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Objective To explore the clinical efficacy and safety of domestic programmed death-1(PD-1)ingibitor combined with lenvatinib in the treatment of advanced hepatocellular carcinoma in the elderly.Methods The clinical data of 37 elderly patients(o-ver 60 years old)with advanced hepatocellular carcinoma,who received domestic PD-1 inhibitors combined with lenvatinib in Zhengzhou Yihe Hospital from September 2021 to July 2022 were collected.Modified Response Evaluation Criteria in Solid Tumors(mRECIST)was used to evaluate the efficacy of intrahepatic lesions,and Response Evaluation Criteria in Solid Tumors(RECIST)1.1 was used to evaluate the efficacy of extrahepatic metastatic lesions.Kaplan-Meier method was used to evaluate the survival curve.Results Among the 37 elderly patients with hepatocellular carcinoma,8 patients achieved partial response,15 patients achieved stabilization,and 14 patients a-chieved disease progression.The objective response rate and the disease control rate were 21.6%(8/37)and 62.2%(23/37),respec-tively,and the median progression-free survival time was 5.885months(95%CI:5.374-6.397 months).The overall incidence rate of treatment-related adverse events was 51.4%(19/37).The most common adverse events were fatigue 27.0%(10/37),rash 27.0%(10/37)and hypertension 21.6%(8/37).Conclusion Domestic PD-1 inhibitors combined with lenvatinib is an effective and safe therapy for elderly patients with advanced hepatocellular carcinoma.
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BACKGROUND@#Ever-growing tissue regeneration causes pressing need for large population of stem cells. However, extensive cell expansion eventually leads to impaired regenerative potentials. In this study, chromobox protein homolog 7 (CBX7) was overexpressed to rejuvenate late passage dental pulp stem cells (DPSCs-P9). @*METHODS@#The recruitment of copper ions (Cu2+ )-activated hypoxia-inducible factor-1a (HIF-1a) to the CBX7 gene promoter was confirmed by chromatin immunoprecipitation assay. Functions subsequent to Cu2+ -induced or recombinant overexpression of CBX7 on proliferation, multipotency, odontoblastic differentiation and angiogenesis were investigated in vitro, while murine subcutaneous transplantation model was used to further detect the effects of Cu2+ -induced CBX7 overexpression in vivo. @*RESULTS@#Our data displayed that CBX7 overexpression maintain proliferation and multipotency of DPSCs-P9 almost as strong as those of DPSCs-P3. Both gene level of odontoblast-lineage markers and calcium precipitation were nearly the same between CBX7 overexpressed DPSCs-P9 and normal DPSCs-P3. Moreover, we also found upregulated expression of vascular endothelial growth factor in DPSCs-P9 with CBX7 overexpression, which increased the number of capillary-like structures and migrating co-cultured human umbilical vein endothelial cells as well. These findings indicate CBX7 as an effective factor to rejuvenate late passage stem cells insusceptible to cell expansion. Cu2+ has been proved to achieve CBX7 overexpression in DPSCs through the initiation of HIF-1a-CBX7 cascade. Under Cu2+ stimulation since P3, DPSCs-P9 exhibited ameliorated regenerative potential both in vitro and in vivo. @*CONCLUSION@#Long-term stimulation of Cu2+ to overexpress CBX7 could be a new strategy to manufacture large population of self-renewing stem cells.
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Chronic stress impairs radial neural stem cell (rNSC) differentiation and adult hippocampal neurogenesis (AHN), whereas promoting AHN can increase stress resilience against depression. Therefore, investigating the mechanism of neural differentiation and AHN is of great importance for developing antidepressant drugs. The nonpsychoactive phytocannabinoid cannabidiol (CBD) has been shown to be effective against depression. However, whether CBD can modulate rNSC differentiation and hippocampal neurogenesis is unknown. Here, by using the chronic restraint stress (CRS) mouse model, we showed that hippocampal rNSCs mostly differentiated into astrocytes under stress conditions. Moreover, transcriptome analysis revealed that the FoxO signaling pathway was involved in the regulation of this process. The administration of CBD rescued depressive-like symptoms in CRS mice and prevented rNSCs overactivation and differentiation into astrocyte, which was partly mediated by the modulation of the FoxO signaling pathway. These results revealed a previously unknown neural mechanism for neural differentiation and AHN in depression and provided mechanistic insights into the antidepressive effects of CBD.
