Estrogen receptor beta suppresses the androgen receptor oncogenic effects in triple-negative breast cancer / 中华医学杂志(英文版)

BACKGROUND@#Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.@*METHODS@#Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR.@*RESULTS@#Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter -42 bp to -28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial-mesenchymal transition in tumor progression.@*CONCLUSIONS@#This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

Study on the genotype and clinical phenotype of a family with isolated ectopia lentis / 安徽医科大学学报

Objective @#To identify possible associated genetic variants and characterise the clinical presentation of isolated ectopia lentis (IEL) .@*Methods @#Forty - eight members with 5 generations of an IEL family were enrolled in this study. Peripheral blood samples of all members were collected , and clinical manifestations were observed through physical examination and routine ophthalmological examination. Whole⁃exome sequencing (WES) was performed for two patients to identify disease⁃causing variants. The target variants were verified by Sanger sequencing in family members and 200 normal controls. Then , candidate variants were verified using Sanger sequencing in family members and 200 healthy controls. SIFT , PolyPhen and MutationTester were used to predict the protein function. @*Results @#A total of 13 IEL patients in this family which inherited in an autosomal dominant pattern. The mean age at disease onset was 51. 5 years. The main clinical phenotype of this ICE was characterised by ectopia lentis which anterior inclinated to the anterior chamber. As the anterior chamber became shallow , and the angle of the chamber became narrow , and eventually resulted in the secondary glaucoma. A heterozygous missense variantin the fibrillin gene⁃1 (FBN1) gene (c. 3463G > A) was identified by WES , which was present in all patients but was absent in 200 healthy controls. SIFT , PolyPhen and MutationTester predicted that the variant affected protein function.@*Conclusion @#This IEL family is characterized by secondary glaucoma as the first symptom which is caused by ectopia lens with inclination. The c. 3463G > A of FBN1 gene may be the pathogenic mutation leading to IEL in this family.

Comparison between slow and rapid freezing for adrenal gland cryopreservation and xenotransplantation.

The aim of our study was to examine whether slow or rapid cryopreservation of adrenal xenografts affected xenotransplant outcome. Adrenal xenografts were got from newborn piglets (<24 h after birth). Receptor rats were randomly divided into four groups: a bilateral adrenalectomy group, fresh xenotransplantation group, rapid cryopreservation xenotransplantation group, and a slow cryopreservation xenotransplantation group. 30 days after xenotransplantation, the survival rates of rats in the fresh xenotransplantation group, rapid cryopreservation xenotransplantation group and slow cryopreservation xenotransplantation group were 80 %, 60 % and 60 %, respectively, which were significantly higher than 40 % of the bilateral adrenalectomy group. In addition, the survival rate of rats in the slow cryopreservation group was consistently significantly higher than that in the rapid cryopreservation group at 29 days after xenotransplantation. Morphological observation showed that there were a few medulla cells existed in the adrenal glands in the slow cryopreservation group after 30 days of xenotransplantation, but no medulla cells were found in the rapid cryopreservation group. The plasma cortisol level of rats in the fresh xenotransplantation group and the slow xenotransplantation group 30 days after xenotransplantation was significantly higher than that of the rapid cryopreservation group and bilateral adrenalectomy group (P < 0.05). The levels of liver glycogen and cholesterol in the xenotransplantation rats were increased relative to those of the bilateral adrenalectomy rats, and close to normal level. In conclusion, compared with rapidly frozen preserved grafts, slowly frozen preserved grafts not only ensure the structural integrity of adrenal tissues, but also have corresponding physiological functions, which provid a basic research opportunities for the preservation of xenografts and the treatment of adrenal corticosteroid deficiency. Moreover, these findings can provide evidence for xenotransplantation in the treatment of Addison's disease (adrenal cortex hormone deficiency).

