Advances on cardiovascular effects of GLP-lRAs / 中国药理学通报

Glucagon-like peptide-1 ( GLP-1 ) is secreted by gut enteroendocrine cells. GLP-1 receptor agonists ( GLP-1 RAs) control glucose-related augmentation of insulin and suppress glu-cagon secretion. GLP-lRAs also inhibit gastric emptying, food intake and limit weight gain. In the past decade, significant progresses have been made in the investigation on the effects of GLP-1 RAs on cardiovascular system. The potential advantages of oral small-molecule GLP-1 RAs could improve the application of this class of drugs. This review highlights the multiple cardiovascular profiles of GLP-1 RAs in the treatment of cardiovascular diseases to provide new insights into cardiovascular benefits of GLP-1 RAs.

Advances in Modeling of Multiple Myeloma in Mice / 中国医学科学院学报

Multiple myeloma(MM)is a systemic malignancy of plasma cells.Nowadays,the basic research on MM is flourishing with the continuous optimization and innovation of mouse models of MM.Heterologous mouse models of MM established with human-derived cells and immunodeficient mice have been applied in assessing drug efficacy,exploring drug resistance mechanisms,and observing tumor-bone marrow microenvironment interactions.In the last decades,the homologous mouse models of MM established with murine-derived cells or gene-editing technologies have been widely used in the research on the pathogenesis and drug development.Additionally,the stable modeling of targeted organ injury will be a key problem to be tackled in this field.This review summarizes the characteristics and application progress of mouse models of MM.

Active Ingredients of Reduning Injection Maintain High Potency against SARS-CoV-2 Variants / 中国结合医学杂志

OBJECTIVE@#To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin.@*METHODS@#A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43.@*RESULTS@#The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC50) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC50 lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43.@*CONCLUSIONS@#The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.

Genotype and Phenotype of α-Thalassemia Fusion Gene in Huadu District of Guangzhou, Guangdong Province of China / 中国实验血液学杂志

OBJECTIVE@#To explore the carrier rate, genotype and phenotype of α-thalassemia fusion gene in Huadu district of Guangzhou, Guangdong province of China, and provide data reference for the prevention and control of thalassemia.@*METHODS@#A total of 10 769 samples who were screened for thalassemia in Maternal and Child Health Hospital of Huadu District from July 2019 to November 2020 were analyzed retrospectively. Blood cell analysis and hemoglobin (Hb) electrophoresis were performed. Thalassemia genes were analyzed by gap-PCR and PCR-reverse dot blot hybridization (PCR-RDB).@*RESULTS@#A total of 9 cases with α-thalassemia fusion gene were detected in 10 769 samples (0.08%). There were 7 cases with fusion gene heterozygote, 1 case with compound of α-thalassemia fusion gene and Hb G-Honolulu, 1 case with compound of α-thalassemia fusion gene and Hb QS. The MCV results of 4 samples of blood cell analysis were within the reference range, the Hb A2 value of 1 case was decreased, and there were no other abnormalities found.@*CONCLUSION@#The α-thalassemia fusion gene is common in Huadu district of Guangzhou, and heterozygotes are more common, and current screening methods easily lead to misdiagnosis.

Mechanism of VPS26 gene promoting implant osseointegration through Wnt/β-catenin pathway in hyperlipidemia rats / 中华口腔医学杂志

