A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys / 神经科学通报·英文版

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.

Endogenous corticotropin-releasing factor potentiates the excitability of presympathetic neurons in paraventricular nucleus via activation of its receptor 1 in spontaneously hypertensive rats / 生理学报

It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin-releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs.

Research on the establishment of standard limits for perfluorooctanoic acid and perfluorooctane sulfonate in the "Standards for Drinking Water Quality（GB5749-2022）"in China / 中华预防医学杂志

Perfluorinated compounds, especially Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are widely detected in water environments in China. Considering the potential health risks of drinking water exposure routes, PFOA and PFOS have been added to the water quality reference index of the newly issued "Standards for Drinking Water Quality (GB5749-2022)", with limit values of 40 and 80 ng/L, respectively. This study analyzed and discussed the relevant technical contents for determining the limits of the hygiene standard, including the environmental existence level and exposure status of PFOA and PFOS, health effects, derivation of safety reference values, and determination of hygiene standard limits. It also proposed prospects for the future direction of formulating drinking water standards.

Screening for scoliosis and associated factors among primary and middle school students in Shanghai / 中国学校卫生

Objective@#To understand the prevalence and influencing factors of scoliosis among primary and middle school students in Shanghai, so as to provide reference for the prevention and control strategies of scoliosis in children and adolescents.@*Methods@#From September to December 2021, a total of 4 531 students from grade four of primary school to grade three of junior high school from 16 primary and middle schools in 4 districts of Shanghai were selected by multi stage stratified cluster sampling to carry out scoliosis screening and questionnaire survey. Independent sample t-test, Chi-squared test, Fisher s exact probability method and nonparametric Mann Whitney U-test were used for statistical analysis, and multivariate Logistic regression was used to analyze the influencing factors of scoliosis.@*Results@#The on the spot detection rate of scoliosis abnormality was 7.4% and the prevalence was 2.2%, mainly for thoracolumbar scoliosis (60.4%) and the scoliosis angle of 10° -<20°(88.1%). The results showed that the detection rate of scoliosis in boys was 1.6% and in girls was 3.3%, with a statistically significant difference ( χ 2=11.84, P < 0.01). There were significant differences in weight and BMI between scoliosis students and students with negative initial screening( t = -3.77, -5.30, P <0.01). And there was a statistically significant difference in the detection rate of scoliosis with different frequency of classroom seating arrangements ( Z =2.02, P <0.05). The results of multivariate Logistic regression showed that the risk of scoliosis in girls was higher than that in boys ( OR =1.87, 95% CI =1.21-2.88). BMI ( OR =0.89, 95% CI =0.83-0.95) and frequency of classroom seating arrangements ( OR =0.49, 95% CI =0.25-0.93) were correlated with lower rate of scoliosis. After stratification by sex, the frequency of classroom seating arrangements ( OR =0.26, 95% CI =0.10-0.67) in boys and the educational stage ( OR =2.35, 95% CI =1.26-4.41) in girls ( P <0.05) was correlated with higher rate of scoliosis, while BMI ( OR =0.86, 95% CI =0.79-0.94) in girls were correlated with lower rate of scoliosis.@*Conclusion@#Regular screening of scoliosis is an effective method for early detection of scoliosis. Girls in junior high school and low BMI should be paid close attention to. According to the occurrence and influencing factors of scoliosis, comprehensive prevention and control based on family, school, society, and other aspects can be carried out.

Immunotherapy for endometrial carcinoma based on molecular typing / 国际肿瘤学杂志

Endometrial cancer has been identified by The Cancer Genome Atlas program with four molecular subtypes by genome sequence analysis. Clinical trials to select suitable immunotherapeutic agents based on the different immune characteristics of each subtype have been conducted in several countries and have made important progress. The main clinical applications of immune checkpoint inhibitors include anti-programmed cell death protein-1/programmed death-ligand 1 antibodies and poly ADP-ribose polymerase inhibitors. Optimizing drug selection and drug combination based on the target characteristics of different immune checkpoint inhibitors may provide new opportunities for immunotherapy of endometrial cancer and bring new light to improve survival rates.

Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019 / 中华外科杂志

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during 2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019 / 中华外科杂志

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

Trends in the prevalence of Internet addiction among adolescents from 2004 to 2019 in Shanghai / 中国学校卫生

Objective@#To analyze the trends of Internet addiction among adolescents in Shanghai, so as to provide theoretical evidence for the prevention and control of Internet addiction in adolescents.@*Methods@#A multistage stratified cluster random sampling method was conducted, and 92 171 junior and senior high school students in Shanghai were selected for questionnaire survey in 2004-2019. Evaluation of Internet addiction, loneliness, academic pressure and depression among middle school students.@*Results@#In 2004-2019, the rate of Internet addiction among middle school students in Shanghai was 4.3%, which without significant differences by year( t =1.8, P >0.05). The detection rate of Internet addiction in boys (5.3%) was higher than that in girls (3.4%) ( χ 2=186.8, P <0.01), and was highest in secondary vocational school (7.7%), followed by senior high school (4.6%) and junior middle school students (2.8%) ( χ 2=746.5, P <0.01). The prevalence of Internet addiction in girls, senior high school students, secondary vocational school students, students aged 16-20, students with loneliness or high academic pressure showed an increasing trend in 2004-2019, with the average annual increase rate ( APC ) of 6.62%, 5.45%, 2.13%, 3.36%, 4.09% and 3.60% respectively ( P <0.05).@*Conclusion@#Internet addiction among adolescents in Shanghai showed an increasing trend in some groups from 2004-2019, but without significant differences by year in the overall groups. Comprehensive prevention and control programs are needed for adolescent Internet addiction, especially for those with mental health problems.

Characteristics and trends of adolescents health risk behaviors in Shanghai from 2004 to 2019 / 中国学校卫生

Objective@#To analyze the trend of adolescent health risk behaviors in Shanghai, and to provide reference for the comprehensive intervention of middle school students health risk behaviors.@*Methods@#Based on the health risk behavior questionnaire of Chinese Center for Disease Control and Prevention, the questionnaire was adapted according to the actual monitoring needs. It was divided into junior high school version and senior high school version. From 2004 to 2019, using the method of multistage stratified cluster random sampling, 59 209 middle school students who completed the questionnaire in 6 surveys were selected for analysis. @*Results@#From 2004 to 2019, in the 7 days prior to the survey, 9.2%-50.6% of middle school students drank a glass of soda more than or equal to once a day and 54.2%-76.1% of middle school students reported eating dessert twice or more. Within 7 days, 48.3%-60.7% of middle school students had≥60 min of exercise per day for less than or equal to 3 days, and 16.1%- 35.2% of middle school students reported too much extracurricular activities, and the reporting rate increased year by year with the annual percent change ( APC ) of 5.15%( t =9.28, P <0.01). The reporting rate of long time online learning was 6.0%-13.6%, which showed an upward trend among high school students, with the APC of 5.35%( t =3.14, P <0.05). The reporting rate of middle school students pedestrian safety problems decreased from 69.1% in 2004 to 27.6% in 2019, with the APC of -6.28%( t =-8.18, P <0.01), but the reporting rate of cycling safety problems have increased in recent years. The reporting rate of intentional injury behaviors decreased by year such as fighting, bullying, etc. The reporting rate of initial smoking age ≤13 years old decreased, but attempted drinking behavior increased in junior middle school students, and the APC was 1.61%( t =3.48, P <0.05). A total of 1.6%-3.4% of middle school students had an Internet addiction behavior tendency. The detection rate of Internet addiction tendency was increasing in high school students and girls, and APC was 6.59% and 10.29% respectively( t =6.37, 8.62, P <0.01).@*Conclusion@#From 2004 to 2019, unintentional injury behavior, intentional injury behavior and substance addiction behavior of middle school students in Shanghai have improved. However, unhealthy diet and physical inactivity are still high. In the follow up. It need to focus on adverse diet and lack of physical activity behavior and take comprehensive intervention measures to control them.

Trends of smoking and drinking behaviors among adolescents in Shanghai from 2004 to 2019 / 中国学校卫生

