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1.
World J Psychiatry ; 14(1): 8-14, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38327881

ABSTRACT

Breast cancer (BC)is the most common malignant tumor in women, and the treatment process not only results in physical pain but also significant psychological distress in patients. Psychological intervention (PI) has been recognized as an important approach in treating postoperative psychological disorders in BC patients. It has been proven that PI has a significant therapeutic effect on post-operative psychological disorders, improving patients' negative emotions, enhancing their psychological resilience, and effectively enhancing their quality of life and treatment compliance.

2.
World J Gastrointest Surg ; 16(1): 248-256, 2024 Jan 27.
Article in English | MEDLINE | ID: mdl-38328313

ABSTRACT

BACKGROUND: Intestinal tuberculosis is a chronic disease caused by Mycobacterium tuberculosis that mainly affects the ileum and cecum. Small bowel tuberculosis, characterized by predominant involvement of the small intestine, is an extremely rare condition with highly atypical clinical presentations, making diagnosis even more challenging. CASE SUMMARY: We report three cases of small intestinal tuberculosis, two of the patients presented primarily with abdominal pain, and one presented with gastrointestinal bleeding. All patients underwent blood tests and imaging examinations. Small bowel endoscopy (SBE) revealed that the main lesions in these patients were intestinal stenosis or gastrointestinal bleeding caused by small intestinal ulcers. One patient ultimately underwent surgical treatment. Following a complex diagnostic process and comprehensive analysis, all patients were confirmed to have small intestinal tuberculosis and received standard antituberculosis treatment, leading to an improvement in their condition. CONCLUSION: Patients with SBTs present with nonspecific symptoms such as abdominal pain, weight loss, and occasional gastrointestinal bleeding. Accurate diagnosis requires a thorough evaluation of clinical symptoms and various tests to avoid misdiagnosis and complications.

5.
World J Clin Cases ; 10(31): 11574-11578, 2022 Nov 06.
Article in English | MEDLINE | ID: mdl-36387792

ABSTRACT

BACKGROUND: There is a high annual incidence of acute, nonvariceal upper gastrointestinal bleeding in Chinese adults. Early endoscopic intervention can reduce rates of rebleeding, surgery, and mortality. The metal clip is the most common method for establishing homeostasis; however, it possesses several limitations. In patients with bleeding secondary to large gastric ulcers, the clip will often fail to stop the bleeding. This article highlights the use of an elastic traction ring as a novel hemostatic method for patients with upper gastrointestinal bleeding. CASE SUMMARY: An elderly male presented to the emergency room with complaints of hematemesis and melena. Endoscopic examination revealed an ulcer (Forrest IIa) in the lesser curvature of the gastric antrum. Six tissue clips and one elastic traction ring were inserted into the stomach cavity to suture the ulcer. The patient recovered quickly without postoperative gastrointestinal bleeding. Two months later, the patient's ulcer was significantly healed. CONCLUSION: To our best knowledge, this is the first report to demonstrate the safety and efficacy of elastic traction rings for upper gastrointestinal bleeding. Elastic traction rings should be considered a routine therapeutic modality for patients with upper gastrointestinal bleeds.

6.
World J Clin Cases ; 10(29): 10695-10700, 2022 Oct 16.
Article in English | MEDLINE | ID: mdl-36312467

ABSTRACT

BACKGROUND: Here we report a rare case of submucosal esophageal abscess evolving into intramural submucosal dissection. CASE SUMMARY: An 80-year-old woman was admitted to our emergency department with a chief complaint of dysphagia and fever. Laboratory tests showed mild leukocytosis and elevated C-reactive protein level. Computed tomography showed thickening of the esophageal wall. Upper endoscopy showed a laceration of the esophageal mucosa and a submucosal mass. Spontaneous drainage occurred, and we could see purulent exudate from the crevasse. We closed the laceration with endoscopic clips. The patient did not remember swallowing a foreign body; however, she ate crabs before the symptoms occurred. We prescribed the patient with antibiotic, and the symptoms were gradually relieved. Two months later, upper endoscopy showed that the laceration was healed, and the submucosal abscess disappeared. However, intramural esophageal dissection was formed. We performed endoscopic incision of the septum using dual-knife effectively. CONCLUSION: In conclusion, we are the first to report the case of esophageal submucosal abscess evolving into intramural esophageal dissection. The significance of this case lies in clear presentation of the evolution process between two disorders. In addition, we recommend that endoscopic incision be considered as one of the routine therapeutic modalities of intramural esophageal dissection.