Objective: To investigate the mechanism of VPS26 effect on osteogenesis and adipogenesis differentiation of rat bone marrow mesenchymal stem cells (BMSC) in high fat environment, and to explore the effect of VPS26 on implants osseointegration of high fat rats and ectopic osteogenesis in nude mice. Methods: BMSC were cultured under normal osteogenic induction (osteogenic group) and high-fat osteogenic induction (high-fat group).High-fat group was transfected with VPS26 enhancer and inhibitor, and the expression levels of osteogenesis related genes and adipogenesis related genes were examined. Osteogenesis and adipogenesis of BMSC were detected by alkaline phosphatase (ALP) staining and oil red O staining after 7 and 14 days of induction.In osteogenic group,the binding of VPS26 to β-catenin was detected by immunofluorescence staining and immunoprecipitation, and dual luciferase reporter assay (TOP Flash) was used to analyze the TOP/FOP ratio. Eighteen male 12-week hyperlipidemic Wista rats (160-200 g) were implanted with implants, and six in each group were injected with VPS26 overexpression lentivirus (LV-VPS26 group), negative control lentivirus (LV-nc group) and saline (blank control group).Micro-CT analysis , HE and oil red O staining were used to evaluate the osseointegration of the implants and lipid droplets formation of the femur samples. Twenty female 6-week nude mice (30-40 g) were divided into five groups and subcutaneously implanted with osteogenic BMSC non-transfected and transfected LV-VPS26, LV-nc, shVPS26, and shscr lentivirus on the back. Samples were used to observe ectopic osteogenesis. Results: The mRNA expression levels of ALP in the high-fat group BMSC after overexpression of VPS26 (1.56±0.09) were significantly higher than those of the negative control (1.01±0.03) (t=10.09, P<0.001), while those of peroxisome proliferator-activated receptor-γ (PPAR-γ) (t=6.44, P<0.001) and fatty acid-binding protein4 (FABP4) (t=10.01, P<0.001) were lower than those of the negative control. Western blotting results showed that compared with the negative control, protein expression of ALP and Runt-related transcription gene 2 was enhanced in the high-fat group BMSC after overexpression of VPS26 while PPAR-γ and FABP4 were inhibited. ALP activity of BMSC in the high-fat group was stronger after overexpression of VPS26, and the formation of lipid droplets was weaker than that in negative control. The results of immunofluorescence, immunoprecipitation and dual luciferase reporter assays showed co-localization and interaction of VPS26 with β-catenin and a significant 43.10% increase in the TOP/FOP ratio (t=-3.17, P=0.034). VPS26 overexpression enhanced osseointegration and decreased the number of lipid droplets in high-fat rat and enhanced ectopic osteogenesis of nude mice. Conclusions: VPS26 activated osteogenesis differentiation and inhibited adipogenic differentiation of BMSCs through Wnt/β-catenin pathway, promoting osseointegration of high-fat rat implants and ectopic osteogenesis of nude mice.

Glycosylphosphatidylinositol biosynthesis deficiency 15 caused by GPAA1 gene mutation: a rare disease study / 中国当代儿科杂志

A boy, aged 6 years, attended the hospital due to global developmental delay for 6 years and recurrent fever and convulsions for 5 years. The boy was found to have delayed mental and motor development at the age of 3 months and experienced recurrent fever and convulsions since the age of 1 year, with intermittent canker sores and purulent tonsillitis. During the fever period, blood tests showed elevated white blood cell count, C-reactive protein, and erythrocyte sedimentation rate, which returned to normal after the fever subsides. Electroencephalography showed epilepsy, and genetic testing showed compound heterozygous mutations in the GPAA1 gene. The boy was finally diagnosed with glycosylphosphatidylinositol biosynthesis deficiency 15 (GPIBD15) and periodic fever. The patient did not respond well to antiepileptic treatment, but showed successful fever control with glucocorticoid therapy. This article reports the first case of GPIBD15 caused by GPAA1 gene mutation in China and summarizes the genetic features, clinical features, diagnosis, and treatment of this disease, which provides a reference for the early diagnosis and treatment of GPIBD15.

Research progress on the association and mechanism between dietary rhythm, circadian rhythm and cardiovascular health in children and adolescents / 中国学校卫生

Abstract@#Hypertension in children can have adverse health effects such as vascular damage, cardiac metabolic risk, and organ damage during childhood, and can also increase the risk of hypertension in adulthood. Obesity has been recognized as an important cause of elevated blood pressure in children. By reviewing and summarizing relevant literature at home and abroad, the study analyzes the relationship between dietary and circadian rhythm and explores the role and mechanism of circadian rhythm in terms of the metabolic health of youth, thereby providing a scientific basis for the prevention and treatment of cardiovascular diseases in this population and to identify directions for future research.

