Erythropoietic protoporphyria with liver cirrhosis as the main manifestation： A case report / 临床肝胆病杂志

Erythropoietic protoporphyria （EPP） is a rare inherited metabolic disease that often involves skin， blood， and nervous systems， and EPP with the main manifestations of severe liver damage and acute abdominal pain is extremely rare. By reviewing the clinical data and genetic testing results of a patient with EPP， this article discusses the clinical features and pathogenic genes of this disease， in order to improve the understanding of the disease among hepatologists and achieve early diagnosis and treatment.

Effects of chronic restraint stress on the expression of N6-methyladenosine and related enzymes in the hippocampus of mice / 解剖学报

Objective To investigate the effect of chronic restraint stress on the expression of N6-methyladenosine (m6A)and related enzymes in the hippocampus of mice. Methods Twenty C57BL/6J male mice were randomly divided into control group and chronic restraint stress (CRS) group, the model group was given for 3 weeks chronic restraint stress to establish a mouse anxiety model. Open field test and elevated plus maze test were used to detect anxiety-like behavior; Immunohistochemistry and m6A RNA methylation assay were used to detect the expression changes of mouse hippocampal m6A; Western blotting and Real-time PCR were used to analyze hippocampal m6A related enzymes expression. Results 1.The behavioral results showed that, compared with the control group, the CRS group showed significantly reduced time spent in the center of the open field(P<0.01), the CRS group showed significantly reduced exploration time in the open arm of elevated plus maze (P<0.0001); 2. Immunohistochemical results showed that, compared with the control group, the hippocampal m6A content in the CRS group reduced significantly (P < 0.001); The results of the m6A RNA methylation assay showed that, compared with the control group, the CRS group showed significantly reduced amount of hippocampal m6A(P<0.05); 3. Real-time PCR results showed that the expression of hippocampal demethylase anaplastic lymphoma kinase B(AlkB) homolog 5(ALKBH5) (P<0.001) and fat mass and obestity associated protein(FTO) (P< 0.05) in the CRS group significantly up-regulated, the expression of methylase Wilms' tumour 1-associating protein (WTAP) (P<0.05) was significantly down-regulated compared with the control group; The expression of m6A methylation binding protein YTH domaincontaining family protein 3 (YTHDF3) (P < 0.05) and YTH domaincontaining protein 2 (YTHDC2) (P < 0.01) was significantly up-regulated. Western blotting result showed that, compared with the control group, the mouse hippocampal demethylase ALKBH5 (P < 0.05) and FTO (P < 0.05) expression in the CRS group significantly up-regulated, the expression of WTAP (P<0.01) was significantly down-regulated; m6A methylation binding protein YTHDF3 (P<0.01) and YTHDC2 (P<0.05) were significantly up-regulated. Conclusion In the anxiety model induced by chronic restraint stress, the expression of m6A in the hippocampus of mice is down-regulated. The mechanism may be related to the up-regulation of the m6A demethylase ALKBH5 and FTO or the down-regulation of the methylase WTAP.

Rho A/ROCK signaling pathway involved in hyper responsiveness to aortic contraction in mice with type 2 diabetes / 中国药理学通报

Aim To investigate the mechanism of RhoA/ROCK signaling pathway in abnormal aortic contractility in type 2 diabetes (T2DM) mice. Methods The experiment was divided into two groups, the control group (db/m mice) and the model group (db/db mice). Changes of the response to different methods were measured in aorta rings using a Multi Myograph System. At the same time, the protein expression changes of aortic smooth muscle contraction signaling pathway in mice were determined by Western method. Results Compared with the control group, the blood glucose and body weight levels of the mice in the T2DM group significantly increased, and the cardiac function was abnormal (P <0. 01). The contractile response of the aorta of the diabetic mice induced by the contractile agents Phe, 5-HT and CaCl

Investigation of extrauterine growth restriction in very preterm infants in Chinese neonatal intensive care units / 中华儿科杂志

