Noninvasive Diagnostic Technique for Nonalcoholic Fatty Liver Disease Based on Features of Tongue Images / 中国结合医学杂志

OBJECTIVE@#To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease (NAFLD) based on features of tongue images.@*METHODS@#Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, after a series of corrections and data cleaning. The algorithm was trained on images using labels and several anthropometric indexes for inputs, utilizing machine learning technology. Finally, a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD.@*RESULTS@#A total of 720 subjects were enrolled in this study, including 432 patients with NAFLD and 288 healthy volunteers. Of them, 482 were randomly allocated into the training set and 238 into the validation set. The diagnostic model based on logistic regression exhibited excellent performance: in validation set, it achieved an accuracy of 86.98%, sensitivity of 91.43%, and specificity of 80.61%; with an area under the curve (AUC) of 0.93 [95% confidence interval (CI) 0.68-0.98]. The decision tree model achieved an accuracy of 81.09%, sensitivity of 91.43%, and specificity of 66.33%; with an AUC of 0.89 (95% CI 0.66-0.92) in validation set.@*CONCLUSIONS@#The features of tongue images were associated with NAFLD. Both the 2 diagnostic models, which would be convenient, noninvasive, lightweight, rapid, and inexpensive technical references for early screening, can accurately distinguish NAFLD and are worth further study.

Benzyl isothiocyanate induces cell cycle arrest and apoptosis in cervical cancer through activation of p53 and AMPK-FOXO1a signaling pathways / 中国药理学通报

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

Evaluation of gastric emptying after drinking carbohydrates before cesarean section by gastric ultrasonography / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of gastric antrum ultrasonography in evaluating gastric emptying after oral administration of 300 mL carbohydrates two hours before cesarean section, and to analyze the risk factors of gastric emptying in pregnant women.@*METHODS@#From August 2020 to February 2021, a total of 80 patients, aged 22-43 years, body mass index (BMI) < 35 kg/m2, gestational age≥36 weeks, falling into American Society of Anesthesiologists (ASA) physical status Ⅰ or Ⅱ, scheduled for cesarean sections in Peking University International Hospital were recruited and divided into two groups: the intervention group (n=40)and the control group (n=40). In the intervention group, solid food was restricted after 22:00, the patients were required to take 300 mL carbohydrates two hours before cesarean section. In the control group, solid food and liquid intake were restricted after 22:00 the night before surgery. All the patients received assessment of preoperative feeling of thirst and starvation with visual analogue scale (VAS). The cross-sectional area (CSA)of gastric antrum was measured in supine position and right supine position before anesthesia, the gastric volume (GV)and the gastric volume/weight(GV/W)of the two groups was further calculated. Perlas A semi-quantitative grading assessments were performed in each patient. The blood pressure and heart rate were recorded at admission(T0), 5 minutes after anesthesia (T1), immediately after fetal delivery (T2) and at the end of the surgery (T3). The occurrence of nausea and vomiting during the operation and 24 hours after the operation were recorded.@*RESULTS@#One case in each group was excluded because the antrum was not clearly identified during the ultrasound assessments. In the semi-sitting position, the CSA was (5.07±1.73) cm2 in the intervention group vs. (5.24±1.96) cm2 in the control group, respectively; in the right lateral decubitus position, CSA was (7.32±2.17) cm2 in the intervention group vs. (7.25±2.24) cm2 in the control group, GV was (91.74±32.34) mL vs. (90.07±31.68) mL, GV/W was (1.27±0.40) mL/kg vs. (1.22±0.41) mL/kg, respectively; all the above showed no significant difference between the two groups (P > 0.05). Perlas A semi-quantitative grading showed 0 in 20 patients (51.3%), 1 in 16 (41%), 2 in 3 (7.7%)in the intervention group and 0 in 22 (56.4%), 1 in 15 (38.5%), 2 in 2 (5.1%)in the control group, the proportion of Perlas A semi-quantitative grading showed no significant difference between the two groups (P > 0.05). For the patients with Perlas A semi-quantitative grade 2 (3 cases in the intervention group and 2 cases in the control group), metoclopramide 0.2 mg/kg was intravenously injected before anesthesia. No aspiration case was observed in this study. The intervention group was endured less thirst and hunger (P < 0.05). There was no significant difference in blood pressure and heart rate between the two groups at each time point (P > 0.05). There was no significant difference in the incidence of intraoperative hypotension between the two groups (P > 0.05). There was no significant difference in the incidence of nausea intraoperatively and postoperatively between the two groups (P > 0.05).@*CONCLUSION@#Ultrasonography of gastric antrum can provide objective basis for evaluating gastric emptying of pregnant women perioperatively. 300 mL carbohydrates intake two hours before surgery, which does not increase GV and the risk of reflux aspiration, and is helpful in minimizing disturbance to the patient's physiological status, therefore leading to better clinical outcome.

