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Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.
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Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8+ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8+ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.
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New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.
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Objective:To explore the predictive effect of CHA2DS2-VASc score on the long-term prognosis of acute pulmonary embolism (APE).Methods:Patients who were diagnosed with acute pulmonary embolism in the department of respiratory medicine of Binzhou Second People′s Hospital and Hebei Provincial People′s Hospital from October 2014 to October 2018 were continuously included, and the included patients were divided into two groups according to the CHA2DS2-VASc score: 319 cases in the low CHA2DS2-VASc group (<4 points), and 79 cases in the high CHA2DS2-VASc group (≥4 points). Then the propensity score matching method was used to balance the covariates between the two groups, and then the CHA2DS2-VASc score was used to predict the long-term prognosis of acute pulmonary embolism.Results:The Geneva score, D-dimer level and APE-related adverse events in high CHA2DS2-VASc group were significantly higher than those with low CHA2DS2-VASc group, with statistically significant differences ( P<0.05). The multiple COX regression model showed that the incidence of pulmonary embolism associated adverse events was significantly increased 2.820-fold (95% CI: 1.366-5.822) in the high CHA2DS2-VASc group compared with in the low CHA2DS2-VASc group. After propensity score matching, high CHA2DS2-VASc score was still a strong predictor of poor prognosis in patients with acute pulmonary embolism ( HR: 3.421, 95% CI: 2.164-5.408). Conclusions:After using propensity score matching method balances confounding bias, high CHA2DS2-VASc score is still an independent prognostic risk factors of acute pulmonary embolism.
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Objective:To explore the value of regional cerebral oxygen saturation (rScO 2) and anesthesia depth monitoring in predicting postoperative cognitive dysfunction (POCD) in patients with non-macrovascular surgery. Methods:A retrospective analysis of 147 patients with non-macrovascular surgery under general anesthesia admitted to the First Affiliated Hospital of Xi'an Jiaotong University from August 2017 to June 2019 was performed and divided into the POCD group ( n=37) and the non-POCD group ( n=110) according to the presence/absence of postoperative POCD. The changes of bispectral index (BIS) and rScO 2 in patients before anesthesia induction (T 0), endotracheal intubation (T 1), 2 hours after operation (T 2), after operation (T 3), and at extubation (T 4) were recorded, and the predictive value for the occurrence of POCD was analyzed by receiver operating characteristic (ROC) curve. Results:There was no statistically significant difference in anesthesia time, operation time and operation type between the two groups ( P>0.05). There was no significant difference in BIS and rScO 2 levels between the two groups at T 0, T 1 and T 4 ( P>0.05). BIS and rScO 2 levels in the POCD group at T 2 and T 3 were lower than those in the non-POCD ( P<0.05). Both BIS and rScO 2 of the two groups reached the lowest value at T 2, and the reduction rate of rScO 2 in the POCD group was higher than that in the non-POCD group [(31.84±3.27)% vs (14.81±2.52)%, P<0.05]. The ROC curve of BIS-T 2, rScO 2-T 2, BIS-T 3, rScO 2-T 3, rScO 2 reduction from the baseline value to predict POCD in patients with non-macrovascular surgery was plotted, and the AUCs were 0.514, 0.617, 0.505, 0.633, 0.724, respectively. The highest AUC value of 0.808 was found for combined detection at T 2 (rScO 2 and BIS). Conclusions:The combined detection of intraoperative regional cerebral oxygen saturation and anesthesia depth monitoring is of good clinical application value in predicting postoperative cognitive dysfunction in patients with non-macrovascular surgery.