Objective: To comprehensively assess the current status of extrauterine growth restriction (EUGR) in very preterm infants (VPI) and its associated factors in Chinese neonatal intensive care units (NICU). Methods: In this cohort study, 6 179 preterm infants born at <32 weeks' gestation were included, who were admitted to 57 hospitals in the China Neonatal Network in 2019 and hospitalized for ≥7 days. EUGR was evaluated by a cross-sectional definition (weight at discharge<10th percentile for postmenstrual age), a longitudinal definition (decline in weight Z score>1 from birth to discharge), and weight growth velocity. The comparison between infants with and without EUGR was conducted by t-test, Mann-Whitney U test or χ2 test as appropriate. Multivariable Logistic regression models were used to evaluate associations between EUGR with different definitions and maternal and neonatal factors, clinical practices, and neonatal morbidities. Results: A total of 6 179 VPI were enrolled in the study, with a gestational age of (29.8±1.5) weeks and birth weight of (1 365±304) g; 56.2% (3 474) of them were male. Among them, 48.4% (2 992 VPI) were cross-sectional EUGR and 74.9% (4 628 VPI) were longitudinal EUGR. Z score of weight was (0.13±0.78) at birth and decrease to (-1.35±0.99) at discharge. The weight growth velocity was 10.13 (8.42, 11.66) g/(kg·d). Multivariate Logistic regression analysis showed that among the influential factors that could be intervened after birth, late attainment of full enteral feeds (ORadjust=1.01, 95%CI 1.01-1.02, P<0.001; ORadjust=1.01, 95%CI 1.01-1.02, P<0.001), necrotizing enterocolitis≥Ⅱstage (ORadjust=2.64, 95%CI 1.60-4.35, P<0.001; ORadjust=1.62, 95%CI 1.10-2.40, P<0.001) and patent ductus arteriosus (ORadjust=1.94, 95%CI 1.50-2.51, P<0.001; ORadjust=1.63, 95%CI 1.29-2.06, P<0.001) were all associated with increased risks of both cross-sectional and longitudinal EUGR. In addition, late initiation of enteral feeds (ORadjust=1.06, 95%CI 1.02-1.09, P=0.020) and respiratory distress syndrome (ORadjust=1.45, 95%CI 1.24-1.69, P<0.001) were all associated with cross-sectional EUGR. Breast milk feeding (ORadjust=1.33, 95%CI 1.05-1.68, P<0.001) was associated with a higher risk of longitudinal EUGR. Conclusions: The incidence of EUGR in VPI in China is high. Some modifiable risk factors provide priorities to improve postnatal growth for VPI. Nutritional management of VPI and the efforts to decrease the incidence of complications are still the focus of clinical management in China.

The application and effect of "Trinity" emergency chain in the management of patients with epidemic respiratory tract infection under the coordination of multi-branches / 中华急诊医学杂志

Objective:To summarize the application and effect of "Trinity" emergency chain in the management of patients with epidemic respiratory tract infection under the cooperation of multiple hospitals and districts, and to provide a reference for medical institutions to improve the risk response ability.Methods:Based on the collaborative management of multi-branches, the "Trinity" emergency chain of pre-hospital-emergency-critical care, identification-triage-treatment, expansion-training-dispatch was implemented to optimize and integrate medical resources.Results:During the two months, 43,000 patients were admitted to the fever clinic, with an increase of 36.08%. The average waiting time for treatment was 19.83 min, and the average admission time to ICU was 25.35 min.Conclusions:The "Trinity" emergency chain treatment scheme under the coordination of multi-branches can effectively deal with the public health events of respiratory tract infectious diseases, improve the efficiency of rescue and treatment, and enhance the risk response ability of medical institutions.

Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats

Abstract Objectives: This study aimed to explore the effects of bone marrow-derived Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) treating diabetic foot ulcers in rats. Methods: Models of T2DM rats were induced by a high-fat diet and intraperitoneal injection of STZ in SD rats. Models of Diabetic Foot Ulcers (DFUs) were made by operation on hind limbs in diabetic rats. Rats were divided into four groups (n = 6 for each group), i.e., Normal Control group (NC), Diabetes Control group (DM-C), MSC-CM group and Mesenchymal Stem Cells group (MSCs). MSC-CM group was treated with an injection of conditioned medium derived from preconditioned rats' bone marrow MSCs around ulcers. MSCs group were treated with an injection of rats' bone marrow MSCs. The other two groups were treated with an injection of PBS. After the treatment, wound closure, re-epithelialization (thickness of the stratum granulosums of the skin, by H&E staining), cell proliferation (Ki67, by IHC), angiogenesis (CD31, by IFC), autophagy (LC3B, by IFC and WB; autoly-sosome, by EM) and pyroptosis (IL-1β, NLRP3, Caspase-1, GSDMD and GSDMD-N, by WB) in ulcers were evaluated. Results: After the treatment wound area rate, IL-1β by ELISA, and IL-1β, Caspase-1, GSDMD and GSDMD-N by WB of MSC-CM group were less than those of DM group. The thickness of the stratum granulosums of the skin, proliferation index of Ki67, mean optic density of CD31 and LC3B by IFC, and LC3B by WB of MSC-CM group were more than those of DM group. The present analysis demonstrated that the injection of MSC-CM into rats with DFUs enhanced the wound-healing process by accelerating wound closure, promoting cell proliferation and angiogenesis, enhancing cell autophagy, and reducing cell pyroptosis in ulcers. Conclusions: Studies conducted indicate that MSC-CM administration could be a novel cell-free therapeutic approach to treat DFUs accelerating the wound healing process and avoiding the risk of living cells therapy.

The prevalence and associated factors of metabolic syndrome among Tibetan pastoralists in transition from nomadic to settled urban environment / 中华流行病学杂志

Objective: To study the prevalence and associated factors of metabolic syndrome (MS) among Tibetan pastoralists in transition from high altitude nomadic to settled urbanized environment, especially dietary factors. Methods: The community-based cross-sectional study included 920 Tibetan adults (men 419, women 501). Data were collected using questionnaires, anthropometric measurements, and biomarker tests. Questionnaires included socio-economic, lifestyle characteristics and food consumption. Principal component analysis was used to identify dietary patterns. The risk factors of MS and its components were analyzed by logistic regression model. Results: The prevalence rates of MS and its components were 32.8% (MS), 83.7% (decreased HDL-C), 62.1% (central obesity), 36.7% (elevated blood pressure), 11.8% (elevated TG), and 7.9% (elevated blood glucose), respectively. The prevalence of overweight was 31.2%, obesity 30.3%. Multivariate analysis showed smoking was associated factor for both of decreased HDL-C (OR=1.239, 95%CI: 1.025-1.496) and elevated TG (OR=1.277, 95%CI: 1.038-1.571). Alcohol drinking appeared as associated factor of elevated TG (OR=1.426, 95%CI: 1.055-1.927). However, physical activity showed as a protective factor for central obesity, decreased HDL-C, and elevated TG. With the increase of age, the adherence to the urban and western dietary patterns decreased, and that to the pastoral dietary pattern increased. By quintiles of dietary pattern scores, the urban dietary pattern was significantly associated with MS (trend test P=0.016). Conclusions: Tibetan pastoralists had high prevalence of both MS and obesity. Smoking, alcohol drinking, the transition from pastoral dietary pattern to urban dietary pattern and inadequate physical activity served as associated factors for MS and its components.

Synthesis and evaluation on triglyceride inhibitory activities of novel indole alkaloids / 药学学报

Three tricyclic [6,5,7] and six tetracyclic [6,5,5,5] novel indole alkaloids were synthesized and evaluated on triglyceride inhibitory activities for the first time. Among them, compound 4c showed the most potent activity with IC50 value of 6.35 μmol·L-1. Meanwhile, compound 4c also exhibited a good safety profile at the cellular level. Preliminary mechanism study indicated that 4c might increase intracellular lipid metabolism by activating AMPK. These results provide a novel family of lead compounds for the discovery of anti-NAFLD candidates.

Bioinformatics analysis on structure and function and expression vector construction of SARS-CoV-2 related protein TMPRSS2 / 中国药理学通报

Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.

