Rho GTPase activating protein 21-mediated regulation of prostate cancer associated 3 gene in prostate cancer cell

The overexpression of the prostate cancer antigen 3 (PCA3) gene is well-defined as a marker for prostate cancer (PCa) diagnosis. Although widely used in clinical research, PCA3 molecular mechanisms remain unknown. Herein we used phage display technology to identify putative molecules that bind to the promoter region of PCA3 gene and regulate its expression. The most frequent peptide PCA3p1 (80%) was similar to the Rho GTPase activating protein 21 (ARHGAP21) and its binding affinity was confirmed using Phage Bead ELISA. We showed that ARHGAP21 silencing in LNCaP prostate cancer cells decreased PCA3 and androgen receptor (AR) transcriptional levels and increased prune homolog 2 (PRUNE2) coding gene expression, indicating effective involvement of ARHGAP21 in androgen-dependent tumor pathway. Chromatin immunoprecipitation assay confirmed the interaction between PCA3 promoter region and ARHGAP21. This is the first study that described the role of ARHGAP21 in regulating the PCA3 gene under the androgenic pathway, standing out as a new mechanism of gene regulatory control during prostatic oncogenesis.

Stimulation of mouse hematopoietic stem cells by angiogenin and DNA preparations

Immature hematopoietic progenitors are a constant source for renewal of hemocyte populations and the basic component of the tissue and cell repair apparatus. A unique property of these cells of internalizing extracellular double-stranded DNA has been previously shown. The leukostimulatory effect demonstrated in our pioneering studies was considered to be due to the feature of this cell. In the present research, we have analyzed the effects of DNA genome reconstructor preparation (DNAgr), DNAmix, and human recombinant angiogenin on both hematopoietic stem cells and multipotent progenitors. Treatment with bone marrow cells of experimental mice with these preparations stimulates colony formation by hematopoietic stem cells and proliferation of multipotent descendants. The main lineage responsible for this is the granulocyte-macrophage hematopoietic lineage. Using fluorescent microscopy as well as FACS assay, co-localization of primitive c-Kit- and Sca-1-positive progenitors and the TAMRA-labeled double-stranded DNA has been shown. Human recombinant angiogenin was used as a reference agent. Cells with specific markers were quantified in intact bone marrow and colonies grown in the presence of inducers. Quantitative analysis revealed that a total of 14,000 fragment copies of 500 bp, which is 0.2% of the haploid genome, can be delivered into early progenitors. Extracellular double-stranded DNA fragments stimulated the colony formation in early hematopoietic progenitors from the bone marrow, which assumed their effect on cells in G0. The observed number of Sca1+/c-Kit+ cells in colonies testifies to the possibility of both symmetrical and asymmetrical division of the initial hematopoietic stem cell and its progeny.

Finite element analysis of cervical intervertebral discs after removing different ranges of uncinate processes / 解剖学报

Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C

Isolation and structural identification of a potassium ion channel Kv4.1 inhibitor SsTx-P2 from centipede venom / 浙江大学学报·医学版

OBJECTIVES@#To isolate potassium ion channel Kv4.1 inhibitor from centipede venom, and to determine its primary and spatial structure.@*METHODS@#Ion-exchange chromatography and reversed-phase high-performance liquid chromatography were performed to separate and purify peptide components of centipede venom, and their inhibiting effect on Kv4.1 channel was determined by whole-cell patch clamp recording. The molecular weight of isolated peptide Kv4.1 channel inhibitor was identified with MALDI-TOF, its primary sequence was determined by Edman degradation sequencing and two-dimensional mass spectrometry, its patial structure was established based on iterative thread assembly refinement online analysis.@*RESULTS@#A peptide SsTx-P2 was separated from centipede venom with the molecular weight of 6122.8, and its primary sequence consists of 53 amino acid residues, showed as NH2-ELTWDFVRTCCKLFPDKSECTKACATEFTGGDESRLKDVWPRKLRSGDSRLKD-OH. Peptide SsTx-P2 potently inhibited the current of Kv4.1 channel transiently transfected in HEK293 cell, with 1.0 μmol/L SsTx-P2 suppressing 95% current of Kv4.1 channel. Its spatial structure showed that SsTx-P2 shared a conserved helical structure.@*CONCLUSIONS@#The study has isolated a novel peptide SsTx-P2 from centipede venom, which can potently inhibit the potassium ion channel Kv4.1, and its spatial structure displays a certain degree of conservation.