Objective@#To analyze the trends of smoking and drinking behaviors among adolescents in Shanghai from 2004 to 2019, and to provide theoretical evidence for effective tobacco and alcohol interventions among adolescents.@*Methods@#Data regarding smoking and drinking behaviors from adolescent health risk behavior surveillance program in Shanghai from 2004 to 2019 were collected, and the prevalence of ever smoking, current smoking, ever drinking and current drinking were comparatively analyzed.@*Results@#The prevalence of ever smoking, current smoking, ever drinking and current drinking among boys were significantly higher than those among girls in 2004 to 2019( χ 2=58.20-347.44, P <0.01). Except the prevalence of ever drinking in 2012, the prevalence of ever smoking, current smoking, ever drinking and current drinking in vocational school students were the highest in each survey( χ 2=111.19-1 196.61, P <0.01). From 2004 to 2019, the standardized rates of smoking and drinking of boys and girls showed a downward trend ( APC =-6.20--1.80, P <0.05). The standardized ever smoking rate and the standardized ever drinking rate of both boys and girls declined significantly from 2004 to 2019（ APC=-5.00, -1.80, P ＜0.05）. The overall standardized rate of ever smoking decreased from 21.02% in 2004 to 12.23% in 2019, and that of ever drinking decreased from 60.52% in 2004 to 47.17 % in 2019）. However, the overall standardized rates of current smoking and current drinking did not reach statistically significance（ P >0.05）.@*Conclusion@#From 2014 to 2019,the prevalence of ever smoking and ever drinking among adolescents in Shanghai over the observed period showed a declining trend by years, but there was no significant change in current smoking and current drinking among adolescents. Specific interventions targeting on smoking and drinking behaviors among adolescents need to be strengthened.

Establishment of artificial neural network model for predicting lymph node metastasis in patients with stage Ⅱ-Ⅲ gastric cancer / 中华胃肠外科杂志

Objective: To establish a neural network model for predicting lymph node metastasis in patients with stage II-III gastric cancer. Methods: Case inclusion criteria: (1) gastric adenocarcinoma diagnosed by pathology as stage II-III (the 8th edition of AJCC staging); (2) no distant metastasis of liver, lung and abdominal cavity in preoperative chest film, abdominal ultrasound and upper abdominal CT; (3) undergoing R0 resection. Case exclusion criteria: (1) receiving preoperative neoadjuvant chemotherapy or radiotherapy; (2) incomplete clinical data; (3) gastric stump cancer.Clinicopathological data of 1231 patients with stage II-III gastric cancer who underwent radical surgery at the Fujian Medical University Union Hospital from January 2010 to August 2014 were retrospectively analyzed. A total of 1035 patients with lymph node metastasis were confirmed after operation, and 196 patients had no lymph node metastasis. According to the postoperative pathologic staging. 416 patients (33.8%) were stage Ⅱ and 815 patients (66.2%) were stage III. Patients were randomly divided into training group (861/1231, 69.9%) and validation group (370/1231, 30.1%) to establish an artificial neural network model (N+-ANN) for the prediction of lymph node metastasis. Firstly, the Logistic univariate analysis method was used to retrospectively analyze the case samples of the training group, screen the variables affecting lymph node metastasis, determine the variable items of the input point of the artificial neural network, and then the multi-layer perceptron (MLP) to train N+-ANN. The input layer of N+-ANN was composed of the variables screened by Logistic univariate analysis. Artificial intelligence analyzed the status of lymph node metastasis according to the input data and compared it with the real value. The accuracy of the model was evaluated by drawing the receiver operating characteristic (ROC) curve and obtaining the area under the curve (AUC). The ability of N+-ANN was evaluated by sensitivity, specificity, positive predictive values, negative predictive values, and AUC values. Results: There were no significant differences in baseline data between the training group and validation group (all P>0.05). Univariate analysis of the training group showed that preoperative platelet to lymphocyte ratio (PLR), preoperative systemic immune inflammation index (SII), tumor size, clinical N (cN) stage were closely related to postoperative lymph node metastasis. The N+-ANN was constructed based on the above variables as the input layer variables. In the training group, the accuracy of N+-ANN for predicting postoperative lymph node metastasis was 88.4% (761/861), the sensitivity was 98.9% (717/725), the specificity was 32.4% (44/136), the positive predictive value was 88.6% (717/809), the negative predictive value was 84.6% (44/52), and the AUC value was 0.748 (95%CI: 0.717-0.776). In the validation group, N+-ANN had a prediction accuracy of 88.4% (327/370) with a sensitivity of 99.7% (309/310), specificity of 30.0% (18/60), positive predictive value of 88.0% (309/351), negative predictive value of 94.7% (18/19), and an AUC of 0.717 (95%CI:0.668-0.763). According to the individualized lymph node metastasis probability output by N+-ANN, the cut-off values of 0-50%, >50%-75%, >75%-90% and >90%-100% were applied and patients were divided into N0 group, N1 group, N2 group and N3 group. The overall prediction accuracy of N+-ANN for pN staging in the training group and the validation group was 53.7% and 54.1% respectively, while the overall prediction accuracy of cN staging for pN staging in the training group and the validation group was 30.1% and 33.2% respectively, indicating that N+-ANN had a better prediction than cN stage. Conclusions: The N+-ANN constructed in this study can accurately predict postoperative lymph node metastasis in patients with stage Ⅱ-Ⅲ gastric cancer. The N+-ANN based on individualized lymph node metastasis probability has better accurate prediction for pN staging as compared to cN staging.