Effect of preoperative carbohydrates intake on the gastric volume and the risk of reflux aspiration in patients positioning in trendelenburg undergoing gynecological laparoscopic procedures / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of 300 mL carbohydrates intake two hours before sur-gery on the gastric volume (GV) in patients positioning in trendelenburg undergoing gynecological laparoscopic procedures by using gastric antrum sonography, and further assess the risk of reflux aspiration.@*METHODS@#From June 2020 to February 2021, a total of 80 patients, aged 18-65 years, body mass index (BMI) 18-35 kg/m2, falling into American Society of Anesthesiologists (ASA) physical status Ⅰ or Ⅱ, scheduled for gynecological laparoscopic procedures positioning in trendelenburg were recruited and divided into two groups: the observation group (n =40) and the control group (n=40). In the observation group, solid food was restricted after 24:00, the patients were required to take 300 mL carbohydrates two hours before surgery. In the control group, solid food and liquid intake were restricted after 24:00 the night before surgery. The cross-sectional area (CSA) of gastric antrum was measured in supine position and right lateral decubitus position before anesthesia. Primary outcome was gastric volume (GV) in each group. Secondary outcome included Perlas A semi-quantitative grading and gastric volume/weight (GV/W). All the patients received assessment of preoperative feeling of thirsty and hunger with visual analogue scale (VAS).@*RESULTS@#Complete data were available in eighty patients. GV was (58.8±23.6) mL in the intervention group vs. (56.3±22.1) mL in the control group, GV/W was (0.97±0.39) mL/kg vs. (0.95±0.35) mL/kg, respectively; all the above showed no significant difference between the two groups (P > 0.05). Perlas A semi-quantitative grading showed 0 in 24 patients (60%), 1 in 15 patients (37.5%), 2 in 1 patient (2.5%) in the intervention group and 0 in 25 (62.5%), 1 in 13 (32.5%), 2 in 2 (5%) in the control group, the proportion of Perlas A semi-quantitative grading showed no significant difference between the two groups (P > 0.05). A total of 3 patients (1 in the intervention group and 2 in the control group) with Perlas A semi-quantitative grading 2 were treated with special intervention, no aspiration case was observed in this study. The observation group endured less thirst and hunger (P＜0.05).@*CONCLUSION@#Three hundred mL carbohydrates intake two hours before surgery along with ultrasound guided gastric content monitoring does not increase gastric volume and the risk of reflux aspiration in patients positioning in trendelenburg undergoing gynecological laparoscopic surgery, and is helpful in minimizing disturbance to the patient's physiological needs, therefore leading to better clinical outcome.

The effect of feeding methods on fecal metabolites of infants delivered by cesarean section based on non-targeted metabolomics / 中华实用儿科临床杂志