A novel technology to reduce astringency of tea polyphenols extract and its mechanism / 中草药·英文版

Objective: Tea polyphenols are natural extracts used widely throughout the world. However, the severe astringency of tea polyphenols has reduced patient compliance. Based on the analysis of the formation mechanism of astringency, this paper hopes to propose a new method to control the astringency of tea polyphenols and improve patient compliance without changing its effect. Methods: Artificial saliva was used to prepare the tea polyphenols solution with different pH, using β-casein to imitate salivary protein, and preparing 1.2 mg/mL β-casein solution. A fluorescence quenching test was used to study the interaction between tea polyphenols and β-casein, combined with the stability test results of the compound, we can choose the pH with weak binding but good stability as the best pH for masking astringency. The taste-masking tablets were prepared under the best pH conditions, and the Xinnaojian Original Tablets were prepared according to the conventional preparation method. The disintegration time limit and solubility were tested respectively. The astringency of Xinnaojian original tablets and taste-masking tablets was evaluated by visual analogue scale (VAS). Results: The result of the fluorescence quenching test prompted that the combination force was the weakest when the pH was 4.9. Further synchronous fluorescence analysis showed that an increase in pH resulted in a decrease of the binding sites between tea polyphenols and β-casein, and this decrease was closely related to changes in tryptophan residues in β-casein. Both original and taste-masking Xinnaojian Tablets were prepared. Volunteers’ VAS scores illustrated that the astringency improved significantly with the masking tablets (P < 0.05). Conclusion: This pH-adjusting masking treatment had little effect on the recovery of polyphenols from the tablets or the dissolution of the tablets. This study provides a novel and feasible astringency masking technology for tea polyphenols and its preparation.

Understanding the dual character of negative and positive results in acupuncture-moxibustion clinical trials in foreign countries / 中国针灸

The differences in the objective, starting point, disease spectrum and interventions of acupuncture-moxibustion clinical trials at home and abroad are collected. By taking two articles of acupuncture-moxibustion clinical trials in foreign countries accepted by

The effect of hematoma puncture drainage before decompressive craniectomy on the prognosis of hypertensive intracerebral hemorrhage with cerebral hernia at a high altitude / 中华创伤杂志(英文版)

PURPOSE@#Rapid decompressive craniectomy (DC) was the most effective method for the treatment of hypertensive intracerebral hemorrhage (HICH) with cerebral hernia, but the mortality and disability rate is still high. We suspected that hematoma puncture drainage (PD) + DC may improve the therapeutic effect and thus compared the combined surgery with DC alone.@*METHODS@#From December 2013 to July 2019, patients with HICH from Linzhi, Tibet and Honghe, Yunnan Province were retrospectively analyzed. The selection criteria were as follows: (1) altitude ≥1500 m; (2) HICH patients with cerebral hernia; (3) Glascow coma scale score of 4-8 and time from onset to admission ≤3 h; (4) good liver and kidney function; and (5) complete case data. The included patients were divided into DC group and PD + DC group. The patients were followed up for 6 months. The outcome was assessed by Glasgow outcome scale (GOS) score, Kaplan-Meier survival curve and correlation between time from admission to operation and prognosis. A good outcome was defined as independent (GOS score, 4-5) and poor outcome defined as dependent (GOS score, 3-1). All data analyses were performed using SPSS 19, and comparison between two groups was conducted using separate t-tests or Chi-square tests.@*RESULTS@#A total of 65 patients was included. The age ranged 34-90 years (mean, 63.00 ± 14.04 years). Among them, 31 patients had the operation of PD + DC, whereas 34 patients underwent DC. The two groups had no significant difference in the basic characteristics. After 6 months of follow-up, in the PD + DC group there were 8 death, 4 vegetative state, 4 severe disability (GOS score 1-3, poor outcome 51.6 %); 8 moderate disability, and 7 good recovery (GOS score 4-5, good outcome 48.4 %); while in the DC group the result was 15 death, 6 vegetative state, 5 severe disability (poor outcome 76.5 %), 4 moderate disability and 4 good recovery (good outcome 23.5 %). The GOS score and good outcome were significantly less in DC group than in PD + DC group (Z = -1.993, p = 0.046; χ@*CONCLUSION@#PD + DC treatment can improve the good outcomes better than DC treatment for HICH with cerebral hernia at a high altitude.