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Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3
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Objective:To investigate the correlation between serum phosphorus levels and outcomes of weaning from mechanical ventilation in elderly chronic obstructive pulmonary disease(COPD)patients with type Ⅱ respiratory failure.Methods:A total of 142 hospitalized elderly COPD patients with type Ⅱ respiratory failure receiving mechanical ventilation in our hospital from August 2016 to December 2018 were retrospectively enrolled.Patients were divided into the successful weaning group(n=101)and the unsuccessful weaning group(n=41)based on weaning outcomes.General data, blood phosphorus levels on admission and before spontaneous breathing trials(SBT)and the incidence of hypophosphatemia were compared between the two groups.The logistic regression equation was used to analyze the related factors for the unsuccessful weaning, and the receiver operating characteristics(ROC)curve was drawn to analyze the value of serum phosphorus levels in predicting the failure of weaning.Methods:Compared with the successful weaning group, Acute Physiology and Chronic Health evaluation Ⅱ(APACHEⅡ)scores, rapid shallow breathing index(RSBI), and serum creatinine(Cr), C-reactive protein(CRP)levels were higher, while the oxygenation index(PaO 2/FiO 2), serum albumin(ALB)and magnesium levels were lower in the unsuccessful weaning group than in the successful weaning group( P<0.05). The incidences of hypophosphatemia on admission and before SBT were higher in the unsuccessful weaning group than in the successful weaning group(34.2% or 34/41 vs.17.8% or 18/101, 46.3% or 19/41 vs.25.7% or 26/101, χ2=4.452 and 5.716, P<0.05). Serum phosphorus levels on admission and before SBT were lower in the unsuccessful weaning group than in the successful weaning group[(0.82±0.21) mmol/L vs.(1.05±0.23) mmol/L, (0.71±0.19) mmol/L vs.(1.02±0.22) mmol/L, t=5.171 and 7.646, P<0.05)]. Multivariate logistic regression analysis showed that hypophosphatemia on admission or before SBT was an independent risk factor for unsuccessful weaning in elderly COPD patients with type Ⅱ respiratory failure( P<0.05). The areas under the ROC curve(AUC)of hypophosphatemia on admission and before SBT for predicting the failure of weaning was 0.657 and 0.776, respectively, and with 0.84 mmol/L and 0.76 mmol/L as the respective optimal threshold values, the sensitivity and specificity were 67.3% and 68.3% for AUC on admission and 76.5% and 85.6% for AUC before SBT, respectively.AUC of the serum phosphorus level was higher before SBT than on admission( Z=3.142, P<0.05). Conclusions:The decrease of blood phosphorus levels is common in elderly COPD patients with type Ⅱ respiratory failure, and hypophosphatemia has a high incidence and may be an independent risk factor for the failure of weaning.Blood phosphorus levels should be closely monitored in order to guide clinical weaning.
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PD-1 and CTLA-4 antibodies offer great hope for cancer immunotherapy. However, many patients are incapable of responding to PD-1 and CTLA-4 blockade and show low response rates due to insufficient immune activation. The combination of checkpoint blockers has been proposed to increase the response rates. Besides, antibody drugs have disadvantages such as inclined to cause immune-related adverse events and infiltration problems. In this study, we developed a cyclic peptide C25 by using Ph.D.-C7C phage display technology targeting LAG-3. As a result, C25 showed a relative high affinity with human LAG-3 protein and could effectively interfere the binding between LAG-3 and HLA-DR (MHC-II). Additionally, C25 could significantly stimulate CD8 T cell activation in human PBMCs. The results also demonstrated that C25 could inhibit tumor growth of CT26, B16 and B16-OVA bearing mice, and the infiltration of CD8 T cells was significantly increased while FOXP3 Tregs significantly decreased in the tumor site. Furthermore, the secretion of IFN- by CD8 T cells in spleen, draining lymph nodes and especially in the tumors was promoted. Simultaneously, we exploited T cells depletion models to study the anti-tumor mechanisms for C25 peptide, and the results combined with MTT assay confirmed that C25 exerted anti-tumor effects CD8 T cells but not direct killing. In conclusion, cyclic peptide C25 provides a rationale for targeting the immune checkpoint, by blockade of LAG-3/HLA-DR interaction in order to enhance anti-tumor immunity, and C25 may provide an alternative for cancer immunotherapy besides antibody drugs.