Objective:To explore the effect of breast feeding versus mixed feeding on fecal metabolites of infants delivered by cesarean section.Methods:This was a cross-sectional study.Fecal samples were collected from 23 healthy 1-month-old infants delivered by cesarean section from autumn 2021 and winter 2022 in two maternal and infant care facilities in the North and South of Xi′an city.The samples were divided into the breast feeding group (11 cases) and mixed feeding group (12 cases). Fecal metabolites were analyzed by the non-targeted metabolomic approach and gas chromatography-mass spectrometry coupling, and differentially expressed fecal metabolites between groups were screened using the non-parametric Mann- Whitney U test.Metabolic pathways enriched in them were further analyzed. Results:A total of 155 metabolites were characterized, including 57 sugars and sugar derivatives, 34 fatty acids, 25 organic acids, 22 amino acids, 8 esters, 4 nucleosides, 3 vitamins and 2 other substances.The relative contents of the differentially expressed fecal metabolites were measured, and it was found that some types of sugars and sugar derivatives were highly expressed in the fecal samples of breast feeding group, while amino acids, organic acids and fatty acids were highly expressed in those of the mixed feeding group.A total of 28 metabolic pathways enriched in differentially expressed fecal metabolites were obtained.Among them, alanine, aspartic acid and glutamic acid metabolism, valine, leucine and isoleucine metabolism, arginine metabolism and the tricarboxylic acid (TCA) cycle influenced infant health.Conclusions:Feeding methods have an effect on the fecal metabolites in infants delivered by cesarean section born infants, and mixed feeding may speed up the process of TCA cycle and amino acid metabolism in the intestine of infants delivered by cesarean section to a certain extent.

Effect and mechanism of p-hydroxybenzaldehyde on experimental intestinal fibrosis / 中国药理学通报

Aim To investigate the effect of p-hydroxybenzaldehyde ( HD) on intestinal fibrosis in mice based on mouse intestinal fibrosis model and in vitro EMT model,and to explore the underlying mechanism Methods HE staining, Masson staining, immunohisto-chemistry ,qPCR, Western blot and other experimental methods were used to verify the effect of HD on intestinal fibrosis in mice and the potential mechanism. Results In vivo experiments showed that compared with the normal group, the DSS-induced intestinal fibrosis model group had shortened colon, increased colon his-topathological score, increased collagen volume fraction, and significantly increased collagen I expression. After treatment with 4, 10, and 25 mg • kg

Chemical Components and Pharmacological Effect of Trib. Lorantheae in China： A Review / 中国实验方剂学杂志

Trib. Lorantheae used as traditional Chinese materia medica has a long history. There are 41 genera of Trib. Lorantheae， of which 6 belong to China， all have medicinal value， mainly distributed in Southwest， Southern， and Central and Southern China， with abundant resources. Twenty-two species of Trib. Lorantheae are used as medicinal materials or herbs in China. It mainly includes Taxillus. chinensis， T. sutchuenensis， Scurrula parasitica， Loranthus tanakae， Dendrophthoe pentandra， S. ferruginea， etc.， of which T. chinensis is the most widely used. The main chemical components of Trib. Lorantheae include flavonoids， terpenoids， sterols， phenylpropanoids， curcumins， phenolic acids， violate oils， sugars， and other compounds. Modern studies show that the extracts and monomer compounds of Trib. Lorantheae have various pharmacological effects such as anti-inflammation， anti-tumor， anti-oxidation， anti-osteoporosis， bacteriostasis， anti-virus， and lowering blood sugar， blood pressure， and lipid. It is believe that most active components related to their pharmacological effects are flavonoids， most of which are the main pharmacodynamic substances of the parasitic plants of Trib. Lorantheae， playing an important role in anti-inflammation， anti-tumor， anti-oxidation， anti-osteoporosis， and other pharmacological effect. This paper systematically summarized the literature and data on plants of Trib. Lorantheae and reviewed their chemical components and pharmacological effects， which provided references for the research， development， and utilization of Trib. Lorantheae.

Detection of Carbamazepine and Its Metabolites in Blood Samples by LC-MS/MS / 法医学杂志

OBJECTIVES@#To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*METHODS@#The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent. The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18, 95Å column. The mobile phase A aqueous solution containing 0.1% formic acid and 10 mmol/L ammonium acetate, and mobile phase B mixed organic solvent containing acetonitrile/methanol (Vacetonitrile∶Vmethanol=2∶3) were used for gradient elution at the flow rate of 1.00 mL/min. An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring.@*RESULTS@#The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range, with correlation coefficients (r) greater than 0.995 6. The limits of detection were 3.00, 0.40 and 1.30 ng/mL, respectively. The limit of quantitation were 8.00, 1.00 and 5.00 ng/mL, respectively. The extraction recoveries ranged from 76.00% to 106.44%. The relative standard deviations of the intra-day and inter-day precisions were less than 16%. Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71 μg/mL and 252.14 ng/mL, respectively.@*CONCLUSIONS@#This method has high sensitivity and good selectivity, which is suitable for the detection of carbamazepine and its metabolites in blood samples, and can be used for carbamazepine-related forensic identifications.