Effect of spontaneous breathing on atelectasis during induction of general anesthesia in patients undergoing laparoscopic resection of gastrointestinal tumors / 肿瘤研究与临床

Objective:To explore the effect of spontaneous breathing during induction of general anesthesia on atelectasis in patients undergoing laparoscopic resection of gastrointestinal tumors.Methods:A total of 60 patients aged 18-60 years scheduled for laparoscopic resection of gastrointestinal tumors under general anesthesia in the First Hospital of Shanxi Medical University from October 2021 to August 2022 were selected. The body mass index was 18.5-28.0 kg/m 2 and the American Society of Anesthesiology grade wasⅠ-Ⅱ. All patients were divided into the spontaneous breathing group (group S, 30 cases) and the controlled breathing group (group C, 30 cases) according to the random number table method. Patients in group S received 0.2-0.3 mg/kg etomidate (pumping at the speed of 200 ml/h) and 2 μg/kg remifentanil (slowly injected more than 30 s) for anesthesia induction; patients in group C received 0.2-0.3 mg/kg etomidate and 2 μg/kg remifentanil (slowly injected more than 30 s) and 0.2 mg/kg cisatracurium. After bispectral index (BIS) decreased to 80, the patients had no response to the language stimulation; and then the mask was used to closely fit the face and maintain spontaneous breathing in group S; patients in group C received manual positive pressure ventilation. Atelectasis scores were collected immediately after endotracheal intubation (T 1) and 15 min after transferring to the recovery room (T 3), and oxygenation index (OI) was collected 5 min after endotracheal intubation (T 2) and at T 3. The postoperative pulmonary complication (PPC) on the 3rd day after the operation was recorded. Results:A total of 56 patients were finally enrolled, 27 cases in group S and 29 cases in groups C. Compared with group C, the atelectasis score of group S at T 1 and T 3 decreased [T 1: (2.4±0.8) scores vs. (4.2±0.7) scores, t = -9.12, P < 0.001; T 3: (8.2±1.8) scores vs. (10.5±1.6) scores, t = -4.96, P < 0.001]. The OI increased at T 2 and T 3 in group S [T 2: (334±11) mmHg (1 mmHg = 0.133 kPa) vs. (323±13) mmHg, t = 3.45, P = 0.001; T 3: (362±23) mmHg vs. (347±25) mmHg, t = 2.31, P = 0.025]. The incidence of PPC was 20.7% (6/29) and 18.5% (5/27), respectively in group C and group S on the 3rd day after the operation, and the difference was statistically significant ( χ2 = 0.04, P = 0.838). Conclusions:Maintaining spontaneous breathing during induction of general anesthesia can reduce atelectasis caused by general anesthesia and improve oxygenation for patients undergoing laparoscopic resection of gastrointestinal tumors.

Effect of continuous positive pressure ventilation strategy during induction of general anesthesia on atelectasis after induction in obese patients / 中华麻醉学杂志

Objective:To evaluate the effect of continuous positive airway pressure(CPAP) ventilation strategy during induction of general anesthesia on atelectasis after induction in obese patients.Methods:A total of 86 patients, aged 30-60 yr, with body mass index of 28-35 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱor Ⅲ, scheduled for elective cerebrovascular intervention under general anesthesia, were divided into 2 groups ( n=43 each) using a random number table method: CPAP group (group C) and routine group (group R). Group C received CPAP 5 cmH 2O-assisted ventilation after preoxygenation for spontaneous breathing and disappearance of spontaneous breathing. Chest CT scan and arterial blood gas analysis were performed after entering the operating room (T 1) and 5 min after endotracheal intubation (T 2) to calculate the percentage of atelectasis area and to record PaO 2. Dynamic lung compliance and plateau pressure were recorded at T 2. Mean minute ventilation under controlled breathing, P ETCO 2, and use of vasoactive drugs during induction were recorded. The occurrence of reflux and aspiration during mask ventilation was recorded. The development of pulmonary complications within 3 days after operation was recorded. Results:Compared with group R, the percentage of atelectasis area at T 2 was significantly decreased, PaO 2, dynamic lung compliance and plateau pressure were increased ( P<0.05), and no significant change was found in mean minute ventilation, P ETCO 2, requirement for vasoactive drugs and incidence of pulmonary complications in group C ( P>0.05). No reflux or aspiration was observed during mask ventilation. Conclusions:CPAP (5 cmH 2O) strategy during anesthesia induction can reduce the degree of atelectasis after induction in obese patients.

