Biosensor analysis technology and its research progress in drug development of Alzheimer's disease / 药学学报

Biosensor analysis technology is a kind of technology with high specificity that can convert biological reactions into optical and electrical signals. In the development of drugs for Alzheimer's disease (AD), according to different disease hypotheses and targets, this technology plays an important role in confirming targets and screening active compounds. This paper briefly describes the pathogenesis of AD and the current situation of therapeutic drugs, introduces three biosensor analysis techniques commonly used in the discovery of AD drugs, such as surface plasmon resonance (SPR), biolayer interferometry (BLI) and fluorescence analysis technology, explains its basic principle and application progress, and summarizes their advantages and limitations respectively.

Hypoxic Preconditioning Improves Hypoxic Survival and Proliferation of Mesenchymal Stem Cells by Modulating Lysine Crotonylation / 中国生物化学与分子生物学报

Hypoxic preconditioning could improve the survival of mesenchymal stem cells (MSCs) in ischemic or hypoxic environments, but its exact mechanism remains to be further explored. This study aims to determine the role of lysine crotonylation (Kcr) in regulating the survival and proliferation of peripheral blood mesenchymal stem cells (PBMSCs) in the hypoxic culture. PBMSCs were isolated and cultured from rat peripheral blood mononuclear cells, and their surface markers were identified by flow cytometry. PBMSCs were first subjected to hypoxic/ normoxic preconditioning: hypoxic (1% O

The progression of the extent of lymph node dissection in radical resection of pancreatic head cancer / 中华外科杂志

Pancreatic cancer is a malignant tumor of digestive system with poor prognosis,and surgical resection is still the only hope for a radical cure. Although the current consensus and guidelines describe in detail the standard and extended range of lymph node dissection,the selection of specific range of lymph node dissection and its impact on prognosis are still controversial. Current studies have not only proposed some improved extent of lymph node dissection, such as total mesopancreas excision and Heidelberg triangle dissection, but also suggested different extent of lymph node dissection for ventral and dorsal pancreatic head cancer. In addition, the prognosis of pancreatic head cancer in uncinate process and non-uncinate process is different after para-aortic lymph node dissection, which is worthy of further study. Neoadjuvant therapy or conversion therapy provides more surgical opportunities for patients with pancreatic cancer. For these patients, Heidelberg triangle dissection has potential value in improving prognosis. This paper summarizes the exploration and latest progress of standard and extended lymph node dissection, lymph node dissection of specific site of pancreatic head cancer and the extent of lymph node dissection after neoadjuvant/transformation therapy in recent years.

Acupoints compatibility rules of acupuncture for depression disease based on data mining technology / 中国针灸

Based on data mining technology, the acupoints compatibility rules of acupuncture for depression diseases were explored. The randomized controlled trial (RCT) articles regarding acupuncture for depression diseases published from establishment of database to September 2nd, 2022 were searched in CNKI database, Wangfang database, VIP database, SinoMed database, PubMed, EMbase, Web of Science and Cochrane Library. The use frequency of acupoints, meridian tropism, selection of special acupoints and acupoint association rules for five common depression diseases, including primary depression, post-stroke depression, menopausal syndrome, psychoneurosis and anxiety disorder, were analyzed by Python programming language. Cytoscape software was used to analyze the acupoint association and the disease-acupoint co-occurrence network. As a result, totally 387 articles were included, and 319 acupoints prescriptions for the above five common depression diseases were extracted, involving 159 acupoints. The use frequency of acupoints was 2 574 times in total. The frequently-used acupoints were Baihui (GV 20), Sanyinjiao (SP 6), Taichong (LR 3), Neiguan (PC 6), Shenmen (HT 7), Yintang (GV 24+), Zusanli (ST 36), Hegu (LI 4), Sishencong (EX-HN 1) and Taixi (KI 3), etc. The frequently involved meridians were the governor vessel, foot-taiyang bladder meridian, foot-taiyin spleen meridian, and foot-jueyin liver meridian. The frequency of the special acupoints from high to low was crossing points, five-shu points, yuan-primary points, back-shu points, luo-connecting points, and eight confluent points, etc, which were often used in combination with "Baihui (GV 20)-Yintang (GV 24+)" (the highest degree of association). At the same time, the analysis of the co-occurrence network of depression diseases and acupoints showed that the core acupoints group of acupuncture for depression diseases were Baihui (GV 20), Taichong (LR 3), Shenmen (HT 7), Zusanli (ST 36), Neiguan (PC 6) and Sanyinjiao (SP 6). In conclusion, acupuncture treatment for depression diseases has gradually formed a rule of acupoint compatibility, with special acupoint as the main body and "unblocking the governor vessel, and regulating the spirit and qi " as the main therapeutic principle.

