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Objective To systematically review the efficacy and safety of bevacizumab biosimilars versus original drugs in treatment of metastatic colorectal cancer.Methods PubMed,Embase,Cochrane Library,CNKI,WanFang Data,VIP and SinoMed databases were electronically searched to collect the randomized controlled trials(RCTs)of bevacizumab biosimilar in patients with metastatic colorectal cancer from inception to June 18,2023.Two reviewers independently screened the literature,extracted data,and assessed the risk of bias of the included studies,and a meta-analysis was conducted using Stata 17.0 software.Results A total of 4 RCTs involving 1 052 patients were included.The results of meta-analysis showed that no significant difference was found in overall response rate(RD=﹣0.01,95%CI ﹣0.06 to 0.05,P=0.86),progression free survival(HR=1.00,95%CI 0.91 to 1.09,P=0.94),the total incidence of adverse drug reactions(RR=1.05,95%CI 0.85 to 1.31,P=0.91)and the incidence of severe adverse events(RR=0.886,95%CI 0.377 to 2.081,P=0.60)between bevacizumab biosimilars group and original drugs group.Conclusion The current evidence shows that bevacizumab biosimilar is equivalent to original drugs in treatment of metastatic colorectal cancer.Due to limited quality and quantity of the included studies,more high quality studies are required to verify the above conclusions.
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Objective:To study the protective effect of Fuzheng Quxie prescription on liver injury by influencing the expressions of tumor necrosis factor (TNF)-α, apoptosis factor (Fas), apoptosis factor ligand (FasL), and macrophages (CD68) in the liver tissues of concanavalin A(ConA) model mice. Method:The sixty mice were randomly divided into normal group, model group,bicyclol group (62.5 mg·kg-1), and low, medium and high-dose Fuzheng Quxie prescription groups(50.3,67.0,83.8 g·kg-1). The normal group and the model group were given the equal volume of pure water for 7 d. They were fasted for 12 hours before the last administration. At 2nd hour after the last administration, phosphate buffer(PBS) was injected into the caudal vein of the normal group, and ConA (20 mg·kg-1) was injected into the caudal vein of the other groups for modeling. The animals were put to death six hours later after the injection, and the expressions of TNF-α, Fas, FasL and CD68 in liver tissues were observed by immunohistochemistry. Result:Compared with normal group, the expressions of TNF-α, Fas, FasL and CD68 in the liver tissues of the model group were significantly increased(Pα, FasL and CD68 in liver tissues of the bicyclol group were significantly decreased compared with the model group(Pα, FasL and CD68 in liver tissues were significantly decreased in medium and high-dose Fuzheng Quxie prescription groups (PPConclusion:Fuzheng Quxie prescription can effectively reduce the apoptosis of liver cells in ConA model mice by inhibiting Kupffer cells and Fas/FasL system activation.
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BACKGROUND: Human tooth bone graft has been used for bone deficiency in dental implantation, but the strength and quality of newly formed bones with human tooth bone graft are in need of sound investigation. OBJECTIVE: To investigate the compressive strength of newly formed rabbit tibia after repair with human tooth bone graft. METHODS: Orthodontic teeth, loose molars, bicuspid premolars extracted from patients were taken to prepare human tooth bone grafts. Human tooth bone graft and bovine bone graft were independently placed into the rabbit tibia defects of 5 mm in diameter. Non-injured site served as control group. RESULTS AND CONCLUSION: The newly formed rabbit tibia after repair with human tooth bone graft had more intact microstructure and higher maximum compressive strength and stiffness relative to that after repair with bovine bone graft. These findings indicate human tooth bone graft is superior to bovine bone graft in the repair of tibia defects in rabbits.
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Zoonotic pathogen Corynebacterium pseudotuberculosis is the etiological agent of Caseous lymphadenitis (CLA),a chronic infectious disease throughout almost the whole world,which is extremely difficult to control.The pathogenesis of C.pseudotuberculosis is closely related to its virulence factors.In this paper,the virulence factors of C.pseudotuberculosis are reviewed,and it is proposed to further identify and analyze the roles and correlations of other different virulence factors in the pathogenesis of C.pseudotuberculosis infection,which is important for understanding the pathogenic mechanism and identify candidate vaccine of C.pseudotuberculosis.
