Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

A glass micropipette vacuum technique of cerebrospinal fluid sampling in C57BL/6 mice / 生理学报

The purpose of this study was to establish a suitable method for extracting cerebrospinal fluid (CSF) from C57BL/6 mice. A patch clamp electrode puller was used to draw a glass micropipette, and a brain stereotaxic device was used to fix the mouse's head at an angle of 135° from the body. Under a stereoscopic microscope, the skin and muscle tissue on the back of the mouse's head were separated, and the dura mater at the cerebellomedullary cistern was exposed. The glass micropipette (with an angle of 20° to 30° from the dura mater) was used to puncture at a point 1 mm inboard of Y-shaped dorsal vertebral artery for CSF sampling. After the first extraction, the glass micropipette was connected with a 1 mL sterile syringe to form a negative pressure device for the second extraction. The results showed that the successful rate of CSF extraction was 83.33% (30/36). Average CSF extraction amount was (7.16 ± 0.43) μL per mouse. In addition, C57BL/6 mice were given intranasally ferric ammonium citrate (FAC) to establish a model of brain iron accumulation, and the CSF extraction technique established in the present study was used for sampling. The results showed that iron content in the CSF from the normal saline control group was not detected, while the iron content in the CSF from FAC-treated group was (76.24 ± 38.53) μmol/L, and the difference was significant. These results suggest that glass micropipette vacuum technique of CSF sampling established in the present study has the advantages of simplicity, high success rate, large extraction volume, and low bleeding rate, and is suitable for the research on C57BL/6 mouse neurological disease models.

Research advances on the role of nuclear factor-erythroid 2-related factor 2 in wound healing / 中华烧伤杂志

Wound healing is one of the common pathophysiological processes in the body. How to improve the condition of wound healing to promote rapid wound healing has always been a hotspot in research. Oxidative stress is one of the important factors affecting wound healing. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a classic antioxidant stress factor as well as a factor with great potential in facilitating wound healing. The activation of Nrf2 can regulate the downstream antioxidant stress elements and play roles of anti-apoptosis and cell homeostasis maintaining, which improves wound healing environment and promotes wound repair. This paper summarized the common agonists and inhibitors of Nrf2 and reviewed the roles of Nrf2 in promoting skin wound healing including diabetic ulcers, radiation injury, and ischemia-reperfusion injury, etc.

Study on related factors and characteristics of multimorbidity of overweight and obesity-related diseases in children in Hunan Province / 中华预防医学杂志

From January 2019 to December 2021, overweight and obese children who visited in health outpatient Center of Hunan Children's Hospital were studied to explore and analyze the rate, related factors and patterns of multimorbidity of overweight and obesity-related diseases in children in Hunan Province. Univariate and multivariate logistic regression models were used to analyze the multimorbidity-related factors of overweight and obesity-related diseases in children. Association rules (apriori algorithm) were used to explore the multimorbidity patterns of overweight and obesity-related diseases in children. A total of 725 overweight and obese children were included in this study. The multimorbidity rate of overweight and obesity-related diseases in children was 46.07% (334/725). Age, waist circumference, the frequency of food consumption such as hamburgers and fries and adding meals before bedtime were multimorbidity-related factors of overweight and obesity-related diseases in children. The multimorbidity associated with nonalcoholic fatty liver disease (NAFLD) was relatively common. The patterns with the top three support degrees were "NAFLD+dyslipidemia","NAFLD+hypertension" and "NAFLD+hyperuricemia". The patterns with the top three confidence and elevation degrees were "Hypertension+dyslipidemia => NAFLD","Hyperuricemia => NAFLD" and "NAFLD+hypertension => dyslipidemia".

Analysis of dyslipidemia management status in atrial fibrillation patients with very high and high risk of atherosclerotic cardiovascular disease / 中华心血管病杂志

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.

