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The invalid patents associated with schistosomiasis control were retrieved in the Chinese Patent Database of China National Intellectual Property Administration, the Baiten database and the incoPat database, and the overall trends, legal status, types, patent indexing and technical fields of all retrieved invalid patents were analyzed. As of December 30, 2020, there were totally 859 patents relating to schistosomiasis control, and 512 were invalid patents, with an invalid rate of 59.6%. The number of patent applications and invalid patents peaked in 2018, including 71 patent applications and 53 invalid patents. Among the 511 schistosomiasis control-related invalid patents with complete records, there were 425 invention patents, 81 utility model patents and 5 design patents, and 219 patents (42.9%) were invalid due to the termination of the patented right and 292 (57.1%) due to loss of the right for patent applications. The major technical points included medicines (chemicals), basic research, devices and detections, and the specialized fields were mainly concentrated in A61P33, G01N33, C12N15, C07K14 and A01N65. Our data demonstrate a high invalid rate of patents relating to schistosomiasis control in China. Secondary development and mining of the invalid patents in relation to schistosomiasis are recommended to make use of their values in the national schistosomiasis elimination program of China.
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BACKGROUND@#Zinc finger and BTB domain-containing protein 46 (Zbtb46) is a transcription factor identified in classical dendritic cells, and maintains dendritic cell quiescence in a steady state. Zbtb46 has been reported to be a negative indicator of acute myeloid leukemia (AML). We found that Zbtb46 was expressed at a relatively higher level in hematopoietic stem and progenitor cells (HSPCs) compared to mature cells, and higher in AML cells compared to normal bone marrow (BM) cells. However, the role of Zbtb46 in HSPCs and AML cells remains unclear. Therefore, we sought to elucidate the effect of Zbtb46 in normal hematopoiesis and AML cells.@*METHODS@#We generated Zbtb46 and Zbtb46Mx1-Cre mice. The deletion of Zbtb46 in Zbtb46Mx1-Cre mice was induced by intraperitoneal injection of double-stranded poly (I). poly (C) (poly(I:C)), and referred as Zbtb46 cKO. After confirming the deletion of Zbtb46, the frequency and numbers of HSPCs and mature blood cells were analyzed by flow cytometry. Serial intraperitoneal injection of 5-fluorouracil was administrated to determine the repopulation ability of HSCs from Zbtb46 and Zbtb46 cKO mice. The correlation between Zbtb46 expression and prognosis was analyzed using the data from the Cancer Genome Atlas. To investigate the role of Zbtb46 in AML cells, we knocked down the expression of Zbtb46 in THP-1 cells using lentiviral vectors expressing small hairpin RNAs targeting Zbtb46. Cell proliferation rate was determined by cell count assay. Cell apoptosis and bromodeoxyuridine incorporation were determined by flow cytometry.@*RESULTS@#The percentages and absolute numbers of HSPCs and mature blood cells were comparable in Zbtb46 cKO mice and its Zbtb46 littermates (Zbtb46vs. Zbtb46 cKO, HPC: 801,310 ± 84,282 vs. 907,202 ± 97,403, t = 0.82, P = 0.46; LSK: 86,895 ± 7802 vs. 102,210 ± 5025, t = 1.65, P = 0.17; HSC: 19,753 ± 3116 vs. 17,608 ± 3508, t = 0.46, P = 0.67). The repopulation ability of HSCs from Zbtb46Mx1-Cre mice was similar to those from Zbtb46 control (P = 0.26). Zbtb46 had elevated expression in AML cells compared to total BM cells from normal control. Knockdown of Zbtb46 in THP-1 cells led to a significant increase in cell apoptosis and reduced cell growth and proliferation.@*CONCLUSION@#Collectively, our data indicate that Zbtb46 is essential for survival and proliferation of AML cells, but dispensable for normal hematopoiesis.
