Clinical analysis of 14 cases of head and neck carcinosarcoma / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the clinicopathological characteristics, treatment and prognosis of head and neck carcinosarcoma. Methods: The clinical data of 14 patients with head and neck carcinosarcoma treated in the First Affiliated Hospital of Zhengzhou University from January 2010 to May 2020 were retrospectively analyzed, including 11 males and 3 females, with age range from 30 to 72 years old. Clinicopathological characteristics, treatments and follow-up results of patients were evaluated. Kaplan-Meier method was used to estimate the cumulative survival rate. Results: Histopathological examination showed the co-existence of malignant epithelial and mesenchymal components in all cases. Immunohistochemical staining of 13 cases showed cytokeratin and epithelial membrane antigens were positively expressed in the epithelial areas, whereas vimentin was positive in the malignant mesenchymal tissue area. Among 14 cases, 5 cases were treated with surgery, 3 cases with surgery and radiotherapy, and 6 cases with surgery, radiotherapy and chemotherapy. The follow-up time was 2-81 months, with a median follow-up time of 22.5 months. Except for one patient who was lost to follow-up in 21 months after treatment, among the remaining 13 patients, 4 patients had recurrence, 8 patients died, and 5 patients had a tumor-free survival. The Kaplan-Meier analysis showed that the 1, 3, and 5-year cumulative survival rates of 14 patients with head and neck carcinosarcoma were 64.3%, 57.1%, and 42.9%, respectively. Conclusions: Carcinosarcoma of the head and neck is rare in clinic, histopathological and immunohistochemical examinations are important basis for diagnosis, and surgery is a preferred treatment. Carcinosarcoma of the head and neck has a poor prognosis, and patients should be followed up for a long time.

Impact of gender on hepatic pathology and antibody - mediated immunity caused by Schistosoma japonicum infection in C57BL/6 mice / 中国血吸虫病防治杂志

Objective To investigate the effect of gender on hepatic pathology and antibody-mediated immunity in Schistosoma japonicum-infected C57BL/6 mice. Methods Female and male C57BL/6 mice were infected with S. japonicum, and the hepatic pathological changes were observed using HE and picrosirius red staining in mice 8 weeks post-infection. The serum specific IgG antibody levels against the soluble adult worm antigen (SWA) and soluble egg antigen (SEA) were measured in mice using enzyme-linked immunosorbent assay (ELISA), and the percentages of follicular helper T (Tfh) cells and regulatory T (Treg) cells were detected in mouse spleen and lymph nodes using flow cytometry. Results HE staining showed no significant difference in the mean area of a single hepatic egg granuloma between female and male mice 8 weeks post-infection with S. japonicum [(28.050 ± 3.576) × 104 μm2 vs. (26.740 ± 4.093) × 104 μm2; t = 0.241, P = 0.821], and picrosirius red staining revealed no statistical differences between female and male mice in terms of the mean proportion of picrosirius red stained hepatic tissues [(7.667 ± 1.856)% vs. (7.667 ± 1.764)%; t = 0, P = 1] or the mean optical density [(0.023 ± 0.003) vs. (0.027 ± 0.007); t = 0.447, P = 0.678]. ELISA detected no significant differences in the serum IgG antibody levels against SWA [(2.098 ± 0.037) vs. (1.970 ± 0.071); t = 1.595, P = 0.162] or SEA [(3.738 ± 0.039) vs. (3.708 ± 0.043); t = 0.512, P = 0.623] between female and male mice 8 weeks post-infection with S. japonicum. Flow cytometry detected significantly greater percentages of Tfh cells in the spleen [female mice, (8.645 ± 1.356)% vs. (1.730 ± 0.181)%, t = 5.055, P = 0.002; male mice, (8.470 ± 1.161)% vs. (1.583 ± 0.218)%, t = 5.829, P = 0.001] and lymph nodes [female mice, (3.218 ± 0.153)% vs. (1.095 ± 0.116)%, t = 11.040, P < 0.001; male mice, (3.673 ± 0.347)% vs. (0.935 ± 0.075)%, t = 8.994, P = 0.001) of both female and male mice 8 weeks post-infection with S. japonicum than in uninfected mice; however, no significant differences were seen between female and male mice 8 weeks post-infection with S. japonicum in terms of the percentages of Tfh cells in the spleen [(8.645 ± 1.356)% vs. (8.470 ± 1.161)%; t = 0.098, P = 0.925] or lymph nodes [(3.218 ± 0.153)% vs. (3.673 ± 0.347)%; t = 1.332, P = 0.241]. There was no significant difference in the proportion of Treg cells in the spleen of male mice between infected and uninfected mice [(10.060 ± 0.361)% vs. (10.130 ± 0.142)%; t = 0.174, P = 0.867], while a higher proportion of Treg cells was seen in the spleen of female mice 8 weeks post-infection with S. japonicum than in uninfected mice [(10.530 ± 0.242)% vs. (9.450 ± 0.263)%; t = 3.021, P = 0.023]. There was no significant difference in the proportion of Treg cells in the spleen between female and male mice infected with S. japonicum [(10.530 ± 0.242)% vs. (10.060 ± 0.361)%; t =1.077, P = 0.323]. In addition, the proportions of Treg cells were significantly greater in the lymph node of S. japonicum -infected female [(17.150 ± 0.805)% vs. (13.100 ± 0.265)%; t = 4.781, P = 0.003] and male mice [(18.550 ± 0.732)% vs. (12.630 ± 0.566)%; t = 6.402, P = 0.001] than in uninfected mice; however, no significant difference was seen between female and male mice 8 weeks post-infection [(17.150 ± 0.805)% vs. (18.550 ± 0.732)%; t = 1.287, P = 0.246]. Conclusion There are no gender-specific hepatic pathological changes or antibody-mediated immunity in C57BL/6 mice post-infection with S. japonicum.