Effect of fosinopril on angiotensin converting enzyme 2 and vascular endothelial growth factor in diabetic retinopathy mice / 解剖学报

Objective To explore the protective effect of fosinopril (Fos) on streptozotocin ( STZ) induced diabetic retinopatfry( DR) mice and on the expression of angiotensin converting enzyme 2(ACE2) and vascular endothelial growth factor (VEGF) in DR mice. Methods Totally forty-eight healthy male Kunming mice, thirty-six were randomly selected, and a diabetic mouse model induced by STZ was constructed after 6 weeks of high-fat diet. After the successful establishment of the model, the thirty-six mice were randomly divided into three groups: model group, Fos low concentration ( 5 mg/kg) group, and Fos high concentration ( 10 mg/kg) group. The remaining twelve mice were served as the control group. After 8 weeks administration, the bod)' weight and blood glucose level of mice in each group were determined. The change in the retinal structure was verified by HE staining. The serum level of VEGF was measured by ELISA. The expression of ACE2 in the retina tissue was verified by immunohistochemistry. The expression of ACE2 mRNA in diabetic retinopatlry was analyzed by Real-time PCR. The levels of ACE2 and VEGF protein in diabetic retinopatlry were detected by Western blotting. Results Fos ( 5 mg/kg, 10 mg/kg ) reduced significantly the proliferation of neovascularization in the inner boundaiy layer, down-regulated the expression of VEGF in the serum of diabetic mice and promoted the expression of ACE2 in the retina tissue of diabetic mice. In addition, the effect of the high concentration group of Fos had a stronger effect than the lower concentration group (P<0. 0 5 ) . Conclusion Fos has a protective effect on the retinopatlry of diabetic mice. This protective effect ma)' be mediated through the increased expression of ACE2 and the reduction of VEGF expression.

Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9 / 中西医结合学报

OBJECTIVE@#To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation.@*METHODS@#Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9.@*RESULTS@#EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.@*CONCLUSION@#Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.

Pharmacokinetic effects of metformin hydrochloride, food and alcohol on Ramulus Mori (Sangzhi) alkaloids / 药学学报

Ramulus Mori (Sangzhi) alkaloids (SZ-A) are a group of polyhydroxy alkaloids extracted and isolated from the traditional Chinese medicine mulberry twig, which is mainly used for the treatment of type 2 diabetes mellitus (T2DM). In addition to acting as a glycosidase inhibitor in the small intestine after oral administration, SZ-A can also be absorbed into blood and widely distributed to target organs related to diabetes, exerting multiple pharmacological effects. It is important to elucidate the possible pharmacokinetic influences of SZ-A for its clinical rational applications, such as drug interactions, the effects of food and alcohol on the absorption of SZ-A. However, studies in this area are limited. Therefore, the pharmacokinetic interactions between orally administrated SZ-A (50 mg·kg-1) and metformin hydrochloride (Met, 200 mg·kg-1) in Sprague-Dawley (SD) rats were examined. Then, the effect of food (standard feed) on the pharmacokinetics of SZ-A was investigated using fasting administration of SZ-A (50 mg·kg-1) in rats as a control. Finally, we investigated the pharmacokinetic characteristics of SZ-A (50 mg·kg-1) in different concentrations alcohol solutions using aqueous solution of SZ-A administered to rats as a control to evaluate the effect of alcohol on the bioabsorption of SZ-A. The results showed no significant pharmacokinetic interactions between SZ-A and Met after combination treatment. The standard feed had little effect on the pharmacokinetic profile of SZ-A. Alcohol retarded the absorption of SZ-A, resulting in a significant decrease in the Cmax of SZ-A. The decrease was greater at higher alcohol concentrations; however, no significant difference was observed in the AUC0-t. These results support the clinical rational applications of SZ-A. All animal protocols were approved by the Ethics Committee of Kangtai Medical Laboratory Service Hebei Co., Ltd. (Hebei, China) (No. MDL2022-01-17-1).

Clinical Impact of Drug Adherence of Tyrosine Kinase Inhibitors in Children with Ph-Positive Acute Lymphoblastic Leukemia / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to explore the impact of ABL1–tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients’ prognosis from TKIs intake practices. @*Materials and Methods@#Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated. @*Results@#Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia. @*Conclusion@#TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.

Research Progress on the Mechanism of Tubulin in Megakaryopoiesis and Regulation of Platelet Count--Review / 中国实验血液学杂志

Tubulin affects platelets count through the control of mitosis and the formation of pro-platelets during the maturation of megakaryoblast to platelets. Tubulin is involved in maintaining the integrity of platelet skeleton, and also participates in the change of platelet morphology during platelet activation. Some new anti-tumor drugs targeting cell mitosis are trying to reduce the effect on tubulin in order to reduce the side effect of drugs on platelet formation. In some patients with thrombocytopenia, the variation and polymorphism of the tubulin gene affect the structure of microtubule multimers, which leads to the decrease of platelet formation. This review summarized the latest progresses of tubulin in the regulation of megakaryopoiesis and thrombopoiesis.

