 3 months after onset, 215 patients (61.0%) had good outcomes, 137 (38.9%) had poor outcomes. Univariate analysis showed that the median ENR×10 2 level of the poor outcome group was significantly lower than that of the good outcome group ( Z= –7.305, P<0.01). Multivariate logistic regression analysis showed that lower ENR×10 2 was an independent risk factor for poor outcomes at 3 months after intravenous thrombolysis (odds ratio 0.619, 95% confidence interval 0.514-0.745; P<0.01). ROC curve analysis showed that the area under the curve for ENR×10 2 predicting the poor outcomes after intravenous thrombolysis was 0.731 (95% confidence interval 0.678-0.784; P<0.01). The optimal cutoff value was 0.625 and the corresponding sensitivity and specificity were 94% and 40%, respectively. Conclusion:Lower ENR before intravenous thrombolysis in patients with AIS is independently associated with the poor outcomes at 3 months.

Systemic immune-inflammation index predicts hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the predictive value of systemic immune-inflammatory index (SII) for hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods:Patients with AIS received intravenous thrombolysis in the Department of Neurology, Huai’an First People’s Hospital from July 2019 to July 2022 were included retrospectively. The head CT was performed at 24 h after intravenous thrombolysis and determined whether HT existed. sICH was defined as brain parenchymal hematoma, and the National Institutes of Health Stroke Scale (NIHSS) scores increased by ≥4 compared with the baseline, or the patient died within 36 h after onset. Multivariate logistic regression analysis was used to determine the independent correlation between SII and HT and sICH after intravenous thrombolysis. The receiver operating characteristics (ROC) curve was used to evaluate the predictive value of SII for HT and sICH after intravenous thrombolysis. Results:A total of 352 patients with AIS received intravenous thrombolysis were enrolled, including 240 males (68.1%), aged 66.46±12.00 years. The median baseline NIHSS score was 8 (interquartile range, 5-13), and the median SII is 531.91×10 9/L (interquartile range, 351.20-896.91×10 9/L). HT occurred in 62 patients (17.6%) and sICH occurred in 27 patients (7.7%). Univariate analysis showed that the SII of the HT group was significantly higher than that of the non-HT group ( Z=–2.731, P=0.006), and the SII of the sICH group was significantly higher than that of non-sICH group ( Z=–4.125, P<0.01). Multivariate logistic regression analysis showed that the increased SII was the independent risk factor for HT (odds ratio [ OR] 1.001, 95% confidence interval [ CI] 1.000-1.001; P=0.004) and sICH ( OR 1.001, 95% CI 1.001-1.002; P<0.01). ROC curve analysis shows that the area under curve of SII predicting HT was 0.610 (95% CI 0.535-0.686; P=0.006), and the best cutoff value was 488.48×10 9/L. The corresponding sensitivity and specificity were 69% and 47% respectively. The area under the curve of SII predicting sICH was 0.739 (95% CI 0.636-0.842; P<0.01), and the best cutoff value was 846.56×10 9/L, the corresponding sensitivity and specificity were 70% and 77% respectively. Conclusion:The increased SII at admission can predict the risks of HT and sICH in patients with AIS after intravenous thrombolysis.

Diagnosis and treatment recommendations of dialysis patients with SARS-CoV-2 infection for primary care clinicians / 西安交通大学学报(医学版)

End-stage renal disease (ESRD) patients undergoing outpatient hemodialysis (HD) and home peritoneal dialysis (PD) are high risk population of severe and critical types caused by SARS-CoV-2 infection. In order to improve the quality of diagnosis and treatment in dialysis patients with SARS-CoV-2 infection, we wrote this recommendation for primary care clinicians. During the epidemic period of SARS-CoV-2 infection, all patients should be instructed to strengthen self-management. Once the SARS-CoV-2 infection was found in dialysis patients, early stratified management should be carried out within 72 hours after the first positive nucleic acid or antigen test results, which includes early antiviral therapy, early recognition, and transferring severe patients from community or primary hospital to a referral hospital promptly. Guidance for dietary and sports rehabilitation after SARS-CoV-2 infection should also be started as soon as possible.

Mechanism of TRPC in promoting extracellular matrix deposition of glomerular mesangial cells / 西安交通大学学报(医学版)

【Objective】 To explore the role and mechanism of TRPC in promoting extracellular matrix (ECM) deposition in rat glomerular mesangial cells (HBZY-1). Methods Immunofluorescence staining was performed to observe the distribution and expression of TRPC1 and TRPC6 in HBZY-1 cells. After AngⅡ stimulation, qRT-PCR and Western blotting were used to detect the mRNA and protein expressions of Gαq/PLCβ4/TRPC signaling pathway main proteins and ECM deposition indicators (α-SMA, collagenⅢ and fibronectin). By silencing the expressions of TRPC1 and TRPC6 by RNA interference, the expressions of ECM deposition indicators were detected. Changes in [Ca2+]i influx were determined through Fluo-4AM Ca2+ imaging. 【Results】 Both TRPC1 and TRPC6 were expressed in HBZY-1, and were mainly located in cell membrane and cytoplasm. After AngⅡ stimulation, Gαq/PLCβ4/TRPC signaling pathway was activated, and the mRNA and protein expressions of Gαq, PLCβ4, TRPC1 and TRPC6 were all increased (P<0.05). [Ca2+]i influx also increased (P<0.01), and the mRNA and protein expressions of ECM deposition indicators (α-SMA, ColⅢ and Fn) were upregulated (P<0.05). Silencing the expressions of TRPC1 and TRPC6 by RNA interference led to decreased [Ca2+]i influx (P<0.05), and downregulated mRNA and protein expressions of ECM deposition indicators in HBZY-1 cells (P<0.05). The results suggested that inhibition of TRPC expressions could inhibit AngⅡ induced ECM deposition in HBZY-1 cells, which might be associated with decreased [Ca2+]i influx. 【Conclusion】 TRPC may be a novel therapeutic target of renal fibrosis.

TRPC6 involves in endoplasmic reticulum stress induced apoptosis of glomerular mesangial cells / 西安交通大学学报(医学版)

【Objective】 To explore the role and mechanism of TRPC6 in apoptosis of glomerular mesangial cells (HBZY-1) induced by endoplasmic reticulum stress (ERS). 【Methods】 The experiment groups were classified as follows: normal control (NC), thapsigargin (TG), TG+SKF96365, and TG+TRPC6 siRNA groups. Transcription and protein expressions of TRPC6 and ERS related proteins (GRP78 and Caspase12) were detected by qRT-PCR and Western blotting. Additionally, cell apoptosis was measured by flow cytometry and Hoechst33258. Finally, Fluo-4 AM Ca2+ imaging technique was used to determine changes of intracellular calcium ( [Ca2+] i) by laser scanning confocal microscope. 【Results】 Morphological changes of apoptotic cells were characterized by nuclear enrichment or nuclear fragmentation, and the apoptosis rate was increased after TG stimulation. The expressions of TRPC6 and ERS related proteins (GRP78 and Caspase12) were elevated in TG group compared with NC group (P<0.05). Pre-incubation of HBZY-1 cells with SKF96365 and TRPC6 siRNA decreased cell apoptosis (P<0.05). The entry of [Ca2+] i also increased after TG stimulation (P<0.05). The expressions of TRPC6, GRP78 and Caspase12 were downregulated compared with TG group after treatment with SKF96365 and TRPC6 siRNA accompanied by decreased [Ca2+] i (P<0.05). 【Conclusion】 Taken together, this study suggests that inhibition of TRPC6 can alleviate TG-induced HBZY-1 cell apoptosis.