Identification of microRNAs as novel biomarkers for esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas (TCGA) and bioinformatics / 中华医学杂志(英文版)

Background@#MicroRNAs (miRNAs) have played important roles in the regulation of gene expression in many cancers, but their roles in esophageal squamous cell carcinoma (ESCC) are still unclear. The aim of this study was to determine the potential ESCC-specific key miRNAs from a large sample dataset in The Cancer Genome Atlas (TCGA).@*Methods@#Integrative bioinformatics analysis was used to identify key ESCC-specific miRNAs related to the ESCC patients’ tumor histological grade and lymphatic metastasis from TCGA. Next, these key miRNA potential gene regulatory functions and relationships with ESCC patients’ clinical characteristics and overall survival were analyzed. Finally, three key miRNAs were selected randomly and quantificational real-time polymerase chain reaction (qRT-PCR) was used to validate in 51 newly diagnosed ESCC patients’ tissues samples (collected from Nov. 2017 to Feb. 2019, in Wuwei, China) whether the bioinformatics analyses results were reliable and valid. Two-tailed Student’s t test, Pearson Chi-squared test and Kaplan-Meier survival analysis were used in this study.@*Results@#Thirty-five ESCC-specific miRNAs from TCGA database were investigated (fold-change > 2.0, P < 0.05), and 28 participated in the miRNAs-mRNAs co-expression network construction, while 17 were related with ESCC patients’ tumor histological grade, TNM stage, and lymphatic metastasis (P < 0.05). Meanwhile, six miRNAs (including miR-200b-3p, miR-31-5p, miR-15b-5p, miR-141-3p, miR-135b-5p, and miR-195-5p) were correlated with overall survival of ESCC patients (log-rank, P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p were selected for verification of the expression levels in 51 ESCC patients’ tissue samples by using qRT-PCR. We found that the fold-changes between qRT-PCR and TCGA were completely consistent. The results also suggested that miR-135b-5p, miR-15b-5p, and miR-195-5p were significantly correlated with tumor differentiation degrees (P < 0.05), miR-195-5p was significantly correlated with tumor TNM stage (P < 0.05), and miR-135b-5p was significantly correlated with lymph-node metastasis (P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p expression levels, ESCC patient clinical features association analysis results and the aforementioned TCGA bioinformatics analyses were similar.@*Conclusion@#This study identified key ESCC-related miRNAs. The key miRNAs are worthy of further investigation as potential novel biomarkers for diagnosis, classification, and prognosis of ESCC.

Identification of microRNAs as novel biomarkers for esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas (TCGA) and bioinformatics / 中华医学杂志(英文版)

BACKGROUND@#MicroRNAs (miRNAs) have played important roles in the regulation of gene expression in many cancers, but their roles in esophageal squamous cell carcinoma (ESCC) are still unclear. The aim of this study was to determine the potential ESCC-specific key miRNAs from a large sample dataset in The Cancer Genome Atlas (TCGA).@*METHODS@#Integrative bioinformatics analysis was used to identify key ESCC-specific miRNAs related to the ESCC patients' tumor histological grade and lymphatic metastasis from TCGA. Next, these key miRNA potential gene regulatory functions and relationships with ESCC patients' clinical characteristics and overall survival were analyzed. Finally, three key miRNAs were selected randomly and quantificational real-time polymerase chain reaction (qRT-PCR) was used to validate in 51 newly diagnosed ESCC patients' tissues samples (collected from Nov. 2017 to Feb. 2019, in Wuwei, China) whether the bioinformatics analyses results were reliable and valid. Two-tailed Student's t test, Pearson Chi-squared test and Kaplan-Meier survival analysis were used in this study.@*RESULTS@#Thirty-five ESCC-specific miRNAs from TCGA database were investigated (fold-change > 2.0, P < 0.05), and 28 participated in the miRNAs-mRNAs co-expression network construction, while 17 were related with ESCC patients' tumor histological grade, TNM stage, and lymphatic metastasis (P < 0.05). Meanwhile, six miRNAs (including miR-200b-3p, miR-31-5p, miR-15b-5p, miR-141-3p, miR-135b-5p, and miR-195-5p) were correlated with overall survival of ESCC patients (log-rank, P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p were selected for verification of the expression levels in 51 ESCC patients' tissue samples by using qRT-PCR. We found that the fold-changes between qRT-PCR and TCGA were completely consistent. The results also suggested that miR-135b-5p, miR-15b-5p, and miR-195-5p were significantly correlated with tumor differentiation degrees (P < 0.05), miR-195-5p was significantly correlated with tumor TNM stage (P < 0.05), and miR-135b-5p was significantly correlated with lymph-node metastasis (P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p expression levels, ESCC patient clinical features association analysis results and the aforementioned TCGA bioinformatics analyses were similar.@*CONCLUSION@#This study identified key ESCC-related miRNAs. The key miRNAs are worthy of further investigation as potential novel biomarkers for diagnosis, classification, and prognosis of ESCC.