The characteristics and correlations of vaginal flora in women with cervical lesions / 中华肿瘤杂志

Objective: To explore the characteristics and correlations of vaginal flora in women with cervical lesions. Methods: A total of 132 women, including 41 women diagnosed with normal cervical (NC), 39 patients with low-grade cervical intraepithelial neoplasia (CIN 1), 37 patients with high-grade cervical intraepithelial neoplasia (CIN 2/3) and 15 patients with cervical squamous cell carcinoma (SCC), who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January 2018 to June 2018, were enrolled in this study according to the inclusive and exclusive criteria strictly. The vaginal flora was detected by 16S rDNA sequencing technology. Co-occurrence network analysis was used to investigate the Spearman correlations between different genera of bacteria. Results: The dominant bacteria in NC, CIN 1 and CIN 2/3 groups were Lactobacillus [constituent ratios 79.4% (1 869 598/2 354 098), 63.6% (1 536 466/2 415 100) and 58.3% (1 342 896/2 301 536), respectively], while Peptophilus [20.4% (246 072/1 205 154) ] was the dominant bacteria in SCC group. With the aggravation of cervical lesions, the diversity of vaginal flora gradually increased (Shannon index: F=6.39, P=0.001; Simpson index: F=3.95, P=0.012). During the cervical lesion progress, the ratio of Lactobacillus gradually decreased, the ratio of other anaerobes such as Peptophilus, Sneathia, Prevotella and etc. gradually increased, and the differential bacteria (LDA score >3.5) gradually evolved from Lactobacillus to other anaerobes. The top 10 relative abundance bacteria, spearman correlation coefficient>0.4 and P<0.05 were selected. Co-occurrence network analysis showed that Prevotella, Peptophilus, Porphyrinomonas, Anaerococcus, Sneathia, Atopobium, Gardnerella and Streptococcus were positively correlated in different stages of cervical lesions, while Lactobacillus was negatively correlated with the above anaerobes. It was found that the relationship between vaginal floras in CIN 1 group was the most complex and only Peptophilus was significantly negatively correlated with Lactobacillus in SCC group. Conclusions: The increased diversity and changed correlations between vaginal floras are closely related to cervical lesions. Peptophilus is of great significance in the diagnosis, prediction and early warning of cervical carcinogenesis.

Advances in liquid-phase microextraction technology and its application in biological sample pretreatment / 药学学报

Liquid-phase microextraction is a novel pretreatment technique for biological samples developed on the basis of liquid-phase extraction technology, which is simple, rapid, economical, and environmentally friendly, and has been widely used in the analysis of biological matrix samples such as blood, urine, and saliva. In this paper, we review the basic principles of the main modes of liquid-phase microextraction techniques, i.e., single-drop microextraction, dispersive liquid-liquid microextraction, and hollow-fiber liquid-phase microextraction, and the progress of their applications in biological sample pretreatment by reviewing the literature in the past five years, with a view to providing technical support and reference for sample pretreatment in the fields of in vivo drug analysis, pharmacokinetic studies and new drug development.