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Animaux , Humains , Souris , Cannabidiol/pharmacologie , Différenciation cellulaire , Dépression/prévention et contrôle , Hippocampe/métabolisme , Cellules souches neurales , Neurogenèse/physiologieRésumé
Objective:To investigate the efficacy and prognostic factors of palliative radiotherapy for advanced gastric cancer.Methods:From January 2013 to December 2018, the clinical data of 390 patients with advanced gastric cancer in the Cancer Center of Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected. Patients were divided into two groups—combined chemoradiotherapy group ( n=95) and chemotherapy alone group ( n=295) according to the treatment method. Patients were followed up by outpatient reviews, phone calls or text messages at regular intervals. The clinical efficacy and prognostic factors of palliative radiotherapy in patients with advanced gastric cancer were retrospectively analyzed. Results:The median survival time and the 6-month, 1-year, 2-year survival rates of combined chemoradiotherapy group and chemotherapy alone group were respectively 28.07 months versus 11.27 months, 89.0% versus 69.0%, 68.0% versus 40.0%, 51.0% versus 15.0%. The survival rate of the combined chemoradiotherapy group was significantly higher than that of the chemotherapy alone group ( χ2=27.400, P<0.001). The median survival time of the combined chemoradiotherapy group was significantly longer than that of chemotherapy alone group in both 289 first-time diagnosed patients ( χ2=23.681, P<0.001) and 101 recurrent gastric cancer patients ( χ2=5.164, P=0.023), with median survival time being 28.07 months versus 11.47 months and 16.37 months versus 10.53 months respectively. Chemotherapy regimen before radiotherapy ( χ2=7.019, P=0.030), disease control before radiotherapy ( χ2=4.689, P=0.030), Eastern Cooperative Oncology Group (ECOG) score before radiotherapy ( χ2=8.529, P=0.014) and radiotherapy area ( χ2=4.763, P=0.029) were factors influencing the prognosis of patients with advanced gastric cancer undergoing palliative radiotherapy. Multivariate analysis showed that ECOG score ( HR=2.252, 95% CI: 1.288-3.935, P=0.004) and disease control before radiotherapy ( HR=2.604, 95% CI: 1.183-5.730, P=0.017) were independent prognostic factors. Conclusion:The efficacy of combined chemoradio-therapy is significantly better than chemotherapy alone in both first-time diagnosed and recurrent advanced gastric cancer. Chemotherapy regimen before radiotherapy, disease control before radiotherapy, ECOG score before radiotherapy and radiotherapy area are factors influencing the prognosis of patients with advanced gastric cancer undergoing palliative radiotherapy. ECOG score and disease control before radiotherapy are independent prognostic factors.
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Objective To explore the diagnostic value of thyroglobulin measurement with fine‐needle aspiration ( FNA‐Tg ) in detecting papillary thyroid carcinoma ( PTC ) metastatic lymph nodes ,and analyze the impact of different factors on the diagnostic accuracy of FNA‐Tg . Methods One hundred and fifty‐four lymph nodes from 138 patients w ho underwent total thyroidectomy and cervical lymphadenectomy were enrolled . Ultrasonography ,fine needle aspiration cytology ( FNAC) and FNA‐Tg results were acquired in all patients . T he diagnostic value of FNAC ,FNA‐Tg and the combination of the two methods were compared in suspicious PTC metastatic lymph nodes . T he influence of lymph nodes size ,lymph nodes cystic change and serum thyroglobulin antibody( TgAb) on the accuracy of FNAC and FNA‐Tg were analyzed . Results T he sensitivities of FNAC ,FNA‐Tg ,and the combination of the two methods in the diagnosis were 79 .5% , 95 .5% and 97 .7% ,respectively . T he specificities were 100% ,93 .9% and 100% ,respectively . T he size and cystic change of lymph nodes had effects on the accuracy of FNAC( P <0 .05) ,w hile they had no effect on the accuracy of FNA‐Tg ( P =0 .42 ,0 .67 ) . T he serum TgAb level had no influence on the accuracy of FNAC and FNA‐Tg ( P = 0 .88 ,0 .34 ) . Conclusions FNA‐Tg is sensitive to metastatic lymph nodes in PTC w hich not affected by the lymph nodes size ,the lymph nodes cystic change and serum TgAb level . Application of FNA‐Tg with FNAC can improve the sensitivity of diagnosis ,w hich is important in the diagnosis of PTC metastatic lymph nodes .