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Ketamine (KTM), a N-methyl-D-aspartate (NMDA) receptor antagonist, was found to has an anti-inflammatory effect, but some patients suffered from exacerbated pro-inflammatory reactions after anesthesia with KTM. The present study was aimed to examine the underlying mechanism of pro-inflammatory effects of KTM. In this study, RAW264.7 cells were exposed to KTM and NMDA alone or combined for 30 min before lipopolysaccharide (LPS) stimulation. The expression levels of IL-6 and TNF-α were detected by RT-PCR and ELISA, and those of NMDA receptors by RT-PCR in RAW264.7 cells. Additionally, the TLR4 expression was determined by RT-PCR and flow cytometry, respectively. The results showed that in RAW264.7 cells, KTM alone promoted the TLR4 expression, but did not increase the expression of IL-6 or TNF-α. In the presence of LPS, KTM caused a significantly higher expression of IL-6 and TNF-α than LPS alone. NMDA could neither alter the IL-6 and TNF-α mRNA expression, nor reverse the enhanced expression of IL-6 and TNF-α mRNA by KTM in LPS-challenged cells. After TLR4-siRNA transfection, RAW264.7 cells pretreated with KTM no longer promoted the IL-6 and TNF-α expression in the presence of LPS. In conclusion, KTM accelerated LPS-induced inflammation in RAW264.7 cells by promoting TLR4 expression, independent of NMDA receptor.
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Ketamine (KTM), a N-methyl-D-aspartate (NMDA) receptor antagonist, was found to has an anti-inflammatory effect, but some patients suffered from exacerbated pro-inflammatory reactions after anesthesia with KTM. The present study was aimed to examine the underlying mechanism of pro-inflammatory effects of KTM. In this study, RAW264.7 cells were exposed to KTM and NMDA alone or combined for 30 min before lipopolysaccharide (LPS) stimulation. The expression levels of IL-6 and TNF-α were detected by RT-PCR and ELISA, and those of NMDA receptors by RT-PCR in RAW264.7 cells. Additionally, the TLR4 expression was determined by RT-PCR and flow cytometry, respectively. The results showed that in RAW264.7 cells, KTM alone promoted the TLR4 expression, but did not increase the expression of IL-6 or TNF-α. In the presence of LPS, KTM caused a significantly higher expression of IL-6 and TNF-α than LPS alone. NMDA could neither alter the IL-6 and TNF-α mRNA expression, nor reverse the enhanced expression of IL-6 and TNF-α mRNA by KTM in LPS-challenged cells. After TLR4-siRNA transfection, RAW264.7 cells pretreated with KTM no longer promoted the IL-6 and TNF-α expression in the presence of LPS. In conclusion, KTM accelerated LPS-induced inflammation in RAW264.7 cells by promoting TLR4 expression, independent of NMDA receptor.
Subject(s)
Animals , Male , Mice , Anesthetics, Dissociative , Pharmacology , Cell Survival , Gene Expression Regulation , Inflammation Mediators , Pharmacology , Interleukin-6 , Genetics , Ketamine , Pharmacology , Lipopolysaccharides , Pharmacology , Macrophages , Metabolism , N-Methylaspartate , Pharmacology , Signal Transduction , Toll-Like Receptor 4 , Genetics , Metabolism , Tumor Necrosis Factor-alpha , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To explore the effects of basic fibroblast growth factor (bFGF) on human bone marrow mesenchymal stem cell (hBMMSC) damaged by irradiation and its underlying mechanisms.</p><p><b>METHODS</b>hBMMSC was irradiated with 0, 6, 12 Gy X ray, then flow cytometry, cell counting kit-8 (CCK-8), Western blot and alizarin red staining were used to detect the effects of X ray on apoptosis, proliferation and osteogenic differentiation of hBMMSC; 0, 1, 5, 10, 20 ng/ml bFGF was added to hBMMSC irradiated with X ray for selecting the suitable bFGF reaction concentration; then the Western blot was used to detect the expression of PDGFRα so as to evaluate whether the expression of PDGFRα participated in bFGF-mediated recovery of hBMMSC proliferation and osteogenic differentiation after irradiation.