Cystectomy ; Fatal Outcome ; Female ; Glial Fibrillary Acidic Protein ; metabolism ; Granular Cell Tumor ; pathology ; secondary ; surgery ; Humans ; Immunohistochemistry ; Middle Aged ; S100 Proteins ; metabolism ; Urinary Bladder ; chemistry ; pathology ; surgery ; Urinary Bladder Neoplasms ; metabolism ; pathology ; surgery ; Vaginal Neoplasms ; metabolism ; secondary ; surgery

Esophageal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Melanoma ; metabolism ; pathology ; Melanoma-Specific Antigens ; metabolism ; Middle Aged ; S100 Proteins ; metabolism

Oxidative stress is a redox imbalance in the body, which is one of the important factors leading to tissue damage and diseases. The nuclear factor E2-related factor 2 (Nrf2)-Kelch like ECH-associated protein 1 (Keap1) signaling pathway is not only an important defense system against oxidative damage, but also one of the key signaling pathways of the antioxidant capacity. Numerous studies have shown that targeting the Keap1-Nrf2 signaling pathway to activate Nrf2 has become an effective strategy for the treatment of oxidative stress and related diseases. Using small molecules to directly block the Keap1-Nrf2 protein-protein interaction (PPI) is one of the important directions for activating Nrf2 and exerting the cytoprotective effect, which can avoid the potential side effects of covalent modification of Nrf2. On the other hand, the Keap1 is an efficient E3 ubiquitin ligase that has been used in the design of proteolysis targeting chimeras (PROTACs). This review summarizes the research progresses of Keap1-Nrf2 protein interaction inhibitors and degraders based on the Keap1 E3 ubiquitination system in recent years.

Objective To address the neural basis of Chinese idioms processing with different kinds of stimuli using an event-related fMRI design.Methods Sixteen native Chinese speakers were asked to perform a semantic decision task during fMRI scanning.Three kinds of stimuli were used: Real idioms (Real-idiom condition);Literally plausible phrases (Pseudo-idiom condition,the last character of a real idiom was replaced by a character with similar meaning);Literally implausible strings (Non-idiom condition,the last character of a real idiom was replaced by a character with unrelated meaning).Reaction time and correct rate were recorded at the same time.Results The error rate was 2.6%,5.2% and 0.9% (F = 3.51,P0.05 )for real idioms,pseudo-idioms and wrong idioms, respectively.Similar neural network was activated in all of the three conditions.However,the right hippocampus was only activated in the real idiom condition,and significant activations were found in anterior portion of left inferior frontal gyrus (BA47)in real-and pseudo-idiom conditions,but not in non-idiom condition.Conclusion The right hippocampus plays a specific role in the particular wording of the Chinese idioms.And the left anterior inferior frontal gyms (BA47)may be engaged in the semantic processing of Chinese idioms.The results support the notion that there were specific neural bases for Chinese idioms processing.

OBJECTIVETo study the expression of phosphatase and tensin homology deleted on chromosometen ten (PTEN) protein, a tumor suppressor gene in breast cancer and its correlation with p27(kip1) and cyclin D1 expression.

METHODSPTEN protein expression, p27(kip1) and cyclin D1 protein expression were detected by immunohistochemical method in paraffin sections from 61 women with primary breast cancer. PTEN protein expression was compared with clinico-pathologic parameters as related to p27(kip1) and cyclin D1.

RESULTSPTEN, being shown in the cytoplasm, was negative in 6.6% (4/61), reduced in 41.0% (25/61) and positive in 52.5% (32/61) samples. PTEN expression level was correlated with axillary lymph node status, loss of estrogen receptor stain, recurrence and metastasis. On univariate analysis, the disease-free survival rate of patients with higher PTEN expression (> 50% cells stained) was better than those with lower expression (P = 0.0101). However, there was no correlation between p27(kip1), cyclin D1 expression or PTEN expression.

CONCLUSIONPTEN, its lower expression being correlated with poor outcome of breast cancer patients, plays a prominent role in breast cancer. p27(kip1) or cyclin D1 may not be the primary downstream genes of PTEN in breast cancer.

