OBJECTIVETo investigate the balance function of the patients with unilateral vestibular hypofunction (UVH) by timed balance tests and static posturography (SPG).

METHODSSixty-five subjects with UVH and 92 healthy subjects were taken the timed balance tests under differential stance including (1) standard Romberg test, (2) feet apart stance test, (3) tandem and (4) unilateral standing tests with eyes open and eyes closed. The average timing that subjects kept balance before falling in each standing conditions was recorded by stopwatch as the timed result. The body sway velocity during the test (1) and (2) were also recorded by the SPG.

RESULTSThe timed results of the tandem and unilateral standing with eyes open and eyes closed in the UVH group were decreased (P < 0.001) compared with the control group. The body sway velocity of the standard Romberg test and foot apart stance with eyes open was not different between the UVH group and control group (P-value was 0.118 and 0.110 for the two tests respectively), and the difference was significant in the eyes closed condition (P < 0.001). For the two groups, the body sway velocity of foot apart standing was decreased than that of the standard Romberg test with eyes open and eyes closed (P < 0.05 or P < 0.001). Significant correlations were not found between the timed results and sway velocity results in both two groups respectively (P > 0.05).

CONCLUSIONSAccording to clinical assessment of balance function in UVH, the tandem and unilateral stance test could provide the additional information about the upright stance to the SPG measurement. The effect of foot position on the results of SPG should been considered in clinic.

Adult ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Neurologic Examination ; Postural Balance ; Vestibular Diseases ; physiopathology

ABSTRACT:OBJECTIVE To investigate the role of connexin proteins (Cx), which form gap junctions (GJ), in progression and chemotherapeutic sensitivity of cervical cancer (CaCx). METHODS We analyze the expression of Cx26, Cx30, Cx32 and Cx43 in human specimens consisting of: Normal cervix (n=78), CaCx FIGO stage Ⅰ (n=148), CaCx FIGO stage Ⅱ (n=165). InCaCx cell lines, Hela- Cx32 (induced expression by doxycycline), C- 33A (endogenously express Cx32) and siHa (transiently transfected plasmid with Cx32), we detected the role of Cx32 against tostreptonigrin/cisplatin-induced apopotosisin presence or absence of functional GJ through using GJ inhibitors or low density cultural.Furtherly, we observed the relativity of Cx32 and EGFR expression in human specimens. Also, we detected the role of EGFR signaling pathway in the process of Cx32 anti-apoptosis through suppressed EGFR expression by inhibitors or siRNA sequences in cell lines. RESULTS We firstly demonstrated the expression of Cx32 was highly upregulated and accumulated in cytoplasm in the CaCx specimens, and the degree of upregulation correlated with advanced FIGO stages. Thus,in three human cervical cell lines, Cx32 was shown to suppress apoptosis when GJ formation is inhibited. No matter in cases of CaCx or cell lines, Cx32 expression was highly correlated with expression of EGFR and the EGFR pathway is an essential component of the Cx32-induced anti-apoptotic effect. CONCLUSION Cx32, traditionally tumor suppressive protein, was shown to be tumor protective against chemotherapy through EGFR pathway in a GJ-independent way.

OBJECTIVETo investigate the effects of two histone deacetylase (HDAC) inhibitors, valproic acid (VPA) and TSA, on the expression of vascular endothelial growth factor (VEGF) and its receptor KDR of the leukemia cell line Kasumi-1 cells, and to explore their potential mechanism in leukemia angiogenesis.

METHODKasumi-1 cells were treated with VPA and TSA at different concentrations for 3 days. The mRNA and protein expression levels of VEGF and KDR were determined by semi-quantitative RT-PCR and Western blot, and the bFGF mRNA by semi-quantitative RT-PCR.

RESULTSAs compared with that of control groups, VPA at 3 mmol/L downregulated the VEGF mRNA expression level for VEGF(121) from 0.632 ± 0.014 to 0.034 ± 0.004 and for VEGF(165) from 0.526 ± 0.021 to 0.015 ± 0.001, for KDR mRNA from 0.258 ± 0.034 to 0.038 ± 0.000, and for bFGF mRNA from 0.228 ± 0.017 to 0.086 ± 0.015. TSA downregulated the VEGF mRNA and KDR mRNA at concentration of 100 nmol/L, but its effect on bFGF mRNA only at higher concentration.