Evolution and development of potent monobactam sulfonate candidate IMBZ18g as a dual inhibitor against MDR Gram-negative bacteria producing ESBLs

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Gender differences in the influence of emotional intelligence on the situation selection among college students / 中华行为医学与脑科学杂志

Objective:To investigate the effect of emotional intelligence (EI) in situation selection among college students under different gender.Methods:Using the emotional intelligence scale to test 416 students from an university in Chengdu, and 42 students (high emotional intelligence: high EI) and 42 students (low emotional intelligence: low EI) were selected as preselected subjects according to their scores. A total of 40 subjects, including 20 in the high EI group (10 males and 10 females) and 20 in the low EI group (10 males and 10 females), were selected to participate in the experiment by excluding subjects who gave up the experiment and taking into account both genders. Using the emotion picture selection task, the eye movement data of the subjects watching the situation picture and the reaction time of selecting the situation picture again were recorded respectively.The R language Bruce R package was used for three-factor analysis of variance. If there was interaction effect, the post simple effect analysis was carried out.Results:(1) About the eye-movement data before picture selection, the females with higher EI scores had significantly greater saccade amplitude when viewing negative pictures than the females with lower EI scores ((2.79±1.58)°, (2.46±0.85)°, F(1, 36)=7.39, P=0.007), and the males with high EI scores had less saccade amplitude when viewing all pictures than the males with low EI scores ((2.00±0.83)°, (2.17±0.85)°, F(1, 36)=6.58, P=0.011). The females with high EI scores had a significantly faster saccade velocity than the females with low EI scores((98.93±35.60)°/s, (92.81±20.56)°/s, F(1, 36)=8.39, P=0.004), and the males with high EI scores had a significantly slower saccade velocity than the males with low EI scores ((79.35±18.55)°/s, (85.11±18.53)°/s, F(1, 36)=6.70, P=0.01). The females with high EI scores had a significantly shorter fixation duration for negative emotional pictures than the females with low EI scores ((2 654.7±530.85) ms, (2 877.87±205.44) ms, F(1, 36)=30.38, P<0.001), and the males with high EI scores had a significantly shorter fixation duration for positive emotional pictures than the males with low EI scores ((2 839.74±405.34) ms, (2 932.83±228.07) ms, F(1, 36)=9.46, P=0.002). About the fixation number, females gazed at the negative pictures significantly less than males ((9.43±2.31), (10.24±2.05), F(1, 36)=21.49, P<0.01). (2) In terms of choice response times, the females with high EI scores chose to look back at positive neutral pictures with shorter reaction times than the females with low EI scores (positive: (726.79±329.12) ms, (924.51±758.34) ms, F(1, 36)=9.07, P=0.003; neutral: (783.46±543.54)ms, (962.44±463.57)ms, F(1, 36)=6.23, P=0.013), and the males with high EI scores chose to look back with longer reaction times than the males with low EI scores, but the difference was only significant when viewing neutral pictures ((1 092.29±905.52) ms, (871.27±461.68) ms, F(1, 36)=9.07, P=0.002). Conclusion:The influence of emotional intelligence on the process of situation selection is different by gender: the higher the emotional intelligence of female college students, the faster they can process negative emotional information in the process of situation selection, and the broader and more dispersed the processing patterns; the higher the emotional intelligence of male college students, the faster they can process positive emotional information in the process of situation selection, and the more concentrated the processing patterns.

Identification of serological biomarkers for diagnosis of rheumatoid arthritis using a protein array-based approach / 南方医科大学学报