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Objective To evaluate the dietary quality of children aged 3 to 6 years during the kindergarten period in Lanzhou City using the Dietary Balance Index (DBI). Methods Based on kindergarten grades and geographical locations, 304 recipes for different semesters from 2014 to 2017 in 40 kindergartens in Lanzhou City were randomly selected with a sampling ratio of 5%(291 recipes with no recipes 13 copies) as the research object. Adjusted DBI indicators for children aged 3 to 6 years were used to evaluate the dietary quality of the recipes during the kindergarten period in the sample. Using the Kruskal-Wallis H rank-sum test, the food consumption rates and DBI evaluation results of the kindergartens in Lanzhou City were analyzed. Results Results of the sub-group diet scores that were close to the recommended intake (DBI scores between-2 to 2) showed that cereals, fresh vegetables, nuts and beans, fish, shrimp, eggs, and snacks accounted for the ideal intake of more than 80%of all the recipes. The diet scores of fruits, meat, and processed products ranged from 50%to 80%, and that for milk accounted for only 26.8%. Analyzing the type of food intake showed that the proportion of recipes that included eating more than six types of food per day was 98.3%. Analyzing by kindergarten level and year showed that the overall dietary quality problems with the studied recipes were mainly caused by insufficient intake and dietary imbalance, and the difference was statistically significant. Among them, the lack of intake in 2017 and the degree of dietary imbalance were greater compared to the other years. The level of insufficiency and dietary imbalance in the third-grade kindergartens were higher than those in the first- and second-grade kindergartens. Dietary pattern A recipes accounted for 63.6% of the kindergarten recipes, and there were no recipes for dietary patterns C, F, G, H, and I. Conclusion The dietary quality problems of kindergartens in Lanzhou City were mainly reflected in the inadequate dietary intake and dietary imbalance. The supervision of dietary quality by kindergartens should be strengthened and the concept of a balanced diet should be promoted. The dietary management of third-grade kindergartens should be simultaneously strengthened.
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ABSTRACT:Objective To compare the short-term efficacy of hand-assisted laparoscopic surgery and laparoscopy-assisted radical operation,and evaluate the safety of hand-assisted laparoscopic surgery and its effect on systemic stress inflammation in colorectal cancer.Methods Totally 100 patients who had colorectal cancer and underwent radical operation from September 2012 to March 2016 were selected and divided into hand-assisted laparoscopy group (Group A,n=6 3 )and laparoscopy-assisted group (Group B,n=3 7 )according to the random number table.We compared operation index,postoperative complications and systemic inflammatory response levels in the two groups.Results Group B outperformed Group A in operation time,bleeding volume and drainage volume (P0 .0 5 ).Systemic inflammatory reaction index of neutral granulocyte number and C reactive protein (CRP)showed no significant differences between the two groups (P>0 .0 5 ),but inflammatory cytokine IL-6 level in Group B was significantly higher than the that in Group A (P<0.05).Conclusion Hand-assisted laparoscopic surgery has shorter operation time,lower bleeding volume than laparoscopy-assisted operation in the treatment of colorectal cancer,but the latter one has more advantages in postoperative gastrointestinal function recovery.The inflammatory cytokine IL-6 level in hand-assisted laparoscopic surgery is higher than that in laparoscopy,suggesting that the choice of operation methods should be based on the actual situation in clinical application.
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Objective To evaluate the expressions of Cyr61 and β‐catenin protein in gallbladder carcinoma tissues and investigate their association with the clinicopathologic features of gallbladder carcinoma patients . Methods The expressions of Cyr61 and β‐catenin protein in 50 cases of gallbladder carcinoma and 19 cases of normal tissue were detected by immunohistochemical S‐P method .Results ① The positive expression rate of Cyr61 in gallbladder carcinoma tissues was 66 .0% (33/50) ,which was significantly higher than that in the normal tissues group (26 .3% ) .The expression of Cyr61 was related to tumor differentiation ,TNM stage and lymph node metastasis of gallbladder carcinoma (P=0 .010 ,P=0 .014 ,P=0 .007;P<0 .05) .② The positive expression rate ofβ‐catenin in gallbladder carcinoma tissues was 84 .0% (42/50) ,which was significantly higher than that in the normal tissues group 15 .7% (3/19);the expression of β‐catenin was related to tumor differentiation ,TNM stage and lymph node metastasis of gallbladder carcinoma (P=0 .018 ,P=0 .002 ,P=0 .024;P<0 .05) .③ Correlation test showed that Cyr61 andβ‐catenin were positively correlated in gallbladder carcinoma and adjacent normal tissues (r=0 .378 , P< 0 .05) .Conclusion Cyr61 and β‐catenin are highly expressed in gallbladder carcinoma tissues . Cyr61 andβ‐catenin expressions are closely related to the clinicopathologic features (tumor differentiation ,TNM staging and lymph node metastasis) in gallbladder carcinoma .Cyr61 and β‐catenin may have a synergistic effect in promoting progression and development of gallbladder carcinoma .Combined detection of Cyr61 and β‐catenin in gallbladder carcinoma tissues will contribute to the clinical diagnosis and prognosis .