7.
Acta Pharmacol Sin ; 43(2): 387-400, 2022 Feb.
Article in English | MEDLINE | ID: mdl-33864023

ABSTRACT

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovitis and the destruction of small joints. Emerging evidence shows that immunoglobulin D (IgD) stimulation induces T-cell activation, which may contribute to diseases pathogenesis in RA. In this study, we investigated the downstream signaling pathways by which IgD activated T cells as well as the possible role of IgD in the T-B interaction. Peripheral blood mononuclear cells were isolated from peripheral blood of healthy controls and RA patients. We demonstrated that IgD activated T cells through IgD receptor (IgDR)-lymphocyte-specific protein tyrosine kinase (Lck)-zeta-associated protein 70 (ZAP70)/phosphatidylinositol 3-kinase (PI3K)/nuclear factor kappa-B (NF-κB) signaling pathways; IgD-induced CD4+ T cells promoted the proliferation of CD19+ B cells in RA patients. A novel fusion protein IgD-Fc-Ig (composed of human IgD-Fc domain and IgG1 Fc domain, which specifically blocked the IgD-IgDR binding) inhibited the coexpression of IgDR and phosphorylated Lck (p-Lck) and the expression levels of p-Lck, p-ZAP70, p-PI3K on CD4+ T cells, and decreased NF-κB nuclear translocation in Jurkat cells. Meanwhile, IgD-Fc-Ig downregulated the expression levels of CD40L on CD4+ T cells as well as CD40, CD86 on CD19+ B cells in RA patients and healthy controls. It also decreased the expression levels of CD40L on CD4+ T cells and CD40 on CD19+ B cells from spleens of collagen-induced arthritis (CIA) mice and reduced IL-17A level in mouse serum. Moreover, administration of IgD-Fc-Ig (1.625-13 mg/kg, iv, twice a week for 4 weeks) in CIA mice dose-dependently decreased the protein expression levels of CD40, CD40L, and IgD in spleens. IgD-Fc-Ig restrains T-cell activation through inhibiting IgD-IgDR-Lck-ZAP70-PI3K-NF-κB signaling, thus inhibiting B-cell activation. Our data provide experimental evidences for application of IgD-Fc-Ig as a highly selective T cell-targeting treatment for RA.


Subject(s)
Arthritis, Rheumatoid/drug therapy , B-Lymphocytes/drug effects , Immunoglobulin D/therapeutic use , Lymphocyte Activation/drug effects , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism , Receptors, Fc/therapeutic use , Signal Transduction/drug effects , T-Lymphocytes/drug effects , Animals , Coculture Techniques , Flow Cytometry , Humans , Immunoglobulin D/metabolism , Male , Mice , Mice, Inbred DBA , Microscopy, Confocal , Recombinant Proteins
8.
Front Endocrinol (Lausanne) ; 13: 1073164, 2022.
Article in English | MEDLINE | ID: mdl-36686447

ABSTRACT

Background: Physicians need an appropriate embryo transfer strategy to address the challenge of reducing multiple birth rates, while maintaining the couples' live birth rate during assisted reproductive technology. Methods: We included 10,060 frozen embryo transfer cycles from January 2015 to March 2020 in reproductive medical center of Ruijin hospital, Shanghai, China. Patients were grouped according to the number and grade of cleavage-stage embryo or blastocysts transferred. Live birth rate and multiple live birth rate were compared among groups of women of different ages. Multivariable logistic regression models were used to estimate the risk of multiple live birth using different combinations of transferred embryos. Results: The transfer of double good-quality embryos was an independent predictor for multiple birth in women aged <30 years and those aged 36-39 years [<30 years: aOR =1.54 (95% CI: 1.14-2.06, P < 0.01); 36-39 years: aOR =1.84 (95% CI: 1.0-3.4, P < 0.01)]. Further, for women aged <36 years, the transfer of good-quality + poor-quality blastocysts was an independent predictor for multiple birth rate [<30 years: aOR=2.46 (95% CI: 1.45-4.18, P < 0.01); 31-35 years: aOR =4.45 (95% CI: 1.97-10.06, P < 0.01)]. Conclusions: Single-good-quality blastocyst transfer is recommended for women of all ages. When good-quality cleavage embryos are available, the choice of single or double embryo transfer with good- or average-quality embryo should depend on the age of women. Double embryo transfer with the highest possible grade of embryos is recommended for women aged ≥40 years.