OBJECTIVE@#To study the cytokine patterns in patients with rheumatoid arthritis (RA) and healthy individuals and identify candidate serum biomarkers for clinical diagnosis of RA.@*METHODS@#This study was conducted among 59 patients diagnosed with RA in our hospital from 2015 to 2019 with 46 age- and gender-matched healthy subjects who received regular physical examinations in our hospital as the control group. Serological autoimmune profiles of 5 RA patients and 5 healthy control subjects were obtained from human cytokine microarrays. We selected 4 differentially expressed cytokines (LIMPII, ROBO3, Periostin and IGFBP-4) and 2 soluble cytokine receptors of interest (2B4 and Tie-2) and examined their serum levels using enzyme-linked immunosorbent assay in 54 RA patients and 41 healthy control subjects. Spearman correlation test was performed to assess the correlation of serum cytokine and soluble receptor expression levels with the clinical features including rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score (DAS28) and health assessment questionnaire (HAQ). Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic capability of these cytokines.@*RESULTS@#We identified 6 dysregulated cytokines and soluble receptors (2B4, LIMPII, Tie-2, ROBO3, periostin and IGFBP-4) in RA patients (P < 0.01). The serum levels of LIMPII, ROBO3 and periostin were significantly correlated with the disease activity indicators including RF (P < 0.001), CRP (P < 0.001), DAS28 (P < 0.001) and HAQ (P < 0.001) in RA patients. Among the 6 candidate cytokines, 2B4 showed the largest area under the curve (AUC) of 0.861 for RA diagnosis (P < 0.001), followed then by LIMPII, ROBO3, periostin, Tie-2 and IGFBP-4.@*CONCLUSION@#Serum levels of LIMPII, ROBO3 and periostin can be indicative of the disease activity of RA, and serum 2B4, LIMPII, periostin, ROBO3, IGFBP-4 and Tie-2 levels may serve as biomarkers for the diagnosis of RA.

Serum Retinol-Binding Protein Levels Are Associated with Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus: A Real-World Study

Background@#The association of serum retinol-binding protein (RBP) levels with nonalcoholic fatty liver disease (NAFLD) remains controversial. Furthermore, few studies have investigated their relationship in type 2 diabetes mellitus (T2DM) patients. Therefore, the aim of the present study was to explore the association between serum RBP levels and NAFLD in Chinese inpatients with T2DM. @*Methods@#This cross-sectional, real-world study included 2,263 Chinese T2DM inpatients. NAFLD was diagnosed by abdominal ultrasonography. The subjects were divided into four groups based on RBP quartiles, and clinical characteristics were compared among the four groups. The associations of both RBP levels and quartiles with the presence of NAFLD were also analyzed. @*Results@#After adjustment for sex, age, and diabetes duration, there was a significant increase in the prevalence of NAFLD from the lowest to the highest RBP quartiles (30.4%, 40.0%, 42.4%, and 44.7% for the first, second, third, and fourth quartiles, respectively, P<0.001 for trend). Fully adjusted multiple logistic regression analysis revealed that both increased RBP levels (odds ratio, 1.155; 95% confidence interval, 1.012 to 1.318; P=0.033) and quartiles (P=0.014 for trend) were independently associated with the presence of NAFLD in T2DM patients. @*Conclusion@#Increased serum RBP levels were independently associated with the presence of NAFLD in Chinese T2DM inpatients. Serum RBP levels may be used as one of the indicators to assess the risk of NAFLD in T2DM patients.

Effect of Modified Chaihu Shugansan and Its Disassembled Formulas on ACE2- Ang （Ⅰ-Ⅶ）-MasR Axis in Rats with Myocardial Ischemia and Depression / 中国实验方剂学杂志

