ABSTRACT
Hepatitis C is distributed worldwide and possesses a hidden characteristic. The traditional methods of screening and diagnosis of hepatitis C infection commonly used in clinics are based on anti-HCV antibody and HCV RNA detection. Advances in HCV antigen detection technologies can apparently reduce the window period for anti-HCV antibodies, providing new clinical evidence for the early detection, diagnosis, and treatment of HCV infection. This article is a current review of HCV antigen detection methodologies, clinical applications, and detection strategies.
Subject(s)
Hepatitis C , RNA, Viral , Humans , Sensitivity and Specificity , Hepatitis C/diagnosis , Hepacivirus/genetics , Hepatitis C AntibodiesABSTRACT
Objective: To study the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with iodine-125 (125â ) seed strands implantation in patients with hepatocellular carcinoma combined with portal vein tumor thrombosis. Methods: 25 cases with diffuse intrahepatic tumor combined with tumor thrombus type â ¢/â £ requiring TIPS were simultaneously implanted with 125â seed strand. Tumor thrombus was controlled with 125I seed implantation brachytherapy to keep the TIPS pathway unobstructed, reduce the portal vein pressure, and observe the changes in the cause of death of the patients. During the same period, 30 cases without TIPS and seed strand implantation were used as controls. Data between groups were compared using t-test, Chi-Squared test or Fisher's exact test. Results: TIPS combined with 125â seed strand implantation was safe in patients with diffuse hepatocellular carcinoma combined with type III/IV portal vein tumor thrombus, and 92.0% (23/25) of the patients maintained unobstructed TIPS pathway. Compared with the control group, patients in the treatment group died of fewer lead-related complications, and most died from chronic liver failure (84.0% vs. 56.7%, χ2 = 4.771, P=0.029). The incidence of upper gastrointestinal bleeding was significantly decreased (12.0% vs. 46.7%, χ2 =7.674, P=0.006) and ascites severity was significantly improved (mild 40.0% vs. 16.7%, moderate 52.0% vs. 20.0%, severe 8.0% vs. 46.7%, χ2 =13.246 , P=0.001). Conclusions: TIPS combined with 125â seed strand implantation is safe and feasible in patients with diffuse intrahepatic tumor combined with tumor thrombus type â ¢/â £. Moreover, it can effectively keep the shunt patency and reduce portal vein pressure, thereby reducing the incidence of upper gastrointestinal bleeding and improving the degree of ascites. TIPS combined with 125â seed strand implantation may be used as a standard treatment modality for patients requiring TIPS therapy combined with tumor thrombus type â ¢/â £.
Subject(s)
Carcinoma, Hepatocellular , Hypertension, Portal , Liver Neoplasms , Portasystemic Shunt, Transjugular Intrahepatic , Thrombosis , Venous Thrombosis , Ascites/etiology , Carcinoma, Hepatocellular/pathology , Gastrointestinal Hemorrhage/etiology , Humans , Hypertension, Portal/complications , Iodine Radioisotopes , Liver Neoplasms/pathology , Portal Vein/pathology , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Retrospective Studies , Thrombosis/complications , Thrombosis/pathology , Treatment Outcome , Venous Thrombosis/complicationsABSTRACT
Objective: To investigate the efficacy, safety and prognostic factors of percutaneous biliary stent combined with iodine-125 seed chain brachytherapy (radiotherapy) in the treatment of malignant obstructive jaundice. Methods: Data of 107 cases with malignant obstructive jaundice treated with percutaneous biliary stent implantation from January 2017 to December 2020 were retrospectively analyzed. Among them, 58 cases received biliary stent combined with iodne-125 seed chain brachytherapy (study group), and 49 cases received biliary stent implantation (control group). The changes of bilirubin, stent patency time, complications, overall survival (OS) and prognostic factors were analyzed in both groups. Results: The incidence of complications in the study group and the control group were 17.2% and 18.3% respectively, and the difference was not statistically significant (P=0.974). Serum total bilirubin levels were decreased significantly in both groups at one month after surgery (P<0.001). Postoperative stent patency time was significantly better in the study group (10.0±1.6 months) (95% CI: 8.2ï½12.5) than that in the control group (5.2±0.4 months) (95% CI: 4.1ï½6.0, P<0.001). The median OS was longer in the study group (11.2±1.8 months) (95% CI: 9.2ï½12.8) than that in the control group (8.0±1.1 months) (95% CI: 8.0ï½12.8, P<0.001). Multivariate analysis result showed that stent combined with brachytherapy (HR=0.08, 95% CI:0.04ï½0.15, P<0.001) and receiving further anti-tumor therapy after surgery (HR=0.27, 95% CI:0.15~0.49, P<0.001) were independent risk factors affecting the patency of biliary stents. Preoperative percutaneous transhepatic biliary drainage (HR=0.46, 95%CI:0.28ï½0.74, P=0.002), stent combined with brachytherapy (HR=0.23, 95%CI:0.14ï½0.39, P<0.001) and receiving further anti-tumor therapy after surgery (HR=0.37, 95%CI:0.22ï½0.61, P<0.001) were independent risk factors affecting OS. Conclusion: Percutaneous biliary stent combined with brachytherapy is safe and effective in the treatment of malignant obstructive jaundice, which can significantly prolong the patency time of biliary stent and the survival time of patients.
Subject(s)
Brachytherapy , Cholestasis , Jaundice, Obstructive , Bilirubin , Brachytherapy/adverse effects , Cholestasis/complications , Humans , Jaundice, Obstructive/etiology , Jaundice, Obstructive/surgery , Retrospective Studies , Stents/adverse effects , Treatment OutcomeABSTRACT
Objective: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE)-hepatic arterial infusion chemotherapy (HAIC)-targeted-immune quadruple therapy in patients with intermediate and advanced-stage hepatocellular carcinoma (HCC). Methods: 101 patients with intermediate and advanced stage HCC were enrolled according to the inclusion and exclusion criteria, and then they were divided into a combination group and a control group. Patients in the combination group was treated with TACE-HAIC-targeted-immune quadruple therapy, while the control group was only treated with TACE therapy. The overall survival (OS), progression-free survival (PFS), and treatment-related adverse reactions were statistically analyzed in the two groups of patients. Statistical analysis was carried out by t-test, χ2 test, rank sum test, Kaplan-Meier curve, log-rank test, Cox regression (or proportional hazards model) analysis according to different data. Results: The tumor objective response rate and disease control rate as evaluated by mRECIST 1.1 criteria in the combination group were 80% and 94%, respectively, which were significantly higher than those in the control group, 41.2% (P<0.001) and 74.5% (P=0.007). The OS and PFS of the combination group were 15.6 months [95%CI 11.3-NA ] and 8.8 months [95%CI 6.9-12.0], respectively, which were significantly better than the control group at 6.1 months [95%CI 5.3-6.6] (P<0.001) and 3.2 months [95%CI 3.0-3.6] (P<0.001). Gastric ulcer incidence was significantly higher in the combination group (9/50, 18%) than that in the control group (2/51, 3.9%) (P=0.023). Conclusion TACE-HAIC-targeted-immune quadruple therapy is a more effective treatment mode for intermediate and advanced-stage HCC than TACE alone, and attention should be paid to the monitoring of target immune-related adverse reactions.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Retrospective Studies , Infusions, Intra-Arterial , Treatment OutcomeABSTRACT
Objective: The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China. Methods: This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems. Results: According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%). Conclusion: Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.