Whole exome sequencing and analysis of hypohidrotic ectodermal dysplasia patients / 中华口腔医学杂志

Objective: To detect gene mutation in patients with hypohidrotic ectodermal dysplasia (HED) by using whole exome sequencing, to analyze the pathogenicity of the mutations, and to provide reference for the genetic diagnosis of HED patients. Methods: Peripheral blood genomic DNA was extracted from each of the HED patients and their family members collected in Peking University School and Hospital of Stomatology from August 2016 to August 2021. Whole exome sequencing and sanger sequencing were performed to detect gene mutations. Functions of the rare variants after the database filtering were analyzed by bioinformatics tools. Results: Three reported mutations of ectodysplasin A (EDA) gene (c.2T>C, c.161A>G, c.467G>A) and a mutation of ectodysplasin A receptor (EDAR) gene (c.871G>A) were detected by whole genome sequencing in four HED patients, and were verified by Sanger sequencing in four HED families. The EDAR gene mutation founded in this research was reported in HED patients for the first time. Bioinformatics tools predicted that the mutations of EDA gene detected in this study were highly species conserved and disease-causing. The combined annotation dependent depletion (CADD) scores of EDA gene mutations c.2T>C, c.161A>G and c.467G>A were 22.5, 26.3 and 25.5 respectively, and the genomic evolutionary rate profiling (GERP) scores were 2.16, 2.26 and 2.18 respectively. The EDAR gene mutation c.871G>A detected in this study was species conserved and possibly disease-causing. The CADD and GERP scores of EDAR gene mutation c.871G>A were 22.0 and 1.93 respectively. Conclusions: Three reported mutations of EDA gene and a previously unreported mutation of EDAR gene were detected in four HED families. Different mutations of EDA gene and EDAR gene could make different influence on the protein function and lead to the occurrence of HED.

Mechanism of Xiao Chaihutang in Treatment of Alzheimer's Disease： Based on Network Pharmacology and in vitro Experimental Verification / 中国实验方剂学杂志

ObjectiveTo investigate the potential mechanism of Xiao Chaihutang （XCHT） in the treatment of Alzheimer's disease （AD） based on network pharmacology and bioinformatics. MethodThe active components of XCHT and corresponding targets were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and the differentially expressed genes related to AD were searched from Gene Expression Omnibus （GEO）. Thereby， the common targets of XCHT and AD were yielded， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis of the common targets. The component-target network and protein–protein interaction （PPI） network were constructed. Furthermore， amyloid β-protein （Aβ）1-40 was used to induce AD in PC12 cells and then the AD cells were intervened with XCHT. Afterward， cell viability was detected by Cell Counting Kit-8 （CCK-8） assay and cell morphology was observed based on 4'，6-diamidino-2-phenylindole （DAPI） staining. Cell membrane potential was determined and apoptosis was detected by flow cytometry， and cellular immunofluorescence detects the expression of B-cell lymphoma-2 （Bcl-2）/Bcl-2-related X protein （Bax）. Moreover， immunofluorescence assay was performed. ResultA total of 190 active components and 41 anti-AD targets of XCHT were screened out. The key components included mairin， quercetin， berberine， protoporphyrin， 24-ethylcholest-4-en-3-one， and β-D-ribofuranoside， and the core targets were sigma non-opioid intracellular receptor 1 （SIGMAR1）， checkpoint kinase 1 （CHEK1）， protein tyrosine phosphatase non-receptor type 6 （PTPN6）， protein kinase C（PRKCH）， inhibitor of nuclear factor kappa B kinase subunit beta （IKBKB）， cathepsin D （CTSD）， cysteine aspartate protease-3 （Caspase-3）， Bax， and Bcl-2-like protein 1 （Bcl-2L1）. The anti-AD targets of XCHT were involved in 302 GO terms （P < 0.05）， particularly the regulation of neuronal cell apoptosis， and 73 KEGG pathways （P<0.05）. The major pathways and biological processes included the apoptosis pathway， virus infection pathway， lipid and atherosclerosis pathway， and cancer-related pathways. In the in vitro experiment， the model group demonstrated the decrease in cell survival rate （P<0.05）， increase in apoptosis rate （P<0.05）， and down-regulation of mitochondrial membrane potential and Bcl-2/Bax ratio compared with the blank control. Compared with the model group， XCFT group showed the increase in cell survival rate （P<0.05）， decrease in apoptosis rate （P<0.05）， and up-regulation of mitochondrial membrane potential and Bcl-2/Bax ratio. ConclusionBased on network pharmacology， this study reveals the multi-component， multi-target， and multi-pathway characteristics of XCHT in the treatment of AD， laying a foundation for further research on the material basis and mechanism of this prescription.