Effect of continuous positive airway pressure ventilation during induction of anesthesia on perioperative atelectasis and oxygenation in elderly patients / 中华麻醉学杂志

Objective:To evaluate the effect of continuous positive airway pressure (CPAP) ventilation during induction of anesthesia on perioperative atelectasis and oxygenation in elderly patients.Methods:Forty-six elderly patients of either sex, aged 65-80 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective cerebrovascular intervention surgery under general anesthesia, were divided into 2 groups ( n=23 each) according to the random number table method: control group (group C) and CPAP ventilation group (group CPAP). During induction of anesthesia, CPAP was set at 5 cmH 2O during spontaneous breathing, and PEEP was set at 5 cmH 2O when spontaneous breathing disappeared, and the ventilation mode was changed to pressure-controlled ventilation (PCV) mode in group CPAP. CPAP was not set, and PEEP was set at 0 cmH 2O for PCV when spontaneous breathing disappeared in group C. During anesthesia maintenance, PCV-volume guaranteed mode was used in both groups, and PEEP was set at 5 cmH 2O. Whole lung CT scanning was performed immediately after radial artery catheterization (T 0), at 1 min after endotracheal intubation (T 1), and before tracheal extubation (T 2) at the end of operation to calculate the percentage of atelectasis area at 1 cm above the right diaphragm. At T 0, T 1, T 2 and 30 min after entering postanesthesia care unit (T 3), blood samples from the radial artery were taken to record PaO 2 and PaCO 2 and calculate the oxygenation index (OI). Results:Compared with the baseline at T 0, the percentage of atelectasis area was significantly increased at T 1 and T 2 in two groups ( P<0.05); PaO 2 was significantly increased at T 1 and T 2 and decreased to T 0 level at T 3, OI was decreased at T 1 and T 2 and increased to T 0 level at T 3 in two groups ( P<0.05). Compared with group C, the percentage of atelectasis area was significantly decreased and PaO 2 and OI were increased at T 1 and T 2 in group CPAP ( P<0.05). There was no significant difference in PaCO 2 at each time point between the two groups ( P>0.05). Conclusions:CPAP ventilation during induction of anesthesia can reduce the development of perioperative atelectasis and improve the oxygenation in elderly patients.

Meta-analysis of randomized controlled trials of exposure and response prevention for obsessive compulsive disorder / 中华行为医学与脑科学杂志