</p><p><b>RESULTS</b>The proliferation and osteogenic differentiation of hBMMSC decreased remarkably after irradiation. bFGF promoted the recovery of proliferation and osteogenic differentiation of irradiated hBMMSC compared with untreated irradiated hBMMSC (P < 0.05); 5 ng/ml bFGF was identified as the optimal concentration. A significant difference in the number of apoptotic cells could be detected only between the 0 Gy group and 12 Gy group at the 24 h time point, while no differences were detected at later time points. Irradiated hBMMSC showed remarkable decrease of PDGFRα expression, while the PDGFRα expression increased after bFGF was added.</p><p><b>CONCLUSION</b>Irradiation dose not show significant effect on apoptosis of hBMMSC, but the bFGF displays a effect on repairing the irradiation damage of hBMMSC and promotes the recovery of hBMMSC proliferation and osteogenic differentiation. The damage of hBMMSC proliferation and osteogenic differentiation associates with downregulation of PDGFRα expression induced by irrediation. PDGFRα involves in repairing effect of bFGF on irradiation damage of hBMMSC.</p>
Subject(s)
Humans , Apoptosis , Bone Marrow Cells , Cell Differentiation , Cell Proliferation , Cells, Cultured , Fibroblast Growth Factor 2 , Mesenchymal Stem Cells , Osteogenesis , Receptor, Platelet-Derived Growth Factor alphaABSTRACT
Objective The aim of the study was to investigate the epidemic situation,clinical symptom,diagnosis and epidemiological characteristics of human Fasciola gigantica infection in Dali,Yunnan province.It will also provide a scientific basis for fasciolosis control and prevention.Methods Epidemic data were collected and patient's clinical signs and symptoms were studied.Serum soluble antigen of Fasciola gigantica of patients and part of family members and health people in the same village was detected using enzyme-linked immunosorbent assay (ELISA) and the eggs of Fasciola gigantica in stool were observed under microscope.Sequencing and PCR amplification of Fasciola gigantica eggs had been done.Sequencing results were analyzed using basic local alignment search tool (BLAST) program of the U.S.National Center for Biotechnology Information (NCBI) and the similarity of the two in the sequence of nucleic acid was compared.Furthermore,patients were experimentally given orally therapeutic doses of Triclabendazole 10 mg·kg-1·d-1 daily for 2 days,and kept in the hospital for observation for one week.Moreover,host and vector were investigated in the surrounding ditches of Dali prefecture and Limnaea peregra snail samples were collected.All the snails were squashed by glass sheet in order to detect the cercarie.Cow dung and sheep manure was collected in the Limnaea peregra distribution environment,and the eggs in the feces were checked by microscope after washing and precipitation.Results All the 26 patients had a continued hyperpyrexia with distinct alimentary system symptoms of nausea,vomiting,stomachache,abdominal distension as well as hepatomegaly,sensitive to percussion,different levels of liver damage detected by CT.All the patients had an eaten history of raw Herba Houttuyniae and other aquatic plants,and the course of the disease was similar,with the same epidemiological characteristics.ELISA detection was used in the 26 patients,family members and other healthy population,the results of all the 26 patients were positive(100.0％,26/26) ; the positive rates of the 57 family members and other health people of the same village were 31.6％ (18/57) and 17.1％ (6/35),respectively.The results of sequencing and BLAST program showed that the pathogen was Fasciola gigantica with the similarity between 99％-100％.PCR amplification also confirmed that the eggs were Fasciola gigantica eggs with an approximately 1000 bp band on agarose gel.After treatment with Triclabendazole,body temperature of the patients dropped to normal and symptoms improved markedly.Moreover,329 Limnaea peregra snails were collected including 5 ones with redia and one-tailed cercariae which were preliminary identified as the larva of Fasciola gigantica.There were also eggs of Fasciola gigantica detected in one stool of cattle and one of goat.Conclusions Eating raw food is the leading cause of the onset of the disease.Triclabendazole is the drug of choice to treat Fasciolasis.Health education should be strengthened by government and disease prevention and control departments in order to make the local residents to understand the potential hazard of eating raw aquatic vegetable and drinking unboiled water,which is the key to prevent the occurrence of the disease.