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Background and purpose:Cytotoxic T lymphocyte (CTL) plays a vital role in the process of anti-tumor immunology. The aim of this study was to investigate whether changes in concentration of IL-2 (50, 200 and 1 000 U/mL) would affect the sub-population and cytotoxic function of cells cultivated by peptide-specific CTL induction systemin vitro and also observe whether using the concentration of IL-2 at a range of 50-1 000 U/mL isbeneifcial to regulatory cells (Tregs) enrichment.Methods:Peripheral blood from 10 healthy donors and 10 cancer patients that were HLA-A2 positive, were collected in the study. HLA-A2 restricted CTL epitope P321 (ILIGETIKI) derived from COX-2 pulsed with different concentrations of IL-2 were used to induce peptides-speciifc CTLin vitro. Flow cytometry was performed to analyze the proliferative capability, the proportion of different T-cell subsets, and secretion of perforin, granzyme B and IFN-γ. IFN-γ secretion was assessed by ELISpot assay.Results:High concentration of IL-2 increased the proliferative activity. The percentage of CD4+ T cells of cancer patient group was signiifcantly higher than that of healthy donor group, while the percentage of CD8+ T cells of cancer patient group was signiifcantly lower than that of healthy donor group. And there was no signiifcant difference in the percentages of CD4+ T cells, CD8+ T cells and Tregs among groups with different IL-2 concentrations. No difference was seen in cytokine (perforin, granzyme B, IFN-γ) secretion capacity of CD8+ T cells. ELISpot study revealed that high-dose IL-2 resulted in the increasing of IFN-γ secretion.Conclusion:The sub-population and the function of cells cultured by peptide-speciifc CTL induction systemin vitro are not affected by different concentrations of IL-2. Furthermore, high concentrations of IL-2 (50-1 000 U/mL) do not provide the enrichment for Tregs. Higher concentration of IL-2 is likely to cause high secretion of IFN-γ in ELISpot assay. In order to exclude the distraction of NK cells or NKT cells, the concentration of 50 U/mL is better choice.
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Objective To investigate the effects of ropivacaine infiltration combined with dezocine on the agitation during recovery from general anesthesia in the patients undergoing cerebral surgery.Methods Sixty patients of both sexes,aged 18-64 yr,of ASA physical status Ⅰ or Ⅱ,undergoing elective neurosurgery under general anesthesia,were randomly divided into 4 groups (n =15 each) using a random number table:control group (group C),ropivacaine group (group R),dezocine group (group D),and ropivacaine + dezocine group (group RD).Group C received local infiltration with normal saline 20 ml at 10 min before skin incision,and normal saline 2 ml was injected intravenously at 30 min before the end of operation.The patients received local infiltration with 0.5% ropivacaine 20 ml at 10 min before skin incision,and normal saline 2 ml was injected intravenously at 30 min before the end of operation in group R.Group D received local infiltration with normal saline 20 ml at 10 min before skin incision,and dezocine 10 mg was injected intravenously at 30 min before the end of operation.The patients received local infiltration with 0.5% ropivacaine 20 ml at 10 min before skin incision,and dezocine 10 mg was injected intravenously at 30 min before the end of operation in group RD.The time for recovery from anesthesia,extubation time,and development of agitation after extubation in PACU were recorded.Agitation was assessed and scored.Ramsay sedation score and VAS score were recorded immediately after extubation.The development of cardiovascular events and respiratory depression was recorded within 10 min after extubation.Before induction of anesthesia (T0),at the end of surgery (T1) and immediately after extubation (T2),blood samples were collected from the dorsal artery of foot for deter mination of the levels of blood glucose,plasma cortisone,epinephrine and norepinephrine.Results Compared with group C,the agitation score,incidence of agitation,VAS score,and incidence of postoperative hypertension were significantly decreased in R,D and RD groups,especially in R and D groups.The time for recovery from anesthesia and time for extubation were significantly shorter in R and RD groups than in group C.Ramsay sedation scores were significantly higher at the onset of extubation in R,D and RD groups than in group C.Ramsay sedation scores were significantly higher in D and RD groups than in group R.Compared with group C,the levels of blood glucose,plasma cortisone,epinephrine and norepinephrine were significantly decreased in R,D and RD groups,especially in group RD.Conclusion Ropivacaine infiltration combined with dezocine can reduce the agitation during recovery from general anesthesia in the patients undergoing cerebral surgery.