Subject(s)
Hypertension, Portal , China/epidemiology , Hepatic Veins , Humans , Hypertension, Portal/diagnosis , Liver Cirrhosis , Portal PressureABSTRACT
Objective: To investigate the expression of Fermintin family homologous protein 2 (FERMT2) in non-small cell lung cancer and its clinical significance. Methods: Seventy-two patients with non-small cell lung cancer were collected at Xinxiang Central Hospital, Henan Province, from January 2015 to January 2017.There were 48 male and 24 female patients, the age ranged from 37 to 78 years (mean 58 years). The expression of FERMT2 in tumor samples and para-cancerous tissues were detected by immunohistochemistry. Protein and mRNA expression of FERMT2 were detected by Western blot and real-time fluorescence quantitative PCR, respectively. Western blot method was also used to detect integrin-related protein expression, including integrin beta 1 (CD29), vascular cell adhesion molecule (VCAM1), and mobile related protein-1 (MRP1). Results: Immunohistochemistry showed that the positive rates of FERMT2 expression were 81.9%(59/72)in carcinoma tissue and 15.4%(11/72) in para-cancerous tissues, and the difference was statistically significant (P<0.01). Positive FERMT2 expression was different in tumors at different tumor stages: 11/17 at stage â , 16/20(80.0%)at stage â ¡, 17/20(85.0%)at stage â ¢, and 15/15 at stage â £, and there was a significant difference between each stage (P<0.01). By real-time PCR and Western blot, the expression of FERMT2 in non-small cell lung cancer tissues was significantly higher than that of para-cancerous tissue (P<0.01). The expression levels of integrin related proteins (integrin ß1, VCAM1 and MRP1) in tumor tissues were significantly higher than those in para-cancerous tissues, and positively correlated with the expression of FERMT2 (r=0.531, P<0.01; r=0.483, P<0.01; r=0.612, P<0.01). Conclusions: FERMT2 is highly expressed in non-small cell lung carcinomas. Its expression is closely correlated with the tumor clinical stage. It is hypothesized that FERMT2 may promote tumor metastasis through interactions with integrin-like protein.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Adult , Aged , Blotting, Western , Female , Humans , Immunohistochemistry , Male , Membrane Proteins , Middle Aged , Neoplasm Proteins , Real-Time Polymerase Chain ReactionABSTRACT
Chondrocytes, which are embedded within the growth-plate or the intervertebral disc, are sensitive to environmental stresses, such as inflammation and hypoxia. However, little is known about the molecular signaling pathways underlying hypoxia-induced mitochondrial dysfunction and apoptosis in chondrocytes. We first examined the apoptosis, caspase-3 activity, and apoptosis-associated markers in human chondrocyte cell line C28/I2 under normoxia or hypoxia. We then investigated mitochondrial dysfunction and the activation of cyclic adenosine monophosphate response element-binding protein (CREB) signaling in the same human chondrocyte cell line. Our results indicated that hypoxia induced apoptosis and reduced CREB phosphorylation in chondrocytes. Upregulated mitochondrial superoxide and reactive oxygen species levels, and reduced mitochondrial membrane potential and complex IV activity were observed in hypoxia-treated C28/I2 cells. In conclusion, the present study confirmed reduced CREB phosphorylation, apoptosis induction, and mitochondrial dysfunction in the hypoxia-treated chondrocyte cells. This implies the key role played by CREB signaling in hypoxia-induced mitochondrial dysfunction and apoptosis in chondrocytes.