ObjectiveTo observe the effects of modified Chaihu Shugansan（CHSG） and its disassembled formulas on angiotensin-converting enzyme 2 （ACE2）-angiotensin （Ⅰ-Ⅶ） ［Ang （Ⅰ-Ⅶ）］-mitochondrial assembly receptor （MasR） axis in hyperlipidemic rats with myocardial ischemia and depression， and to explore the underlying mechanism of its prevention and treatment of myocardial ischemia and depression. MethodA total of 108 male SD rats were randomly divided into a normal group， a model group， a modified CHSG group （11.7 g·kg-1）， a Quyu Huatan disassembled formula group （4.05 g·kg-1）， a Shugan Xingqi disassembled formula group （3.15 g·kg-1）， a Jianpi Yangxue disassembled formula group （4.5 g·kg-1）， a fluoxetine group （0.001 8 g·kg-1）， a trimetazidine group （0.005 4 g·kg-1）， and a simvastatin group （0.001 8 g·kg-1）， with 12 rats in each group. The hyperlipidemia model with myocardial ischemia and depression was induced with a high-fat diet combined with injection of isoproterenol （ISO） and chronic unpredictable mild stress （CUMS） in rats in the model group and groups with drug intervention for eight weeks. The rats in each group with drug intervention were treated correspondingly by gavage from the first day of modeling， while those in the normal group and the model group received the same amount of normal saline. The behavioral changes of rats in each group were observed by open field test and forced swimming test. Left ventricular fractional shortening （LVFS） and left ventricular ejection fraction （LVEF） were measured by echocardiography. The serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected by the enzyme-labeled apparatus. Hematoxylin-eosin （HE） staining was used to observe the histomorphological changes of the heart. The serum levels of angiotensin Ⅱ （AngⅡ）， ACE2， and Ang（Ⅰ-Ⅶ） were detected by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression of ACE2 and MasR in the hippocampus and the heart was detected by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the normal group， the model group showed reduced movement time， distance， and average speed in the central area of the open field （P<0.01）， prolonged immobility time of rats in the forced swimming test （P<0.01）， decreased LVFS and LVEF （P<0.01）， inflammatory exudation and disorderly arranged fiber in heart tissues， elevated serum levels of TC， LDL-C， AngⅡ， ACE2 and Ang（Ⅰ-Ⅶ）， diminished HDL-C （P<0.01）， dwindled mRNA and protein expression of ACE2 in the hippocampus and the heart and MasR in the hippocampus， and up-regulated mRNA and protein expression of MasR in the heart （P<0.01）. Compared with the model group， the modified CHSG group displayed increased movement time， distance， and average speed in the center area of the open field （P<0.01）， shortened immobility time in the forced swimming test （P<0.01）， increased LVFS and LVEF （P<0.01）， relieved heart injury， reduced serum levels of TC， LDL-C， AngⅡ， ACE2， and Ang（Ⅰ-Ⅶ）， elevated level of HDL-C （P<0.01）， up-regulated mRNA and protein expression of ACE2 in the hippocampus and the heart and MasR in the hippocampus， and down-regulated mRNA and protein expression of MasR in the heart （P<0.01）. Each disassembled formula could improve the above indexes to a certain extent （P<0.05， P<0.01）， but the effect of the whole formula was optimal. ConclusionThe modified CHSG and its disassembled formulas have the effects of resisting depression， improving myocardial injury， and reducing blood lipid. Due to the synergistic effects of stasis-resolving/phlegm-eliminating drugs， liver-smoothing/Qi-moving drugs， and spleen-tonifying/blood-nourishing drugs in the formula， the modified CHSG is superior to each disassembled formula in efficacy. Its mechanism may be related to the activation of the ACE2-Ang （Ⅰ-Ⅶ）-MasR axis.

Postmortem Distribution and Postmortem Redistribution of Carbofuran-7-Phenyl Glucuronic Acid in Rabbits / 法医学杂志

OBJECTIVES@#To establish a carbofuran intragastric administration death model in rabbits, and to observe the postmortem distribution and postmortem redistribution of carbofuran-7-phenyl glucuronic acid (Glu-7PH) in rabbits.@*METHODS@#The postmortem distribution: Rabbits were given an administration of 1/2LD50, LD50, 2LD50 carbofuran. Dead rabbits were dissected immediately. Rabbits that had remained alive 2 hours were sacrificed by carbon dioxide (CO2) inhalation and dissected immediately. The myocardium, cardiac blood, liver, spleen, lung, kidney, brain and right hindlimb muscle were collected. The postmortem redistribution: After giving an administration of 4LD50 carbofuran, the myocardium, cardiac blood, liver, spleen, lung, kidney, brain, and right hindlimb muscle were collected at 0, 12, 24, 48, and 72 h postmortem in supine position at 15 ℃ room temperature. The quantity of Glu-7PH was determined by LC-MS/MS.@*RESULTS@#The postmortem distribution: Among the three dose groups, there were significant differences in the quantities of Glu-7PH in different tissues. The postmortem redistribution: There was no significant difference in the Glu-7PH quantities in cardiac blood, mycardium, spleen, kidney, brain and right hindlimb muscle, but there was a significant difference in the Glu-7PH quantities in the liver and lung.@*CONCLUSIONS@#The mycardium, cardiac blood, liver, lung, kidney, brain and hindlimb muscle of rabbits can be used as appropriate samples for Glu-7PH detection. However, it should be noted that Glu-7PH was redistributed postmortem in rabbit liver and lung.