Clinical Significance of High Expression of Endoplasmic Reticulum Stress-related Proteins Glucose-regulating Protein 78 and X-box Binding Protein 1 induced by Fusobacterium Nucleatum in Esophageal Squamous Cell Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo analyze the induction effect of Fusobacterium nucleatum （Fn） on endoplasmic reticulum stress-related proteins Glucose-regulating protein 78（GRP78） and X-box binding protein 1（XBP1） in esophageal squamous cell carcinoma （ESCC）， and to explore its potential mechanism and clinical significance. MethodsESCC cells KYSE150 and KYSE140 were infected with Fn for 12 h， 24 h and 48 h. The oxidative stress indexes （ROS， MDA and SOD） and the expression of GRP78 and XBP1 in each group were detected by oxidative stress index kit and Western blot. The experiment was divided into Fn groups， Fn+siNC1 groups， Fn+siGRP78 groups， Fn+siNC2 groups and Fn+siXBP1 groups； the oxidative stress indexes， paclitaxel （PTX） response efficacy， abilities of proliferation， invasion and metastasis in each group were compared. The infection of Fn and the expression of GRP78 and XBP1 in 234 ESCC and paracancerous tissues were detected by RNA scope and immunohistochemistry. The correlation between each factor and clinicopathological characteristics of patients was analyzed by Chi-square test. The influence of each factor on the survival of patients was compared by Kaplan-meier survival estimate. ResultsCompared with Fn uninfected KYSE150 and KYSE140 cells， the content of ROS and MDA was gradually increased， the activity of SOD was gradually decreased， and the expression of GRP78 and XBP1 was gradually increased in Fn infected groups （12 h， 24 h and 48 h） （P < 0.05）. Compared with Fn groups， Fn+siNC1 groups， and Fn+siNC2 groups， ROS and MDA contents were decreased， SOD activity was increased， PTX response efficacy was enhanced， and abilities of proliferation， invasion and metastasis were decreased in Fn+siGRP78 and Fn+siXBP1 groups （P < 0.05）. The rates of Fn， GRP78 and XBP1 in ESCC tissues were 43.16%， 69.66% and 60.68%， respectively. And the three indexes were significantly consistent （P < 0.05）. The patients with positive Fn infection and high expression of GRP78 and XBP1 were mostly males with a history of smoking and drinking， and the tumor differentiation degree was low， the invasion degree was deep， the lymph node metastasis rate was high， and the clinical stage was mostly stage Ⅲ/Ⅳ. The 5-year survival time of patients with above positive indexes was shortened （P < 0.05）. ConclusionsFn could induce endoplasmic reticulum stress by inducing the high expression of GRP78 and XBP1， and promote the malignant evolution of ESCC.

High-intensity laser therapy combined with targeted hand function training for the treatment of grade 1-2 thumb carpometacarpal osteoarthritis / 中国骨伤

OBJECTIVE@#To explore clinical effect of high-intensity laser therapy(HILT) combined with targeted hand function training on pain and lateral pinch force in grade 1-2 thumb carpometacarpal(CMC) osteoarthritis(OA).@*METHODS@#From April 2020 and April 2022, 42 female patients with thumb CMC OA grade 1 to 2, aged from 58 to 80 years old with an everage of (68.90±7.58) years old were divided into observation group of 21 patients who received HILT and targeted hand function training for 4 weeks, and 21 patients in control group who received ultrashort wave therapy combined with using of an orthosis for 4 weeks. Visual analogue scale(VAS) was applied to evaluate degree of pain, function of finger was evaluated by dynamometer to measure lateral pinch force at baseline, immediately following intervention at 4 and 12 weeks following intervention.@*RESULTS@#VAS and lateral pinch force at immediately and 12 weeks after intervention betwwen two groups were better than that of before intervention(P<0.05). Compared with control group, the degree of pain in observation group improved more(immediately after intervention t=3.37, P<0.05, 12 weeks after intervention t=9.05, P<0.05), lateral pinch force higher than that of control group (immediately after intervention t=-2.55, P<0.05, 12 weeks after intervention t=9.51, P<0.05).@*CONCLUSION@#High-intensity laser therapy combined with targeted hand function training is more effective than traditional methods in improving pain and lateral pinch force in grade 1-2 thumb carpometacarpal osteoarthritis.