Investigation of the molecular genetic causes of non-syndromic primary ovarian ınsufficiency by next generation sequencing analysis

ABSTRACT Objective: The aim of this study is to investigate the molecular genetic causes of non-syndromic primary ovarian insufficiency (POI) cases with the gene panel based on next generation sequencing analysis and to establish the relationship between genotype and phenotype. Subjects and methods: Twenty three cases aged 14-40 years followed up with POI were included. Patients with a karyotype of 46, XX, primary or secondary amenorrhea before the age of 40, with elevated FSH (>40 IU/mL) and low AMH levels (<0.03 ng/mL) were included in the study. Molecular genetic analyzes were performed by the next generation sequencing analysis method targeted with the TruSightTM Exome panel. Results: Median age of the cases was 17.8 (14.0-24.3) years, and 12 (52%) cases admitted before the age of 18. Fifteen (65%) patients had consanguineous parents. In 2 (8.6%) cases, variants detected were in genes that have been previously proven to cause POI. One was homozygous variant in FIGLA gene and the other was homozygous variant in PSMC3IP gene. Heterozygous variants were detected in PROK2, WDR11 and CHD7 associated with hypogonadotropic hypogonadism, but these variants are insufficient to contribute to the POI phenotype. Conclusion: Genetic panels based on next generation sequencing analysis technologies can be used to determine the molecular genetic diagnosis of POI, which has a highly heterogeneous genetic basis.

Are monocyte-to-HDL and C-reactive protein-to-albumin ratios useful for the diagnosis and follow-up of Takayasu arteritis?

SUMMARY OBJECTIVE: In this study, we aimed to investigate the role of erythrocyte sedimentation rate, C-reactive protein, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio, red blood cell distribution width, mean platelet volume, monocyte/HDL ratio, and C-reactive protein/albumin ratio in the diagnosis and treatment follow-up of active and remission Takayasu arteritis patients compared with healthy control group. METHODS: This is a retrospective case-control study in which 56 Takayasu arteritis patients and 40 age- and sex-matched healthy control were included. The blood values of Takayasu arteritis patients were analyzed during their active period and post-treatment remission periods, after comparing them with the healthy control. Furthermore, all parameters were evaluated by receiver operating characteristic analysis. RESULTS: Erythrocyte sedimentation rate, C-reactive protein, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio, monocyte/HDL ratio, and C-reactive protein/albumin ratio values were significantly higher in active Takayasu arteritis patients compared with healthy control and remission Takayasu arteritis groups. In the receiver operating characteristic analysis performed in active Takayasu arteritis and Takayasu arteritis patients in remission, C-reactive protein had the highest power to indicate disease activity, followed by C-reactive protein/albumin ratio, erythrocyte sedimentation rate, and monocyte/HDL ratio. When Takayasu arteritis in remission was compared with the healthy control, a significant difference was found between erythrocyte sedimentation rate, C-reactive protein, red blood cell distribution width, and C-reactive protein/albumin ratio, while no significant difference was found between monocyte/HDL ratio values. CONCLUSION: C-reactive protein/albumin ratio and red blood cell distribution width can be used in the diagnosis of Takayasu arteritis, and C-reactive protein/albumin ratio, red blood cell distribution width, and monocyte/HDL ratio measurements can be used in the follow-up. As C-reactive protein/albumin ratio is more powerful than C-reactive protein in differentiating the Takayasu arteritis group from the healthy control group, evaluation of C-reactive protein/albumin ratio together with albumin instead of evaluation of C-reactive protein alone when diagnosing the disease may help us to obtain more accurate results in daily practice.