Research progress of chemokines and their receptors in breast cancer / 药学学报

Chemokines are small cytokines with chemotactic activity, they are involved in regulating immune responses and inflammatory responses. In the development of tumors, chemokines are multi-functional mediators that not only affect the infiltration of immune cells into the tumor, but also have an important impact on tumor growth, angiogenesis, invasion, and metastasis. Besides, they are important targets of tumor therapy. Here we review chemokines involved in the regulation of signaling pathways, analyze the mechanism of chemokines in the development of breast cancer, summarize the chemokines targeted drugs for breast cancer in recent years and make a prospect about the role of chemokines in anti-breast cancer therapy.

The cell cycle inhibitor p21 promote mouse lung fibrosis by activating alveolar macrophages / 药学学报

This study was to determine the expression of the cell cycle inhibitor p21 in alveolar macrophages (AMs) and the role of p21 in activation of AMs in bleomycin (BLM) injury-induced lung fibrosis. The expression of CD206 in AMs was measured by immunofluorescence staining. Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect the expression of macrophage activation markers. The coculture assay for macrophage and fibroblast was employed to explore the effect of macrophage on fibroblast activation. Immunofluorescence staining and western blotting assay were adopted to detect the expression of p21 in fibrotic tissues. AMs were treated with p21 knockdown or overexpression virus, RT-PCR and the co-culture system were used to explore the effect of p21 expression on macrophage activation. The Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College approved all of the protocols for this research. Our results showed that the expression of CD206 and macrophage activation markers was increased in AMs from fibrotic mice, indicating that AMs from fibrotic mice were associated with a profibrotic phenotype. Moreover, the expression of p21 was upregulated in AMs after BLM treatment. Depletion of p21 suppressed macrophage activation, while overexpression of p21 promoted the profibrotic phenotype of AMs from healthy mice. In summary, BLM injury causes the progressive accumulation of p21 in AMs, which induces the production of a number of profibrotic factors promoting the development of pulmonary fibrosis.

Pirfenidone and nintedanib inhibit the lung alveolar regeneration in chronic pulmonary fibrosis mouse / 药学学报

The aim of this study was to determine whether the anti-fibrotic effects of pirfenidone (Pirf) and nintedanib (Nint) associated with the regulation of the alveolar epithelial type 2 cell (AEC II)-mediated lung alveolar regeneration in single- and multiple-dosage animal models of bleomycin-induced pulmonary fibrosis. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences. We found that the Pirf and Nint treatment of mice decreased the lung weight index, inflammation level, and the content of hydroxyproline compared with nontreated fibrotic mice in the single dosage model. Also, Pirf and Nint increased the oxygen saturation level and improved the lung functions in fibrotic mice, indicating that both drugs have anti-fibrotic effects in this model. However, the anti-fibrotic effects of Pirf and Nint were not observed in the multiple-dosage model. Further studies showed that Pirf and Nint decreased the expression of β-catenin, Axin2, c-Myc, Cyclin D1, and inhibited the Wnt/β-catenin signaling pathway, suggesting that Pirf and Nint did not produce anti-fibrotic effects in the multiple-dosage model due to their inhibiting the Wnt/β-catenin pathway and suppressing the stemness of AEC II, namely, suppressing AEC II-mediated lung alveolar regeneration.

Effect of Danggui Buxuetang on PKD1/NF-κB/MnSOD Signal Pathway in Bleomycin-induced Pulmonary Fibrosis in Rats / 中国实验方剂学杂志