Bio-based molecules for biosynthesis of nano-metallic materials / 生物工程学报

Nano-metallic materials are playing an important role in the application of medicine, catalysis, antibacterial and anti-toxin due to their obvious advantages, including nanocrystalline strengthening effect, high photo-absorptivity, high surface energy and single magnetic region performance. In recent years, with the increasing consumption of global petrochemical resources and the aggravation of environmental pollution, nanomaterials based on bio-based molecules have aroused great concern. Bio-based molecules refer to small molecules and macromolecules directly or indirectly derived from biomass. They usually have good biocompatibility, low toxicity, degradability, wide source and low price. Besides, most bio-based molecules have unique physical, chemical properties and physiological activity, such as optical activity, acid/alkali amphoteric property, hydrophilic property and easy coordination with metal ions. Thus, the corresponding nano-materials based on bio-based molecules also have unique functions, such as anti-inflammatory, anti-cancer, anti-oxidation, antiviral fall blood sugar and blood fat etc. In this paper, we give a comprehensive overview of the preparation and application of nano-metallic materials based on bio-based molecules in recent years.

Mechanism of resveratrol in alleviating neuroinflammation after cerebral ischemia reperfusion by inhibiting Toll like receptor 4 signaling pathway / 中华神经医学杂志

Objective To explore the mechanism of resveratrol in alleviating neuroinflammation after cerebral ischemia-reperfusion injury by inhibiting Toll like receptor 4 (TLR4) signaling pathway. MethodsSixty adult male SD rats were randomly divided into sham-operated group, cerebral ischemia-reperfusion injury group, and resveratrol treatment group (n=20). Rat models of transient middle cerebral artery occlusion (MCAO) in the latter two groups were prepared by modified thread embolization method; reperfusion was performed after 2 h of occlusion, and 20 mg/kg normal saline or resveratrol via tail vein injection was given 15 min before model preparation and one min before reperfusion, respectively. At 72 h after MACO, neurological severity scale (NSS) was applied to evaluate the neurological functions of rats. Enzyme linked immunosorbent assay was performed to detect the expressions of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-αand anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor (TGF)-β. Reverse transcription-polymerase chain reaction was performed to detect the mRNA expressions of M1 signature markersIL-1βandCD32and M2 signature markersCD206andArginase-1. Western blotting was used to detect the expressions of TLR4 signaling molecules TLR4, myeloid differentiation protein 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6), IL-1 receptor associated kinase 1 (IRAK1) and nuclear factor (NF)-κB.ResultsAs compared with those in the sham-operated group, rats in the cerebral ischemia-reperfusion injury group had significantly decreased NSS scores, significantly elevated levels of IL-1β, IL-6, TNF-α, IL-4, IL-10, and TGF-βin the damaged brain tissues, significantly elevated mRNA expression levels ofIL-1β,CD32,CD206, andArginase-1, and significantly elevated protein expression levels of TLR4, MyD88, TRAF6, IRAK1 and NF-κB (P<0.05). As compared with rats in the cerebral ischemia-reperfusion injury group, rats in the resveratrol treatment group had significantly decreased NSS scores, significantly decreased levels of IL-1β, IL-6, and TNF-α, significantly elevated levels of IL-4, IL-10, and TGF-βin the damaged brain tissues, significantly deceased mRNA expression levels ofIL-1βandCD32, significantly elevated mRNA expression levels of CD206andArginase-1, and significantly decreased protein expression levels of TLR4, MyD88, TRAF6, IRAK1 and NF-κB (P<0.05).ConclusionResveratrol inhibits microglia M1-type polarization and promotes M2-type polarization after cerebral ischemia reperfusion by inhibiting TLR4 signaling pathway, which further reduces neuroinflammation and neurological deficits.

Effects of different anesthesia methods on cognitive function in elderly patients with intracranial tumors at different time points / 实用肿瘤学杂志