Effect of Preoperative Tumor Under-Staging on the Long-term Survival of Patients Undergoing Radical Gastrectomy for Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to evaluate the effect of preoperative tumor staging deviation (PTSD) on the long-term survival of patients undergoing radical gastrectomy for gastric cancer (RGGC). @*Materials and Methods@#Clinicopathological data of 2,346 patients who underwent RGGC were retrospectively analyzed. The preoperative tumor-lymph node-metastasis (TNM) under-staging group (uTNM) comprised patients who had earlier preoperative TNM than postoperative TNM, and the no preoperative under-staging group (nTNM) comprised the remaining patients. @*Results@#There were 1,031 uTNM (44.0%) and 1,315 nTNM cases (56.0%). Cox prognostic analysis revealed that PTSD independently affected the overall survival (OS) after surgery. The 5-year OS was lower in the uTNM group (41.8%) than in the nTNM group (71.6%). The patients less than 65 years old, with lower American Society of Anaesthesiologists score, 2-5 cm tumor located at the lower stomach, and cT1 or cN0 preoperative staging would more likely undergo D1+ lymph node dissection (LND) in uTNM (p 2 cm and body mass index ≤ 22.72 kg/m2 were independent risk factors of preoperative TNM tumor under-staging in patients with cT1N0M0 staging (p < 0.05). @*Conclusion@#Underestimated tumor staging is not rare, which possibly results in inadequate LND and affects the long-term survival for patients undergoing RGGC. D2 LND should be carefully performed in patients who are predisposed to this underestimation.

Sensitivity evaluation of ArcCheck in detecting leaf open time errors of helical tomotherapy delivery / 中华放射肿瘤学杂志

Objective:To evaluate the sensitivity of the ArcCheck dosimetry system in detecting the leaf open time errors during the center and off-center helical tomotheray delivery quality assurance (DQA).Methods:Nine nasopharyngeal carcinoma (NPC) patients were selected in this study. Two DQA plans were created for each patient: the" center" plan was created by moving the image of the ArcCheck phantom to place the high dose region on the phantom center and the " off-center" plan was created by offsetting the phantom and putting several diodes through a higher does region. Leaf open time errors of 2, 4, 6, 8 and 10 ms were introduced to the Sinogram which was modified using Matlab. Each intentional error plan and original (no error) plan for each patient were measured using both " center" and " off-center" DQA methods, the γ analysis was performed to evaluate the DQA results. The different dose and distance error criteria of 3%/3 mm, 3%/2 mm and 2%/2 mm were selected, and different thresholds of 5%, 10% and 15% were selected for γ analysis. The gradient and the minimum detectable error approach were taken to quantitatively analyze the sensitivity. The correlation between different dose distance error criteria and different thresholds was also evaluated by Pearson correlation analysis. Results:The absolute value of γ gradient of the " center" DQA plans were larger than those of the " off-center" plans in all different γ criteria (all P<0.05). The stricter the γ criteria were adopted, the more sensitive DQA results of leaf open time error were obtained. The minimum detectable error was 2 ms in all different γ criteria for the " center" DQA plan. The minimum error detectability of the " off-center" DQA plan was weaker than that of the " center" DQA plan. The γ passing rates of three different dose distance error criteria were significantly strongly correlated for the " center" DQA plan ( R2>0.9). For the " off-center " DQA plan, only the 3%/3 mm and 3%/2 mm criteria were significantly strongly correlated ( R2>0.9). Significant strong correlation was observed in the γ passing rate at different thresholds between the " off-center" and " center" DQA plans. Conclusions:The " center" DQA plan method is more sensitive than the " off-center" DQA plan method in all γ criteria, and the γ passing rates in different γ criteria are strongly correlated for the " center" DQA plan. The " center" DQA plan method is recommended.