Aucubin combined with ADSCs-exos protects TBHP-induced nucleus pulposus cells via TLR4/NF-κB pathway / 中国中药杂志

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-β-galactosidase(SA-β-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1β(IL-1β), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1β and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1β and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.

Research trends and hot spots of Chuanxiong Rhizoma from 2010 to 2023 / 中国中药杂志

This study aims to objectively and quantitatively analyze the research status and hot spots of Chuanxiong Rhizoma and provide guidance for further research and clinical application of this herbal medicine. Firstly, the research articles involving Chuanxiong Rhizoma from 2010 to 2023 were retrieved from seven databases including Web of Science, PubMed, Medline, CNKI, VIP, Wanfang, and SinoMed. Then, NoteExpress and manual reading were employed to complete the de-duplication and screening of the articles, and the annual number of publications and journals was analyzed. Finally, CiteSpace was used for systematic analysis of the research institutions, authors, and keywords, and the corresponding knowledge maps were established. After screening, 1 137 articles in Chinese and 433 articles in English were included, and the annual number of publications showed an increasing trend. Chinese Journal of Experimental Traditional Medical Formulae and Journal of Ethnopharmacology were the top Chinese and English journal in the number of publications. Chengdu University of Traditional Chinese Medicine and Nanjing University of Chinese Medicine published the most articles in Chinese and English, respectively. PENG Cheng and FENG Yi were the authors published more articles in Chinese and English. Ferulic acid, signaling pathway, mechanism, headache, ligustrazine, and apoptosis were frequent keywords. A total of 20 clusters and 30 bursts were generated. The comprehensive analysis showed that the research trends and hot spots in this field mainly focused on pharmacological components and isolation, pharmacological effects and mechanism, clinical application and efficacy, compatibility and efficacy of drug pairs, quality evaluation and control, and cultivation and germplasm improvement.

Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

Pharmacokinetic study about compatibility of Eucommia ulmoides and Psoralea corylifolia / 中草药·英文版

OBJECTIVE@#The compatibility of Eucommia ulmoides (Eu) and Psoralea corylifolia (Pc) on the pharmacokinetic (PK) properties in the rat was explored in this study.@*METHODS@#Eu extract, Pc extract and the combined extracts (crude drug ratio was 2:1) was administered by gavage, respectively. Two PK experiments were conducted. In first one, the blood samples were collected via the occuli chorioideae vein to get the PK properties of the components. In second one, the blood samples were simultaneously collected via the internal jugular vein or portal vein at different time points and the concentrations of target ingredients were detected by LC/MS/MS to clear the location where the interaction of Eu and Pc took place in vivo.@*RESULTS@#Eight of 11 ingredients in Eu and Pc extract were determined in rat plasma. The exposure levels of geniposidic acid (GPA), aucubin (AU), geniposide (GP), pinoresinol diglucoside (PDG), psoralen glycosides (PLG) and isopsoralen glycosides (IPLG) were decreased 1/5-2/3 after administration of combined extracts. Comparing to the combined administration, the exposure of GPA and AU in plasma of single Eu administration collected via the portal vein were decreased 1/3-2/3, and the values of AUC0-24h and AUC0-∞ of GP collected from the portal vein or internal jugular vein were double increased. The other components' parameters were not significantly changed.@*CONCLUSION@#In summary, the Pc and Eu combined administration could affect the exposure of the main components of Eu extract in rats due to the changed intestinal absorption. The research on the compatibility of Pc and Eu was helpful to guide the clinical administration of Eu and Pc simultaneously.

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.