MicroRNA-98-5p targeting ribonucleotide reductase small subunit M2 regulating cisplatin resistance in cervical cancer cells / 解剖学报

Objective To investigate the regulation and mechanism of microRNA (miR)-98-5p on cisplatin sensitivity in cisplatin-resistant cervical cancer cells. Methods The cisplatin(DDP) +miR-NC group (transfected miR- NC), DDP + miR-98-5p group (transfected miR-98-5p mimics), DDP + si-NC group (transfected si-NC), DDP + si- ribonucleotide reductase subunit M2 (RRM2) group (transfected si-RRM2), DDP + miR-98-5p + pcDNA group (co- transfected miR-98-5p mimics and pcDNA), DDP + miR-98-5p + pcDNA-RRM2 group (co-transfected miR-98-5p mimics and pcDNA-RRM2) were transfected into HeLa/DDP cells by liposome method. Real-tim PCR, Western blotting, CCK-8, Transwell chamber and dual luciferase reports gene detection assay were used to detect the expression of miR-98-5p, RRM2, cyclin Dl, P21, matrix metalloproteinase (MMP)-2 and MMP-9 in cells, inhibition rate, half inhibitory concentration(IC

Advances in small molecular inhibitors of IL-6/STAT3 signaling pathway / 药学学报

As a pleiotropic cytokine, interleukin-6 (IL-6) participates in many physiological activities in vivo. IL-6 plays an important role in the physiology and pathology of chronic inflammation, autoimmune diseases, tumors and other diseases through diverse mechanisms. At present, inhibitors targeting IL-6/IL-6R have been shown to improve treatments for some inflammatory diseases such as rheumatoid arthritis and systemic juvenile idiopathic arthritis. IL-6 binds to a specific receptor to activate the downstream JAK/STAT3 signaling pathway. However abnormally activated STAT3 often appears in various types of malignant tumors and participates in the occurrence and development of tumors. In addition, studies have shown that IL-6 is a key factor in the cytokine storm associated with COVID-19 patients. The physiological participation of IL-6/STAT3 pathway in complex diseases makes this pathway become a research hotspot for drug discovery. Therefore, we summarize the latest research progress of small molecular inhibitors on IL-6/STAT3 signaling pathway, in order to provide a reference for the development of IL-6/STAT3 related drug in the future.

Epidemiology and pathogen composition of enterovirus in children with hand, foot and mouth disease in Guangyuan, Sichuan / 公共卫生与预防医学

Objective To investigate the epidemiology and pathogenic characteristics of enterovirus in children with hand, foot and mouth disease (HFMD) in Guangyuan area, and to provide a basis for the development of HFMD prevention and control strategies. Methods A total of 759 children with HFMD clinically diagnosed in Guangyuan area from January 2019 to January 2021 were randomly selected. The seasonal, age, gender, regional distribution and pathogen distribution characteristics of HFMD were analyzed by descriptive epidemiological methods. Results The incidence of HFMD was seasonal and presented a typical bimodal distribution, with the summer peak occurring from April to July (χ2=8.714, P2=7.542, P2=5.915, P2=8.455, P2=5.174, P<0.05). A total of 388 HFMD cases were tested positive for viral nucleic acid, with a positive rate of 51.12%, In mild cases, Cox A16, EV71, and other enteroviruses accounted for 27.64%, 29.54% and 29.54%, respectively. The proportion of EV71 in severe cases was 89.47%. Conclusion HFMD is widely distributed in Guangyuan area, with obvious seasonal and population differences. The prevention and control of HFMD should be strengthened in key areas, high incidence seasons and key populations, and the vaccination of children ≤3 years old should be further promoted to prevent the outbreak of HFMD.

Prevalence and trend of low vision among primary and secondary school students in Wuhan from 2019 to 2020 / 中国学校卫生

Objective@#To provide a largescale assessment the prevalence of poor vision in 2020 among children and adolescents in Wuhan City, Hubei province and to provide basis for healthy vision promotion.@*Methods@#This crosssectional epidemiological study was conducted among 156 783 students, who lived in Wuhan during the COVID-19 period participated the vision screening through the online applet designed by Wuhan Center for Adolescent Poor Vision Prevetion and Control under the guidance of their guardians between June 19 and July 6, 2020. The demographic information and daily hours spent on various activities in the past week were investigated. The corresponding visual acuity data of students in 2019 before the COVID-19 outbreak was extracted from school vision monitoring records for each semester, which was measured by the experienced eye care professionals.@*Results@#The detection rate of poor vision (51.04%) in 2020 was significantly higher than that in 2019(43.04%)( χ 2=68 944.95, P <0.01). After adjustment for covariates, the odds ratio and 95% confidence interval for poor vision were 1.17(1.13-1.20), 1.07(1.04-1.10), 0.67 (0.65-0.69) and 0.62(0.60-0.64) in students with online class time, recreational screen time, indoor and outdoor activity time in the highest tertile, compared with the lowest tertile groups.@*Conclusion@#Increased rate of poor vision among primary and secondary schoool students deserves further concern. It is necessary to strengthen intervention of eyesight protection. Policies and programs aimed at improving opportunities for physical activities and decreasing multiple screen behaviors should be given priority.