CONCLUSIONHDAC inhibitors might inhibit the leukemia angiogenesis by regulating the expression of VEGF and its recptor.

Angiogenesis Inducing Agents ; Cell Line ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; RNA, Messenger ; genetics ; Valproic Acid ; pharmacology ; Vascular Endothelial Growth Factor A

OBJECTIVETo analyze retrospectively the quantity and activation status of the tumor infiltrating cytotoxic lymphocytes in breast cancer and the draining lymph nodes, and its relation to the clinical pathological significance.

METHODSSeventy-four breast cancer samples with their corresponding axillary lymph nodes were histologically typed and staged. Cytotxic lymphocytes were analyzed by immunohistochemistry with the monoclonal antibodies against CD8, CD56, granzyme B and perforin.

RESULTSThe number of infiltrating CD8(+) T cells in the cancerous interstitial tissue were much higher than that in the tumor parenchyma. Compared with the metastatic tumor samples, the CD8(+) T cells were more intensive in the primary tumors (35.7 +/- 16.0 vs. 23.7 +/- 9.6). The tumor infiltrating CD8(+) T cells of patients with 5 years survivals were more than that of the dead cases in this follow-up series death (32.9 +/- 14.1 vs. 20.1 +/- 9.9). There was no significant difference of activated tumor infiltrating cytotoxic T cell analyzed by using the activation marker granzyme B(+) and there was also no significant correlation between the intensity of CD8(+), CD56(+) cells and the clinicopathological stages. However, percentages of the activated cytotoxic lymphocytes in Stage I groups were significantly higher than those in stage III and IV. Moreover, the number of perforin(+) cells was significantly less than that of granzyme B(+) cells, particularly in the cancerous tissue, indicating a dysfunctional status of tumor infiltrating cytotoxic lymphocytes.

CONCLUSIONSActivated cytotoxic lymphocytes may play a significant role against the tumor progression and is associated with a favorable prognosis to some extent. However, a putative dysfunctional status of cytotoxic lymphocytes at tumor site may compromise the host immunity against cancer.

Adult ; Aged ; Axilla ; Breast Neoplasms ; metabolism ; pathology ; CD56 Antigen ; metabolism ; CD8 Antigens ; metabolism ; Female ; Follow-Up Studies ; Granzymes ; metabolism ; Humans ; Immunohistochemistry ; Lymph Nodes ; metabolism ; pathology ; Lymphatic Metastasis ; Lymphocytes, Tumor-Infiltrating ; metabolism ; pathology ; Middle Aged ; Neoplasm Staging ; Perforin ; metabolism ; Retrospective Studies ; Survival Rate ; T-Lymphocytes, Cytotoxic ; metabolism ; pathology

OBJECTIVETo investigate in vivo inhibitory effect of histone deacetylase (HDAC) inhibitor valproic acid (VPA) on xenografted Kasumi-1 tumor in nude mice and its mechanism.

METHODSXenografted Kasumi-1 tumor mouse model was established by subcutaneous inoculation of Kasumi-1 cells. Xenotransplanted nude mice were assigned into control or VPA treatment groups. Volume of the xenografted tumors was measured and compared between the two groups. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) was applied to detection of tumor cell apoptosis. The gene expression of GM-CSF, HDAC1, Ac-H3 and survivin was studied with semi-quantitative RT-PCR and Western blotting. ChIP method was used to assay the effects of VPA on acetylation of histone H3 within GM-CSF promoter region.

RESULTS(1) VAP significantly inhibited xenografted Kasumi-1 tumor growth. The calculated inhibition rate was 57.25%. (2) Morphologic study showed that VPA induced differentiation and apoptosis of Kasumi-1 tumor cells. The apoptosis index of VAP treatment group [(3.661 +/- 0.768)%] was significantly higher than that of control group [(0.267 +/- 0.110)%]. (3) Comparing to those in control group, the level of nuclear HDAC1 protein was significantly decreased, the Ac-H3 protein expression level was increased, the mRNA and protein expression levels of GM-CSF and acetylation of histone H3 were remarkably increased, and the gene expression level of survivin significantly decreased in VPA treatment group.