Subject(s)
Chondrocytes/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Mitochondria/metabolism , Apoptosis/genetics , Cell Hypoxia/genetics , Cell Line , Chondrocytes/pathology , Cyclic AMP Response Element-Binding Protein/biosynthesis , Electron Transport Complex IV/genetics , Humans , Membrane Potential, Mitochondrial/genetics , Mitochondria/pathology , Phosphorylation , Reactive Oxygen Species/metabolism , Signal Transduction , Superoxides/metabolismABSTRACT
Objective: To summarize the effects of disease-modifying drugs for spinal muscular atrophy (SMA) on the ventilation support of type 1 children after acute respiratory failure. Methods: A case-control study was conducted, including the data of clinical characteristics, medication and ventilation supports of 38 SMA patients of type 1 with pneumonia and acute respiratory failure hospitalized in Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2020 to July 2023. Children were divided into the treatment group and the untreated group based on whether they started and persisted in using Nusinersen or Risdiplam or not before hospitalization. The differences of ventilation support between the 2 groups were analyzed. The children of the treatment group were divided into the improved group and the unimproved group based on whether they could be avoid of prolonged dependence on continuous mechanical ventilation in the next six months after discharge. The differences in clinical characteristics between the two groups were analyzed. T-test and χ2 test were used for comparison. Results: Among the enrolled children, 19 were male and 19 were female. The age was 1.3 (0.6, 2.0) years at the time of hospitalization due to pneumonia. There were 26 cases in the treatment group and 12 cases in the untreated group. The treatment group had a higher proportion of patients without prolonged dependence on continuous mechanical ventilation in the next six months after discharge (69% (18/26) vs. 2/12, χ2=9.10, P<0.05). Eighteen children were improved among the treated group, while 8 children were not. The improved group had a larger age of first onset of acute respiratory failure (1.6 (0.4, 3.4) vs. 0.5 (0.3, 0.7) years, Z=2.07, P<0.05), a longer duration of medication taken before hospitalization (3.6 (2.4, 8.7) vs. 1.2 (1.2, 2.4) months, t=2.74, P<0.05), and a smaller proportion with underlying diseases (1/18 vs. 6/8, χ2=13.58, P<0.05). Conclusions: SMA disease-modifying drugs are useful for type 1 children to avoid of prolonged dependence on continuous mechanical ventilation after acute respiratory failure. The patients who take medication longer, or have acute respiratory failure for the first-time at an older age, or without underlying diseases are more likely to avoid of.
Subject(s)
Respiration, Artificial , Respiratory Insufficiency , Spinal Muscular Atrophies of Childhood , Humans , Female , Male , Respiratory Insufficiency/therapy , Respiratory Insufficiency/etiology , Infant , Case-Control Studies , Spinal Muscular Atrophies of Childhood/therapy , Spinal Muscular Atrophies of Childhood/drug therapy , Child, Preschool , Oligonucleotides/therapeutic use , Pneumonia , HospitalizationABSTRACT
Objective: To explore the effect of cell division cycle 42 (CDC42) on root development and its regulation on cell proliferation and migration in Hertwig's epithelial root sheath (HERS). Methods: Trace the spatiotemporal expression of CDC42 in root development process [postnatal day 5 (P5), P7, P14] through immunofluorescence staining. Nine eight-week-old C57BL/6J male mice were randomly divided into 3 groups using a simple random sample method (n=3 in each group). P3 tooth germ was cultured in air-liquid system for 1 day and then transplanted to renal capsule each to observe tooth root development. The control group implanted tooth germ only. The phosphate buffered saline (PBS) group implanted tooth germ and gel beads soaked with PBS, while the ML141 group implanted tooth germ and gel beads soaked with CDC42 inhibitor (ML141). Cdc42 in HERS cells was inhibited via lentivirus transfection. Cell counting kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay and scratch assay were performed. The distribution of Golgi apparatus (GM130) and cytoskeleton (F-actin) in migrated cells were mapped via immunofluorescence staining. Results: CDC42 was expressed in epithelial cells of HERS, polarized ameloblasts and odontoblasts, as well as adjacent dental papilla and dental follicle cells during tooth root development. The root length of the ML141 group [(0.61±0.09) mm] was substantially shorter than that of control group [(1.03±0.19) mm, P=0.007] and PBS group [(0.98±0.10) mm, P=0.021] according to the data of renal capsule transplantation. After lentiviral transfection, the relative expression of Cdc42 in knockdown group (0.31±0.33) was significantly lower than that in control group (1.05±0.08) (t=15.38, P<0.001), demonstrating the knockdown efficiency closed to 70%. Cell viabilities were significantly inhibited in knockdown group (0.87±0.04, 0.96±0.10, 0.59±0.06, respectively) compared with those in control group (1.09±0.13, 1.55±0.32, 1.10±0.09, respectively) after 3, 4 and 5 days (t=3.16, P=0.016; t=4.23, P=0.002; t=5.08, P<0.01), and the cell proliferation ability in knockdown group [(1.65±0.64)%] also decreased than that in the control group [(4.02±1.12)%](t=5.21, P<0.001). In addition, the cell migration rates after 24 and 48 h [(45.1±4.2)%, (56.4±8.3)%] in knockdown group were obviously lower than those in the control group [(63.8±7.4)%, (80.2±7.8)%] (t=3.78, P=0.019; t=3.62, P=0.023). After Cdc42 was knocked down, Golgi apparatus distributed along the nucleus while behaved oriented in the control group. Conclusions: CDC42 plays an important role in the regulation of root length during root development, which may mediate root elongation by affecting the migration and proliferation of HERS cells.