Expressions of SP and NK1R in eosinophil-enriched blood cells from patients with atopic dermatitis / 西安交通大学学报(医学版)

Objective To investigate the expressions of substance P(SP)and neurokinin receptor(NK1R)in eosinophil-enriched cells from patients with atopic dermatitis(AD)so as to elucidate their possible roles in AD. Methods Blood samples were collected from healthy controls(HCs)and AD patients,and incubated with the extracts of Artemisia pollen,dust mite,and Platanus pollen for 1 h.The expressions of SP and NK1R in eosinophil-enriched cells were detected by flow cytometry.Results Level of NK1R in eosinophil-enriched cells from AD patients increased by 41% compared with that of HCs when cultured with the medium only(P= 0.001).In addition,the expression of SP in AD patients decreased by 1.17 folds(P＜0.001),and mean fluorescence intensity (MFI)of SP+eosinophils decreased by 55%(P＜0.001).However,allergens had little effect on the expressions of SP and NK1R in eosinophil-enriched cells from AD patients and HCs.Conclusion Upregulated expression of NK1R in AD indicates that eosinophil-derived NK1R may play an important role in AD.Antagonists or blockers of NK1R might be effective preparations for AD treatment.

Upregulated expression of substance P and its receptor in blood eosinophils of patients with allergic rhinitis complicated with asthma / 西安交通大学学报(医学版)

Objective To detect the expression of substance P(SP)and NK1 receptor(NK1R)in eosinophils of patients with allergic rhinitis complicated with asthma(AR+ AS)and elucidate their roles in the pathogenesis. Methods Levels of SP and NK1R in eosinophils were detected by flow cytometry after stimulation with crude extracts of Artemisia pollen,dust mite and Platanus pollen,respectively.Results The proportion of SP+cells in patients with AR+AS was 1.5 folds higher than that of healthy controls(HCs)(Z= -2.041,P= 0.041).The ratio of NK1R+cells and the mean fluorescent intensity were increased by 26.4%(Z= -3.207,P=0.001)and 85.9%(Z= -4.774,P＜ 0.001),respectively.In addition,0.1 μg/mL of Artemisia pollen extract induced an increase of SP+eosinophils in AR+AS patients by approximately 68.1%(Z= -2.637,P=0.008).However,no significant difference was detected in the expressions of SP and NK 1R in blood eosinophils of HCs when stimulated with allergens.Conclusion Eosinophil-derived SP and NK1R may play an important role in the development of AR+AS.SP and NK1R may be the potential targets for AR+AS treatment.

Distinguishing Vogt-Koyanagi-Harada disease from multiple central serous chorioretinopathy with OCT and FFA / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the image features of Vogt-Koyanagi-Harada disease (VKH) and multiple central serous chorioretinopathy (CSC) by fundus fluorescein angiography (FFA) and optical coherence tomography (OCT).METHODS:Thirty-two eyes of 17 patients with VKH and thirty-five eyes of 30 patients with multiple CSC were collected from 2009 to 2016 in my hospital.RESULTS:All the eyes with VKH were found small and dense fluorescein leakage in the early stage.The 17 eyes (53%) with VKH were found fluorescein accumulation in the final stage;24 eyes (75%) with VKH were found high fluorescence of optic disc.All of eyes with multiple CSC were found multifocal leakage in the early stage.And 2 eyes (6%) with multiple CSC were found high fluorescence of optic disc.There were 28 eyes (14 patients) with VKH and 25 eyes (22 patients) with multiple CSC had been done OCT in my hospital.Retinal pigment epithelial fold was only found in VKH.Fluctuation of internal limiting membrane (ILM) and membrane structure had higher sensitivity to diagnostic VKH from to multiple CSC, with sensitivity of 54% and 68% respectively.CONCLUSION:There are some similarities as well as differences between FFA and OCT in diagnosis of VKH and multiple CSC.A combination usage of FFA and OCT can be more effective in distinguishing VKH from multiple CSC.