CONCLUSIONVAP significantly inhibits xenografted Kasumi-1 tumor growth and induces tumor cell differentiation and apoptosis. The mechanism may be decrease of survivin gene expression, inhibition of nuclear expression of HDAC, promotion of histone protein acetylation level and acetylation of histone H3 within GM-CSF promoter region, and increase of GM-CSF transcription.

Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Mice ; Mice, Nude ; Valproic Acid ; pharmacology ; Xenograft Model Antitumor Assays

OBJECTIVETo compare the immunophenotypic and clinical characteristics between NPM1 mutated acute myeloid leukemia (AML) (NPM1m(+)AML) and unmutated AML(NPM1m(-)AML) not otherwise characterized (NOS) under similar FAB subtypes constituent ratio.

METHODSImmunophenotyping and NPM1 gene mutation type-A, B and D and other leukemic related fusion genes were detected by multiparameter flow cytometry and real time RT-PCR or PCR, respectively. 104 AML patients with NPM1m(+)AML and performed immunophenotyping assay were included, 97 with NPM1m(-)AML.

RESULTSThere were significant difference between the two groups at presentation in terms of sex, white blood count(WBC), platelet counts (PLT), blast ratio, normal karyotype ratio, WT1 expression level, FLT3-ITD mutation positive rate and remission rate of first course of induction therapy (P < 0.05). On the immunophenotype, the expression of early differentiation antigens (CD34, HLA-DR, CD117, CD38), lymphocytic antigens (CD7, CD4, CD19, CD2), myeloid and monocytic differentiation-associated antigens (CD13, CD14, CD15) were lower, and that of CD33 as well as CD123 were higher in NPM1m(+)AML patients. Among them, only CD34, HLA-DR, CD7, and CD4 positive cases were significantly lower in NPM1m(+)AML group than in NPM1m(-)AML group (P < 0.05), the rest of them had significant difference in the number of positive cells (P < 0.05). Above features were further analyzed between the M1/M2 and M4/M5 subgroups. M1/M2 cases retained the women prominent and had a higher WT1 expression level (P < 0.05). The expression of monocytic differentiation-associated antigens including HLA-DR and lymphocytic antigens were higher and that of CD117 were lower in M4/M5 subtype (P < 0.05). Among them, the positive rates of HLA-DR, CD64, CD11b, CD10, CD15, and CD4 were significantly higher in M4/M5 than in M1/M2 in NPM1m(+)AML group (P < 0.05).

CONCLUSIONThe most clinical characteristics in NPM1m(+)AML patients are consistent with reports, but some immunophenotype are different to the previous reports under similar FAB subtypes constituent ratio. The major immunophenotypic features of NPM1m(+)AML patients are lower expression of progenitor, myeloid and lymphoid lineage antigens. Monocytic differentiation-associated antigens are only higher expression in M4/M5 cases when comparison with M1/M2 cases within NPM1m(+)AML group.

Adolescent ; Adult ; Aged ; Antigens, CD ; metabolism ; Child ; Child, Preschool ; Female ; HLA-DR Antigens ; immunology ; Humans ; Immunophenotyping ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; immunology ; Male ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; Young Adult

Three-dimensional ordered porous carbon materials exhibit potential application prospects as excellent drug supports in drug delivery systems due to their high specific surface area, tunable pore structure, and excellent biocompatibility. In this study, three-dimensional ordered porous carbon materials were prepared using Acanthopanax senticosus herbal residues as raw material and KOH as activating agent through a one-step pyrolysis method. The prepared carbon-based material was systematically characterized by powder X-ray diffraction, scanning electron microscopy, N₂ adsorption-desorption and Fourier-transform infrared spectroscopy. The results show that the three-dimensional ordered porous carbon materials prepared with KOH as the activator via pyrolysis possess abundant functional groups, high porosity, and high specific surface area, with a specific surface area of 1 471.6 m²·g^-1. The three-dimensional ordered porous carbon materials prepared at 800 ℃ exhibits a high drug loading capacity (78.0%) and drug release rate (86.8%) for 5-fluorouracil. Three-dimensional orderly porous carbon materials show significant application advantages in drug construction, and their high specific surface area and adjustable pore size structure significantly improve the drug load rate and drug release rate, providing a solid foundation for the development of efficient and accurate drug delivery system.