Subject(s)
Birth Rate , Live Birth , Pregnancy , Humans , Female , Live Birth/epidemiology , Retrospective Studies , China/epidemiology , Embryo Transfer , Pregnancy, Multiple
9.
Vision Res ; 186: 13-22, 2021 09.
Article in English | MEDLINE | ID: mdl-34004350

ABSTRACT

Cone photoreceptors are the first neurons along the visual pathway that exhibit center-surround antagonistic receptive fields, the basic building blocks for spatial information processing in the visual system. The surround responses in cones are mediated by the horizontal cells (HCs) via multiple feedback synaptic mechanisms. It has been controversial on which mechanisms are responsible for the surround-elicited depolarizing responses in cones (ΔVCone(s)), and whether the surround responses of various types of cones are mediated by the same HC feedback mechanisms. In this report, we studied ΔVCone(s)) of four types of cones in the salamander retina, and found that they are mediated by feedback synapses from A-type, B-type or A- and B-type HCs. ΔVCone(s) are observable in the presence of concomitant center light spots, and surround + center light stimuli of various intensity, size and wavelength differentially activate the feedback synapses from A- and B-type HCs to cones. We found that ΔVCone(s) of the L-cones are mediated by both A- and B-type HCs, those of the P- and S-cones by B-type HCs, and those of the A-cones by the A-type HCs. Moreover, our results suggest that B-type HCs mediate ΔVCone(s) through both GABAergic and GluT-ClC feedback synaptic mechanisms, and A-type HCs mediate ΔVCone(s) via the GluT-ClC feedback mechanism. Feedback synaptic mechanisms that increase calcium influx in cone synaptic terminals play important roles in mediating the antagonistic surround responses in the postsynaptic bipolar cells, but they may not generate enough current to depolarize the cones and significantly contribute to ΔVCone(s).


Subject(s)
Retinal Cone Photoreceptor Cells , Synapses , Feedback , Retina , Visual Pathways
11.
J Exp Clin Cancer Res ; 40(1): 23, 2021 Jan 07.
Article in English | MEDLINE | ID: mdl-33413564

ABSTRACT

BACKGROUND: Alpha actinins (ACTNs) are major cytoskeletal proteins and exhibit many non-muscle functions. Emerging evidence have uncovered the regulatory role of ACTNs in tumorigenesis, however, the expression pattern, biological functions, and underlying mechanism of ACTN1 in hepatocellular carcinoma (HCC) remain largely unexplored. METHODS: Immunohistochemical analysis of a HCC tissue microarray (n = 157) was performed to determine the expression pattern and prognostic value of ACTN1 in HCC. In vitro loss-of-function study in HCC cells were carried out to investigate ACTN1 knockdown on cell proliferation. In vivo subcutaneous xenograft model and intrahepatic transplantation model were generated to decipher the contribution of ACTN1 in the tumor growth of HCC. Gene set enrichment analysis, quantitative real-time PCR, Co-immunoprecipitation, immunofluorescence and western blotting were performed to identify the underlying molecular mechanism. RESULTS: It was found that ACTN1 was significantly upregulated in HCC tissues and closely related to llpha-fetoprotein level, tumor thrombus, tumor size, TNM stage and patient prognoses. Knockdown of ACTN1 suppressed in vitro cell proliferation and in vivo tumor growth of HCC cells. Mechanistically, knockdown of ACTN1 increased Hippo signaling pathway activity and decreased Rho GTPases activities. Mechanistically, ACTN1 could competitively interact with MOB1 and decrease the phosphorylation of LATS1 and YAP. The growth-promoting effect induced by ACTN1 was significantly abrogated by pharmacological inhibition of YAP with verteporfin or super-TDU. CONCLUSIONS: ACTN1 is highly expressed in HCC tissues and acts as a tumor promoter by suppressing Hippo signaling via physical interaction with MOB1. ACTN1 may serve as a potential prognostic marker and therapeutic target for HCC.