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Objective To explore the risk factors of cerebral infarction in youth,and to provide evidence for prevention and control. Methods A total of 105 patients aged 35 -45 years old with cerebral infarction in the affiliated hospital of Shaoxing University from January 2010 to October 2014 were recruited as the cerebral infarction group . The healthy people without neurological symptoms were recruited as the control group. The two groups were compared for the risk factors of cerebral infarction in the youth. Results Logistic regression analysis showed that high blood pressure,diabetes,lipid disorders, smoking,obesity,unstable plaque,high homocysteine and anti - cardiolipin antibodies were the risk factors for cerebral infarction in the youth. The value of ORs and 95% CIs interval value for high blood pressure,diabetes,lipid disorders, smoking,obesity,unstable plaque,high homocysteine and anti - cardiolipin antibodies was 14. 614(0. 469 -47. 273),5. 129 (1. 541 -28. 466),44. 970(2. 789 -101. 549),26. 180(1. 085 - 51. 912),45. 196(2. 572 - 205. 674),258. 786(4. 892 -367. 678),14. 585(1. 770 - 49. 662)and 5. 145(1. 005 - 20. 293),respectively. Conclusion High blood pressure, diabetes,lipid disorders,smoking,obesity,unstable plaque,high homocysteine and anti - cardiolipin antibodies were closely related with cerebral infarction in the youth,and it is necessary to prevent and control the influencing factors and diseases.
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Objective To explore the relationship between serum anti - cardiolipin antibodies( ACA ) and recurrent cerebral infarction( RCI),and to provide the clinical evidence for the prevention and treatment of RCI. Methods One hundred and ten patients with RCI,120 patients with primary cerebral infarction( PCI)and 150 healthy controls were recruited. Serum ACA was detected using quantitative enzyme linked immunosorbent assay( ELISA)and the positive rate of ACA was compared between these three patient groups. Results The positive rate of serum ACA of RCI group (31. 82%)was higher than that of PCI group( 15. 00%)( P <0. 05 ). Compared with patients above 50 years old (11. 56%),the patients under age of 50 had a higher positive rate of ACA( 57. 89%)( P <0. 05 ). There was no significant difference between males( 22. 52%)and females( 23. 53%) in positive rate of ACA( P > 0. 05 ). The recurrence rate(56. 25%)of ACA positive patients was higher than that of ACA negative patients(29. 79%)after one year follow up(P<0. 05). Conclusion Higher positive rate of serum ACA is observed in RCI patients. The PCI patients with high positive rate of serum ACA has an increased susceptibility for RCI. ACA detection is important for prediction and clinical intervention of the recurrence of cerebral infarction.
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The aim of this study was to investigate the effects of TLR2, TLR9, CD4(+)CD25(+) regulatory T cells (Treg) and transcription factor FoxP3 in the pathogenesis of children with infectious mononucleosis (IM). Thirty-five acute IM patients admitted in our hospital from April 2010 to January 2011 were enrolled in this study. Thirty-five healthy subjects were taken as control. The thirty-five patients before treatment were considered as patients in acute stage, after treatment and without clinical symptom they were thought as patients in recovery stage. The expression levels of TLR2, TLR9 and FoxP3 mRNA were detected by real time PCR using SYBR Green I. The expression of T lymphocyte subset CD4(+)CD25(+) in peripheral blood mononuclear cells was detected by flow cytometry. The results showed that the relative levels of TLR2 mRNA (4.03 ± 0.56), TLR9 mRNA (8.88 ± 1.56) in peripheral blood mononuclear cells of IM patients in acute stage were significantly higher than those of the controls [TLR2 mRNA (2.22 ± 0.57), TLR9 mRNA (3.63 ± 1.30)] and IM patients in recovery stage [TLR2 mRNA (2.76 ± 0.83), TLR9 mRNA (5.34 ± 1.60)] (P < 0.01). The result of CD4(+)CD25(+) (2.38 ± 1.32%) and relative level of FoxP3 mRNA(2.82 ± 0.90) in peripheral blood mononuclear cells of IM patients in acute stage were lower than those of the control [CD4(+)CD25(+) (7.85 ± 1.97%), FoxP3 mRNA (4.65 ± 1.23) ] (P < 0.01). There was no significant difference in CD4(+)CD25(+) (6.81 ± 1.84%), FoxP3 mRNA(4.11 ± 1.37) levels between IM patients in recovery stage and the controls (P > 0.05). It is concluded that the expression of CD4(+)CD25(+)regulatory T cells is reduced, and its special transcription factor FoxP3 mRNA is down-regulated, but expression levels of TLR2 mRNA, TLR9 mRNA are up-regulated in IM patients of acute stage.