Comparison of validation results and leaf open time before and after upgrading of helix tomotherapy planning system / 中华放射肿瘤学杂志

Objective:To compare the leaf open time (LOT) parameters and γ passing rates between the 4.0.4 and 4.2.3 helix Tomotherapy planning systems and evaluate the improvement.Methods:Retrospective comparison of the treatment plans of 345 cases selected by 4.0.4 and 4.2.3 versions was performed. The Machine Specific Sinogram of each plan was extracted from the archived plan file to calculate the LOT. The evaluated LOT parameters included the projection time, the maximum LOT, the mean non-zeros time, the time difference between the projection time and the maximum LOT, the relative count of leaves with LOT greater than maximum LOT minus 5 ms, the relative count of leaves with LOT lower than 100 ms and the beam on time. The γ passing rate (criteria: 3 mm/3%, 10% threshold and global error) and the LOT parameters between two version systems were evaluated with the independent t-test. The relationship between the LOT parameters and γ passing rate was analyzed by the multiple linear regression method. Results:The γ passing rate of the Ver 4.0.4 system was 97.86%, significantly lower than 98.6% of the Ver 4.2.3 system ( P<0.001). The time gap between the projection time and the maximum LOT of the Ver 4.2.3 system was significantly less than that of the Ver 4.0.4 system (1 ms vs. 11 ms, P<0.001). For the Ver 4.0.4 system, the multiple linear regression method showed that the maximum LOT ratio and the beam on time were negatively correlated with the γ passing rate (both P<0.001). However, for the Ver 4.2.3 system, only the beam on time showed a negative correlation with the γ passing rate ( P<0.001). Conclusion:The γ passing rate of the Ver 4.2.3 system is significantly higher than that of the Ver 4.0.4 system. The decrease of γ passing rate caused by the leaves near the maximum LOT is properly resolved in the new version system.

Review on the relationship between sphingolipid metabolism and cardiovascular diseases / 解剖学报

As bioactive lipids, sphingolipids participate in the signal transduction of many important physiological processes such as growth and apoptosis. Besides, abnormal levels of sphingolipids were detected in a variety of clinical conditions including hypertension and coronary heart disease, suggesting that sphingolipid metabolism is involved in the occurrence and development of cardiovascular diseases. This paper reviewed the relationship between sphingolipid metabolism with four common cardiovascular diseases, coronary heart disease, hypertension, arrhythmia and heart failure, and the mechanisms involved. What's more, the prospect of sphingolipid pathway as a potential target for the diagnosis and treatment of cardiovascular diseases is put forward.

Curcumin improves endothelial function and plays a cardio-protective effect by reducing level of circulating microparticles in pressure overload-induced myocardial hypertrophy in rats / 中国药理学通报

Aim To observe the cardio-protective effects of curcumin on rats with myocardial hypertrophy, and to further explore the mechanism. Methods Abdominal aorta was constricted in SD rats to establish a pressure overload-induced myocardial hypertrophy model. Rats were divided into sham group, AAC group and curcumin group. They were treated by intragastric administration. Twenty weeks after the operation, cardiac function was evaluated using echocardiogram. The heart rate was recorded using biological function experiment system. The blood pressure and left ventricular pressure were measured by a cannulation into right common carotid artery and left ventricular respectively. Circulating blood MPs level in rats was detected by BCA. Effects of MPs on the viability of human umbilical vein endothelial cell were measured by CCK-8. Results Twenty weeks after surgery, only two rats in AAC group died. The results of echocardiography showed that compared with sham group, left ventricular internal dimension at systole (LVIDs), left ventricular internal diastolic dimension (LVIDd), left ventricular posterior wall diameter (LVPWd), heart rate (HR), mean arterial pressure (MAP) and left ventricular end-diastolic pressure (LVEDP) all significantly increased in AAC group, whereas ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP), maximum upstroke velocity of left ventricular pressure (+ dp/dt

Mechanism of oxymatrine in treatment of collagen-induced arthritis in mice / 中国中药杂志