Subject(s)
Actinin/metabolism , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Carcinoma, Hepatocellular/pathology , Female , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Signal Transduction
12.
Ying Yong Sheng Tai Xue Bao ; 31(10): 3445-3452, 2020 Oct.
Article in Chinese | MEDLINE | ID: mdl-33314834

ABSTRACT

Two-year field experiments were conducted in 2017-2018 to examine the effects of wheat straw returning and fertilization on soil fertility and enzyme activities, as well as the yield and qua-lity of edible sweetpoato. There were five treatments, including conventional fertilization+zero straw (CK), conventional fertilization+50% straw returning (50%S), zero fertilization+100% straw returning (100%S-F), conventional fertilization+100% straw returning (100%S), conventional fertilization+100% straw retuning+150 kg N·hm-2 (100%S+N). The treatments of straw returning and fertilization significantly increased the contents of available phosphorus (P), hydroly-zable nitrogen (N), total N, and organic matter in soils, and increased the activities of soil catalase, alkaline phosphorylase, urease, and invertase. The storage root yield, single root fresh weight and commodity potato rate were significantly increased under the treatments of straw returning and fertilization. The storage root yield was the lowest under the treatment of 50%S. After two years of straw returning, storage root yield and commodity potato rate were the highest under the treatment of 100%S. In general, the contents of starch and protein in sweetpotato were increased after two years of straw returning and fertilization, but the contents of reducing sugar and soluble sugar were decreased under 100%S and 100%S+N treatments. Our results suggested that straw returning in full quantity was better than straw returning in half quantity. The storage root yield and commodity potato rate was the highest under the combination of full quantity straw returning and conventional fertilization, with the taste of sweetpotato being changed. Thus, the amount of nitrogen fertilizer should be appropriately reduced in actual practice.


Subject(s)
Ipomoea batatas , Soil , Agriculture , Fertilization , Fertilizers , Nitrogen/analysis
13.
Am J Transl Res ; 12(6): 3011-3022, 2020.
Article in English | MEDLINE | ID: mdl-32655826

ABSTRACT

A receptive endometrium is a prerequisite for successful embryo implantation, and about one-third of repeated embryo implantation failure attribute to defective endometrial receptivity. Integrin-linked kinase (ILK), a 59kDa serine/threonine-protein kinase, plays a vital role in multiple cellular processes, including cell proliferation, apoptosis, and invasion. However, its role in endometrial receptivity is still unclear. In the current study, we demonstrated that ILK level was significantly downregulated in the serum of patients with unexplained infertility compared with healthy non-pregnancy. Functionally, ILK knockdown inhibited endometrial epithelial cells (EECs) proliferation and invasion, whereas ILK overexpression promoted endometrial EECs proliferation and invasion. ILK inhibition also repressed the adhesion rate of embryonic cells to EECs. In vivo studies further demonstrated that ILK inhibition suppressed endometrium receptivity formation and embryo implantation potential. Mechanistically, the downregulation of ILK inactivated Wnt/ß-catenin signaling and thus resulted in the downregulation of MMP-3 and MMP-9 expression. Importantly, activation of Wnt/ß-catenin signaling, partially recovered ILK inhibition-caused endometrium receptivity defects, and embryo implantation failure. Considered all the current data, it verified that the low expression of ILK exacerbates endometrial receptivity formation by inactivating Wnt/ß-catenin signaling and decreasing the MMP-3/9 expression and indicated that ILK may be applied as an indicator of endometrial receptivity, and as a diagnostic and therapeutic target for infertility.