Adult ; Aged ; Breast Neoplasms ; chemistry ; mortality ; pathology ; Cyclin D1 ; analysis ; physiology ; Cyclin-Dependent Kinase Inhibitor p27 ; Female ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins ; analysis ; physiology ; Lymphatic Metastasis ; Middle Aged ; PTEN Phosphohydrolase ; analysis ; physiology ; Prognosis

OBJECTIVETo observe the effect of bear bile powder (BBP) on the STAT3 pathway and its downstream target genes of nude mice hepatocellular carcinoma (HCC) xenograft, and to explore its mechanism for treating HCC.

METHODSThe subcutaneous xenograft model was established using HepG2 cells. When the subcutaneous transplanted tumor was formed, naked mice were randomly divided into two groups, the BBP group and the control group. Mice in the BBP group were administered with BBP by gastrogavage, once daily for 3 consecutive weeks, while mice in the control group were administered with normal saline by gastrogavage, once daily for 3 consecutive weeks. The body weight and the tumor volume were measured once per week. By the end of medication, the tumor weight was weighed and the tumor inhibition ratio calculated. The apoptosis of the tumor tissue was detected by TdT-mediated dUTP nick end labeling (TUNEL). The expression of Bcl2-associated X protein (Bax), B cell lymphoma/eukemina-2 (Bcl-2), cyclin-dependent protein kinase (CDK4), cyclinD1 were detected by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression levels of signal transducers and transcription activators 3 (p-STAT3), proliferating cell nuclear antigen (PCNA), Bax, Bcl-2, CDK4, and cyclinD1 were determined by immunohistochemistry.

RESULTSBBP could inhibit the tumor volume and tumor weight, showing statistical difference when compared with the control group (P < 0.01). Results of TUNEL showed that BBP could significantly induce the apoptosis of hepatoma carcinoma cells. Results of RT-PCR showed that BBP could up-regulate the expression of Bax and down-regulate mRNA expression of Bcl-2, CDK4, and cyclinD1. Immunohistochemical results showed that BBP could up-regulate the expression of Bax and inhibit the protein expression of p-STAT3, PCNA, Bcl-2, CDK4, and cyclinD1.

CONCLUSIONBBP could induce the apoptosis of hepatoma carcinoma cells and inhibit their proliferation by regulating STAT3 pathway.

Animals ; Bile ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Hep G2 Cells ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Ursidae ; Xenograft Model Antitumor Assays ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo observe the anatomic structure of Huantiao (GB 30) visually, to imitate the inserting process of the needle to explore the safty of needle insertion and improve the therapeutic effect of acupuncture in clinic.

METHODSCombined with anatomic structure of acupoint, muscles and other tissues related with Huantiao (GB 30) were interactively segmented in VOXEL-MAN with the computer graphics technology. Nerves and blood vessels were reconstructed by establishing mathematic model, and the needle-inserting animation of Huantiso (GB 30) was obtained by running script file.

RESULTSThe three-dimensional (3-D) visualization of Huantiao (GB 30) on needle-inserting animation was accomplished, the spatial location and expression of Huantiao (GB 30) in the digitized virtual human body were observed, the virtual inserting process was imitated realistically, and the 3-D animation of needle insertion at Huantiao (GB 30) was created.

CONCLUSIONBuilding mathematic model is favorable for expressing the anatomic structure of Huantiao (GB 30) in 3-D space, imitating the process of needle insertion realistically and observing the spatial structure of the point and the around tissues, which can provide a solid foundation for the safety of needle insertion of acupoints and improve therapeutic effect of acupuncture in clinic.

Acupuncture Points ; Acupuncture Therapy ; instrumentation ; Computer Graphics ; Humans ; Imaging, Three-Dimensional