Effects of alprostadil in β-aminopropanitrile induced aortic dissection in a murine model / 中华心血管病杂志

Objective: To investigate the protective role of alprostadil on aortic dissection. Methods: 26 C57BL6 male mice were divided into control group (normal drinking water, n=13) and model group (1 g·kg-1·d-1 BAPN via drinking water, n=13). On day 14, mRNA expression of inflammatory-related genes as well as EP receptor families were detected by RT-PCR (n=6 each) and EP4 protein levels were determined by Western blot (n=7 each). Another 88 mice were divided into 3 groups: control group (n=22), model group (n=33) and treatment group (n=33). The mice in model group and treatment group were applied with BAPN (1 g·kg-1·d-1) via drinking water. The mice in treatment group received additional intraperitoneal injection with alprostadil (80 μg·kg-1·d-1) for 28 days. The mice in the control and model group received equal volume intraperitoneal injection with 0.9% saline respectively. The body weight and systolic blood pressure, the mortality and morbidity were monitored from the beginning until the designed end of the study. On day 28, the mice were sacrificed and aorta were fixed, embedded and sliced, followed by staining with HE and Victoria Blue. The distribution of EP4 was determined by immunohistochemistry in control (n=6) and model group (n=6). Furthermore, the concentration of PGE1 were tested among model (n=3) and treatment group (n=4). EP4 protein expression was determined in model group (n=7) and treatment group (n=6). Results: On day 14, mRNA expression level of MCP-1 ((2.74±1.55) vs. (1.00±0.49),<0.05) and MMP2((1.38±0.42) vs. (1.00±0.27), P<0.05) was significantly upregulated in model group compared with control group. Protein expression of EP4 receptor also increased in aorta in model group compared with control group (1.48±0.51 vs. 1.00±0.19, P<0.05). In the dissection area, the EP4 expression was also enriched compared with non-dissection area, particularly in endothelial cells and inflammatory cells on day 28. BAPN applied in drinking water (model and treatment groups) successfully induced the aortic dissection in mice, some mice died of the rupture. The elastic fibers were fractured, and the infiltrated immune cells were visible in dissected tissue. False lumen was formed. There was no dissection and death in the control group. Compared with control group, the morbidity and mortality rates were significantly increased in the model group (60.6%, 20/33, 30.3%, 10/33) and the treatment group (72.7%, 24/33, 24.2%, 8/33). The mortality and morbidity rates were similar between model and treatment groups. There is no difference in terms of SBP among three groups (P>0.05). Further study showed that after alprostadil injection, the blood concentration of PGE1 was increased in treatment group ((0.540±0.041 vs. 0.436±0.012)μmol/L, P<0.05). Besides, the EP4 receptor expression was downregulated in the treatment group compared to model group (0.60±0.30 vs. 1.00±0.20, P<0.05). Conclusion: EP4 expression is upregulated in BAPN induced aortic dissection mouse model. No protective effects are observed post alprostadil treatment in this model probably due to the reduced expression of EP4.