Objective:To systematically evaluate the intervention effect of exposure and response prevention (ERP) on obsessive compulsive disorder (OCD).Methods:PubMed, Web of Science Core Collection, EBSCO, Cochrane Library, Embase, Science Direct, Wanfang Data, China National Knowledge Infrastructure and VIP-CSTJ were used to collect randomized controlled studies related to ERP for OCD.Randomized controlled studies that met the criteria were included, with the score of Yale-Brown obsessive-compulsive scale as the primary outcome indicator and the scores of anxiety and depression scale as secondary outcome indicators, while the included literatures were evaluated for literature quality and data extraction.Review Manager 5.3 and Stata 16.0 softwares were used to conduct Meta-analysis on the extracted data.Results:Twenty-seven studies with a total of 1 239 patients were included, and 599 cases in the ERP group and 640 cases in the control group.Meta-analysis results showed that the efficacy of ERP group was significantly better than that of blank control group(MD=-6.55, 95% CI: -8.75--4.35, P<0.001) and significantly better than chlorpromazine control group treatment (MD=-5.88, 95% CI: -8.20--3.56, P<0.001) for improving patients' obsessive-compulsive symptoms, but not significantly different from CBT intervention (MD=0.21, 95% CI: -1.62-2.04, P=0.82), and the efficacy of ERP and CBT had no significant during the post-intervention follow-up period (MD=0.41, 95% CI: -2.45-3.27, P=0.78). For improving patients' depressed mood, ERP was effective in improving patients' depressed mood (SMD=-0.45, 95% CI: -0.74--0.17, P=0.002), but not significantly different from CBT (SMD=-0.05, 95% CI: -0.27-0.16, P=0.62). For improving anxiety, the efficacy of ERP group was not different from that of control group (SMD=-0.17, 95% CI: -0.56-0.23, P=0.41). Conclusion:ERP has good feasibility in improving obsessive-compulsive symptoms and depression in patients with OCD.However, long-term efficacy was not verified for improving anxiety and maintaining long-term efficacy during the follow-up period.

Predictive value of early lactate/albumin ratio in the prognosis of sepsis / 中华危重病急救医学

Objective:To investigate the prognostic value of early serum lactate, albumin, and lactate/albumin ratio (L/A) on the 28-day prognosis of adult patients with sepsis.Methods:A retrospective cohort study was conducted among adult patients with sepsis admitted to the First Affiliated Hospital of Xinjiang Medical University from January to December in 2020. Gender, age, comorbidities, lactate within 24 hours of admission, albumin, L/A, interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and 28-day prognosis were recorded. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of lactate, albumin and L/A for 28-day mortality in patients with sepsis. Subgroup analysis of patients was performed according to the best cut-off value, Kaplan-Meier survival curves were drawn, and the 28-day cumulative survival of patients with sepsis was analyzed.Results:A total of 274 patients with sepsis were included, and 122 patients died at 28 days, with a 28-day mortality of 44.53%. Compared with the survival group, the age, the proportion of pulmonary infection, the proportion of shock, lactate, L/A and IL-6 in the death group were significantly increased, and albumin was significantly decreased [age (years): 65 (51, 79) vs. 57 (48, 73), pulmonary infection: 75.4% vs. 53.3%, shock: 37.7% vs. 15.1%, lactate (mmol/L): 4.76 (2.95, 9.23) vs. 2.21 (1.44, 3.19), L/A: 0.18 (0.10, 0.35) vs. 0.08 (0.05, 0.11), IL-6 (ng/L): 337.00 (97.73, 2 318.50) vs. 55.88 (25.26, 150.65), albumin (g/L): 27.68 (21.02, 33.03) vs. 29.62 (25.25, 34.23), all P < 0.05]. The area under the ROC curve (AUC) and 95% confidence interval (95% CI) of lactate, albumin, and L/A were 0.794 (95% CI was 0.741-0.840), 0.589 (95% CI was 0.528-0.647), 0.807 (95% CI was 0.755-0.852) for predicting 28-day mortality in sepsis patients. The optimal diagnostic cut-off value of lactate was 4.07 mmol/L, the sensitivity was 57.38%, the specificity was 92.76%. The optimal diagnostic cut-off value of albumin was 22.28 g/L, the sensitivity was 31.15%, the specificity was 92.76%. The optimal diagnostic cut-off of L/A was 0.16, the sensitivity was 54.92%, and the specificity was 95.39%. Subgroup analysis showed that the 28-day mortality of sepsis patients in the L/A > 0.16 group was significantly higher than that in the L/A ≤ 0.16 group [90.5% (67/74) vs. 27.5% (55/200), P < 0.001]. The 28-day mortality of sepsis patients in the albumin ≤ 22.28 g/L group was significantly higher than that in the albumin > 22.28 g/L group [77.6% (38/49) vs. 37.3% (84/225), P < 0.001]. The 28-day mortality in the group with lactate > 4.07 mmol/L was significantly higher than that in the group with lactate ≤ 4.07 mmol/L [86.4% (70/81) vs. 26.9% (52/193), P < 0.001]. The three were consistent with the analysis results of Kaplan-Meier survival curve. Conclusion:The early serum lactate, albumin, and L/A were all valuable in predicting the 28-day prognosis of patients with sepsis, and L/A was better than lactate and albumin.