Objective The objective of this study was to observed the effect of target control intravenous (TCI) anesthesia and intravenous inhalational anesthesia in the postoperative cognitive function in elderly patients with intracranial tumor at different time points.Methods Seventy patients were divided into the experimental and control groups according to the different methods of intraoperative anesthesia.The experimental group was selected to treat with propofol combined with remifentanil TCI anesthesia,and the control group was treated with intravenous anesthetics combined with inhalation isoflurance.Recovery time of respiration,time of opening eyes,extuation time,orientation recovery time,OAAS score before and after operation,and cognitive function (MMSE)were observed in two groups.Results They were no differences in the recovery time of respiration,time of opening eyes and extubation time in two groups (P ＞ 0.05).The orientation recovery time in the experimental group was 20.4 ± 5.8 min and 23.2 ± 4.3 min in the control group.They had significantly different between experimental and control groups (P ＜ 0.05).The time of extubation,leaving the operating room and after 1 h of extubation,OAAS point for the experimental group was 3.3 ± 0.5,4.2 ± 0.4,4.6 ± 0.6 min,respectively,and 2.3 ± 0.2,3.3± 0.4,3.9 ± 0.3 in the control group,respectively.They were significantly different between the experimental and control groups(P ＜ 0.05).Prior to treatment,there was no significant difference in MMSE score between the two groups(P ＞0.05).MMSE score was 25.0 ±0.4 and 27.9 ± 1.1 in the experimental group after treatment for 24 h and 48 h,respectively.MMSE score in the control group was 23.2 ±0.9 and 25.8 ± 1.3 after treatment for 24 and 48 h,respectively.There had a significant different from two groups (P ＜ 0.05).Conclusion For elderly patients with intracranial tumor surgery,TCI anesthesia with propofol and remifentanil is stable and awake,and the effect on postoperative cognitive function is relatively small.

Effect of FTY720 on retinal leukocytes adhesion and vascular permeability in diabetic rats / 中华眼底病杂志

Objective To evaluate the effect of FTY720 on retinal leukocytes adhesion and vascular permeability in diabetic retinopathy (DR) model,and explore its mechanism.Methods Ninety male Wister rats were randomly divided into normal control group,diabetic group and FTY720 group,thirty rats in each group.Diabetes was induced by giving a single intraperitoneal injection of streptozocin.FTY720 group was administered with FTY720 at a dose of 0.3 mg/kg by oral gavage daily for 3 months after establishment of diabetes.All rats were used for experiments following intervention for 3 months in FTY720 group.Immunohistochemical staining was used to observe the expression and distribution of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1),and the positive cells were counted.Real-time reverse transcription PCR was used to measure mRNA expression of ICAM-1 and VCAM-1.Fluorescein isothiocyanate-Concanavalin A perfusion was used to detect retinal leukocytes adhesion.Evans blue (EB) perfusion was used to analyze retinal vascular permeability.Immunofluorescence staining was used to detect retinal inflammatory cells infiltration.Results In diabetic group,both ICAM-1(t =12.81) and VCAM-1 (t=11.75) positive cells as well as their mRNA expression (t=16.14,9.59) were increased compared with normal control group,with statistical significance (P＜ 0.05).In FTY720 group,both ICAM-1(t=-9.93) and VCAM-1 (t=-6.61) positive cells as well as their mRNA expression (t=-15.28,-6.10) were decreased compared with diabetic group,with statistical significance (P＜ 0.05).Retinal leukocytes adhesion (t=16.32) and EB permeability (t=17.83) were increased in diabetic group compared with normal control group,while they were decreased in FTY720 group compared with diabetic group(t=-9.93,-11.82),with statistical significance (P＜0.05).There were many CD45 positive leukocytes infiltration in retina of diabetic group,including CD11b positive macrophage/activated microglia,while both of them were little in FTY720 group.Conclusions FTY720 can decrease retinal leukocytes adhesion,reduce retinal vascular permeability and inflammatory cells infiltration,which is associated with down-regulation of ICAM-1 and VCAM-1.

Effects of C3 F8 or silicon oil tamponade on postoperative vitreous hemorrhage and visual prognosis after vitrectomy for proliferative diabetic retinopathy / 中华眼底病杂志