ABSTRACT
Brucellosis has become a global zoonotic disease, seriously endangering the health of people all over the world. Vaccination is an effective strategy for protection against Brucella infection in livestock in developed countries. However, current vaccines are pathogenic to humans and pregnant animals, which limits their use. Therefore, it is very important to improve the safety and immune protection of Brucella vaccine. In this study, different bioinformatics approaches were carried out to predict the physicochemical properties, T/B epitope, and tertiary structure of Omp2b and Omp31. Then, these two proteins were sequentially linked, and the Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) variable region was fused to the N-terminal of the epitope sequence. In addition, molecular docking was performed to show that the structure of the fusion protein vaccine had strong affinity with B7 (B7-1, B7-2). This study showed that the designed vaccine containing CTLA-4 had high potency against Brucella, which could provide a reference for the future development of efficient brucellosis vaccines.
Subject(s)
Bacterial Vaccines , Brucellosis , CTLA-4 Antigen , Brucellosis/prevention & control , Brucella , Bacterial Vaccines/immunology , CTLA-4 Antigen/immunology , Humans , Animals , Epitopes/immunology , Molecular Docking Simulation , Computational Biology , Bacterial Proteins/immunology , Amino Acid Sequence , Protein Structure, Tertiary , Recombinant Fusion Proteins/immunologyABSTRACT
Objective: To summarize the risk factors of tracheal extubation failure in children with spinal muscular atrophy (SMA) combined with pneumonia. Methods: In this retrospective study, clinical data of 34 children with SMA combined with pneumonia who were hospitalized in Children's Hospital Affiliated to Capital Institute of Pediatrics from August 2018 to December 2021 were analyzed. According to whether the extubation was successful or not, they were divided into the success group and the failure group. The risk factors that may affect the success of extubation between two groups were derived by comparing the clinical characteristics by Mann-Whitney U test and Chi-square test, followed by multivariate Logistic regression. Results: Among the 34 cases, there were 14 males and 20 females, aged 10.8 (6.0,25.2) months at the time of hospitalization, 31 cases were type 1 SMA and 3 cases were type 2. Eleven children were unable to eat independently before intubation, 22 were treated with airway clearance techniques and 28 had multiple pulmonary infections. There were 21 cases in the success group and 13 cases in the failure group. The failure group had higher maximum partial pressure of arterial carbon dioxide level during intubation and higher rate of consolidation changes in chest images before extubation (81 (49,86) vs. 48 (43,56) mmHg (1 mmHg=0.133 kPa), 6/13 vs. 10%(2/21), Z=-2.55, χ2=5.99, both P<0.05). Multivariate Logistic regression analysis showed that tube feeding before intubation (OR =39.88, 95%CI 3.36-473.29, P=0.003) and not receiving airway clearance therapy (OR =14.55, 95%CI 1.35-156.78, P=0.027) were independent risk factors for extubation failure. Conclusions: The independent risk factors of tracheal extubation failure in children with SMA combined with pneumonia are unable to eat independently before intubation and not receiving airway clearance therapy. Therefore, the conditions to improve the success of extubation consist of having the ability to eat independently before intubation, using airway clearance techniques to improve ventilation and to make the chest images as clear as possible.