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<p><b>OBJECTIVE</b>To explore the genetic basis for a Chinese pedigree affected with congenital hypofibrinogenamia.</p><p><b>METHODS</b>Peripheral blood samples were collected from 9 members from the pedigree. Routine coagulation tests including activated partial thromboplastin time (APTT), thrombin time (TT), the prothrombin time (PT) were carried out. The activity of fibrinogen (Fg: C) was measured using Clauss method, and fibrinogen antigen (Fg: Ag) was measured with immunoturbidimetry. All exons and exon-intron boundaries of the fibrinogen Aα, Bβ and γ chain genes were amplified using PCR, which was followed by direct sequencing. Suspected mutation was confirmed by reverse sequencing. The mutant fibrinogen was analyzed with Swiss-PdbViewer.</p><p><b>RESULTS</b>The proband showed prolonged APTT, PT and TT. Her functional fibrinogen (Fg: C) and antigen fibrinogen (Fg: Ag) levels were reduced to 0.69 g/L and 0.72 g/L, respectively. Her mother and grandmother also had a low levels of fibrinogen, which were 0.99 g/L and 0.83 g/L for Fg: C, 1.02 g/L and 0.87 g/L for Fg: Ag, respectively. The results of other members from the pedigree were all within the normal range. Genetic analysis reveled a heterozygous G>T mutation at nucleotide 7590 in exon 8 of γ gene in the proband, which was predicted to be a novel Ser313Ile mutation. The mutation was also found in her mother and grandmother. Model analysis showed that the Ser313Ile mutation disturbed the hydrogen bonds between Ser313, Asn319 and Asp320. Moreover, the mutation also altered the mutual electrostatic force and affected the folding and instability of the mutant fibrinogen.</p><p><b>CONCLUSION</b>The heterozygous Ser313Ile mutation probably underlies the hypofibrinogenemia in this pedigree.</p>
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Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Afibrinogénémie , Génétique , Fibrinogène , Chimie , Génétique , Hétérozygote , Mutation , PedigreeRésumé
Objective To investigate the application value of shear wave elastography (SWE) combined with superb micro-vascular imaging (SMI) in differentiating malignant and benign thyroid masses.Methods Seventy-eight patients diagnosed by ultrasound and verified with postoperative pathological analysis were enrolled.Conventional two-dimensional ultrasound was applied to observe the masses.SWE was performed to evaluate the elasticity and the Young's modulus (AveT1) value acquired.ROC curve was drawn to calculate the sensibility and specificity using the cut-off value of AveT1.SMI was applied to define Adler's grading standard according to the degree of blood supply.The sensitivity,specificity and accuracy of SWE and SWE combined with SMI in differentiating malignant and benign thyroid masses were analyzed.Results ①According to pathological analysis,there were 42 benign and 44 malignant masses;②The AveT1 value between malignant and benign groups were all significantly different (P <0.01).41.4 kPa was used as the best cut-off value of AveT1.The area under the ROC curve were 0.83 with sensitivity 86.9% and specificity 88.1%;③There were more masses with the Alder class Ⅱ-Ⅲ in malignant group than those in benign group,and the difference was statistically significant (P <0.01);④Quantified with SWE or SWE combined with SMI,the sensitivity were 86.9% and 91.3%,specificity were 88.1% and 92.8%,and accuracy were 87.5% and 94.1 %,respectively,and the difference was statistically significant (P < 0.01).Conclusions SWE combined with SMI represents an excellent application value in differentiating malignant and benign thyroid masses,which could improve the sensitivity,specificity and accuracy of the diagnosis for thyroid masses using ultrasound.
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Myeloma is a malignancy associated with significant immune dysfunction imparted by both the disease itself as well as many of the immunosuppressive therapies that have been used in the past.The growing body of preclinical data regarding immunoregulatory mechanisms that appear active in myeloma has begun to be translated to clinical trials targeting these signalling axes.This review summarized the current understanding of the basic biology of several immune checkpoint pathways that may be important in myeloma and provide an up-to-date overview of recent and ongoing clinical trials of immune checkpoint inhibitors in myeloma.Finally,several current challenges and possible future direction of immune checkpoint blockade in myeloma will be reviewed.