Morphometry of the Middle Cerebral Arteries: A Radio-Anatomical Study Based on Computed Tomography Angiography Findings / Morfometría de las Arterias Cerebrales Medias: Un Estudio Anátomo-Radiológico Basado en los Hallazgos de la Angiografía por Tomografía Computada

SUMMARY: Middle cerebral artery (MCA), which has the largest irrigation area of the arteries that feed the brain, is an important artery whose microanatomy should be well known because of its vascular variation. In pathologies which are known to affect the cerebrovascular system such as type 2 diabetes mellitus (T2DM) and hypertension, morphometric characteristics of MCA gain importance. The aim of this study is to compare the morphometric characteristics of M1 segment of MCA in T2DM and hypertensive patients with those of healthy control group by using computed tomographic angiography (CTA). The study was carried out with retrospective morphometric analysis of CTA images of 200 individuals between 40 and 65 years of age. The individuals were grouped in four as hypertensive patients (group 1), patients with T2DM (group 2), patients with hypertension and T2DM (group 3) and healthy control group (group 4). Length and diameter measurements of M1 segment were performed and recorded by using 3D CTA images. While statistically significant difference was found between bilateral M1 segment diameters of both women and men (p0.05). As a result of the post hoc analysis performed, it was concluded that right and left M1 segment diameter of group 1, group 2 and group 3 was found to be different from group 4 in both sexes (p<0.05). We believe that this study will both be a guide in radio-anatomic assessments to be performed and also increase microanatomic level of information in the surgical treatment of the artery by showing the morphometric changes that occur in M1 segment of MCA in T2DM diseases.

La arteria cerebral media (ACM), que otorga la mayor área de irrigación de las arterias que alimentan el cerebro, es un vaso importante cuya microanatomía debe ser bien conocida por su variación vascular. En patologías que afectan al sistema cerebrovascular, como la diabetes mellitus tipo 2 (DM2) y la hipertensión, las características morfométricas de la ACM cobran importancia. El objetivo de este estudio fue comparar las características morfométricas del segmento M1 de la ACM en pacientes con DM2 e hipertensos con las del grupo control sano mediante el uso de angiografía por tomografía computada (TC). El estudio fue realizado através de análisis morfométrico retrospectivo de imágenes de TC de 200 individuos entre 40 y 65 años de edad. Los individuos fueron divididos en cuatro grupos, como pacientes hipertensos (grupo 1), pacientes con DM2 (grupo 2), pacientes con hipertensión y DM2 (grupo 3) y grupo control sano (grupo 4). Las mediciones de longitud y diámetro del segmento M1 se realizaron y registraron utilizando imágenes 3D TC. Si bien se encontraron diferencias estadísticamente significativas entre los diámetros bilaterales de los segmentos M1 de mujeres y hombres (p0,05). Como resultado del análisis post hoc realizado, se concluyó que el diámetro de los segmentos M1 derecho e izquierdo del grupo 1, grupo 2 y grupo 3 fue diferente del grupo 4 en ambos sexos (p<0.05). Creemos que este estudio será una guía en las evaluaciones anátomo-radiológicas y también mejorará el nivel de información microanatómica en el tratamiento quirúrgico al mostrar los cambios morfométricos que ocurren en el segmento M1 de la ACM en las enfermedades con DM2.

Principles and Practices of Effective Food Safety Risk Communication – Introducing the Asia-Pacific Economic Cooperation Food Safety Risk Communication Framework

This paper describes the principles and practices of effective food safety risk communication developed under the “Asia-Pacific Economic Cooperation Food Safety Risk Communication Framework and Associated Guidelines”. The framework recommends that effective food safety risk communication needs to be centered on the clear goal of protecting consumer health by ensuring transparency and timeliness, and communication on food safety matters should be conducted in a two-way process. It emphasizes the need to provide the public with credible information based on science and evidence and highlights that food safety is a shared responsibility among all stakeholders, including industry, government agencies, media organizations and consumers. It further highlights that food safety risk communication needs to be conducted in a consistent, systematic, inclusive, consultative, and preventative manner. The framework also indicates that effective food safety risk communication needs to pay attention to the backgrounds, experiences, and needs of concerned audiences. It stresses the importance of continuous improvement of the communication system to ensure food safety risk communication to be effective. Focusing on effective communications in response to food safety incidents, emergency or crisis situations, as well as everyday food safety communications, these principles and practical guidelines will help food safety regulators, food industry, food safety educators and other stakeholders improve their communications with target audiences.