Effects of Shoutai Pill Containing Serum on Bioactivity Behavior of Trophoblast Cells of Spontaneous Abortion Patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of Shoutai Pill (STP) containing serum on bioactivity behaviors of trophoblast cells in spontaneous abortion (SA) patients such as cell proliferation, invasion, migration and secretion.</p><p><b>METHODS</b>Trophoblast cells in artificial abortion in normal pregnancy and SA patients were isolated and cultured in vitro, which were then treated with STP containing serum at various concentrations (5%, 10%, 20%, respectively). Blank serum was taken as the normal control group and dydrogesterone containing serum as the dydrogesterone control group. The proliferation, cycle distribution, invasion and migration capacity, and beta human chorionic gonadotropin (p-HCG) level were detected by methyl thiazolyl tetrazolium (MTT) colorimetry, flow cytometry (FCM), Transwell experiments, and ELISA, respectively.</p><p><b>RESULTS</b>Compared with the normal control group, the activity of cell proliferation obviously decreased, ratios of apoptotic cells (SubGO/G1) and G2/M phase were obviously elevated, S phase cell ratio was obviously reduced (all P < 0.05). Transwell experiments indicated invasion and migration capacity obviously decreased, secreted beta-HCG level were obviously reduced after 72-h intervention (P < 0.05). Compared with the SA group, the activity of cell proliferation obviously increased, ratios of apoptotic cells and G2/M phase were obviously reduced, S phase cell ratio was obviously elevated, invasion and migration capacity were obviously enhanced, secreted beta-HCG level were obviously elevated after 72-h intervention in the dydrogesterone control group and each STP containing serum group (all P < 0.05). The activity of trophoblastic cell proliferation, S phase cell ratio, invasion and migration capacity, and secreted beta-HCG level were strengthened along with increased STP containing serum. Besides, the effects of 20% STP containing serum group were significantly superior to those of the dydrogesterone control group (P < 0.05).</p><p><b>CONCLUSION</b>STP containing serum could dose-dependently enhance the proliferative activity of trophoblastic cells, invasion and migration capacity, secretion of beta-HCG, and reduce the apoptosis of trophoblast cells, which might be one of mechanisms for STP preventing and treating SA.</p>

lnnercapsular phacoemulsification with primary intraocular lens implantation in the treatment of lens dislocation / 国际眼科杂志(Guoji Yanke Zazhi)

To observe the clinical results of innercapsular phacoemulsification with primary intraocular lens ( lOL ) implantation in the treatment of lens dislocation.METHODS: A total of 23 cases ( 23 eyes ) of lens dislocation ( lla and llb ) were underwent innercapsular phacoemulsification combined with primary lOL implantation. lOL implantation were underwent during operation, the complications of intraoperative and postoperative, postoperative vision, intraocular pressure ( lOP ) , corneal endothelial cell, lOL location were analyzed.RESULTS: The operations were successfully completed for all patients in accordance with the pre - surgery program; lens nucleus or its fragments did not crash into the vitreous cavity; 20 cases of corneal edema and 17 cases of lOP presented at the first day after surgery, the deviation or displacement of lOL and serious complications such as retinal detachment were not appeared. At the first week postoperation, the average lOP was 15. 81 ± 2. 10mmHg, with statistically significant differences when compared with the preoperative ( P0. 05) CONCLUSlON: lnnercapsular phacoemulsification combined with primary lOL implantation in the treatment of the whole lens dislocation (‖a and ‖b ) can restore function in patients with diplopia and control lOP effectively, reduce corneal endothelial cell damage, which is an effective method to treat the whole traumatic lens dislocation.