Research advances on borderline developmental dysplasia of the hip / 中华骨科杂志

BDDH (borderline developmental dysplasia of the hip) or BHD (borderline hip dysplasia) is a disease with more controversies in the following aspects, including definition, diagnosis and interventions. The proportion of radiographic BDDH is 3.5 times that of developmental dysplasia of the hip (DDH) in the asymptomatic general population, and can exceed 40% in specific cohorts including female collegiate athletes. Up till now, researchers have not reached a consensus on its definition. The diagnosis depends largely on personal history, physical examinations and radiographic examination. The interventions, including non-operative approaches, hip arthroscopy and periacetabular osteotomy, are used. Inappropriate treatment may exacerbate symptoms and accelerate hip joint degeneration. Recent studies on BDDH with regard to its definition, diagnosis and interventions were reviewed. Lateral centre-edge angle (LCEA) measured on AP pelvis was crucial but not enough in defining BDDH, for it only reflects lateral coverage of the hip while anterior and posterior coverage may vary dramatically. Given that hips with an LCEA less than 20 degrees associated with developing osteoarthritis, we recommended that LCEA between 20 to 25 degrees be used as the radiographic criterion in the primary screening. Further evaluation of symptoms and physical examinations should be follow to identify hip instability and/or impingement. Periacetabular osteotomy must be indicated for hips with predominant instability and it can be performed with or without hip arthroscopy which is aimed to address labral lesion or cam deformity on the femoral side. Hip arthroscopy is indicated for hip with predominant impingement symptoms. However, there is no consensus on the outcomes of the two procedures currently. Further studies are still required to confirm long-term results. Thus, it is imperative to choose the right indications for each procedure.

Ancient DNA Damage Analysis of Late Quaternary Mammalian Fossil Samples in Northeast China / 中国生物化学与分子生物学报

The advancement of the next generation sequencing (NGS) technology has promoted the development of ancient DNA research. Ancient DNA has made outstanding contributions in various fields such as human origin, animal evolution, etc. How to effectively extract and mine the genetic information from fossil and sub-fossil remains excavated from specific locations is a prerequisite for optimizing their important roles in many fields. In this study, we correlated the two main indicators of DNA damage (terminal base replacement rate, average fragment length) with the possible factors such as the burial time, geological epochs, tissue types, and sequencing library construction methods. The results show that the end base replacement rate of ancient DNA from Northeastern China is positively correlated with the water content of the environment and the ages of the samples. Among samples of different geological epochs, ancient DNA end base replacement rates have significant differences. On the contrary, different tissue types of the remains have no significant effects on the end base replacement rate of ancient DNA. The average fragment size of the molecules has no obvious correlation with the factors mentioned above. The results provide both solid data for investigating the characteristics of ancient DNA from specimens collected in Northeastern China, and valuable information for collecting appropriate samples from different geographical locations and the downstream storage before wet lab procedures after excavation.

Dajianzhong decoction in treating visceral pain of irritable bowel syndrome based on ERK 1/2/nuclear factor kB signal pathway / 解剖学报