Analysis of risk factors of postoperative acute kidney injury in elderly patients with intertrochanteric fractures / 国际外科学杂志

Objective:To investigate the risk factors of postoperative acute kidney injury (AKI) in the elderly patients with intertrochanteric fractures.Methods:The clinical data of elderly patients who underwent surgery for intertrochanteric fractures in Second Affiliated Hospital of Chongqing Medical University from July 2018 to December 2022 were retrospectively analyzed, which was divided into AKI group and non-AKI group according to whether AKI occurred after surgery, with 33 cases in the AKI group and 274 cases in the non-AKI group. The data from two groups of patients including age, gender, body mass index, underlying diseases, Charlson comorbidity index(CCI), pre- and postoperative related laboratory indicators, American Society of Anesthesiologists classification, anesthesia and surgical methods, operation time, intraoperative hypotension, blood transfusion, perioperative medication and other electronic case data were compared. Measurement data with normal distribution were represented as the mean±standard deviation ( ± s), and comparison between groups was conducted using t-test. The measurement data of non-normal distribution were expressed by median (interquartile range) [ M( Q1, Q3)], and the Mann-Whitney U test was used for comparison between groups. Comparison between groups of count data was conducted using the Chi-square test or Fisher exact test. Univariate analysis was conducted on the pertinent indicators of the two groups, and the indicators with statistically significant were chosen for incorporation into the multivariate Logistic regression analysis to investigate the independent risk factors for postoperative AKI. Results:The incidence of postoperative AKI was 10.75% in elderly patients with intertrochanteric fractures. Results of the univariate analysis showed that there were significant differences between the two groups in diabetes mellitus, chronic kidney disease, CCI ≥2, baseline serum creatinine, preoperative blood urea nitrogen, preoperative estimated glomerular filtration rate, preoperative and early postoperative serum albumin levels, intraoperative hypotension, and perioperative blood transfusion( P<0.05). Results of multivariate Logistic regression analysis showed that CCI ≥ 2 ( OR =3.231, 95% CI: 1.150-9.074, P =0.026) and intraoperative hypotension ( OR =4.617, 95% CI: 1.746-12.205, P=0.002) were associated with the occurrence of AKI after intertrochanteric fracture surgery. Conclusion:CCI≥2 and intraoperative hypotension are independent risk factors of postoperative AKI in the elderly patients with intertrochanteric fractures.

Establishment of a reporter system for estimating activation of human hepatic stellate cells based on COL1A1 promoter and enhanced green fluorescent protein / 北京大学学报(医学版)