Alterations of CD4+CXCR5+Tfh cells and its transcription regulatory factors in children with asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the alterations of follicular T helper cells (CD4(+)CXCR5(+)Tfh cells, Tfh) on circulating T lymphocytes in children with asthma, and to study the expression of transcription regulatory factors BCL-6 and BLIMP-1 mRNA.</p><p><b>METHODS</b>Sixty-four children with asthma and 25 healthy controls were enrolled in this study. On the basis of the disease, the children with asthma were classified into acute phase group (n=36) and remission phase group (n=28). The flow cytometry was used to detect the proportion of CD4(+)CXCR5(+)Tfh cells on CD4(+)T lymphocytes. Real-time PCR was performed to detect the levels of BCL-6 mRNA and BLIMP-1 mRNA. The double -antibody Sandwich ELISA was used to detect plasma concentrations of total IgE, IL-2, IL-6 and IL-21.</p><p><b>RESULTS</b>The proportion of CD4(+)CXCR5(+)Tfh cells was significantly higher in the acute group than in the control group and the remission group (P<0.05). Transcription levels of BCL-6 mRNA were significantly higher, while the inhibitory factors BLIMP-1 mRNA was significantly lower in the acute group than in the remission group and control group (P<0.05). The plasma concentration of IL-6 in the acute group increased significantly compared with the control group (P<0.05). Plasma concentrations of total IgE and IL-21 increased significantly, in contrast, plasma IL-2 concentration decreased significantly in the acute group, compared with the control group and the remission group (P<0.05). Correlation analysis showed that both IL-21 and IL-6 concentrations were positively correlated with the proportion of CD4(+)CXCR5(+)Tfh cells (r=0.76, r=0.46 respectively; P<0.05), while IL-2 level was negatively correlated with the proportion of Tfh cells (r=-0.68, P<0.05).</p><p><b>CONCLUSIONS</b>The abnormal proportion of CD4(+)CXCR5(+)Tfh cells might be involved in the immunological pathogenesis of acute asthma in children. The increased expression of BCL-6 mRNA and decreased expression of BLIMP-1 mRNA as well as the alterations of plasma total IgE, cytokines IL-2, IL-6 and IL-21 in microenvironment might be account for the increased proportion of CD4(+)CXCR5(+)Tfh cells in children with acute asthma.</p>

Impact of hypothyroidism on sperm motility of male rats / 中国地方病学杂志

Objective To study the impact of hypothyroidism on sperm motility in male rat.Methods According to body weight,20 male Wistar rats were randomly divided into control group and hypothyroidism group (1 ml/100 g/day,0.1％ propylthiouracil by intragastric administration for 60 days) 10 rats in eachgroup.Body weight of these rats was observed every 3 days.After the last intragastric administration,all rats were killed.The levels of thyroid hormones [total triiodothyronine (T3),total thyroxine (T4),and thyroid stimulating hormone (TSH)] were measured by radioimmunoassay.Sperm motility parameters[average path velocity(VAP),straight fine velocity (VSL),straightness (STR),amplitude of lateral head displacement (ALH),sperm density(p),curvilinear velocity (VCL),linearity(LIN),wobble (WOB),mean angular deviation (MAD) and beat cross frequency (BCF)] were measured by a WLJY-9000 color-detection system.Results Compared with the control groups[(298.20 ± 12.15) g,(344.00 ± 13.73)g],the weights of hypothyroidism group of the 30 days[(239.00 ± 15.02) g] and the 60 days [(232.67 ± 17.86)g] were significantly lower(t =7.704,11.380,all P ＜ 0.05).The levels of T3[(373.3 ± 101.3) ng/L] and T4 [(4.00 ± 0.89) × 103 ng/ml] of hypothyroidism group were significantly decreased compared with that of the control groups [(1000.0 ± 273.5)ng/L,(44.33 ± 7.84)× 103 ng/L,t =5.262,12.520,all P ＜ 0.05].Level of TSH[(5.77 ± 0.89) × 103 U/L] of hypothyroidism group was significantly increased compared with that of the control group[(1.87 ± 0.70) × 103 U/L,t =8.413,P ＜ 0.05].Values of VAP[(27.45 ± 1.59)μm/s],VSL [(21.08 ± 1.10)μm/s],STR[(70.53 ± 3.48)％] and ALH[(1.96 ± 0.26)μm] of hypothyroidism group were significantly increased compared with that of the control groups[(24.38 ± 2.59)μm/s,(17.99±2.06)μm/s,(65.93 ± 2.71)％,(1.53 ± 0.27)μm,t =2.687,2.404,2.420,3.175,all P ＜ 0.05].p[(5.07 ± 0.74)109/L] of hypothyroidism group was significantly decreased compared with that of the control group [(8.76 ± 1.01)109/L,t =6.463,P ＜ 0.05].VCL[(52.83 ± 5.56)μm/s],LIN[(38.58 ± 3.41)％],WOB[(52.64 ± 3.24)％],MAD [(64.21 ± 6.71) radian/s] and BCF [(8.93 ± 0.62) Hz] of hypothyroidism group were not significantly different compared with that of the control groups[(49.92 ± 6.43) μm/s,(36.52 ± 2.73)％,(52.49 ± 3.49)％,(62.77 ± 7.34)radia/s,(9.32 ± 0.61)Hz,t =0.805,1.089,0.037,0.341,1.033,all P ＞ 0.05].Conclusion Hypothyroidism can affect sperm activity in male rats,decrease sperm density and cause damage to the reproductive system.