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<p><b>BACKGROUND</b>Volatile anesthetics (VAs) may affect varied and complex physiology processes by manipulating Ca(2+)-calmodulin (CaM). However, the detailed mechanism about the action of VAs on CaM has not been elucidated. This study was undertaken to examine the effects of VAs on the conformational change, hydrophobic site, and downstream signaling pathway of CaM, to explore the possible mechanism of anesthetic action of VAs.</p><p><b>METHODS</b>Real-time second-harmonic generation (SHG) was performed to monitor the conformational change of CaM in the presence of VAs, each plus 100 µmol/L Ca(2+). A hydrophobic fluorescence indicator, 8-anilinonaphthalene-1-sulfonate (ANS), was utilized to define whether the VAs would interact with CaM at the hydrophobic site or not. High-performance liquid chromatography (HPLC) was carried out to analyze the activity of CaM-dependent phosphodiesterase (PDE1) in the presence of VAs. The VAs studied were ether, enflurane, isoflurane, and sevoflurane, with their aqueous concentrations 7.6, 9.5, 11.4 mmol/L; 0.42, 0.52, 0.62 mmol/L; 0.25, 0.31, 0.37 mmol/L and 0.47, 0.59, 0.71 mmol/L respectively, each were equivalent to their 0.8, 1.0 and 1.2 concentration for 50% of maximal effect (EC50) for general anesthesia.</p><p><b>RESULTS</b>The second-harmonic radiation of CaM in the presence of Ca(2+) was largely inhibited by the VAs. The fluorescence intensity of ANS, generated by binding of Ca(2+) to CaM, was reversed by the VAs. HPLC results also showed that AMP, the product of the hydrolysis of cAMP by CaM-dependent PDE1, was reduced by the VAs.</p><p><b>CONCLUSIONS</b>Our findings demonstrate that the above VAs interact with the hydrophobic core of Ca(2+)-CaM and the interaction results in the inhibition of the conformational change and activity of CaM. This in vitro study may provide us insight into the possible mechanism of anesthetic action of VAs in vivo.</p>
Subject(s)
Humans , Adenosine Monophosphate , Anesthetics, Inhalation , Pharmacology , Anilino Naphthalenesulfonates , Calmodulin , Chemistry , Physiology , Cyclic Nucleotide Phosphodiesterases, Type 1 , Fluorescence , Hydrophobic and Hydrophilic InteractionsABSTRACT
T-cell acute lymphoblastic leukemia (T-ALL) is the hematological malignancy of bone marrow characterized by the rapid proliferation and subsequent accumulation of immature T lymphocyte and mainly occurs in children and adolescents. In 1991, a kind of activating mutation of Notch 1 was found in a subset of T-ALL with chromosomal translocation t(7;9) for the first time. During the past 20 years since then, understanding of the relationship between Notch 1 activating mutation and T-ALL has been deepened and widened. This review briefly discusses the four main subtypes of Notch 1 activating mutations, also focuses on how these mutations change the normal signaling pathways and genes expression during their participation in the pathogenesis of T-ALL, and how these insights will promote the development of newly targeting therapies for patients with this aggressive form of leukemia.