OBJECTIVE@#To establish a visual reporting system for evaluating the activity of collagen Ⅰ α 1 chain (COL1A1) gene promoter in immortalized human hepatic stellate cells, so as to estimate the activation status of the cells and provide a new cell model for the screening and study of anti-hepatic fibrosis drugs.@*METHODS@#The promoter sequence of human COL1A1 was amplified from the genomic DNA of human hepatocarcinoma cell line HepG2. Based on the pLVX-AcGFP1-N1 plasmid, the recombinant plasmid pLVX-COL1A1-enhanced green fluorescent protein (EGFP) was constructed, in which the enhanced green fluorescent protein gene expression was regulated by the COL1A1 promoter. The monoclonal cell line was acquired by stably transfecting pLVX-COL1A1-EGFP into the immortalized human hepatic stellate cell line LX-2 by the lentivirus packaging system and screening. The cell line was treated with transforming growth factor-β1 (TGF-β1) or co-treated with TGF-β1 and drugs with potential anti-hepatic fibrosis effects. The EGFP fluorescence intensity in cells was analyzed by the fluorescence microscope and ImageJ 1.49 software using a semi-quantitative method. The COL1A1 and EGFP mRNA were detected by reverse transcription real-time quantitative PCR (RT-qPCR), and corresponding proteins were detected by Western blot.@*RESULTS@#The recombinant plasmid pLVX-COL1A1-EGFP with the expression of EGFP regulated by COL1A1 promoter was successfully constructed. Kozak sequence was added to enhance the expression of EGFP, which was identified by double digestion and sequencing. The LX-2 monoclonal cell line LX-2-CE stably transfected with pLVX-COL1A1-EGFP was obtained. After co-treatment with TGF-β1 and 5 μmol/L dihydrotanshinone Ⅰ with potential anti-hepatic fibrosis effect for 24 h, the total fluorescence intensity and the average fluorescence intensity of LX-2-CE were lower than those in TGF-β1 single treatment group (P < 0.05), the intracellular mRNA and protein levels of COL1A1 and EGFP were also lower than those in the TGF-β1 single treatment group (P < 0.05).@*CONCLUSION@#A reporter system for estimating activation of hepatic stellate cells based on COL1A1 promoter regulated EGFP expression is successfully constructed, which could visually report the changes in COL1A1 expression, one of the activation-related markers of hepatic stellate cells, in vitro. It provides a new cell model for the screening and study of anti-hepatic fibrosis drugs.

UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood / 中国中药杂志

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

Chemical constituents from fruits of Morinda citrifolia and their inhibitory effects on proliferation of synoviocytes in vitro / 中国中药杂志

The chemical constituents from the fruits of Morinda citrifolia were systematically explored by chromatographic fractionation methods including silica gel, octadecylsilyl(ODS) gel, Sephadex LH-20 gel, and preparative high performance liquid chromatography(pre-HPLC). The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, as well as the comparisons of their physicochemical and spectroscopic data with the reported data in literature. As a result, 22 isolated compounds from the 90% ethanol extract of the fruits of M. citrifolia were identified, which were moricitritone(1), 2'-deoxythymidine(2), cyclo-(L-Pro-L-Tyr)(3), methyl-5-hydroxy-2-pyridinecarboxylate(4), methyl pyroglutamate(5), bisbenzopyran(6), epipinoresinol(7), 3, 3'-bisdemethyl pinoresinol(8), 3, 3'-bisdemethyltanegool(9), trimesic acid(10), crypticin B(11), kojic acid(12), vanillic acid(13), protocatechoic acid(14), 5-hydroxymethyl furfural(15), blumenol A(16), 1-O-(9Z, 12Z-octadecadienoyl) glycerol(17), mucic acid dimethylester(18), methyl 2-O-β-D-glucopyranosylbenzoate(19), 2-phenylethyl-O-β-D-glucoside(20), scopoletin(21), and quercetin(22). Among them, compound 1 was a new pyrone derivative, compounds 2, 4-7, 10-12, and 17 were isolated from the plants belonging to Morinda genus for the first time, and compound 18 was obtained from M. citrifolia for the first time. Moreover, on the basis of testing the activities of all isolated compounds on inhibiting the proliferation of synovial fibroblasts in vitro by MTS assay, the anti-rheumatoid arthritis activities of all isolated compounds were initially evaluated. The results showed that compounds 1-6, 9, 19, and 20 exhibited remarkable anti-rheumatoid arthritis activities, which displayed the inhibitory effects on the proliferation of MH7A synovial fibroblast cells with the IC_(50) values in the range of(3.69±0.08) to(168.96±0.98) μmol·L~(-1).