OBJECTIVE: To investigate the detection rate and hematologic phenotype of HKαα thalassemia in south Guangxi, in order to provide reference for the prevention and control of thalassemia and prenatal and postnatal care consultation in this region. METHODS: Gene testing was performed on pre-marital medical examinations, pre-pregnancy eugenic health examinations, prenatal examinations and hospitalized thalassemia-positive persons in south of Guangxi, and the results were analyzed. RESULTS: A total of 183 190 thalassemia patients were included in this study, the age was mainly concentrated in 26-35 years old (101 709 cases, accounting for 55.521%), and 40 HKαα mutations were detected, detection rate was 0.022%, including 5 cases in Nanning, 22 cases in Qinzhou, 2 cases in Fangchenggang, 11 cases in Beihai. A total of 29 ethnic groups were included in the survey, but HKαα gene was observed only in Han nationality (0.0380%) and Zhuang nationality (0.0068%). A total of 8 genotypes carrying HKαα mutations were detected in this study ( HKαα/--^SEA, β^N/ β^N, HKαα/αα, β^-28/ β^N, HKαα/αα, β^-50/ β^N, HKαα/αα, β^CD17/ β^N, HKαα/αα, β^CD27/28/β ^N, HKαα/αα, β^CD41-42/ β^N, HKαα/αα, β^CD71-72/ β^N, and HKαα/αα, β^N/ β^N). Except for most cases with HKαα/αα, β^N/ β^N genotypes with no significant changes in the hematological indexes, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) of other genotypes were decreased, showing microcytic hypochromic performance, mild anemia or no anemia. CONCLUSION HKαα carrier is often misdiagnosed as -α^3.7 carrier, which easily leads to missed diagnosis or misdiagnosis. Therefore, it is necessary to continuously improve the diagnostic level of laboratory testing personnels and genetic counselors to avoid unnecessary interventional puncture operations and birth of children with moderate and severe thalassemia.
Child ; Female ; Pregnancy ; Humans ; Adult ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; China ; Genotype ; Phenotype ; Mutation

OBJECTIVETo evaluate the effect of bear bile powder (BBP) on angiogenesis, and investigate the underlying molecular mechanisms.

METHODSA chick embryo chorioallantoic membrane (CAM) assay was used to evaluate the angiogensis in vivo. Human umbilical vein endothelial cells (HUVECs) were treated with 0, 0.25, 0.5, 0.75, and 1.0 mg/mL of BBP for 24, 48 and 72 h, respectively. The 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to determine the viability of HUVECs. Cell cycle progression of HUVECs was examined by fluorescence-activated cell sorting (FACS) analysis with propidium iodide staining. HUVEC migration was determined by wound healing method. An ECMatrix gel system was used to evaluate the tube formation of HUVECs. The mRNA and protein expression of vascular endothelial growth factor (VEGF)-A in both HUVECs and HepG2 human cells were examined by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay, respectively.

RESULTSCompared with the untreated group, BBP inhibited angiogenesis in vivo in the CAM model (P< 0.01). In addition, treatment with 0.25-1 mg/mL of BBP for 24, 48, or 72 h respectively reduced cell viability by 14%-27%, 29%-69% and 33%-91%, compared with the untreated control cells (P< 0.01). Additionally, BBP inhibited the proliferation of HUVECs via blocking the cell cycle G to S progression, compared with the S phase of untreated cells 48.05%± 5.00%, 0.25-0.75 mg/mL BBP reduced S phase to 40.38%± 5.30%, 36.54± 4.50% and 32.13± 3.50%, respectively (Pglt; 0.05). Moreover, BBP inhibited the migration and tube formation of HUVECs, compared with the tube length of untreated cells 100%± 12%, 0.25-0.75 mg/mL BBP reduced the tube length to 62%± 9%, 43%± 5% and 17%± 3%, respectively (p< 0.01). Furthermore, BBP treatment down-regulated the mRNA and protein expression levels of VEGF-A in both HepG2 cells and HUVECs.

CONCLUSIONBBP could inhibit the angiogenesis by reducing VEGF-A expression, which may, in part, explain its anti-tumor activity.

Animals ; Bile ; chemistry ; Cell Cycle ; Cell Movement ; Cell Proliferation ; Chick Embryo ; Chorioallantoic Membrane ; blood supply ; Gene Expression Regulation ; Hep G2 Cells ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; Neovascularization, Physiologic ; Powders ; RNA, Messenger ; genetics ; metabolism ; Ursidae ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

This paper discusses the application of virtual reality technology in the 3-D visible human body and acupuncture research. Based on the 3-D visible human fused with the localization information and hierarchy of acupoints, the paper analyzes the force against the needle and haptic rendering during the needle manipulation according to the physical properties of different tissues. A haptic model is constructed to demonstrate the force behaviors during acupuncture, and the force will be produced and passed to the manipulator by a force feedback device. It enriches the contents of 3-D visible human project, provides a dynamic simulation instrument for acupuncture teaching, and supplies a platform for acupuncture research.
Acupuncture Therapy ; methods ; China ; Computer Simulation ; Feedback ; Humans ; Imaging, Three-Dimensional ; User-Computer Interface ; Visible Human Projects