Objective To investigate whether Dajianzhong decoction can treat visceral pain of irritable bowel syndrome (IBS) by interfering with ERK1/2/nuclear factor kB (NF-kB) pathway and its downstream molecules.Methods The IBS visceral pain rat model was prepared by method such as mother-infant separation, acetic acid enema, and intraperitoneal injection of chicken ovalbumin. Rats were randomly divided into normal control group (normal saline), model group (normal saline), Dajianzhong decoction (10.8 g/kg) treatment group, and the control group of pinaverium bromide (45 mg/kg). Eight rats in each group were given intragastrically for 14 days. To evaluate the visceral sensitivity of rats, abdominal withdrawal reaction (AWR) was used ; the expression of ERK1/2 mRNA, NF-kB mRNA, cyclooxygenase-2 (COX-2)mRNA, and matrix metalloproteinase 9 (MMP-9) mRNA in colon tissue of rats in each group were detected by Real-time PCR; Immunohistochemistry staining method was used to detect the expression of NF-kB and COX-2 in the colon tissue of each group. Results Compared with the normal rats, AWR scores of model rats increased significantly at 60, 40 and 20 mmHg pressure (P0.05). Conclusion Dajianzhong decoction can play a role in treating visceral pain of irritable bowel syndrome ( IBS) by interfering ERK1/2/NF-kB pathway and its downstream molecules..

MicroRNA-128-3p inhibiting epithelial-mesenchymal transition of ovarian cancer cells by regulating zince finger E-bonx binding homeobox 1 / 解剖学报

Objective To investigate the effect of mircoRNA-128-3p (miR-128-3p) on epithelial-mesencfrymal transition (EMT) of ovarian cancer cells and its regulatory mechanism on zinc finger E-box binding homobox 1(ZEB1). Methods Real-time PCR technology was used to detect the expression of miR-128-3p in epithelial ovarian cancer tissue (EOC) and adjacent normal tissue (30 cases each), and to observe whether there was a difference. Two human ovarian cancer cell lines, SK0V3 and A2780, were selected and transfected respectively. MiR-128-3p mimic (miR-128-3p mimic group) and negative control mimic (NC mimic group) were used to detect the expression of miR-128-3p in 4 groups by Real-time PCR to verify the interference effect. Transwell assay was used. The migration and invasion abilities of the four groups of cells were observed. The regulatory relationship between miR-128-3p and ZEBl was verified by dual luciferase assay, and the expression level of ZEBl protein after overexpression of miR-128-3p was detected by Western blotting; pcDNA-ZEBl was transfected into SK0V3 and A2780 cell lines to make it overexpression of ZEBl was divided into NC mimic group, miR-128-3p mimic group, and miR-128-3p mimic+pcDNA-ZEBl group. Western blotting was used to detect the EMT-related protein E-cadherin in 6 groups of cells and the expression level of vimentin. Results Real-time PCR result showed that the expression of miR-128-3p in EOC tissues decreased compared with that in adjacent tissues (P < 0. 01); The relative expression of miR-128-3p in the miR-128-3p mimic group was higher than that in the NC mimic group, while the numbers of migrating cells and invasive cells were lower than those in the NC mimic group (P < 0 . 0 1) . The result of dual luciferase experiments showed that miR-128-3p had a negative regulatory effect on ZEBl. In SK0V3 and A2780 cells, the relative expression of ZEBl protein in the miR-128-3p mimic group was lower than that in the NC mimic group, while the relative protein expression of E-cadhein was higher than that in the NC mimic group (P < 0 . 0 1) . The relative protein expression of E-cadhein in the miR-128-3p mimic+pcDNA-ZEBl group was lower than that in the miR-128-3p mimic group (P < 0 . 0 1) . In SKOV3 and A2780 cells, the relative protein expression of vimentin in the miR-128-3p mimic group was lower than that in the NC mimic group, and the relative protein expression of vimentin in the miR-128-3p mimic+pcDNA-ZEBl group was higher than that in the miR-128-3p mimic group (P < 0 . 0 1) . Conclusion The expression of miR-128-3p decreases in epithelial ovarian cancer tissues, which ma)' be due to the regulation of ZEBl to affect the expression of EMT-related proteins and participate in the EMT process of ovarian cancer cells.