Effect of Xinnao Shutong capsule and its active ingredients on damage of cerebral microvascular endothelial cell barrier integrity caused by oxygen glucose deprivation/reoxygenation and its mechanism / 中国药理学通报

Aim To investigate the effect of XNST and its monomeric components on the barrier structure and tight junction protein expression of brain microvascular endothelial cells damaged by oxygen glucose deprivation/reoxygenation (OGD/R) and the possible mechanism. Methods The mouse brain microvascular endothelial cell line bEnd. 3 was inoculated in the upper layer of the Transwell chamber to establish an OGD/R damage model, and the effect of the drug on the integrity of the endothelial cell barrier was investigated by the transmembrane resistance value and fluorescein-so-dium transmittance. Claudin-5 immunofluorescence staining was used to observe the changes of tight junction structure between endothelial cells. RT-PCR and Western blot were employed to detect mRNA and protein expression levels of tightly linked proteins Claudin-5 , Occludin, ZO-1. Western blot was applied to detect the expression levels of MAPKs (JNK, p38, ERK) , I kappa B a, I kappa B kinase phosphorylated protein expression, and Western blot and immunofluorescence were utilized to detect NF-K.B/p65 nucleation expression. Results XNST and its three monomers could significantly increase endothelial cell resistance and de- crease fluorescein-sodium transmittance. Claudin-5 fluorescence staining showed that the tight junction between cells in the model group was significantly damaged , while XNST and its monomer components could significantly improve its tight structure. RT-PCR and Western blot results showed that it could significantly upregulate the expression of mRNA and protein of Claudin-5, Occludin and ZO-1, and further study on the mechanism showed that XNST and its monomer components could significantly inhibit the phosphoryla-tion of JNK, p38 and ERK, inhibit the phosphorylation of I kappa B a and I kappa B kinases, and significantly inhibit the nuclear translocation of NF-KB/p65. Conclusion Both XNST and its monomeric components can exert cerebroprotective effects by increasing the tight junction structure between cells to promote barrier integrity, and the mechanism may be related to inhibition of NF-kB and MAPKs signaling pathway activation.

Distribution characteristics of tumor infiltrating lymphocytes in EBV-associated lymphoepithelioma-like carcinoma and their clinical significance / 中华病理学杂志

Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20+B cells, CD4+T cells, and FOXP3+Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20+B cells, CD4+T cells and FOXP3+Treg cells in LELC may suggest a better prognosis.

Chemical approaches for the stereocontrolled synthesis of 1,2-cis-β-D-rhamnosides / 中国天然药物

In carbohydrate chemistry, the stereoselective synthesis of 1,2-cis-glycosides remains a formidable challenge. This complexity is comparable to the synthesis of 1,2-cis-β-D-mannosides, primarily due to the adverse anomeric and Δ-2 effects. Over the past decades, to attain β-stereoselectivity in D-rhamnosylation, researchers have devised numerous direct and indirect methodologies, including the hydrogen-bond-mediated aglycone delivery (HAD) method, the synthesis of β-D-mannoside paired with C6 deoxygenation, and the combined approach of 1,2-trans-glycosylation and C2 epimerization. This review elaborates on the advancements in β-D-rhamnosylation and its implications for the total synthesis of tiacumicin B and other physiologically relevant glycans.

Professor GUAN Ling's clinical experience in treating knee osteoarthritis with structure-based medical acupuncture / 中国针灸

This paper summarizes professor GUAN Ling's clinical experience in the treatment of knee osteoarthritis (KOA) with structure-based medical acupuncture (SMA). Based on anatomy and biomechanics and through accurate physical examination, SMA adjusts the mechanical imbalance of muscles to relieve KOA dysfunction, and releases nerve compression to attenuate pain symptoms of KOA. In reference to traditional acupoint selection, and in association with painful areas and mechanical deduction, ashi points located at the rectus femoris, vastus intermedius, vastus medialis and vastus lateralis muscles, etc. are specially stimulated with acupuncture; and the rehabilitation training and health education are the adjuvant treatment for the patients.