Effect of ligustilide on oxygen and glucose deprivation/reperfusion-induced mitochondria fission in PC12 cells / 中国中药杂志

This study aimed to investigate the effect and mechanism of ligustilide, the main active ingredient in Ligusticum wallichii, on mitochondria fission after PC12 cell injury induced by oxygen and glucose deprivation/reperfusion(OGD/R). In the experiment, an OGD/R model was established in vitro, and PC12 cells were pre-treated with ligustilide for 3 h, and then the cell viability was detected by CCK-8 method. The effect of different concentrations of ligustilide on the morphology of PC12 cells after OGD/R injury was observed under an inverted microscope. Transmission electron microscopy was used to observe the mitochondrial fission of PC12 cells after OGD/R injury. DCFH-DA immunofluorescence staining method was used to detect intracellular reactive oxygen species(ROS) changes. Changes in mitochondria membrane potential(MMP) were detected by flow cytometry. Hochest 33258 was used to observe the apoptosis of PC12 cells. Western blot was used to detect changes in cytochrome C(Cyt C) content in mitochondria and cytoplasm, and mitochondrial fission-related proteins Drp 1 and Fis 1. All results showed that compared with the model group, ligustilide significantly increased the survival rate of PC12 cells and the number of cells. Further experiments showed that ligustilide inhibited the release of ROS and decline of mitochondrial membrane potential in PC12 cells after OGD/R injury. Moreover, ligustilide reduced the release of Cyt C and promoted the expressions of Drp1 and Fis1 in mitochondrial fission proteins. Verification experiments showed that mitochondrial fission inhibitor mdivi-1 decreased cell survival rate and inhibited fission. The results indicated that ligustilide exerted neuro-protective effects by promoting mitochondrial fission and reducing cell damage. It preliminary proves that the mechanism of ligustilide on ischemic brain injury may be related to the promotion of mitochondrial fission and the maintenance of cell homeostasis.

Study on anti-inflammatory active components and mechanism of Corydalis Bungeanae Herba / 中国中药杂志

Corydalis Bungeanae Herba is often used to treat a variety of inflammatory diseases in traditional Chinese medicine. In order to determine its chemical material basis, the components of Corydalis Bungeanae Herba were isolated by automated purification system. Flavonoids and alkaloids were prepared, and all such components were identified by mass spectrometry. The effects of the components on the production of inflammatory mediators and pharmacological mechanisms in the lipopolysaccharide(LPS)-induced RAW264.7 cell inflammation model were examined. Mouse macrophages(RAW264.7) were first treated with LPS. The relationship between cell viability and LPS concentration was observed. Then, the effects of flavonoids components and alkaloid components with different administration concentrations on cell viability were detected to determine the maximum administration concentration. Secondly, 2.5, 5, 10 and 20 μg·mL~(-1) flavonoids components and alkaloid components were added respectively to observe the effects and mechanism of different concentrations of flavonoids components and alkaloid components on LPS-induced inflammation of RAW264.7 macrophages. Griess reagent assay was used to detect NO content in cell supernatant. The inflammatory cytokines(TNF-α, IL-1β and IL-6) in cell supernatant were determined by ELISA method. Western blot method was used to detect the intracellular nuclear factor(NF-κB) IκBα phosphorylation(p-IκBα), p65 phosphorylation(p-p65) and protein expression of TLR4, TLR2. The results showed that the alkaloid components inhibited the production of NO, TNF-α, IL-1β and IL-6 in a dose-dependent mannerin the concentration range of 2.5-20 μg·mL~(-1). In inflammation upstream pathways, the inhibitory effect of the alkaloid components on the TLR2 expression level was weaker than that of TLR4. In inflammation downstream, alkaloid components significantly inhibited phosphorylation of IκBα and p65 in a dose-dependent manner. These data suggested that the alkaloid components were the material basis components of Corydalis Bungeanae Herba, and its anti-inflammatory mechanism might be related to inhibiting the transmission of inflammatory signals in TLRs/NF-κB signaling pathways dominated by TLR4, interfering with the activation of inflammatory genes and inhibiting their over expression, and down-regulating the secretion level of inflammatory factors.

The Role of Lubricin in Wound Repair of Musculoskeletal System / 医用生物力学

Lubricin is widely expressed in tissues in the musculoskeletal system, including articulate cartilage, tendon and synovium, which shows a close relationship with the structure and pathology of these tissues. Lubricin plays an important role in lubrication, anti-adhesion, proliferation inhibition and inflammation regulation, which may facilitate the healing of impaired tissues in the musculoskeletal system. This article reviews the research progress on expression and regulation of lubricin as well as its structure and function in wound repair of the musculoskeletal system, so as to provide theoretical evidences for further researches on the role of lubricin in the musculoskeletal system with its related mechanisms and the clinical application of lubricin.