Therapeutic Window of Intravenous Immunoglobulin (IVIG) and its correlation with IVIG-resistant in Kawasaki Disease: a retrospective study

Abstract Objective: To investigate the optimal timing of initial intravenous immunoglobulin (IVIG) treatment in Kawasaki disease (KD) patients. Methods: KD patients were classified as the early group (day 1-4), conventional group (day 5-7), conventional group (day 8-10), and late group (after day 10). Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analyses and receiver operating characteristic (ROC) curve analysis. Results: There were no significant differences in IVIG resistance among the 4 groups (p = 0.335). The sensitivity analysis also confirmed no difference in the IVIG resistance between those who started the initial IVIG ≤ day 7 of illness and those who received IVIG >day 7 of illness (p = 0.761). In addition, patients who received IVIG administration more than 7 days from the onset had a higher proportion of coronary artery abnormalities (p = 0.034) and longer length of hospitalization (p = 0.033) than those who started IVIG administration less than 7 days. The optimal cut-off value of initial IVIG administration time for predicting IVIG resistance was >7 days, with a sensitivity of 75.25% and specificity of 82.41%. Conclusions: IVIG therapy within 7 days of illness is found to be more effective for reducing the risk of coronary artery abnormalities than those who received IVIG >day 7 of illness. IVIG treatment within the 7 days of illness seems to be the optimal therapeutic window of IVIG. However, further prospective studies with long-term follow-up are required.

Assessment of Left Ventricular Diastolic Dysfunction in Cases with Liver Cirrhosis

Background: Cirrhosis is a long-term inflammatory process of hepatic tissue condition that mainly affects people aged 50 to 60. This study aims to assess Left ventricular diastolic dysfunction (LVDD) in cases with cirrhotic liver by conventional, tissue Doppler and two-dimensional speckle tracking echocardiography to clarify the correlation between the severity of cirrhotic liver and LVDD. Methods: A prospective case-control research involved 100 adult cases with confirmed HCV and HBV. Cases were divided into 4 equal group: Group A: Child A cases, group B: Child B cases, group C: Child C cases and group D (Controls): healthy non-hepatic subjects of the same age and sex who have normal blood pressure, nonsmoking participants with no further concomitant problems. Results: Number of cases with LVDD had a statistical noticeable increase in Child A, B, and C (p =0.004, <0.001, and <0.001 respectively. LAVi had a statistical noticeable increase in Child C / B (p =0.013 and p =0.014). Conclusion: Left atrial volume index (LAVi) had a statistical noticeable increase in Child C / B in comparison to the controls but E m, E l were statistical noticeable lower in Child C / B. /E had a statistical noticeable increase in Child C group, LVSRe had a statistical noticeable decrease in Child C group but it was insignificantly different across Child A / B/ C and controls and across Child B / C and controls.

Extracellular Expression and Purification of Spider Neurotoxin Hainantoxin-IV in Escherichia coli / 中国生物化学与分子生物学报

The spider neurotoxin hainantoxin-IV(HNTX-IV), which is isolated from the crude venom of the spider Selenocosia hainana, can specifically inhibit the tetrodotoxin-sensitive(TTX-S) sodium channel, and can selectively inhibit Voltage-gated sodium channel(VGSC) Na

Efficacy and safety of allogeneic hematopoietic stem cell transplantation in the treatment of 28 patients with hepatitis-related aplastic anemia / 中华血液学杂志