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The magnamosis device for stage-one repair of the rectovaginal tistula consists of two arc magnets. Drawing the interrupting thread along the fistula margin via the vaginal side, and pulling the string to arrange the magnets at the fistula base along the long axis of the vagina, we made the magnamosis device automatically clipped to seal the fistula. After removing the threads we kept the device for 2-4 weeks till the natural detachment of it when the compressed tissue in between healed after vascular necrosis. This device utilizing the unique ability of magnamosis to fulfill anastomosis under inflammatory infected state reduces the current high relapse rate and colostomy drawbacks of the conventional rectovaginal neoplasty.
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Female , Humans , Gynecologic Surgical Procedures , Methods , Magnetics , Magnets , Pressure , Rectovaginal Fistula , General Surgery , Wound HealingABSTRACT
Objective To investigate the prognostic value of lymph node status evaluated by computed tomography (CT) in cervical carcinoma treated with radical chemoradiation therapy.Methods 209 patients with FIGO stage Ⅰ B-ⅣA uterine cervical carcinoma treated with radical chemo radiation therapy were enrolled.Lymph node status was evaluated based on site,number and size respectively by CT.Kaplan-Meier method was used to analyze the impact of lymph node status as well as other pathoclinical factors on overall survival (OS).Cox regression model was used to explore the relationship between independent prognostic factors and OS.Results Lymph node metastasis rates for stage Ⅰ B,Ⅱ,Ⅲ and ⅣA patients were 16.7 % (1/6),48.2 % (68/141),57.4 % (31/54) and 87.5 % (7/8),respectively.Variate analysis showed that FIGO stage,anemia before treatment,para-aortic lymph node metastasis,and the number (≥3) and size (maximum diameter ≥ 2.0 cm) of CT positive lymph node were significant unfavorable prognostic factors for OS (P < 0.05).FIGO stage,the number of lymph nodes metastasis,pathologic diagnosis and treatment regimen were identified to be independent prognostic factors in multivariate analysis.Conclusion Under current therapeutic strategy of concomitant chemoradiotherapy,lymph node metastatic status evaluated by pretreatment CT is still a significant and independent prognostic factor for cervical cancer.
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Objective To determine the expression of human telomerase reverse transcriptase (hTERT) and P53 in thyroid carcinoma and its relationship with development and prognosis of the carcinoma. Methods Totally 90 cases of thyroid specimens (60 thyroid carcinomas, 10 thyroid adenomas, 10 goitres and 10 normal thyroid tissues) were studied by SP immunohistochemical method. Results Positive immunoreactivity of hTERT and P53 was higher in thyroid carcinoma (P<0.05). The positive rates of hTERT and P53 were higher in undifferentiated carcinomas, carcinomas with lymph nodes metastasis or at stage Ⅲ+Ⅳ than in well-differentiated carcinomas, carcinomas without lymph nodes metastasis or at stage Ⅰ+Ⅱ (P<0.05). The expression of hTERT was significantly related with that of P53 (P<0.05). Conclusion Over-expressed hTERT and P53 may be related to the carcinogenesis and progression of thyroid carcinoma and hTERT expression is related to P53 protein. Examination of expression of hTERT and P53 proteins may be helpful to judge the thyroid cancer's behavior and prognosis.