Screening of traditional Chinese medicine-derived snail control drug targets based on network pharmacology / 中国血吸虫病防治杂志

Objective To screen the targets of traditional Chinese medicine-derived potential plant molluscicides based on network pharmacology and explore the mechanisms of molluscicidal actions. Methods The traditional Chinese medicines with molluscicidal actions were screened based on retrospective literature reviews, and their molluscicidal efficiency was summarized. The active ingredients and potential targets of traditional Chinese medicines were captured from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Unified Protein Database and literature mining using network pharmacology. The drug-active ingredient-target network was created using the software Cytoscape 3.7.2, and the key targets were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using the Metascape software. Results A total of 27 types of snail control drugs derived from traditional Chinese medicines were screened from publications and classified into 14 categories. Network pharmacology identified 190 active ingredients, and the active ingredients with a high degree in the drug-active ingredient-target network included quercetin, linoleyl acetate, luteolin, beta-carotene, (24S)-ethylcholesta-5,22,25-trans-3beta-ol, fumarine and arctiin, with 181 corresponding potential targets screened. KEGG pathway enrichment analysis revealed that these targets were mainly located in 16 pathways, including the neuroactive ligand-receptor interactions, regulation of adipocyte lipolysis and adrenergic signal in myocardial cells. Conclusions This study preliminarily demonstrates the multi-ingredient, multi-target and multi-pathway mechanisms of action of 27 molluscicides. The screened key ingredient may provide the basis for isolation, purification and pharmacological studies of molluscicides, and the screened key targets and key pathways may facilitate the illustration of mechanisms of actions of traditional Chinese medicine-derived molluscicides and development of novel green molluscicides.

Expression of β-site amyloid precursor protein cleaving enzyme 1 in rat superior cervical ganglion tissues / 解剖学报

Objective To observe the expression and localization of β-site amyloid precursor protein cleaving enzyme 1 (BACEl) in rat superior cervical ganglion and the effect of chronic intermittent frypoxia (CIH) on BACEl level. Methods The expression and distribution of BACEl in superior cervical ganglion were detected by RT-PCR, Western blotting and immunohistochemistry. Totally 16 male SD rats were randomly divided into control group and CIH group, 8 rats in each group. After 2 weeks of modeling, the effect of CIH on BACEl and peroxisome proliferators activated receptor gamma coactivator 1 alpha (PGC-la) mRNA level was detected by RT-PCR. Results BACEl was expressed in rat superior cervical ganglion, and mainly distributed in satellite glial cells and nerve fibers, but not in blood vessels, neurons and small intesely fluorecent(SIF) cells. CIH down-regulated BACEl mRNA level, but up-regulated PGC-la mRNA level ( P < 0.01). Conclusion BACEl is located in satellite glial cells and nerve fibers in the superior cervical ganglion of rats. The decreased level of BACEl ma)' be involved in the regulation of CIH-induced synaptic plasticity of superior cervical ganglion.

Paeonol inhibits rheumatoid arthritis through formyl peptide receptors / 中国药理学通报

Aim To investigate the pharmacological effects of paeonol as a formyl peptide receptor activator on rheumatoid arthritis (HA).Methods The target rlataset was obtained from the high throughput Gene Expression Database ( GEO) , and multiple data sets were combined by USING R language to explore three groups of macrophage differentially expressed genes ( DEGs) in untreated,lipopolysaccharide (LPS) treat¬ment and paeonol and LPS treatment, and their enrich-ment pathway was analyzed.Protein-protein interaction (PPI) networks were constructed in the STRING data¬base anrl visualized in Cytoscape software.The inhibi¬tor}' effect of Hub gene formyl peptide receptor ( FPR) on RA inflammation was validated by TNF-cx stimula¬tion of fibroblast synovial cells ( FLS).Results Through bioinformatics analysis, 169 differential genes ( DEGs) related to inflammation and 275 DEGs related to the mechanism of paeonol action were obtained.Combined analysis of the two groups of DEGs showed that FPR played a key role in the anti-inflammatory mechanism of paeonol.Further studies on the mecha¬nism of paeonol showed that paeonol activated FPR, and the inhibitory effect of paeonol on FLS inflamma¬tion was rescued by TRP-ARg-TRP-TRP-TRP-TRP- TRP-TRP-NH2 (WRW4).Conclusion Paeonol can inhibit the inflammatory development of RA through the FPR pathway.