Objective: To evaluate the efficacy and safety of HLA-haploidentical hematopoietic stem cell transplantation (allo-HSCT) for hepatitis-related aplastic anemia (HRAA) patients. Methods: Retrospective analysis was performed on hepatitis-associated aplastic anemia patients who received haplo-HSCT at our center between January 2012 and June 2022. October 30, 2022 was the final date of follow-up. Results: This study included 28 HRAA patients receiving allo-HSCT, including 18 males (64.3% ) and 10 females (35.7% ), with a median age of 25.5 (9-44) years. About 17 cases of severe aplastic anemia (SAA), 10 cases of very severe aplastic anemia (VSAA), and 1 case of transfusion-dependent aplastic anemia (TD-NSAA) were identified. Among 28 patients, 15 patients received haplo-HSCT, and 13 received MSD-HSCT. The 2-year overall survival (OS) rate, the 2-year failure-free survival (FFS) rate, the 2-year transplant-related mortality (TRM) rate, the 100-day grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) cumulative incidence rate, and the 2-year chronic graft-versus-host disease (cGVHD) cumulative incidence rate were 81.4%, 81.4% (95% CI 10.5% -20.6% ), 14.6% (95% CI 5.7% -34.3% ), 25.0% (95% CI 12.8% -45.4% ), and 4.2% (95% CI 0.6% -25.4% ), respectively. After transplantation, all patients had no significant liver function damage. Compared with the MSD-HSCT group, only the incidence of cytomegaloviremia was significantly higher in the haplo-HSCT group [60.0% (95% CI 35.2% -84.8% ) vs 7.7% (95% CI 0-22.2% ), P=0.004]. No statistically significant difference in the Epstein-Barr virus was found in the 2-year OS, 2-year FFS, 2-year TRM, and 100-day grade Ⅱ-Ⅳ aGVHD cumulative incidence rates and 2-year cGVHD cumulative incidence rate. Conclusion: Allo-HSCT is safe and effective for HRAA, and haplo-HSCT can be used as a safe and effective alternative for newly diagnosed HRAA patients who cannot obtain HLA-matched sibling donors.

Research progress of microparticles in traditional Chinese medicine decoction / 药学学报

Decoction is a classical dosage form of traditional Chinese medicines. In the process of decocting, various complex components produce physical interactions and chemical reactions, among which physical interactions include van der Waals force, hydrogen bond, electrostatic interaction, π-π stacking, etc., and chemical reactions include Maillard reaction, oxidation reaction, hydrolysis reaction, degradation reaction, polymerization reaction, etc. New substances and original ingredients from chemical reactions can be further activated. These effects form the basis of particle formation in the broth. The sizes of the particles in decoctions range from nanoscale to micron scale, mostly composed of polysaccharide, protein matrix, wrapped in water insoluble molecules, can increase the dispersion of insoluble components and the stability of unstable components, as well as reduce the volatile components and toxic components of volatile components, and ultimately achieve the purpose of efficient absorption and toxicity reduction. From the angle of physical change and chemical reaction in the process of decoction, this paper expounds the formation mechanism of particles in decoction, expounds the research method of particles, analyzes the components in particles and the interaction between components, and then explains the pharmacodynamic characteristics of traditional Chinese medicine decoction, which provides the foundation for the modernization of Chinese decoction.

Contamination of common food-borne pathogens in foods sold in Changzhou / 公共卫生与预防医学

Objective To understand the contamination status of common food-borne pathogens in foods sold in Changzhou, and to provide evidence for food safety risk assessment and prevention of food-borne diseases. Methods From 2010 to 2020 , 2 513 samples of 17 types of foods were collected in Changzhou area. The detection of pathogenic bacteria was carried out in accordance with the standard operation procedure specified in the “Workbook for Surveillance on Food Microorganisms and Pathogenic Factors in Jiangsu Province”. Results A total of 260 positive samples of common food-borne pathogens were detected in all 2 513 samples with an overall detection rate of 10.30%. Single factor analysis showed that the detection rate of pathogenic bacteria in non-ready-to-eat samples was higher than that in ready-to-eat samples (χ2=148.875，P =0.000). The detection rate of pathogenic bacteria in bulk samples was higher than that in prepackaged ones (χ2=70.956，P=0.000). There is a difference in the detection rate of food-borne pathogens from different types of sampling sites (χ2=65.017，P=0.000). Logistic regression analysis showed that ready-to-eat food, packaging type, and sampling season were significantly correlated with the detection rate of food-borne pathogens. The detection rate of pathogenic bacteria in samples collected in the third or fourth quarters was higher than that in the first quarter. Conclusion The commercial foods sold in Changzhou have a relatively high level of contamination of food-borne pathogenic bacteria, and they should be fully heated and sterilized before consumption. The relevant departments should strengthen supervision and health education in summer and autumn.