14.
Org Lett ; 22(15): 5984-5989, 2020 08 07.
Article in English | MEDLINE | ID: mdl-32705873

ABSTRACT

An efficient, photoredox-catalyst-free radical alkylation of quinoxalin-2(1H)-ones has been described. This reaction utilizes 4-alkyl-1,4-dihydropyridines (R-DHPs) as alkyl radical precursors and acetoxybenziodoxole (BI-OAc) as an electron acceptor to undergo single-electron transfer with photoexcited R-DHPs. The benign conditions allow for good compatibility in the scope of both quinoxalin-2(1H)-ones and R-DHPs. The synthetic value of the protocol was also demonstrated by the successful functionalization of natural products and drug-based complex molecules.

15.
Clin Transl Gastroenterol ; 12(1): e00282, 2020 12 22.
Article in English | MEDLINE | ID: mdl-33395075

ABSTRACT

INTRODUCTION: Conventional gastrointestinal (GI) endoscopy reports written by physicians are time consuming and might have obvious heterogeneity or omissions, impairing the efficiency and multicenter consultation potential. We aimed to develop and validate an image recognition-based structured report generation system (ISRGS) through a multicenter database and to assess its diagnostic performance. METHODS: First, we developed and evaluated an ISRGS combining real-time video capture, site identification, lesion detection, subcharacteristics analysis, and structured report generation. White light and chromoendoscopy images from patients with GI lesions were eligible for study inclusion. A total of 46,987 images from 9 tertiary hospitals were used to train, validate, and multicenter test (6:2:2). Moreover, 5,699 images were prospectively enrolled from Qilu Hospital of Shandong University to further assess the system in a prospective test set. The primary outcome was the diagnosis performance of GI lesions in multicenter and prospective tests. RESULTS: The overall accuracy in identifying early esophageal cancer, early gastric cancer, early colorectal cancer, esophageal varices, reflux esophagitis, Barrett's esophagus, chronic atrophic gastritis, gastric ulcer, colorectal polyp, and ulcerative colitis was 0.8841 (95% confidence interval, 0.8775-0.8904) and 0.8965 (0.8883-0.9041) in multicenter and prospective tests, respectively. The accuracy of cecum and upper GI site identification were 0.9978 (0.9969-0.9984) and 0.8513 (0.8399-0.8620), respectively. The accuracy of staining discrimination was 0.9489 (0.9396-0.9568). The relative error of size measurement was 4.04% (range 0.75%-7.39%). DISCUSSION: ISRGS is a reliable computer-aided endoscopic report generation system that might assist endoscopists working at various hospital levels to generate standardized and accurate endoscopy reports (http://links.lww.com/CTG/A485).


Subject(s)
Endoscopy, Gastrointestinal/methods , Gastrointestinal Diseases/diagnosis , Gastrointestinal Tract/diagnostic imaging , Health Information Exchange , Image Interpretation, Computer-Assisted/methods , China , Databases as Topic , Gastrointestinal Diseases/pathology , Gastrointestinal Tract/pathology , Humans , Prospective Studies , Reproducibility of Results , Retrospective Studies , Video Recording
16.
Chin Herb Med ; 12(3): 273-280, 2020 Jul.
Article in English | MEDLINE | ID: mdl-36119009

ABSTRACT

Objective: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal interstitial lung disease with high mortality. The pivotal role of Th1/Th2 immunological balance in the development and progression of IPF has been demonstrated previously. This study aimed to evaluate the effect of Jinbei Oral Liquid (JBOL) on IPF and its relationship with Th1/Th2 shift. Methods: Rats were divided into six groups: control group, model group (bleomycin), pirfenidone group (positive group, 54 mg/kg, i.g.) and JBOL (5.4, 10.8 and 21.6 mL/kg, i.g.) groups. The rat model was established by an intratracheal instillation of bleomycin (BLM, 5 mg/kg). One day after injection of BLM, pirfenidone or JBOL was given to rats once daily within 28 consecutive days, respectively. Positron emission tomography/computed tomography (PET/CT) was performed on the treated rats. The extent of alveolitis and fibrosis was observed by H&E and Masson trichrome staining. The contents of TGF-ß1, TNF-α, IL-4 and IFN-γ were further quantified by ELISA assay. Results: PET/CT and histopathological evidence showed the ability of JBOL to attenuate bleomycin-induced alveolitis and fibrosis extent, and the alveolitis lesion score was markedly decreased compared with the model group. The increased expression of inflammatory cytokines TGF-ß1 and TNF-α induced by bleomycin was also suppressed by JBOL. The Th1 response was limited by the reduced IFN-γ after BLM administration, and the Th2 response predominated significantly marked by the increased IL-4. JBOL could increase the level of IFN-γ and markedly increased the ratio of IFN-γ/IL-4. Conclusion: These findings suggested that JBOL may attenuate BLM-induced idiopathic pulmonary fibrosis via reducing inflammatory cell infiltration, pro-inflammatory cytokine release and excessive collagen deposition in rats. One of the mechanisms is the reversion of Th1/Th2 shift caused by BLM.