Sophorae Flavescentis Radix, the root of Sophora flavescens Ait., has been widely applied in the medical field due to its anti-inflammatory, analgesic, bacteriostatic, antiviral, antitumor, and other pharmacological effects. The present study investigated the anti-rheumatoid arthritis effect of oxymatrine(OMT), the active component of Sophorae Flavescentis Radix by observing its effect on the function of B lymphocytes in collagen-induced arthritis(CIA) mice through the Toll-like receptor 9(TLR9)/myeloid differentiation factor 88(MyD88)/signal transducer and activator of transcription 3(STAT3) pathway. The CIA model in DBA/1 J mice was induced by bovine type Ⅱ collagen and complete Freund's adjuvant(CFA). Fifteen days after the primary immunization, mice were treated with OMT for 30 days by intraperitoneal injection. Paw swelling and arthritis index(AI) score were evaluated every 3 days. Joint histopathologic changes were observed by HE staining. Magnetic-activated cell sorting(MACS) was used to isolate B lymphocytes from the spleen of CIA mice spleen. The serum expression level of interleukin(IL)-21 was examined by the enzyme-linked immunosorbent assay(ELISA). The expression of TLR9, STAT3, p-STAT3, and IL-21 in B lymphocytes was detected by Western blot. The mRNA expression of TLR9, STAT3, and IL-21 in B lymphocytes was detected by real-time fluorescence-based quantitative PCR(qRT-PCR). The results showed that OMT could significantly alleviate the paw swelling, decrease the AI score, relieve synovial inflammatory cell infiltration and hyperplasia, reduce the level of inflammatory cytokines, and inhibit the expression of TLR9, STAT3, p-STAT3, and IL-21 of B lymphocytes in CIA mice. Therefore, OMT may alleviate rheumatoid arthritis by regulating TLR9/MyD88/STAT3 pathway in B lymphocytes, providing a valuable reference for the application of OMT in the clinical treatment of rheumatoid arthritis.

Associations of Sarcopenia, Handgrip Strength and Calf Circumference with Cognitive Impairment among Chinese Older Adults / 生物医学与环境科学（英文）

Objective@#To evaluate the associations of sarcopenia, handgrip strength and calf circumference with cognitive impairment among Chinese older adults.@*Methods@#Totally 2,525 older adults were recruited from the Healthy Aging and Biomarkers Cohort Study. Cognitive impairment was assessed by the Chinese Mini-Mental State Examination. Handgrip strength was calculated from the means of the right and left hand values. Calf circumference was measured at the site of maximum circumference of the non-dominant leg. The formula developed by Ishii was used to define sarcopenia. Multiple logistic regression was performed to evaluate the associations of sarcopenia, handgrip strength, and calf circumference with cognitive impairment.@*Results@#The prevalence of cognitive impairment was 34.36%. The adjusted odds ratio ( @*Conclusion@#Sarcopenia, identified by low handgrip strength and low calf circumference, was positively associated with cognitive impairment.

New progress in antitumor research of non-psychoactive cannabidiol / 国际肿瘤学杂志

Cannabidiol is one of the most abundant phytocannabinoids in hemp, which has no psychoactive properties and a variety of pharmacological actions in vivo. Several recent studies indicate that cannabidiol possesses antitumor activity, the diversity of its acting receptor distribution and activation mechanism makes it possible to inhibit tumorigenesis in multiple ways via affecting tumor cell proliferation, inducing apoptosis, inhibiting cell invasion and metastasis, anti-angiogenesis and regulating immune response. Further understanding of the mechanism of cannabidiol in tumors may provide new ideas for the development of new antitumor agents.

Treatment with ß-elemene combined with paclitaxel inhibits growth, migration, and invasion and induces apoptosis of ovarian cancer cells by activation of STAT-NF-κB pathway

In this study, we aimed to analyze the anti-cancer effects of β-elemene combined with paclitaxel for ovarian cancer. RT-qPCR, MTT assay, western blot, flow cytometry, and immunohistochemistry were used to analyze in vitro and in vivo anti-cancer effects of combined treatment of β-elemene and paclitaxel. The in vitro results showed that β-elemene+paclitaxel treatment markedly inhibited ovarian cancer cell growth, migration, and invasion compared to either paclitaxel or β-elemene treatment alone. Results demonstrated that β-elemene+paclitaxel induced apoptosis of SKOV3 cells, down-regulated anti-apoptotic Bcl-2 and Bcl-xl gene expression and up-regulated pro-apoptotic P53 and Apaf1 gene expression in SKOV3 cells. Administration of β-elemene+paclitaxel arrested SKOV3 cell cycle at S phase and down-regulated CDK1, cyclin-B1, and P27 gene expression and apoptotic-related resistant gene expression of MDR1, LRP, and TS in SKOV3 cells. In vivo experiments showed that treatment with β-elemene+paclitaxel significantly inhibited ovarian tumor growth and prolonged the overall survival of SKOV3-bearing mice. In addition, the treatment inhibited phosphorylated STAT3 and NF-κB expression in vitro and in vivo. Furthermore, it inhibited migration and invasion through down-regulation of the STAT-NF-κB signaling pathway in SKOV3 cells. In conclusion, the data suggested that β-elemene+paclitaxel can inhibit ovarian cancer growth via down-regulation of the STAT3-NF-κB signaling pathway, which may be a potential therapeutic strategy for ovarian cancer therapy.