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Objective To explore the effect of token on the pain and compliance of wound care of postoperative children with hypospadias, and provide evidence for the pain management and psycho-behavior intervention of children. Methods Selected 80 cases of hypospadias and they were assigned to the experience group and the control group. The control group was guided by conventional nursing intervention method while the experience group was guided by token intervention. Compare the pain score and compliance of two groups. Results The pain score of the experience group were (2.65±1.89), (2.40± 1.73), (2.10±1.43) points, the control group were (4.10±2.52), (3.35±2.09), (2.90±1.75) points. There were significant differences between the two groups (t=2.912, 2.399,- 2.239, all P<0.05). There were significant differences between the two groups for the compliance (χ2=5.415, 7.587, 9.372, all P<0.05). Conclusion Token can relief the pain of wound care of postoperative children with hypospadias, increase the compliance of wound care of the children.
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Objective@#To explore the feasibility and therapeutic effect of single-staged Han-uvulopalatopharyngoplasty with septoplasty in adults with obstructive sleep apnea-hypopnea syndrome.@*Methods@#Ninety six cases with OSAHS were diagnosed by polysomnography, and they all had retropalatal obstruction and deviation of nasal septum. Patients were divided into study group(48 cases) and control group(48 cases) randomly. Cases in study group were simultaneously treated with Han-uvulopalatopharyngoplasty and septoplasty, while cases in control group were only treated with Han-uvulopalatopharyngoplasty. U saturation skill and coblation-assisted were applied in Han-uvulopalatopharyngoplasty. And nasal septum suture technique was applied in septoplasty. The observation index included the intranasal changes with acoustic rhinometry, the prevalence of common postoperation complications and curative effects after six months follow-up period. SPSS 18.0 was used for statistical analysis.@*Results@#In study group the overall response rate was 83.33%(40/48), while in control group the overall response rate was 62.50%(30/48). There was statistical significance of response rate between test group and control group(χ2=5.275, P<0.05). There was no statistical significance on complication rate between study group and control group(P>0.05). There was no statistical significance on preoperative measurement data(P>0.05).@*Conclusion@#For OSAHS patients with obstructive level at retropalatal plane and nasal plane, Han-uvulopalatopharyngoplasty combined with septoplasty in one stage is safe and effective.
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Objective@#To investigate the pathogen spectrum distribution and drug resistance of febrile neutropenic patients with hematological diseases in Shanghai.@*Methods@#A retrospective study was conducted on the clinical isolates from the febrile neutropenic patients hospitalized in the departments of hematology in 12 general hospitals in Shanghai from January 2012 to December 2014. The drug susceptibility test was carried out by Kirby-Bauer method. WHONET 5.6 software was used to analyze pathogenic bacteria and drug susceptibility data.@*Results@#A total of 1 260 clinical isolates were collected from the febrile neutropenic patients. Gram-positive bacteria accounted for 33.3% and Gram-negative bacteria accounted for 66.7%. Klebsiella pneumoniae (12.5%) , Stenotrophomonas maltophilia (9.5%) , Escherichia coli (9.1%) , Pseudomonas aeruginosa (8.7%) , Acinetobacter baumannii (6.6%) , Staphylococcus aureus (5.6%) and Enterococcus faecium (5.0%) were ranked in the first 7 of all pathogens. In the respiratory tract secretions specimens, non-fermented strains accounted for 56.2%. Stenotrophomonas maltophilia accounted for 15.2%. Enterobacteriaceae and coagulase-negative Staphylococci accounted for 42.3% (104/246) and 32.6% (85/246) respectively in blood samples. Enterobacteriaceae and Enterococcus bacteria accounted for 39.4% (76/193) and 28.5% (55/193) respectively in pus specimens. The detection rates of methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase negative Staphylococci (MRCNS) were 54.3% and 82.5%, respectively. Staphylococcus bacterial strain was not found to be resistant to linezolid, vancomycin and teicoplanin. The detection rate of Enterococcus vancomycin-resistant strains was 8.9%. Enterococcus was not detected resistance to oxazolidinone strains. Enterobacteriaceae bacteria were highly sensitive to carbapenems. The resistance rate of Pseudomonas aeruginosa to imipenem and meropenem was 34.1% and 15.8%, respectively. Stenotrophomonas maltophilia was more sensitive to minocycline hydrochloride, levofloxacin and sulfamethoxazole. The resistance rate of Acinetobacter baumannii only to cefoperazone-sulbactam was less than 10.0%. The antibiotic resistance rate of Klebsiella pneumoniae, Stenotrophomonas maltophilia, Pseudomonas aeruginosa and Acinetobacter baumanii to most of common antibiotics was lower than that of the CHINET surveillance.@*Conclusions@#The pathogenic strain distribution in common infection sites of febrile neutropenic patients was characterized. Bacterial resistance surveillance was better than the CHINET nationwide large sample surveillance in China.