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Objective To investigate the protective effects of midazolam on noise-induced hearing loss in guinea pigs by testing reactive oxygen species (ROS) level in the cochlea and plasma SOD and MDA. Methods Totally forty male pigmented guinea pigs were randomly divided into four groups: control (C) , midazolam (M), normal saline (S) and noise-induced deafened (D) groups, with ten guinea pigs in each. Groups M, S and D were exposed to a continuous noise (4kHz , octave band, 100dB SPL) 3h every day for 3 consecutive days. Group M was treated with midazolam, which was administered intramuscularly (0.1mg/kg) 24h before noise exposure, and immediately upon and during noise exposure. Group S was exposed to noise and treated with the same volume of normal saline intramuscularly, the time of injection was the same as that of Group M. Group C was not exposed to noise, but was treated with midazolam intramuscularly, the time of injection and the dosage were the same as those of Group M. Group S was exposed to noise and treated with normal saline intramuscularly ,the time of injection was same with that of Group M.Group D was exposed to noise only. All animals received auditory brainstem response (ABR) threshold recording before and immediately after noise exposure. Blood was collected when the guinea pigs were killed after the last ABR threshold recording, and serum SOD activity and MDA content were detected. Both the cochleae were removed and prepared for ROS assay. Results After noise exposure, ABR threshold shift (1.6±1.5) and ROS content [(291.10±2.30)u/mL] in Group M were significantly lower than those in Groups S and D [41.7±3.3, 44.3±3.9; (348.52±3.60)u/mL, (315.56±6.70)u/mL, P<0.05]. Serum SOD activity and MDA content were significantly increased in Group M, but the amplitude was less than that in Groups S and D.Conclusion Midazolam can prevent noise-induced hearing loss by reducing the increased ROS level in the cochlea after noise exposure.
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Objective To study the epidemiological patterns of HIV infection prevalent in HongKong.Method The epidemiological patterns of HIV infection in HongKong were analyzed with a mathematic model SI by changing its initial condition,which was used to test the related data.Results The changeable patterns of susceptible accumulative numbers of HIV infection in HongKong and the epidemiological curves and the curve of infection velocity were obtained.Conclusion The epidemic pattern of HIV infection in Hongkong and local infection velocity from 1987 to 2004 were well described using the epidemic model SI.An accumulation of 2 733 cases of HIV infection will be predicted in the year of 2005.The epidemic peak occurred in 2002 to 2004 and the overall HIV epidemic will last for 50 years approximately.
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Objective To determine the expression of P53 and P21 (WAF1/CIP1) in thyroid carcinomas and its relationship with development and prognosis of the carcinoma. Methods 90 cases of thyroid tissues (60 thyroid carcinomas, 10 thyroid adenomas, 10 goitres and 10 normal thyroid tissues) were studied by SP immunohistochemical method. Results Positive immunoreactivity of P53 and P21(WAF1/CIP1) was found only in thyroid carcinomas. The positive rate of the P53 and P21 is 53.3% and 41.7% respectively. The positive-staining rates of P53 were higher in cases of undifferentiated carcinomas, positive metastasis lymph nodes or in stage Ⅲ, Ⅳ than those in the cases of well-differentiated, no metastasis lymph nodes, or in stage Ⅰ,Ⅱ. In addition, the positive-staining of P21(WAF1/CIP1) were lower in cases of undifferentiated carcinomas, positive metastasis lymph nodes or stage Ⅲ, Ⅳ than that in the cases of well-differentiated, no metastasis lymph nodes or in stage Ⅰ,Ⅱ. The P21 (WAF1/CIP1) expression rate in the P53 positive group was lower than that in the P53 negative group (P<0.05). Conclusion The expression of P21(WAF1/CIP1) protein in thyroid cancer is related to P53-depend pathway and P53-independent pathway, mainly the P53-depend pathway. Examination of expression of P53 and P21 (WAF1/ CIP1) proteins may be helpful to judge the thyroid cancers behavior and prognosis.