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Child , Child, Preschool , Female , Humans , Male , Case-Control Studies , Flow Cytometry , Forkhead Transcription Factors , Metabolism , Infectious Mononucleosis , Diagnosis , Allergy and Immunology , Metabolism , Interleukin-2 Receptor alpha Subunit , Metabolism , RNA, Messenger , Metabolism , T-Lymphocytes, Regulatory , Allergy and Immunology , Metabolism , Toll-Like Receptor 2 , Metabolism , Toll-Like Receptor 9 , MetabolismABSTRACT
Discomfort of right eye and right maxilla region occurred after a dental implant placement in a patient who surfered stabilized osteofibrous dysplasia (OFD) of sphenoid sinus. In this article, the case was discussed and the relevant literature was reviewed. The possible causes of eye and maxilla discomfort may be associated with OFD, hyper allergic response to implant material and surgical trauma, and psychical factors as well.
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Humans , Dental Implantation, Endosseous , Dental Implants , Maxilla , Maxillary SinusABSTRACT
As one of the most common malignancies of the salivary glands, mucoepidermoid carcinoma had a rare frequency in mandible. A case of central mucoepidermoid carcinoma of the mandible was reported and relevant literatures were reviewed. The possible etiology, clinical symptom, radiology, histopathology, diagnosis and treatment of central mucoepidermoid carcinoma were discussed.
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Humans , Male , Carcinoma, Mucoepidermoid , MandibleABSTRACT
<p><b>OBJECTIVE</b>To study the expression profiles of osteoprotegerin (OPG) and receptor activator of nuclear factor-KB ligand (RANKL) in the distraction region and to investigate the mechanism of bone remodelling during mandibular distraction osteogenesis.</p><p><b>METHODS</b>Osteotomies were performed and external distractors were installed on the mandibles of 42 adult male SD rats. After a 5-day latency period, the distractors were activated at a rate of 0.4 mm/day for 6 days, followed by a 4-week consolidation period. Radiographs were taken, and specimens were harvested at the end of the latency period, when distraction was completed, and at of 1, 2, 3 and 4 weeks of the consolidation period. Tartrate-resistant acid phosphatase (TRAP) staining was used to detect the activated osteoclasts. Temporospatial expression of OPG and RANKL was investigated by using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Semi-quantitative analysis was used to characterize OPG,RANKL and RANK/OPG ratio.</p><p><b>RESULTS</b>In all time points, OPG and RANKL were co-localized in bone marrow lining cells, osteoblasts and newly embedded osteocytes. OPG mRNA expression increased to a peak level when distraction was completed and maintained the level until the end of 2nd week of the consolidation period. RANKL mRNA expression increased steadily until the end of 1 st week of the consolidation period and maintained a peak level until the end of 3rd week, with a slight decrease at the end of 2nd week. The RANKL/OPG ratio increased continuously and reached its highest level at the end of 3rd and 4th week of the consolidation period. TRAP positive osteoclasts were mainly detected at 2, 3 and 4 weeks of the consolidation period in bone marrow cavities and bone surfaces.</p><p><b>CONCLUSIONS</b>The temporospatial expression patterns of osteoprotegerin and RANKL suggest that osteoblasts and the lineage cell network orchestrates bone remodelling during distraction. Osteogenesis and the most activated bone resorption takes place during 3rd and 4th week of the consolidation phase.</p>
Subject(s)
Animals , Male , Rats , Bone Remodeling , Mandible , Metabolism , General Surgery , Osteogenesis, Distraction , Osteoprotegerin , Genetics , Metabolism , RANK Ligand , Genetics , Metabolism , RNA, Messenger , Genetics , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To establish a novel in-vitro culture device simulating distraction osteogenesis, and to understand the the changes of cytoskeleton of osteoblasts under different magnitudes of mechanical distraction.</p><p><b>METHODS</b>A novel in-vitro culture device simulating distraction osteogenesis was developed with titanium and silicon membrane. The expressions of F-actin cytoskeleton subjected to different magnitudes of distraction were observed in situ under a confocal laser scanning microscope, and protein levels of actin and tubulin alpha were analyzed by electrophoresis of Western blot.</p><p><b>RESULTS</b>The mode of culture device simulating distraction osteogenesis was similar to that of distraction osteogenesis used in clinic. After 24 h mechanical distraction with physiological magnitude, F-actin of osteoblasts was organized and paralleled to the direction of distraction forces. After 24 h mechanical distraction with hyperphysiological magnitude, however, F-actin of osteoblasts became reorganized and disrupted, and protein levels of actin and tubulin alpha decreased.</p><p><b>CONCLUSIONS</b>The novel in vitro culture device simulating distraction osteogenesis is suitable for the study of distraction osteogenesis in vitro. Physiological mechanical distraction causes organization and rearrangement of actin cytoskeleton. However, hyperphysiological mechanical distraction results in reorganization and disruption of actin cytoskeleton.</p>