Subject(s)
Humans , Mutation , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Genetics , Receptor, Notch1 , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To determine the validity of the pulmonary function equipment.</p><p><b>METHODS</b>12 young students (including six males and six females) were enrolled as our research subjects. And the values of oxygen consumption (VO(2)), carbon dioxide production (VCO(2)) and energy expenditures (EE) of the subjects under three typical activity intensities: resting, moderate intensity (on a treadmill with grade 10% and speed 2.7 km/h) and hard intensity (on a treadmill with grade 10% and speed 5.8 km/h) were measured using the pulmonary function equipment (K4b(2)) and Douglas-bag respectively. And the Douglas-bag method was used as reference and the results were compared with the other method.</p><p><b>RESULTS</b>The measured VO(2) values by using the Douglas-bag and the pulmonary function equipment under three typical activity intensities were: at rest (0.22 ± 0.03), (0.22 ± 0.05) L/min (t = 0.120, P > 0.05); moderate intensity condition (0.95 ± 0.12), (0.96 ± 0.14) L/min (t = 0.240, P > 0.05); hard intensity condition (1.63 ± 0.28), (1.54 ± 0.35) L/min (t = 1.487, P > 0.05). For VCO(2) values: at rest (0.18 ± 0.02), (0.18 ± 0.04) L/min (t = 0.425, P > 0.05); moderate intensity (0.82 ± 0.11), (0.83 ± 0.13) L/min (t = 0.579, P > 0.05); hard intensity (1.64 ± 0.27), (1.52 ± 0.39) L/min (t = 2.330, P < 0.05). And for EE values, at rest (269.40 ± 35.70), (267.02 ± 55.39) kJ/h (t = 0.200, P > 0.05); moderate intensity (1165.76 ± 148.06), (1185.91 ± 161.89) kJ/h (t = 0.326, P > 0.05); hard intensity (2062.91 ± 341.97), (1912.27 ± 483.88) kJ/h (t = 1.718, P > 0.05) respectively. The results showed that there were no significant differences between the two methods except the VCO(2) values under high intensity condition was underestimated by the pulmonary function equipment. Bland-Altman test showed that the difference of the two methods was evenly distributed by the mean and standard error of the system was 24.7 kJ/h. Our data showed the results from the Douglas-bag and the pulmonary function equipment were consistent.</p><p><b>CONCLUSION</b>Pulmonary function equipment had good validity in assessing the energy expenditure in Chinese adults.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Young Adult , Energy Metabolism , Physiology , Exercise Test , Oxygen Consumption , Physiology , Respiratory Function Tests , StudentsABSTRACT
Objective To study the elastic features of common femoral artery by echo-tracking(ET)technique in type 2 diabetic(T2DM)patients.Method 60 eases of T2DM and 60 cases in control group,were separated into groups with age,ET technique was used to evaluate the common femoral artery modulus,including pressure strain elastic modulus(Ep),stiffness parameter(β),arterial compliance (AC),augment index(AI).Results Compared with the normal group ,in the T2DM group,β and Ep of common femoral artery were significantly higher(P＜0.01,P＜0.05),and AC was significantly lower(P＜0.05),and the difference in AI was not obvious (P＞0.05).The indexes were most obviouse in 40 to 59-year-old.The correlation parameter of age with β,Ep,AC,AI was 0.74,0.76 (P＜0.001)and 0.62,0.51 (P＞0.05).Conclusion The elasticity declination of common femoral artery in T2DM patients occur in the early stages,the change in 40-59 years old is obvious.β,Ep are apparently age-related indexes,and AC,AI are not.