Objective:To observe the effect of Danggui Buxuetang on lung histopathology and protein kinase D1 (PKD1), nuclear transcription factor-κB (NF-κB) and manganese superoxide dismutase (MnSOD)-mediated oxidative stress pathway in rats with pulmonary fibrosis induced by bleomycin, so as to explore the mechanism of intervention of pulmonary fibrosis.Method:Thirty-two male SPF SD rats were randomly divided into sham operation group, model group, Danggui Buxuetang group and prednisone group, with 8 rats in each group. Except the sham operation group, the other groups were prepared through the intratracheal instillation with bleomycin. After modeling for 24 h, the rats of Danggui Buxuetang group were administered with Danggui Buxuetang (0.81 g·kg-1). The rats of prednisone group were given aqueous solution of prednisone (0.005 g·kg-1). The rats of sham operation group and model group were given the same volume of saline. After 14 days of administration, blood was collected from the femoral artery, serum was separated, and the lungs were taken by thoracotomy. The pathological changes of rat lung tissues were observed by hematoxylin-eosin staining (HE) and Masson trichrome staining, and graded by Szapiel score and Ashcroft score at the same time. The content of serum malondialdehyde (MDA), and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) were determined. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to measure mRNA and protein expressions of PKD1, NF-κB, MnSOD.Result:Compared with the rats in sham operation group, the rats in model group had higher Szapiel scores and Ashcroft scores (P<0.05), higher serum MDA content , but lower SOD, CAT and GSH-Px activities(P<0.01), moreover, the rat lung tissues in model group had higher mRNA and protein expressions of PKD1, NF-κB and MnSOD (P<0.01) than those in sham operation group. Compared with the rats in model group, the Szapiel scores and Ashcroft scores of the rats in Danggui Buxuetang group were decreased significantly（P<0.05）. The serum MDA content was decreased significantly, and SOD, CAT, GSH-Px activities were increased, whereas mRNA and protein expressions of PKD1, NF-κB, MnSOD in the rat lung tissues were decreased（P<0.05，P<0.01）.Conclusion:Danggui Buxuetang can reduce the degree of pulmonary fibrosis by regulating the anti-oxidation pathway of PKD1/NF-κB/MnSOD mitochondrial nucleus and improving the body's antioxidant capacity.

The neural modulation effect of prefrontal cortex and related mechanism in non-pharmacological therapy of chronic pain / 中华行为医学与脑科学杂志

Chronic pain is a public health concern of desiderate to be solved, and analgesics is not always successful and may be difficult to tolerate in clinic.Studies have suggested that the development of chronic pain involves alterations in multiple brain regions.Central modulation mechanisms, especially those soliciting the prefrontal cortex and its related brain regions, may play an important role.Non-pharmacological therapies such as transcranial direct current stimulation, transcranial repetitive magnetic stimulation and cognitive behavior therapy have emerged to be effective interventions of great potential for chronic pain in recent years.Hereby the research progress was reviewed on the neural modulation effect of prefrontal cortex in non-pharmacological treatment of chronic pain, focusing on the related changes in brain structure and function, to further explore the underlying mechanism of pain modulation, and provide theoretical basis to optimize non-pharmacological treatment of chronic pain.

Determination of Escitalopram in Biological Samples by Dispersive Liquid-Liquid Microextraction Combined with GC-MS/MS / 法医学杂志

Objective To establish a method for determination of escitalopram in biological samples by ultrasound-assisted ionic liquid-dispersive liquid-liquid microextraction combined with gas chromatography-tandem mass spectrometry （GC-MS/MS） and provide evidences for forensic determination of cases related to escitalopram. Methods The 1-hexyl-3-methylimidazolium hexafluorophosphate （[C6MIM][PF6]） was selected as an extract solvent to process biological samples. Ultrasound-assisted extraction was used on the samples. Then the samples were detected by GC-MS/MS. Results The linear range of escitalopram in blood and liver were 5.56-1 111.10 ng/mL and 0.025-5.00 mg/g, respectively. The correlation coefficient （r） were greater than 0.999, limit of detection （LOD） were 4.00 ng/mL and 2.00 μg/g, limit of quantitation （LOQ） were 14.00 ng/mL and 6.00 μg/g, respectively. The extraction recovery rates were all greater than 50%, the interday and intraday precision were less than 20%. Escitalopram was detected in blood and liver samples from the actual poisoning case by this method with a content of 1.26 μg/mL and 0.44 mg/g, respectively. Conclusion The ultrasound-assisted ionic liquid-dispersive liquid-liquid microextraction combined with GC-MS/MS is environment friendly, rapid, has good enriching effect and consumes less organic solvent and can be used for forensic determination of escitalopram related cases.