Objective:To summarize the evidence of diet management in patients with chronic kidney disease (CKD) in stage 3-5 D, so as to provide a reference for clinical nursing.Methods:After establishing evidence-based nursing questions, according to the "6S evidence model", the evidence on diet management of patients with CKD in stage 3-5 D was searched by computer, including computer decision support system evidence, guidelines, best evidence summary and systematic review. The search time limit was from the establishment of the database to September 2020. The guideline quality assessment was independently completed by two research nurses and a doctor of nephrology. The quality assessment of non-guideline article was independently completed by two research nurses, and an evidence-based instructor participated in decision-making. The evidence was extracted, evaluated and graded using the Joanna Briggs Institute (JBI) 2014 version of the intervention research evidence pre-grading system.Results:A total of 19 articles that met the requirements were included, including 5 guidelines, 8 systematic reviews, 4 randomized controlled trials, 1 clinical decision, and 1 national standard. A total of 22 pieces of the best evidence on diet management of patients with CKD in stage 3-5 D were summarized from three aspects, namely, diet/nutrition assessment, diet management, teamwork and education.Conclusions:The best evidence of diet management in patients with CKD in stage 3-5 D provides a certain reference for clinical practice, so as to improve the quality of diet management in patients with CKD and the clinical outcomes of patients.

OBJECTIVETo clarify whether A1166C polymorphism of the angiotensin II type 1 receptor (AT(1)R) gene is associated with susceptibility to essential hypertension in Han, Tibetan and Yi populations in China.

METHODSThis study involved 302 normotensive and 446 hypertensive subjects. The polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in genomic DNA. The data were analyzed by ANCOVA, chi-square test, and multiple logistic regression.

RESULTSIn normotensive controls, the A1166 allele frequencies were 0.979, 0.939 and 0.965 in Han, Tibetan and Yi participants, respectively. There was no significant intergroup variation in frequency of the allele in normotensives (chi-square=4.166, P=0.125). The frequency of the A1166 allele in Tibetan male hypertensives was significantly higher than that in normotensives (chi-square=11.46, P=0.001). There was no significant difference in A1166C genotype distribution and allele frequency between normotensives and hypertensives either in the Han (P=0.465) or Yi (P=0.357) populations. Body mass index in the Han and Yi populations (P=0.0001), age in the Tibetan and Yi populations (P=0.0001), and AA genotype in the Tibetan male population (P=0.0034) all were independent risk factors for hypertension. Diastolic blood pressure levels were significantly higher in Tibetan male subjects with the AA genotype than in those with the AC+CC genotype (P=0.0040).

CONCLUSIONThe A1166 allele is very common in Han, Tibetan and Yi populations, approximately 1.35-fold more common than in Caucasians. The A1166 allele of the AT(1)R gene may be a predisposing factor for essential hypertension in Tibetan males. A1166C polymorphism of the AT(1)R gene is probably not involved in the pathogenesis of essential hypertension in Han and Yi populations.

Alleles ; Asian Continental Ancestry Group ; genetics ; Blood Pressure ; genetics ; China ; ethnology ; DNA ; analysis ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genetics, Population ; Genotype ; Humans ; Hypertension ; genetics ; Male ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Receptor, Angiotensin, Type 1 ; genetics ; Tibet

Objective To test the mechanical properties of a self-developed novel anterior mid-distal humerus anatomic locking plate (hereinafter referred to as the new plate) and to improve its design to provide theoretical support for its clinical application. Methods Twenty intact humerus from embalmed human cadavers were obtained and used for the biomechanical test on mid-distal humeral shaft fracture models by using the new plate (group A) and 4.5 mm LC DCP（limited contact dynamic compression plate）(group B), respectively. Both groups were compared under axial compression, medial-lateral bending, medial-lateral three-point bending and external rotation torque. Results The stiffness, strength and stress shielding of the new plate for mid-distal humeral shaft fractures under four different loads were superior to those of 4.5 mm LC-DCP, and the differences were statistically significant(P<0.05). Conclusions The new plate can satisfy the requirements of physical training at early stage for fixed mid-distal humeral shaft fractures, which gives great clinical values.