Objective To compare the effects of intravitreal tamponade of C3 F8 with silicon oil on postoperative vitreous hemorrhage and visual prognosis after vitrectomy for proliferative diabetic retinopathy (PDR).Methods The clinical data of 121 patients (127 eyes)who underwent primary vitrectomy due to PDR were analyzed retrospectively.All the patients were divided into two groups according to different intravitreal tamponade, including C3 F8 tamponade group (53 patients with 56 eyes ) and silicone oil tamponade group (68 patients with 71 eyes).There was no difference of gender (χ2 = 0.956 ),age (t =1.122),duratiion of diabetes (t=0.627),fasting blood glucose (t=1.049),systolic pressure (t=1.056), diastolic pressure (t = 0.5 1 7 ), history of hypertension (χ2 = 0.356 ), nephropathy (χ2 = 1.242 ), preoperative laser photocoagulation (χ2 = 1.225 )and All the patients underwent three port pars plana vitrectomy.The mean follow-up was 2 years ranging from 6 months to 4 years.And then the incidence and onset time of postoperative vitreous hemorrhage and postoperative BCVA of the two groups were compared. Results Postoperative vitreous hemorrhage occurred in 14 of 56 eyes (25.00%)in C3 F8 tamponade group. The average onset time of postoperative vitreous hemorrhage were (64.64 ± 59.09)days ranging from 7 -225 days and mostly were within 30-60 days (35.71%,5/14).Postoperative vitreous hemorrhage also occurred in 7 of 71 eyes (9.89%)of silicone oil tamponade group after silicone oil removal with an average onset time of (25.29±20.46)days ranging from 3-65 days and were mostly within 1 5-30 days (42.86%, 3/7).There was a significant difference in the incidence of postoperative vitreous hemorrhage between the two groups (χ2 = 5.200,P <0.05 ).BCVA of the two groups was improved significantly after operation (Z =2.472,3.1 14;P <0.05).Postoperative BCVA of silicone oil tamponade group was poorer than C3 F8 tamponade group (Z =1.968,P <0.05).Conclusion Both C3 F8 and silicone oil tamponade can improve the visual acuity after vitrectomy for PDR.Compared with C3 F8 ,silicone oil tamponade had lower incidence and late onset of postoperative vitreous hemorrhage after vitrectomy for PDR.

Application of NanoString nCounter System in biomedical fields / 国际生物医学工程杂志

NanoString nCounter Analysis System is a newly developed gene expression detection platform that directly measures multiplexed mRNA levels through digital counting of individual mRNA transcripts.This technology uses as little as 100 ng of RNA and can obtain accurate gene quantitative data from up to 800 genes in one reaction.It requires no reverse transcription,enzymes and amplifications,and its sensitivity and accuracy are comparable to real time quantitative PCR.NanoString technology has been more and more extensively used in frontiers of biomedical research and clinics such as in validation of data from high-throughput platforms,gene expression profiling,gene regulatory network,molecular subtyping,diagnosis and prognosis of diseases.

Gene Detection of Helicobacter pylori from Feces of Patients with Digestic System Disease and Its Clinical Value / 中华医院感染学杂志

OBJECTIVE To set up a kind of Helicobacter pylori(Hp) detection method which can determine the Hp infection and its clinical value for the digestive diseases.METHODS Gastric biopsy was used with gastric mucosa Hp rapid urease test,Hp-IgG was detected by ELISA,and Hp-DNA of feces by fluorescent gene quantitation method.RESULTS From the 96 patients positively determined by gastric biopsy,the positive rate of Hp-DNA of feces was 95.8%,but the positive rate of Hp-IgG was 47.9%.From the 59 Hp-IgG positive patients,the positive rate of gastric biopsy was 45.8%.CONCLUSIONS Gastric biopsy and HP-DNA quantitation of feces are both reliable methods which can determine the Hp infection,but Hp-DNA quantitation of feces is a simple,rapid,reliable and atraumatic test,it can be put into practice widely and more easily.

Management of Clinical Teaching Program by the Use of Excel Software / 中华医学教育探索杂志

Excel is electronic form software with strong function in Microsoft office. We utilize Excel software to manage the clinical teaching program. Clinical teaching program can be rapidly filled by way of duplicating, clipping, pasting, packing, arranging in order, and sieving etc. in the software, column numbers of teaching program can be added according to the need. After gathering teaching program of every research group of teaching into the total teaching program, we can conveniently arrange any column in an order and screens, so that the total teaching program was reset and optimized. The function of management of the total teaching program was so expanded that the quality and efficiency of clinical teaching management were raised.