Berberine alleviates programmed necrosis of metabolic-associated fatty liver disease via activating Nrf2 pathway in mice / 中华肝脏病杂志

Objective: To investigate the effect of berberine on programmed necrosis of hepatocytes induced by metabolic-associated fatty liver disease (MAFLD) in mice and its related molecular mechanism. Methods: Twenty male C57BL/6N mice were randomly divided into four groups (n=5 in each group): control group (S), fatty liver group (H), berberine group(B), nuclear factor erythroid 2-related factor 2 inhibitor group (Nrf2), and all-trans-retinoic acid (ATRA) group (A). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) concentrations were detected at the end of week 12 to calculate fatty liver index (liver mass/body mass ratio). Liver tissue was stained with HE, Masson and Oil Red O, and SAF score was used to evaluate the degree of liver injury. The expression levels of hepatic programmed necrosis-related proteins, namely receptor-interacting protein kinase 3 (RIPK3), phosphorylated mixed series protease-like domain (p-MLKL) and Nrf2 were detected by Western blot method. One-way ANOVA was used for intragroup comparisons and LSD-t tests were used for intergroup comparisons. Results: Compared with S group, H group serum ALT, AST, LDH, TG, TC, TNF-α, IL-1β levels and fatty liver index were significantly increased. The liver tissue was filled with vacuolar-like changes and inflammatory cell infiltration. Numerous red lipid droplets were observed with oil red O staining. Collagen fiber hyperplasia was evident with Masson staining. SAF scores (6.60 ± 0.55 and 0.80 ± 0.45) were significantly increased. The expressions of RIPK3 and p-MLKL were up-regulated. Nrf2 level was relatively increased, and the differences were statistically significant (P < 0.05). Compared with H group, berberine intervention group liver biochemical indexes, lipid levels, pro-inflammatory mediator expression, fatty liver index, and SAF score were significantly reduced, and the expression of RIPK3 and p-MLKL were down-regulated, while Nrf2 levels were further increased, and the differences were statistically significant (P<0.05). Compared with B group, treatment with Nrf2 inhibitor had antagonized the protective effect of berberine on fatty liver. Serum ALT, AST, LDH, TG, TC and TNF-α, IL-1β levels, fatty liver index, and SAF scores were significantly increased and the expressions of RIPK3 and p-MLKL were relatively increased, and the differences were statistically significant (P < 0.05). Conclusion: Berberine can significantly improve the metabolic-associated fatty liver disease injury in mice, and its mechanism is related to activation of Nrf2 and inhibition of programmed necrosis of hepatocytes.

Exploration on the reformation of epidemiology teaching mode for postgraduates / 中华流行病学杂志

Objective: To explore the suitable teaching mode of epidemiology for postgraduates, so as to provide techniques for improving and enhancing the teaching quality. Methods: The course was divided into three stages according to the teaching progress, which was, traditional teaching, traditional teaching and case discussion, online learning and case discussion. The test scores in three stages were compared respectively, and the students' willingness to teaching methods was investigated by questionnaire. Results: The scores of 214 students showed an upward trend in three stages, and the differences were statistically significant (P<0.001). Most students paid more attention to the knowledge systematization and important knowledge. Most students proposed that the teaching time between theoretical knowledge and case discussion should be evenly distributed. More students chose Chinese literature related to their major as teaching cases. Most students believed that case discussion improved the skills of self-study and communication. Conclusion: The epidemiology course for postgraduate should integrate the traditional teaching and case discussion, with online learning as a supplementary, and take effective methods to evaluate, so as to improve the teaching quality of postgraduate.