Surveillance of adverse events following immunization with combined attenuated live measles, mumps and rubella vaccines in Huzhou City from 2015 to 2021 / 预防医学

Objective@#To monitor the adverse events following immunization (AEFI) with combined attenuated live measles, mumps and rubella vaccines (MMR) in Huzhou City from 2015 to 2021, so as to provide insights into the implementation of the MMR immunization strategy.@*Methods@#All AEFI caused by MMR immunization in Huzhou City from 2015 to 2021 were captured from the AEFI Monitoring Information Management System of the Immunization Planning System of Chinese Disease Control and Prevention Information System, and the incidence, clinical features and epidemiological features of AEFI were analyzed descriptively.@*Results@#The reported incidence of AEFI caused by MMR immunization appeared a tendency towards a rise in Huzhou City from 2015 to 2021 (χ2trend=124.126, P<0.001). Totally 324 386 doses of MMR vaccines were immunized, and 317 cases with AEFI were reported, with an reported incidence rate of 9.77/104 doses. Following two-dose immunization, the reported incidence of AEFI caused by two-dose MMR immunization was significantly lower than by one-dose immunization (6.01/104 doses vs. 25.43/104 doses; χ2=113.692, P<0.001). The incidence rates of general reactions, abnormal reactions and coincidental events were 6.20/104 doses, 3.42/104 dose and 0.15/104 doses, respectively. Fever and allergic rash were predominant clinical manifestations of AEFI, and no vaccine quality accident, inoculation accident or psychogenic reaction were reported. There were 246 (77.60%) cases with AEFI within 24 hours following vaccination, and among children with AEFI, there were 173 boys (54.57%), and 200 children (63.09%) age ages of less than one year (63.09%). AEFI was reported in each quarter, and 99 cases (31.23%) were reported in the fourth quarter. The largest number of children with AEFI was reported in Wuxing District (78 cases, 24.61%).@*Conclusions@#The safety of MMR vaccination is high in Huzhou City. General reaction is the predominant AEFI, which mainly occurs within 24 hours following vaccination. Two-dose MMR vaccination does not increase the risk of AEFI.

Preparation of Huoluo Xiaoling gel plaster and its transdermal penetration in vitro / 中国中药杂志

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-β-boswellic(KBA), and 3-acetyl-11-keto-β-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.

Effect of Morus alba extract sanggenon C on growth and proliferation of glioblastoma cells / 中国中药杂志

Glioblastoma is the most common primary cranial malignancy, and chemotherapy remains an important tool for its treatment. Sanggenon C(San C), a class of natural flavonoids extracted from Morus plants, is a potential antitumor herbal monomer. In this study, the effect of San C on the growth and proliferation of glioblastoma cells was examined by methyl thiazolyl tetrazolium(MTT) assay and 5-bromodeoxyuridinc(BrdU) labeling assay. The effect of San C on the tumor cell cycle was examined by flow cytometry, and the effect of San C on clone formation and self-renewal ability of tumor cells was examined by soft agar assay. Western blot and bioinformatics analysis were used to investigate the mechanism of the antitumor activity of San C. In the presence of San C, the MTT assay showed that San C significantly inhibited the growth and proliferation of tumor cells in a dose and time-dependent manner. BrdU labeling assay showed that San C significantly attenuated the DNA replication activity in the nucleus of tumor cells. Flow cytometry confirmed that San C blocked the cell cycle of tumor cells in G_0/G_1 phase. The soft agar clone formation assay revealed that San C significantly attenuated the clone formation and self-renewal ability of tumor cells. The gene set enrichment analysis(GSEA) implied that San C inhibited the tumor cell division cycle by affecting the myelocytomatosis viral oncogene(MYC) signaling pathway. Western blot assay revealed that San C inhibited the expression of cyclin through the regulation of the MYC signaling pathway by lysine demethylase 4B(KDM4B), which ultimately inhibited the growth and proliferation of glioblastoma cells and self-renewal. In conclusion, San C exhibits the potential antitumor activity by targeting the KDM4B-MYC axis to inhibit glioblastoma cell growth, proliferation, and self-renewal.