Candesartan inhibits LPS-induced expression increase of toll-like receptor 4 and downstream inflammatory factors likely via angiotensin II type 1 receptor independent pathway in human renal tubular epithelial cells / 生理学报

The present study was to determine whether candesartan, an angiotensin II type 1 receptor blocker (ARB), exerts anti-inflammatory effects through inhibiting the toll-like receptor 4 (TLR4) pathway in human renal tubular epithelial cells (HKCs). The experiments were carried on cultured HKCs. By means of flow cytometry, Western blot, RT-PCR and ELISA techniques, the TLR4 protein, angiotensin II type 1 receptor (AT1R) and phosphorylated nuclear factor-kappa B (NF-κB) p65 protein level, mRNA levels of macrophage chemoattractant protein-1 (MCP-1) and regulated upon expression normal T cell expressed and secreted (RANTES), as well as MCP-1 and RANTES protein concentrations in conditioned media were measured. The results showed that lipopolysaccharide (LPS) upregulated the TLR4 protein level in cultured HKCs. Application of LPS increased NF-κB activation and induced release of its downstream inflammatory factors including MCP-1 and RANTES. Candesartan reversed LPS-induced upregulation of TLR4 expression, inhibited NF-κB activation, and reduced MCP-1 and RANTES release. However, knockdown on AT1R by siRNA did not change those previous effects of candesartan. These results suggest that candesartan-induced anti-inflammatory effect may be through a novel pathway, independent of AT1R.

Functions of carboxyl-terminus of Hsc70 interacting protein and its role in neurodegenerative disease / 中华医学遗传学杂志

Neurodegenerative diseases are a group of chronic progressive neuronal damage disorders. The cause is unclear, most of them share a same pathological hallmark with misfold proteins accumulating in neurons. Carboxyl-terminus of Hsc70 interacting protein (CHIP) is a dual functional molecule, which has a N terminal tetratrico peptide repeat (TPR) domain that interacts with Hsc/Hsp70 complex and Hsp90 enabling CHIP to modulate the aberrant protein folding; and a C terminal U-box ubiquitin ligase domain that binds to the 26S subunit of the proteasome involved in protein degradation via ubiqutin-proteasome system. CHIP protein mediates interactions between the chaperone system and the ubiquitin-proteasome system, and plays an important role in maintaining the protein homeostasis in cells. This article reviews the molecular characteristics and physiological functions of CHIP, and its role in cellular metabolism and discusses the relationship between CHIP dysfunction and neurodegenerative diseases.

Recent advance in genetic study of hereditary autosomal recessive cerebellar ataxia / 中华医学遗传学杂志

Autosomal recessive cerebellar ataxias (ARCA) are a highly heterogeneous group of rare neurodegenerative diseases affecting both central and peripheral nervous systems. Based on pathological mechanisms, five major types of ARCA may be distinguished, which include mitochondrial ataxia, metabolic disorder, DNA repair defect ataxia, congenital ataxias and degenerative ataxia. This review summarizes clinical features, molecular genetics and recent advances in DNA sequencing of common types of ARCA.

The effects of fluoride on metal elements in the testis tissue of male rats / 中国地方病学杂志

Objective To probe into the effects of fluoride on metal elements in the testis tissue of male rats, and provide experimental basis to further research for reproductive toxicity of fluoride. Methods Thirty-two healthy male Wistar rats, weighting 150 - 180 g, were randomly divided into 4 groups, normal sodium(control) by intragastrie administration for 90 days, and body weight was observed daily. After the last intragastric administration, all rats were killed by cervical dislocation. The contents of calcium(Ca), ferri(Fe), zincum(Zn),cuprum(Cu ) and magnesium(Mg) in the testis tissue were measured by atomic absorption speetrophotometry.Results After 30 days exposure, the difference of body weight between groups was statistically significant(F=3.884, P 0.05). The difference of Ca, Zn and Mg levels among four groups was statistically significant(F = 6.630, 6.844, 5.333, all P 0.05). Conclusion Chronic fluorosis can affect the levels of metal elements in rat testis and damage the reproductive system.