Subject(s)
Pneumonia , Spinal Muscular Atrophies of Childhood , Airway Extubation/adverse effects , Airway Extubation/methods , Child , Female , Humans , Male , Pneumonia/etiology , Pneumonia/therapy , Respiration, Artificial , Retrospective Studies , Risk Factors , Spinal Muscular Atrophies of Childhood/complications , Spinal Muscular Atrophies of Childhood/therapyABSTRACT
AIMS: Leukoaraiosis (LA) is the increase in fluid in cerebral white matter with hyperintensity on T2-weighted MR imaging that occurs in 25% of individuals over 65 years of age and in Alzheimer's disease. Age, hypertension, diabetes mellitus and cardiac disease are the major risk factors for LA. Ischaemia is considered to be the cause of LA, but the aim of the present study is to assess whether changes in arterioles in LA could impede perivascular lymphatic drainage of interstitial fluid from the cerebral white matter. METHODS: We quantified arteriolosclerosis and immunohistochemical changes in the extracellular matrix in arterioles of cerebral white matter in 20 hypertension autopsy cases with LA and in 10 controls. RESULTS: The ratio of the area immunoreactive for collagen types I, III, V and VI to the cross-sectional area of arterioles was significantly higher in LA patients compared with controls (P < 0.001). Changes were observed in collagen IV and laminin. The walls of white matter arterioles in LA were significantly thicker (P < 0.01), and lumina were significantly smaller (P < 0.01). Arterioles had a significantly higher sclerotic index [1 - (internal/external diameter)] in LA than in adjacent cortex or control white matter (P < 0.01). CONCLUSIONS: Our results show that thickening and sclerosis of the walls of arterioles in cerebral white matter in LA are associated with the accumulation of extracellular matrix components. Although these changes may result in decreased perfusion, they could also impede perivascular lymphatic drainage of interstitial fluid from white matter in LA.
Subject(s)
Arterioles/pathology , Brain/pathology , Cerebrovascular Disorders/pathology , Extracellular Matrix/pathology , Leukoaraiosis/pathology , Aged , Arterioles/physiopathology , Brain/blood supply , Brain/physiopathology , Cerebrovascular Disorders/physiopathology , Collagen/metabolism , Extracellular Fluid/physiology , Extracellular Matrix/physiology , Female , Humans , Hypertension/pathology , Hypertension/physiopathology , Immunohistochemistry , Laminin/metabolism , Leukoaraiosis/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Models, Neurological , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/physiology , Sclerosis/pathology , Sclerosis/physiopathologyABSTRACT
Two polarization-independent Michelson fiber interferometers with different optical delays were used to measure the in-band OSNR of an optical signal from 5 to 30 dB within an accuracy of 0.5 dB. Using an expansion of the amplitude autocorrelation function of the signal around zero delay, it was possible to perform measurements without any prior knowledge of the signal. The system is shown to be immune to the effects of modulation frequency (up to 10G), partially and fully polarized noise, chromatic dispersion and poorly biased modulators.