Advances of structure and mechanisms of bromodomain-containing protein 4 and its related research in tumors / 生物工程学报

The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.

Minimally invasive right infra-axillary thoracotomy for transaortic modified Morrow procedure: a series of 60 cases / 中华外科杂志

Objective: To examine the short-term curative effect with minimally invasive right infra-axillary thoracotomy for transaortic modified Morrow procedure. Methods: The clinical data of 60 patients who underwent video-assisted thoracoscopic transaortic modified Morrow procedure from August 2021 to August 2022 at Department of Cardiovascular Surgery, Zhejiang Provincial People's Hospital were retrospectively analyzed. There were 31 males and 29 females, with the age (M (IQR)) of 54.0(22.3) years (range: 15 to 71 years). The echocardiography confirmed the diagnosis of moderate mitral regurgitation in 30 patients, and severe mitral regurgitation in 13 patients. Systolic anterior motion (SAM) was present preoperatively in 54 patients. All 60 patients underwent transaortic modified Morrow procedure through a right infra-axillary thoracotomy using femorofemoral cardiopulmonary bypass. Surgical procedures mainly included transverse aortic incision, exposure of left ventricular outflow tract (LVOT), septal myectomy, and correction of the abnormal mitral valve and subvalvular structures. Results: All 60 patients underwent the programmatic procedures successfully without conversion to full sternotomy. The cardiopulmonary bypass time was (142.0±32.1) minutes (range: 89 to 240 minutes), while the cross-clamp time was (95.0±23.5) minutes (range: 50 to 162 minutes). The patients had a postoperative peak LVOT gradient of 7.0 (5.0) mmHg (range: 0 to 38 mmHg) (1 mmHg=0.133 kPa). A total of 57 patients were extubated on the operating table. The drainage volume in the first 24 h was (175.9±57.0) ml (range: 60 to 327 ml). The length of intensive care unit stay was 21.0 (5.8)h (range: 8 to 120 h) and postoperative hospital stay was 8 (5) days (range: 5 to 19 days). The postoperative septal thickness was 11 (2) mm (range: 8 to 14 mm). All patients had no iatrogenic ventricular septal perforation or postoperative residual SAM. The patients were followed up for 4 (9) months (range: 1 to 15 months), and none of them needed cardiac surgery again due to valve dysfunction or increased peak LVOT gradient during follow-up. Conclusion: Using a video-assisted thoracoscopic transaortic modified Morrow procedure through a right infra-axillary minithoracotomy can provide good visualization of the LVOT and hypertrophic ventricular septum, ensure optimal exposure of the mitral valve in the presence of complex mitral subvalvular structures, so that allows satisfactory short-term surgical results.

Erythropoietin promotes myocardial infarction repair in mice by improving the function of Sca-1+ stem cells / 生理学报

Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures. Erythropoietin (EPO), a glycoprotein cytokine essential to hematopoiesis, has anti-apoptotic and pro-angiogenetic effects. Studies have shown that EPO plays a protective role in cardiomyocytes in cardiovascular diseases, such as cardiac ischemia injury and heart failure. EPO has been demonstrated to protect ischemic myocardium and improve MI repair by promoting the activation of cardiac progenitor cells (CPCs). This study aimed to investigate whether EPO can promote MI repair by enhancing the activity of stem cell antigen 1 positive stem cells (Sca-1+ SCs). Darbepoetin alpha (a long-acting EPO analog, EPOanlg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocyte apoptosis and microvessel density were measured. Lin- Sca-1+ SCs were isolated from neonatal and adult mouse hearts by magnetic sorting technology, and were used to identify the colony forming ability and the effect of EPO, respectively. The results showed that, compared to MI alone, EPOanlg reduced the infarct percentage, cardiomyocyte apoptosis ratio and left ventricular (LV) chamber dilatation, improved cardiac performance, and increased the numbers of coronary microvessels in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin- Sca-1+ SCs likely via the EPO receptor and downstream STAT-5/p38 MAPK signaling pathways. These results suggest that EPO participates in the repair process of MI by activating Sca-1+ SCs.