Research on the mechanism of hypoxia promoting the migration of lung adenocarcinoma A549 cells / 中国应用生理学杂志

Objective: To investigate the mechanism that hypoxia promotes the migration of lung adenocarcinoma A549 cells. Methods: A549 cells were cultured and cells that knockdown of acetyl-CoA carboxylase 1 (ACC1) were obtained by transfection with lentivirus, and cells that knockdown of sterol regulatory element-binding proteins-1 (SREBP-1) were obtained by treated with si-RNA. A549 cells were treated with hypoxia combined with hypoxia inducible factor-1α (HIF-1α) inhibitor PX-478 (25 μmol); Hypoxia combined with linoleic acid (LA) (20 μmol) treated A549 cells with ACC1 knockdown, and A549 cells with SREBP-1 knockdown were treated by hypoxia. Transwell migration assay was used to detect cell migration. Western blot was conducted to detect HIF-1α, ACC1 and epithelial mesenchymal transition (EMT) related proteins, Vimentin, E-Cadherin and SREBP-1; Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was performed to detect the changes of ACC1 and SREBP-1 mRNA in A549 cells after hypoxia and HIF-1α inhibitor PX-478 (25 μmol) treatment. Each experiment was repeated three times. Results: Compared with the normoxic control group, hypoxia promoted the migration of A549 cells (P＜0.01), and up-regulated the expressions of ACC1, HIF-1α (all P＜0.01) and SREBP-1 (P＜0.05). PX-478 (25 μmol) inhibited the migration of A549 cells induced by hypoxia and down-regulated the expression of SREBP-1 (all P＜0.05). ACC1 mRNA and SREBP-1 mRNA levels were increased after hypoxia treatment of A549 cells (all P＜0.05). The levels of ACC1 mRNA and SREBP-1 mRNA were decreased after A549 cells treated with hypoxia combined with PX-478 (25 μmol) for 24 h (P＜0.05, P＜0.01). Knockdown of SREBP-1 in A549 cells was obtained by transfection with si-RNA. Transwell migration assay showed the number of cell migration in si-SREBP-1 group was less than that in normoxia control group (P＜0.01). The si-SREBP-1 group and the si-NC group were treated with hypoxia. Compared with the control group, the number of cell migration in the si-SREBP-1 group was decreased (P＜0.01), however, the difference was not statistically significant compared with the normoxia si-SREBP-1 group (P＞0.05). Western blot showed that the expression of ACC1 in the si-SREBP-1 group was lower than that in the control group (P＜0.01). Compared with the control group, the expression of ACC1 was decreased after si-SREBP-1 group treated with hypoxia (P＜0.01). Knockdown of ACC1 inhibited the migration of A549 cells (P＜0.05). After knockdown of ACC1, the migration number of A549 cells under normoxia and 5% O2 conditions had no significant difference (P＞0.05). Application of LA under hypoxia condition rescued ACC1-knockdown induced inhibitory effect on hypoxia-promoted A549 cell migration (P＜0.05). Conclusion: Hypoxia promotes migration of lung adenocarcinoma A549 cells by regulating fatty acid metabolism through HIF-1α/SREBP-1/ACC1 pathway.

Research progress of aquaporins on the ophthalmic diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Aquaporins(AQPs)is a family of transmembrane channins with low activation energy, high selectivity and rapid transport of water molecules, widely expressed in eye tissues. It was found that AQPs has physiological functions in eye tissue including maintaining the internal lens circulation homeostasis, participating in atrial aqueous circulation, mediating retinal signaling and promoting damage repair. Mutations or abnormal function of AQPs can lead to the occurrence of various ophthalmic diseases. If the expression and function of AQPs can be changed by using certain drugs or technical means, it is expected to become a new target for the treatment of ophthalmic diseases in the future.