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<p><b>OBJECTIVE</b>To compare the long-term efficacy of procedure for prolapse and hemorrhoids (PPH) and Milligan-Morgan hemorrhoidectomy (MMH) in the treatment of III and IV degree internal hemorrhoids.</p><p><b>METHODS</b>One hundred patients were randomly divided into two groups and received PPH (n=42) and MMH (n=58) respectively. After two years, the efficacy, complications and function of defecation were compared.</p><p><b>RESULTS</b>Two years after operation, the morbidities of hydrorrhea (2.38% vs 20.69%, P=0.007), dermal neoplasm formation (9.52% vs 25.86%, P=0.040) and narrowing in the caliber of the stools (2.38% vs 18.97%, P=0.027) were significantly lower in PPH group than those in MMH group (P<0.05). The morbidities of overall complication (9.52% vs 25.86%, P=0.040) and overall abnormal function of defecation (9.52% vs 29.31%, P=0.017) were lower in PPH group than those in MMH group (P<0.05). However, there were no significant differences of the morbidity of relapse (14.29% vs 10.34%, P=0.549), patient satisfactory degree (92.86% vs 87.93%, P=0.636) and overall symptom recurrence rate (19.05% vs 25.86%, P=0.424) between the two groups.</p><p><b>CONCLUSIONS</b>Long-term efficacies of procedure for prolapse and hemorrhoids and Milligan-Morgan haemorrhoidectomy in the treatment of III and IV degree internal hemorrhoids are similar. PPH has better safety, less complications and less effect on abnormal function of defecation compared with MMH.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Hemorrhoids , Pathology , General Surgery , Mucous Membrane , General Surgery , Prolapse , Sutures , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To observe the therapeutic effect of moxibustion on AIDS patients of spleen-kidney yang-deficiency.</p><p><b>METHODS</b>Sixty-six cases of AIDS were divided into a treatment group and a control group, 33 cases in each group. All of the patients were treated with HAART, with moxibustion at Tianshu (ST 25), Shenque (CV 8), Zhongwan (CV 12), Guanyuan (CV 4) added in the treatment group for 3 months. Clinical symptoms and cell immunity were recorded before and after treatment.</p><p><b>RESULTS</b>After treatment, the effective rate was 90.9% in the treatment group, which was better than 66.7% in the control group (P < 0.05). The improvement of the score for clinical symptoms in the treatment group was superior to that in the control group (P < 0.01). After treatment, the CD4 lymphocyte counts increased in the two groups, with no significant difference between the two groups (P > 0.05). Additionally, increase of total lymphocyte count in the treatment group was superior to that in the control group (P < 0.05).</p><p><b>CONCLUSION</b>Moxibustion can increase the therapeutic effect of HAART on AIDS patients and increase the total lymphocyte count.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Acquired Immunodeficiency Syndrome , Allergy and Immunology , Therapeutics , Antiretroviral Therapy, Highly Active , Kidney , Medicine, Chinese Traditional , Moxibustion , Methods , Spleen , Yang Deficiency , Allergy and Immunology , TherapeuticsABSTRACT
Objective To appraise the diagnosis value of pleural membrane biopsy on pleural effussion.Meth- ods 218 patients with pleural effusion who were had pleual menbrane biopsy were retrospectively analyzed.Among them 165 cases were done only once,42 cases were done twice,11 cases were done three times.They were done 271 times of biopsies.Results The pleural membrane biopsy always masculine gender rate was 72.0%,1 pleural mem- brane biopsy succeeds the masculine gender rate was 59.6%,after the masculine gender rate which 2 pleural mem- branes biopsies succeeds was 69.7%.The illness complication formation rate was 8.7%.Conclusion Pleural mem- brane biopsy is a simply,safe and higher diagnosing-rate method.The different spot pleural membrane biopsy may cnhance diagnosis rate.
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<p><b>OBJECTIVE</b>To study the inhibition effect of celastrol on neovascularization.</p><p><b>METHODS</b>The effect of celastrol on the in vitro proliferation of endothelial cell of vessel (ECV) was examined by MTT assay. The effect of celastrol on endothelial cell migration, tube formation on Matrigel and Chick chorioallantoic membrane angiogenesis was also examined. Matrigel plug assay was used to evaluate the effect of celastrol on angiogenesis in vivo.</p><p><b>RESULTS</b>The proliferation of ECV was inhibited significantly by celastrol with IC(50) being 1.33 microg/ml. Celastrol inhibited endothelial cell migration and tube formation in a dose-dependent manner. Celastrol also inhibited angiogenesis both in Matrigel plug of mouse model and in chick chorioallantoic membranes.</p><p><b>CONCLUSION</b>Celastrol, which can inhibit angiogenesis, could be developed as an antiangiogenic drug.</p>