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OBJECTIVE:To investigate general regularity and characteristics of adverse drug reactions/events(ADR/ADE)in-duced by Dezocine injection,and to provide reference for safe and rational drug use in clinic. METHODS:Retrieved from Jiangsu Province ADR Database during Jan. 2009-Aug. 2016,ADR/ADE induced by Dezocine injection was analyzed statistically in re-spects of patient's gender and age,usage and dosage,organs/systems involved in ADR,clinical manifestations and outcome. RE-SULTS:Among 1290 ADR/ADE induced by Dezocine injection,there were 40 cases of severe ADR/ADE(3.10%);medical insti-tutions were main reporting units (1276 cases,98.81%). In ADR/ADE cases,female was more male,with ratio of male to fe-male was 1:1.45. ADR/ADE mostly occurred in 45-65 age group(43.49%). Intravenous medication was main route of administra-tion (1137 cases,88.14%). Initial dose of 577 cases was excessive dose (50.75%). ADR/ADE mainly involved gastrointestinal system (54.99%),central and peripheral nervous system (24.72%) and systemic lesions (5.20%). Severe ADR/ADE manifested as anaphylactic shock,palpitation and dyspnea,etc. But anaphylactic shock was not mentioned in drug package inserts. 1283 ADR/ADE(99.46%)were cured or improved . CONCLUSIONS:It is necessary to strengthen drug safety reevaluation of Dezocine injec-tion after being on the market,improve drug package inserts and enhance patients education as so as to reduce and avoid the occur-rence of ADR/ADE.
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Objective To investigate whether two-dimension speckle tracking imaging(2D-STI) and ICAM-1-targeted myocardial contrast echocardiography could detect the acute cellular rejection of heart transplantation at the early stage.Methods The abdominal heterotopic heart transplantation model was successfully established using Wistar and SD rats.Forty-eight rats were divided into allografts (ALLO) group (n =24) and isografts(ISO) group (n =24).Echocardiography,2D-STI and ICAM-1 targeted myocardial contrast echocardiography were performed at 1,3,5 day after transplantation respectively.After ultrasound imaging,transplanted hearts were harvested for Hematoxylin-eosin staining and immunofluorescence histochemistry to evaluate acute cellular rejection and ICAM-1 expression.Results There were obvious difference between ALLO group and ISO group in echocardiographic parameters at 5 days after transplantation surgery (all P <0.05).Compared with those in ISO group,global circumferential strain and strain rate (GCS,GCSr),and circumferential strain of endo-myocardium (CSendo) decreased in ALLO group at day 3 post-transplantation (all P<0.05).Compared with those in ISO group,all strain parameters in ALLO decreased significantly at postoperative day 5 (all P< 0.05).Myocardial contrast echocardiography using ICAM-1-targeted microbubbles showed that the video intensity in ALLO group was significant higher than that in ISO group at postoperative day 3 and day 5 (all P<0.05).Conclusions 2D-STI and myocardial contrast echocardiography using ICAM-1-targeted microbubbles are sensitive and useful for detecting heart transplant acute rejection at the early stage.