17.
Asian J Androl ; 22(3): 296-301, 2020.
Article in English | MEDLINE | ID: mdl-31339112

ABSTRACT

We aimed to study the association between sperm DNA fragmentation and recurrent pregnancy loss (RPL) in the Chinese population via a retrospective observational study of Chinese couples who had experienced RPL between May 2013 and August 2018. The study population included 461 men from couples with RPL and 411 men from a control group (couples with clinical pregnancy via in vitro fertilization owing to female causes). Routine semen analysis, sperm chromatin analysis, and microscopic (high-power) morphological analysis were performed using semen samples. Semen samples were assessed for volume, sperm count, and motility. The sperm DNA fragmentation index (DFI) was calculated, and the median DFI was obtained. Men were categorized as having normal (37.8%; DFI ≤ 15.0%), moderate (33.6%; 15.0% < DFI < 30.0%), or severe (28.6%; DFI ≥ 30.0%) DNA fragmentation levels. The percentage of men with severe DNA fragmentation was significantly higher in the RPL (42.3%) group than that in the control group (13.1%), whereas the percentage of men with normal levels of DNA fragmentation was significantly lower in the RPL group (22.8%) than that in the control group (54.7%). Subsequent analysis also demonstrated that the sperm DNA fragmentation rate had a moderate reverse correlation with the sperm progressive motility rate (r = -0.47, P < 0.001) and the total motile sperm count (r = -0.31, P < 0.001). We found a positive correlation between RPL and sperm DNA fragmentation. The results suggest that increased sperm DNA damage is associated with RPL.


Subject(s)
Abortion, Habitual/genetics , DNA Fragmentation , Spermatozoa/metabolism , Adult , Case-Control Studies , Chromatin , Flow Cytometry , Humans , Male , Retrospective Studies , Semen Analysis , Sperm Motility
18.
Cell Commun Signal ; 17(1): 99, 2019 08 20.
Article in English | MEDLINE | ID: mdl-31429768

ABSTRACT

BACKGROUND: Excessive estrogen exposure is an important pathogenic factor in uterine endometrial cancer (UEC). Recent studies have reported the metabolic properties can influence the progression of UEC. However, the underlying mechanisms have not been fully elucidated. METHODS: Glutaminase (GLS), MYC and autophagy levels were detected. The biological functions of estrogen-MYC-GLS in UEC cells (UECC) were investigated both in vivo and in vitro. RESULTS: Our study showed that estrogen remarkably increased GLS level through up-regulating c-Myc, and enhanced glutamine (Gln) metabolism in estrogen-sensitive UEC cell (UECC), whereas fulvestrant (an ER inhibitor antagonist) could reverse these effects. Estrogen remarkably promoted cell viability and inhibited autophagy of estrogen sensitive UECC. However, CB-839, a potent selective oral bioavailable inhibitor of both splice variants of GLS, negatively regulated Gln metabolism, and inhibited the effects of Gln and estrogen on UECC's growth and autophagy in vitro and / or in vivo. CONCLUSIONS: CB-839 triggers autophagy and restricts growth of UEC by suppressing ER/Gln metabolism, which provides new insights into the potential value of CB-839 in clinical treatment of estrogen-related UEC.