Impact of fluorine poisoning on sperm motility of male rats / 中国地方病学杂志

Objective To probe into the impact on sperm motility in male rat induced by fluorine poisoning, and provide experimental basis to further research for reproductive toxicity of fluoride. Methods According to bodyweight, 32 male Wistar rats were randomly divided into control group, the low-dose, medium-dose and high-dose group( 100,200,300 mg·kg~(-1)·d~(-1) NaF), and were treated by intragastric administration for 90 days, and the weight of the rats was observed each day. After the last intragastric administration, all rats were killed. The relative weight of liver, kidney and testis was calculated. Rat epididymides were plucked off and spermatozoa released from it. Sperm motility parameters were measured by WLJY-9000 color-detection system of sperm quality. Results Compared with high-dose group[(206.00 ± 18.16)g], the weight of low-dose and medium-dose group [ (235.00 ± 14.56), (235.44 ± 24.99)g] in 30 days were statistically significant increased(all P < 0.05) ; there were no significant differences between the groups in 60 days and in 90 days(F = 0.578,1.893, all P > 0.05). Comparison of organ coefficient of liver, kidney and testis among three groups showed no significant difference(F = 2.148,0.907, 1.801, all P > 0.05). The average path velocity(VAP) of the high-dose group[ (25.04 ± 4.59)μm/s] showed significant increase compared with control group[ (20.22 ± 3.29)μm/s] ; the straight line velocity(VSL) of the low- dose, medium-dose and high-dose group[ (18.82± 3.19), (17.84 ± 4.54), (16.46 ± 2.63)μm/s] showed significant increase compared with control group[ ( 12.48 ± 1.73 ) μm/s ] ; linearity (LIN) of the low-dese, medium-dose and high.dose group[(23.84±1.58)%,(24.99±3.37)%,(26.75±5.07)%]showed significant decrease compared with control group[(33.29±4.00)%];wobble(WOB)of the medium-dose and high-dose group[(47.03±3.98)%,(4921±723)%]showed significant increase compared with control group[(38.09±0.48)%];mean angular deviation (MAD)of the low-dose group[(68.29±5.71)radian/s]showed significant decrease compared with control group [(81.57±8.44)radian/s];beat cross frequency(BCF)ofthe high-dose group[(117±0.61)/s]showed significant increase compared with control group[(9.49±0.34)/s];sperm density(p)of the low-dose and medium-dose group [(1.26±0.24)×10~9/L,(1.84±0.50)×10~9/L]showed significant decrease compared with control group [(3.94±1.10)×10~9/L,all P<0.05].Comparison of the eurvilinearvelocity(VCL),straightness(STR),amplitude of lateral head displacement(ALH)among three groups showed no significant difference(F=0.264,2.209,1.667, all P>0.05).Conclusion Fluorine poisoning could change sperm motility parameters of the rat,reduce the sperm density and cau8e damage to the reproductive system.

Effects of fluorine and aluminum on index of hematologic tests of rats / 中国地方病学杂志

Objective To study the effects of fluorine and aluminum on index of hematologic tests of rats. Methods According to body mass,56 Wistar rats of 130-200 g were randomly divided into control,low-fluorine (F),middle-F,high-F,low-F + aluminum(Al),middle-F + Al,high-F + Al group,8 rats in each group were given a series of doses of fluoride and aluminum,which were (0 + 0),(100 + 0),(200 + 0),(300 + 0),(100 + 10),(200 + 10),(300 + 10)mg/L After 90-day intragastrie administration,blood samples were collected on eyes of rats to undergo blood routine test,including red blood cell (RBC),lymphocyte (LYM),platelet (PLT),hemoglobin (HGB),white blood cell (WBC),hematocrit (HCT),mean corpuscular hemoglobin (MCH),mean corpuscular-hemoglobin concentration(MCHC),mean corpuscular volume(MCV),and at the same time some blood biochemistry indicators related to functio ns of liver and kidney were determined such as aspartic acid aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),Crea(Cr) and Urea. Organ coefficient of liver and kidney were calculated. Results The difference of RBC,HCT,MCV among all groups of rats was statistically significant(F = 3.202,3.316,2.915,P < 0.05). The RBC,HCT of the low-F group[(7.59± 2.40)×10~(12)/L,0.51±0.11],the middle-F group[(8.60±1.16)×10~(12)/L,0.55±0.05],the high-F group[(9.23± 0.60)×10~(12)/L,0.54±0.03],the low-F + Al group[(9.25±0.79)×10~(12)/L,0.53±0.04],the middle-F + Al group[(7.98±2.14)×10~(12)/L,0.49±0.08]and the high-F + Al group[(7.61±3.17)×10~(12)/L,0.49±0.16]were significantly higher than that in the control group[(4.46±3.10)×10~(12)/L,0.31±0.16,P< 0.05 or < 0.01)]. The MCV of the middle-F group[(64.06±6.51)fl],high-F group[(58.67±1.13)fl],low-F + Al group[(57.78± 1.57)fl]and the middle-F + Al group[(63.04±10.64)fl]were significantly higher than the control group[(78.54± 15.57)fl,P < 0.05 or < 0.01]. The difference of AST and Urea among all the groups of mrs serum was statistically significant(F= 2.847,5.549,P < 0.05 or < 0.01). The serum AST of low-F group[(399.00±54.99)U/L],the middle-Fgroup[(465.60±76.99)U/L],the high-F group[(465.80±75.41)U/L],the low-F + Al group[(346.00±69.26) U/L],the middle-F + Al group[(437.40±68.31)U/L]and the high-F + Al group[(403.00±30.61)U/L]were all significantly higher than that in the control group[(336.67±94.34)U/L,P < 0.05],and the high-F group significantly higher than the high-F + Al group(P < 0.05). The serum Urea of the middle-F group[(7.70±0.52)mmol/L],the high-F group[(8.44±1.30)mmol/L],the low-F + Al group[(7.83±0.62)mmol/L],the middle-F + Al group [(7.73±0.47)mmol/L],and the high fluoride + aluminum group[(7.70±0.21)mmol/L]were all significantly higher than that in the control group[(6.55±0.50)mmol/L,P< 0.05 or < 0.01],and the low-F group was significantly lower than the low-F + Al group(P < 0.01),however the high-F group was significantly higher than that in the high-F + Al group(P< 0.05). The liver organ coefficient of the low-F group(2.94±0.36) was higher than the low-F + Al group (2.60±0.15,P < 0.05). Conclusions Fluorine and combination of aluminum and fluorine have toxicity on rats to a certain extent,including the proliferation of crythrocytes of rat,while the cell size gets smaller and the cell quality is deteriorated,meanwhile functions of liver and kidney are impaired. Aluminum shows different joint action in different concentrations of fluorine.