Subject(s)
Fiber Optic Technology/instrumentation , Interferometry/instrumentation , Telecommunications/instrumentation , Equipment Design , Equipment Failure AnalysisABSTRACT
OBJECTIVE: Metabolic syndrome is characterized by abdominal obesity, hypertriglyceridemia and hyperglycemia. Fatty acid binding protein 4 (FABP4), as a member of intracellular lipid chaperones, is not only engaged in lipid transport but involved in inflammation and insulin resistance. The present study was to investigate the effects of BMS309403, a specific FABP4 inhibitor, on metabolic syndrome and its possible molecular mechanisms in islets. MATERIALS AND METHODS: Leptin receptor knockout (Lepr-/-) rat, a novel and representative animal model of metabolic syndrome, was adopted in this study. Lepr-/- male rats and their wild littermates were grouped and intragastrically administered with BMS309403. Glucose Tolerance Test (GTT) and Insulin Tolerance Test (ITT) were performed on all rats. Serum insulin was detected by ELISA. The metabolic characters, as well as liver and kidney functions, were evaluated by serum biochemical assay. Immunohistochemistry and Western blot were adopted to detect the expression levels of FABP4, CD68, GRP78, ATF6, p-IRE1a, and Cleaved caspase-3. RESULTS: Lepr-/- rats showed prominent characteristics of metabolic syndrome with increased FABP4, inflammatory infiltration, ER stress and apoptosis in islets. BMS309403 administration attenuated inflammation, ER stress and apoptosis in Lepr-/- rat islets while stimulating insulin secretion as well as improving manifestation of metabolic syndrome without hepatic and renal toxicity. CONCLUSIONS: FABP4 increased in Lepr-/- rat islets and might be involved in the regulation of islet inflammation and apoptosis via ER stress. FABP4 inhibitor BMS309403 could ameliorate islet inflammation and apoptosis in metabolic syndrome through suppressing ER stress.
Subject(s)
Biphenyl Compounds/pharmacology , Fatty Acid-Binding Proteins/antagonists & inhibitors , Inflammation/drug therapy , Islets of Langerhans/drug effects , Pyrazoles/pharmacology , Receptors, Leptin/antagonists & inhibitors , Administration, Oral , Animals , Biphenyl Compounds/administration & dosage , Endoplasmic Reticulum Stress/drug effects , Fatty Acid-Binding Proteins/genetics , Fatty Acid-Binding Proteins/metabolism , Glucose Tolerance Test , Inflammation/metabolism , Inflammation/pathology , Islets of Langerhans/metabolism , Pyrazoles/administration & dosage , Rats , Rats, Sprague-Dawley , Receptors, Leptin/metabolismABSTRACT
Acute abdomen, abdominal trauma, gastrointestinal bleeding and gastrointestinal tumors are the main conditions that are routinely treated in gastrointestinal surgery department with high incidence and critical condition. These conditions need emergency or selective operations. During the outbreak of the coronavirus disease 2019 (COVID-19), it's a great challenge for us to meet the patients' requirement under the situation. As the COVID-19 was brought under control in China, the Department of General Surgery in Nanfang Hospital resumed regular medical services gradually. Based on our clinical practice, the four major measures of strengthening pre-hospital screening, perioperative prevention and control, medical staff protection, and ward management were adopted. These main measures include the strict implementation of the appointment system and triage system before admission; the conduction of epidemiological and preliminary screening of viral nucleic acids; the chest CT examination during the perioperative period to re-screen COVID-19; the reduction of the risk of droplets and aerosol transmission; the minimally invasive surgery combined with enhanced recovery program in order to reduce patient's susceptibility and shorten the length of postoperative hospital stay; the reinforcement of specific infection control training for medical staff; the strict implementation of hierarchical protection; the establishment of gastrointestinal surgery prevention and control system; the rehearsal of emergency exercise; the installation of quarantine wards; the screening and management of family care-givers; the strict disinfection of environment and materials. Our preliminary practice shows that following the work guidelines issued by the Guangdong Province COVID-19 Prevention and Control Office and adopting precise management strategies in combination with the specific clinical features of gastrointestinal surgery, it is possible to safely resume regular care for the patients and comply to epidemic control at the same time.