Subject(s)
Autophagy/drug effects , Endometrial Neoplasms/drug therapy , Estrogens/pharmacology , Glutamine/metabolism , Cell Proliferation/drug effects , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Female , Glutaminase/metabolism , Humans , Signal Transduction/drug effects , Tumor Cells, Cultured
19.
Drug Des Devel Ther ; 13: 1855-1863, 2019.
Article in English | MEDLINE | ID: mdl-31239640

ABSTRACT

Purpose: The two major ovarian-stimulation protocols for in vitro fertilization are gonadotropin-releasing hormone agonist (GnRH-a) protocol or GnRH antagonist (GnRH-ant) protocol; however, comparisons of their relative efficacy remain controversial. Additionally, conflicting data exist regarding their effects on endometrial receptivity. Thus, this study investigated how GnRH-a and GnRH-ant treatments alter the endometrium during the mid-secretory phase. Patients and methods: We compared proteomic profiles across human endometrium tissues of mid-secretory phase from normal control humans (n=5), patients treated with GnRH-a (n=5), and patients treated with GnRH-ant (n=5). Results: We identified 2088 proteins, with 362 that exhibited significantly different expression. Fuzzy c-means clustering (FCM) using the M Fuzz algorithm analysis showed that the same 87 proteins changed significantly in both the GnRH-a and GnRH-ant groups compared with those in the control. Moreover, Gene Ontology (GO) analysis showed that, of these 87, downregulated proteins were associated with energy metabolism and upregulated proteins were linked to cytoskeleton maintenance. Upregulated proteins involved in complement-mediated immunity were present in 151 proteins that exhibited significantly different expression in the GnRH-ant group only. Conclusion: We demonstrated that comparative proteomic analysis is useful for accessing endometrial receptivity, which seemed more strongly impaired by GnRH-ant than GnRH-a treatments. Our findings also revealed that energy metabolism and immunity response may be the key biological mechanisms underlying human endometrial receptivity.


Subject(s)
Endometrium/drug effects , Fallopian Tube Diseases/drug therapy , Gonadotropin-Releasing Hormone , Hormone Antagonists/pharmacology , Proteomics , Adult , Algorithms , Cluster Analysis , Endometrium/pathology , Fallopian Tube Diseases/pathology , Female , Gonadotropin-Releasing Hormone/agonists , Gonadotropin-Releasing Hormone/antagonists & inhibitors , Humans
20.
Gene ; 702: 66-74, 2019 Jun 20.
Article in English | MEDLINE | ID: mdl-30930224

ABSTRACT

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver with high mortality and frequent recurrence. Although various therapies provide potential cure for HCC patients, unfortunately the five-year survival rate of advanced HCC remains dismal. It is critical to explore the pathogenesis of HCC and identify novel biomarkers for early HCC diagnosis. PSMD4 is a major receptor of the 26S proteasome involved in ubiquitindependent and proteasome-mediated protein degradation. In our study, PSMD4 was overexpressed in HCC tissues and cell lines determined by Northern blot, western blot and immunohistochemistry. The silencing of PSMD4 blocked cell proliferation and tumor growth, induced cell apoptosis and inhibited the proteasome activity. Western blot results showed that the knockdown of PSMD4 blocked the expression of cyclooxygenase 2 (COX2), phosphorylated Sarcoma tyrosine kinase (P-SRC) and Bcl-2, but improved the levels of p53 and Bax in HCC, lung cancer, colorectal cancer, breast cancer and endometrial cancer cell lines. Taken together, these findings indicated that the subunit of 26S proteasome PSMD4 exerts as an oncogene in HCC and other cancers via regulating the expression p53, Bcl-2 and Bax. These findings enriched the pathogenesis of HCC, and provided a new biomarker for cancers diagnosis and a new target for cancers therapy.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/metabolism , Proteasome Endopeptidase Complex/physiology , Animals , Apoptosis , Carcinogenesis , Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cell Line , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/enzymology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Mice, Nude , Proteasome Endopeptidase Complex/biosynthesis , Proteasome Endopeptidase Complex/genetics , Proteasome Endopeptidase Complex/metabolism , RNA Interference , RNA-Binding Proteins
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