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Animals , Rats , Actins , Cells, Cultured , Cytoskeleton , Physiology , Models, Biological , Osteoblasts , Cell Biology , Osteogenesis, Distraction , TubulinABSTRACT
Objective To evaluate the distribution of non-motor symptoms(NMS) and dominant factors impacting on the prevalence of NMS in Parkinson's disease(PD). Methods The NMS questionnaire(NMSQuest) was administered to 128 patients(PD group) and 128 healthy adults(control group).The distribution of items of NMS was analyzed between the two groups,and clinical characteristics were also collected to assess the dominant factors impacting on the prevalence of NMS. Results There were significant differences in the prevalence of NMS between the two groups(P
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<p><b>AIM</b>An in vitro cultured monolayer system of alveolar epithelial cells was used as a model to investigate the transport pathway peptides or proteins, salmon calcitonin (sCT), insulin (INS), recombinant hirudin (rHAV2), and recombinant human growth hormone (rhGH), in pulmonary epithelium in vivo.</p><p><b>METHODS</b>Human lung adenocarcinoma A549 cells formed continuous monolayers with growing polycarbonate filters of Transwell plate. Transport studies of macromolecules in the monolayer system were carried out after 6 days in culture. The transport of peptides or proteins with MW 3,400 - 22,000 was studied in cultured human lung adenocarcinoma A549 cell monolayers at different conditions.</p><p><b>RESULTS</b>The results showed that the apparent permeability coefficients (Papp) of these macromolecules across A549 cell monolayers ranged from 2 x 10(-6) to 5 x 10(-6) cm x s(-1) and exhibited good inverse correlation with molecule weight. No concentration, direction and temperature dependence were observed in the permeation of sCT, INS and rHAV2. While the Papp of rhGH in the BA direction (2.25 x 10(-6) cm x s(-1)) was significantly less than that in the reverse direction. The Papp values of rhGH were concentration and temperature independent in the AB direction.</p><p><b>CONCLUSION</b>These findings suggest that the hydrophilic peptides and proteins, salmon calcitonin, insulin, recombinant hirudin, and recombinant human growth hormone used in this study, appeared to penetrate the A549 cell monolayers via a paracellular pathway by passive diffusion mechanism.</p>
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Humans , Adenocarcinoma , Metabolism , Pathology , Biological Transport , Calcitonin , Pharmacokinetics , Cell Line, Tumor , Epithelial Cells , Metabolism , Hirudins , Pharmacokinetics , Human Growth Hormone , Pharmacokinetics , Insulin , Pharmacokinetics , Lung Neoplasms , Metabolism , Pathology , Peptides , Pharmacokinetics , Permeability , Proteins , Pharmacokinetics , Pulmonary Alveoli , Metabolism , PathologyABSTRACT
<p><b>AIM</b>To study the relationship between cellular membrane fluidity and relative bioavailability (Fr) of protein and peptide drugs combined with absorption enhancers after pulmonary administration in rats.</p><p><b>METHODS</b>A series of model drug salmon calcitonin (sCT) solutions with 6 absorption enhancers (Brij78, sodium cholate, sodium caprylate, 2-hydroxypropyl-beta-cyclodextrin, lecithin and chitosan) were prepared and then delivered to rats by pulmonary route. Serum drug concentration was determined by radioimmunoassay method. Using the techniques of electron spin resonance and fluorescence polarography, the effects of enhancers on pulmonary cellular membrane fluidity were investigated.</p><p><b>RESULTS</b>Fr values of sCT solution with some absorption enhancers (Brij78, sodium cholate, sodium caprylate, lecithin and chitosan) were significantly higher than those without enhancers. Brij78, lecithin and sodium caprylate, not only increased membrane lipid fluidity but also loosed the constitution of membrane protein. The effect of sodium cholate on membrane protein was low. Lipid fluidity was reduced and protein constitution was changed markedly, after pulmonary cellular membrane was treated by 0.5% chitosan solution. This result showed that the absorption enhancing of chitosan mainly came from its effects on membrane protein. Corresponded with lower Fr after pulmonary administration, 2-hydroxypropyl-beta-cyclodextrin (0.5% and 3%) had not significant effects on both lipid fluidity and protein constitution.</p><p><b>CONCLUSION</b>The effects of enhancers on pulmonary absorption of peptide drugs in vivo might be investigated on the grounds of determination of cellular membrane fluidity in vitro.</p>