Polynucleotide repeat expansion of nine spinocerebellar ataxia subtypes and dentatorubral-pallidoluysian atrophy in healthy Chinese Han population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assist the establishment of platform and provide the reference standard for mutation detection in spinocerebellar ataxia (SCA) subtypes 1, 2, 3, 6, 7, 8, 10, 12, 17 and dentatorubral-pallidoluysian atrophy (DRPLA) in Chinese Han population.</p><p><b>METHODS</b>The nucleotide repeat numbers of the 9 SCA subtypes and DRPLA were detected using fluorescence-PCR and capillary gel electrophoresis technique in 300 healthy Chinese Han individuals.</p><p><b>RESULTS</b>Among the 300 healthy controls, the range of the CAG trinucleotide repeat number was 17 to 35 in SCA1, 14-28 in SCA2, 13-41 in SCA3/MJD, 4-16 in SCA6, 5-17 in SCA7, 5-21 in SCA12, 23-41 in SCA17, and 12-33 in DRPLA; and the range of CTA/CTG trinucleotide repeat number on SCA8 locus was 12-43 and the range of ATTCT pentanucleotide repeat number on SCA10 locus was 9-32. Of which, the 12 CTA/CTG repeats of SCA8, 9 ATTCT repeats of SCA10, 23 CAG repeats of SCA17 were the shortest normal repeat number, while the 41 CAG repeats of SCA3/MJD, 32 CAG repeats of SCA10 were the largest normal number that have not been reported.</p><p><b>CONCLUSION</b>The normal ranges of polynucleotide repeats of different subtypes of SCA vary with geographical areas and ethnicities. It might be associated with the genetic and ethnic backgrounds. This is the first normal reference standard of polynucleotide repeat number of these ten SCA subtypes in Chinese Han.</p>

Detection of the CAG trinucleotide repeats of MJD1 gene by recombinant DNA technology / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To establish a stable, accurate and intuitive method for detecting the CAG trinucleotide repeats of MJD1 gene.</p><p><b>METHODS</b>The CAG trinucleotide polymorphism of the MJD1 gene was analyzed by recombinant DNA technology and DNA sequencing in 35 spinocerebellar ataxia 3/Machado-Joseph disease (SCA3/MJD) patients from Mainland China.</p><p><b>RESULTS</b>The range of the CAG repeat of the 35 patients was 65-81 (mean = 72.96 +/- 4.24). The CAG repeats contained two CAAs and one AAG variations in the CAG motif in all the patients and majority of the healthy controls. There was a CGG/GGG polymorphism at the 3' end of the CAG repeat. The GGG allele was consistently associated with smaller CAG repeats in healthy controls. On the other hand, the CGG allele consistently existed in the patients.</p><p><b>CONCLUSION</b>Recombinant DNA technology can stably, accurately and intuitively detect the CAG trinucleotide repeat of the MJD1 gene. It should be used as a major technique to diagnose the SCA3/MJD and analyze the polymorphism of CAG sequence.</p>

Molecular basis of spinocerebellar ataxias subtype caused by nucleotide repeat expansion in noncoding region / 中华医学遗传学杂志

Hereditary spinocerebellar ataxias(SCA) are mainly caused by trinucleotide (CAG/CAA) repeat expansion in open reading frames of corresponding gene. However, SCA8, SCA10 and SCA12 are caused by nucleotide repeat expansion in noncoding region. Recent researches focus on the pathogenesis and hereditary traits, including the instability of nucleotide repeat, the alteration of penetrance, the bias of gender inheritance and the anticipation. The pathogenesis of these three SCA subtypes is different from other subtypes because the repeat expansion in noncoding region has mild influence on translation of polyQ protein. We suggest that the interference on DNA transcription by the abnormal nucleotide expansion, the post-transcriptional toxic effect of abnormal RNA, and the mechanism of bidirectional expression of repeat expansion transcripts play a critical role on SCA8, SCA10 and SCA12 pathogenesis.