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Objective: To research the functional segments of B-FA molecule binding invariant chain and their characters. Methods:The DNA segments (α1α2, sα1α2 and α3TC ) of B-FA genes were respectively cloned and inserted into prokaryotic or eukaryotic expression plasmids,then they were singly or co-transfected with Ii gene into the engineering bacteria E. coli (BL-21)or 293T cells. After induction of expression,affinity chromatography and SDS-PAGE identification,the binding between B-FA segments and Ii molecule and co-localization in cells were observed with Pull-down and Western blot. Results:First three recombinant prokaryotic expression plasmids and four recombinant eukaryotic expression plasmids were constructed. The single molecules expressed by B-FA segments were observed after an affinity chromatography. Secondly the complexes of Ii/B-FA-α1α2 and Ii/B-FA-sα1α2 were detected by a Pull-down from the co-transfected corresponding prokaryotic expression plasmids,but no complex of Ii andα3TC,also in the western blot it was detected that B-FA-α1α2 or B-FA-sα1α2 as functional segment could bind Ii to form complex. Finally in eukaryotic expression 293T cells B-FA-sα1α2 kept localization, the same as B-FA. Conclusion: Chicken B-FA-α1α2 is function segment to bind with Ii molecule and keeps the location characters same as B-FA. The results of this research first time provide experimental evidence about B-FA functional region binding segment to Ii molecule.
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This paper discussed the roots of American ethical review system, the development of twists and turns, and puts forward the enlightenment to our country, the ethical review system mainly include:perfecting the ethical review at the top of specification design, improve specification status;improve the system of education and training, to strengthen the construction of information communication channels, establish standard operating proce-dures, improve the regulatory system;improve the system of continuous review, formulate specific implementation specification.
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<p><b>OBJECTIVE</b>To study the current situation of the prevention and treatment of silicosis in Jinshan District of Shanghai, China, and to provide a scientific basis for the introduction of preventive and control measures for the disease.</p><p><b>METHODS</b>An occupational hygienic investigation was carried out among enterprises exposed to silica dust hazard in Jinshan District using cross-sectional epidemiological study. Based on GBZ 159-2004 Specifications of air sampling for hazardous substances monitoring in the workplace and GBZ/T 192.1-2007 Method for determination of dust in the air of workplace Part 1: Total dust concentration, individual sampling and evaluation of test results were conducted among workers exposed to silica dust.</p><p><b>RESULTS</b>A total of 302 workers in 30 enterprises were exposed to silica dust, and the coverage of employment injury insurance and occupational health inspection rate were 98.3% and 92.4%, respectively. The equipment rate of anti-dust respirators of the enterprises was 56.7%, and the qualification rate of silica dust monitoring in work place was 40.4%. The enterprises exposed to silica dust were mainly those who were operated in dry condition and engaged in manual work using opening-type equipment without negative pressure.</p><p><b>CONCLUSION</b>Enterprises exposed to silica dust in Jinshan District of Shanghai have safety hazards like poor production and protective equipment, incomplete protective articles, and low qualification rate of silica dust test in workplace, so occupational health protection measures need to be strengthened.</p>
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Humains , Polluants atmosphériques d'origine professionnelle , Chine , Études transversales , Poussière , Exposition professionnelle , Santé au travail , Normes de référence , Silicose , Thérapeutique , Lieu de travailRésumé
Objective To analyze the differences with the expression of glucocorticoids receptor isoforms ( GRα, GRβ, GRγand GR-P ) and cytokines [ IL-6, macrophage migration inhibitory factor (MIF), IFN-γand IL-10] between patients with systemic lupus erythematosus (SLE) and rheumatoid ar-thritis ( RA) , and to further understand their correlations with disease activities.Methods Fifty-five pa-tients with SLE, forty-nine patients with RA and thirty-eight healthy subjects were recruited in this study. All patients were steroid-naive.The expression of GRα, GRβ, GRγ, and GR-P in peripheral blood mononu-clear cells at transcript levels were determined by real-time PCR.Enzyme-linked immunosorbent assay was used to detect the expression of IL-6, MIF, IFN-γand IL-10 in serum samples.Results The percentages of GRαin all subjects were the highest among four isoforms of GR, followed by GR-P, GRγand GRβ.Com-pared with healthy subjects, patients with SLE or RA showed significantly decreased expression of GRα( P<0.05), but increased expression of GR-P (P<0.05).The percentages of GR-P in patients with RA were higher than those in patients with SLE (P<0.05).The expression of GRαwas negatively correlated with SLE disease activity index (SLEDAI) and disease activity score 28 (DAS28).SLE or RA patients with high disease activity showed lower expression of GRαthan those with low disease activity.The levels of IL-6, IFN-γand MIF in patients with SLE or RA were significantly higher than those in healthy subjects ( P<0.05).A negative correlation was observed between the expression of IL-6 and GRαin patients with SLE (P<0.05).The expression of IFN-γwas negatively correlated with GRαin patients with RA (P<0.05). Conclusion There were significant differences with the expression of GR isoforms among patients with SLE, patients with RA and healthy subjects, indicating the change of internal environment in patients might be in-volved in GR alternative splicing.GRαwas the predominant isoform and was negatively correlated with dis-ease activities.Oversecretion of cytokines resulted in a decreased expression of GRα.This study would be useful for the diagnosis of the disease status and for monitoring clinical treatment.