Feasibility study on BN rats and RBL-2H3 cells as models of allergic reaction to Yin Zhihuang injection / 中国药理学通报

Aim To explore the establishment of BN rat animal model and RBL-2H3 cell model of allergic reaction to Yinzhihuang injection. Methods ASA test was performed to compare the symptoms and grades of allergic reactions in BN rats and Hartley guinea pigs, and serum IgE and histamine levels were detected. The amount of histamine released from RBL-2H3 cell supernatant was measured after Yinzhihuang injection affected, and the intracellular Ca

Effects of different field processing methods on volatile components of Chuanxiong Rhizoma: an exploration based on headspace gas chromatography-mass spectrometry / 中国中药杂志

The volatile oil of Chuanxiong Rhizoma(CX) is known as an effective fraction. In order to seek a suitable method for processing CX and its decoction pieces, this study selected 16 volatile components as indices to investigate how different processing methods such as washing/without washing, sun-drying, baking, oven-drying and far-infrared drying at different temperatures affected the quality of CX and its decoction pieces(fresh CX was partially dried, cut into pieces, and then dried) by headspace gas chromatography-mass spectrometry(GC-MS), cluster analysis, principal component analysis and comprehensive weighted scoring. The results showed that the rapid washing before processing did not deteriorate the volatile components of CX. Considering the practical condition of production area, oven-drying was believed to be more suitable than sun-drying, baking, and far-infrared drying. The CX decoction pieces with a thickness of 0.3-0.4 cm were recommended to be oven-dried at 50 ℃. The integrated processing(partial drying, cutting into pieces, and drying) did not cause a significant loss of volatile components. For the fresh CX, the oven-drying at 60 ℃ is preferred. The temperature should not exceed 60 ℃, and drying below 60 ℃ will prolong the processing time, which will produce an unfavorable effect on volatile components. This study has provided the scientific evidence for field processing of CX, which is conducive to realizing the normalization and standardization of CX processing in the production area and stabilizing the quality of CX and its decoction pieces.

Interventions for preventing influenza: An overview of Cochrane systematic reviews and a Bayesian network meta-analysis / 中西医结合学报

BACKGROUND@#Influenza places a heavy public health burden in numerous countries every year. In addition to vaccines, there are some interventions that are effective in preventing influenza.@*OBJECTIVE@#This overview of systematic reviews (SRs) aimed to evaluate the efficacy and safety of interventions for influenza prevention.@*SEARCH STRATEGY@#We searched the Cochrane Database of Systematic Reviews, 2020, Issue 1 for relevant Cochrane SRs using the keywords "common cold," "influenza," and "flu."@*INCLUSION CRITERIA@#Cochrane SRs that investigated the prevention of influenza were included. Participants included the general population without influenza or influenza-like symptoms, who were treated with preventative interventions and compared to individuals receiving no treatment or placebo.@*DATA EXTRACTION AND ANALYSIS@#Two reviewers independently screened citations against pre-defined inclusion criteria and extracted data. The methodological quality of these SRs was evaluated using the Assessing the Methodological Quality of Systematic Reviews-II (AMSTAR-II) guidelines. The primary outcome of our analysis was the incidence of influenza, and the secondary outcomes were the incidence of influenza-like illness and hospitalization. In addition to the narrative summary of SR findings, we also pooled data from homogeneous trials among these SRs and produced evidence mapping. We conducted a network meta-analysis to compare the effect across interventions and used the Cochrane approach to grading of recommendations, assessment, development, and evaluation (GRADE) to assess the quality of evidence.@*RESULTS@#Eleven Cochrane SRs were included, covering five medications, eleven vaccinations and four complementary therapies. Among these SRs, 73% scored "high" quality on AMSTAR-II rating. We found that eight interventions, including amantadine, garlic, and six different vaccines, were beneficial for reducing the incidence of influenza compared to placebo, while oseltamivir, zanamivir, Ganmao capsule, Echinacea, and another three types of vaccine were probably beneficial. Ganmao capsule ranked highest for influenza prevention in the network meta-analysis, followed by amantadine, garlic, and vaccines of all types. Monovalent inactivated parenteral vaccine was found to be beneficial in reducing the incidence of influenza-like illness. None of the interventions reduced the hospitalization rate.@*CONCLUSION@#High-quality evidence showed that garlic or vaccine had advantages in preventing influenza, and that vitamin C is not effective. The effect of other interventions needs to be further verified with high-quality evidence.

Orlistat induces ferroptosis-like cell death of lung cancer cells / 医学前沿

Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers, including lung cancer; however, targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need. In this study, we tested the anticancer activity of orlistat, an FDA-approved anti-obesity drug, in human and mouse cancer cells in vitro and in vivo, and we found that orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. In addition, we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2, a molecule regulating the lipid droplet homeostasis, as a novel target of orlistat. Moreover, in a mouse xenograft model, orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control (P < 0.05). Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.