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Acetylation regulated by histone deacetylases (HDAC) has a broad influence on plenty of physiological processes and regulation of malignant tumor.HDAC inhibitors can promote tumor cell apoptosis and have little effect on normal cells,so they have been developed a new kind of anti-tumor agent,and part of them have entered clinical trials.Vorinostat and romidepsin have been approved by FDA for treating cutaneous T cell lymphoma patients with progressive,persistent and recurrent disease.Studies of the molecular mechanisms of the HDAC inhibitors will contribute to the further clinical application.
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Objective To profile the omp1 genotypes of Chlamydia trachomatis (Ct) in patients with nongonococcal urethritis (cervicitis) in Guangzhou region. Methods Swab samples were obtained from the urethra of males and cervix of females in clinical settings of venereology and gynecology as well as at outreach sites for the prevention and control of sexually transmitted diseases (STDs). DNA was extracted from the swabs and nested PCR was performed to amplify the variable domain (VD) 1 - 3 of omp1 gene of Ct followed by gene sequencing. The genotypes of Ct were determined based on the amino acid mutation in VD 1 - 2 of omp1 gene. Results Totally, 1208 swabs were collected. Of them, 132 were Ct positive, and 130 positive samples underwent genotyping. Ten ompl genotypes were determined in total, including serotype E (38, 29.23%), D (25, 19.23%), J(24, 18.46%), F(21, 16.15%), G(7, 5.38%), H(5, 3.85%), K(5, 3.85%), B(2, 1.54%), Ja (2, 1.54%), I (1, 0.77%). E, D, J and F were the dominant type of Ct in this region, and amounted to 83% of all the Ct isolates. Mutations were observed within VD 1 and 2 of omp1 gene in serotype D, B and K.Serotypes were undetermined for Ct in 2 patients with mixed infection. Conclusions In Guangzhou region, E,D, F and J are the predominant genotypes of Ct, and amount to 83% of all the Ct isolates. Ct serotype B is also observed in the urethra of males and cervix of females in this region.
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In recent years, mass outbreaks of highly pathogenic (HP) porcine reproductive and respiratory syndrome virus (PRRSV) have spread all over the Chinese swine industry. Based on the first infectious cDNA clone of HP PRRSV strain pJX143 and that of an attenuated PRRSV, pAPRRS, constructed in our group, we constructed several chimeric clones with various substitutions of structural protein genes (ORF4-7) and 3' UTR between attenuated pAPRRS and virulent pJX143.Upon transfection of MA-104 cultured cells, all chimeric constructs pSX12, p5NX12, and p56N12 were rescued. The rescued viruses maintained the similar virological properties, based on the results of the growth curve of the rescued viruses. To test if the chimeric viruses can be used as a vaccine candidate, vSX12 and v56N12 vaccinated pigs were challenged with the HP PRRSV JX143 strain. As a result, the vSX12 vaccinated pigs were all seroconverted by 14-day-post vaccination, while v56N12 vaccinated pigs showed poor antibody response. Upon challenge, the vSX12-vaccinated group showed no signs of clinical PRRS syndrome, and virema period was shorten to 6 days post-challenge. Our results demonstrated that 1) vSX12 chimeric virus is a good vaccine candidate; 2) the virulence determinants of HP PRRSV probably located in coding regions other than ORF3-7 and 3' UTR, as our chimeric viruses were proved to be attenuated.