Subject(s)
Coronavirus Infections/prevention & control , Cross Infection/prevention & control , Digestive System Surgical Procedures , Gastrointestinal Diseases/surgery , General Surgery/organization & administration , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Betacoronavirus , COVID-19 , China , Communicable Disease Control/methods , Disease Outbreaks , Guideline Adherence , Humans , Length of Stay , SARS-CoV-2ABSTRACT
Objective: To study the short-term and long-term efficacy of the non-invasive ventilation treatment in children with spinal muscular atrophy (SMA) and sleep-disordered breathing. Methods: This was a prospective research to study the effect of night-time non-invasive ventilation in children with SMA and moderate to severe sleep-disordered breathing during March 2016 to January 2018, from the Pulmonary Department of Capital Institute of Pediatrics Affiliated Children's Hospital. Patients were divided into the treated group (with night-time non-invasive ventilation) and the control group (without ventilator). Sleep breathing pressure titration was suggested to the patients who were prepared to receive non-invasive ventilation. All cases were followed up for one year. Parameters'changes in polysomnography were assessed (paired t-test) in titration patients. Frequency of respiratory tract infection during the next year in the patients with and without ventilation was collected and compared (Mann-Whitney U-test). Results: Seventeen cases were recruited. The average age was (5.1±2.9) years, 10 cases were boys and 7 cases were girls. In the titration group (8 patients), after non-invasive ventilation, the average apnea hypopnea index was (3.8±2.5) times/h (t=4.086, P=0.005), hypopnea index was (2.4±1.2) times/h (t=2.779, P=0.027), average oxygen saturation during total sleep time was 0.966±0.007 (t=-5.292, P=0.001), and the minimum oxygen saturation was 0.906±0.023 (t=-3.938, P=0.006). All the above parameters were significantly improved after treatment. Than before, which was (16.6±9.7) times/h, (7.2±4.7) times/h, 0.946±0.015, 0.786±0.092 respectively. Ventilator mode for the 9 children with long time non-invasive ventilation at home was Bi-level positive airway pressure S/T. The positive airway pressure was set at 8-14 cmH(2)O (1 cmH(2)O=0.098 kPa) in inspiratory phase and 4-6 cmH(2)O in expiratory phase. In the treated group (9 patients), the average frequency of upper respiratory tract infection was 1.0 (0, 3.0) times/year (Z=-2.245, P=0.023), the lower respiratory tract infection was 0 (0, 0) times/year (Z=-3.189, P=0.001), hospitalization was 0 (0, 0) times/year (Z=-3.420, P<0.01), and admission to intensive care unit was 0 (0, 0) times/year (Z=-3.353, P=0.029). All the above indexes were significantly decreased compared with the control group (8 patients), which was 3.0 (2.3, 7.0) times/year, 2.0 (1.3, 4.5) times/year, 1.0 (1.0, 4.3) times/year, 0.5 (0, 1.0) times/year respectively. Conclusion: Non-invasive ventilation is efficient to SMA children with sleep-disordered breathing, and also can reduce the incidence of respiratory tract infections for children with SMA.
Subject(s)
Noninvasive Ventilation/methods , Sleep Apnea Syndromes/therapy , Spinal Muscular Atrophies of Childhood/therapy , Child , Child, Preschool , Female , Humans , Male , Noninvasive Ventilation/adverse effects , Polysomnography , Prospective Studies , Sleep Apnea Syndromes/diagnosis , Spinal Muscular Atrophies of Childhood/diagnosis , Treatment OutcomeABSTRACT
In this paper, the polarization response of a GaAs based two-photon absorption microcavity photodetector has been studied. The deviation in the dependence of the detector response from that of bulk GaAs is shown to be due to the birefringence of the cavity. A theoretical model based on the convolution of the cavity birefringence and the polarization dependence of two-photon absorption in GaAs is described and shown to match the measured polarization dependence of the microcavity detector very well.
ABSTRACT
OBJECTIVES: Employ conventional X-ray diffraction (XRD) to analyze three clinically important nickel-titanium orthodontic wire alloys over a range of temperatures between 25 and -110 degrees C, for comparison with previous results from temperature-modulated differential scanning calorimetry (TMDSC) studies. METHODS: The archwires selected were 35 degrees C Copper Ni-Ti (Ormco), Neo Sentalloy (GAC International), and Nitinol SE (3M Unitek). Neo Sentalloy, which exhibits superelastic behavior, is marketed as having shape memory in the oral environment, and Nitinol SE and 35 degrees C Copper Ni-Ti also exhibit superelastic behavior. All archwires had dimensions of 0.016in.x0.022in. (0.41 mm x 0.56 mm). Straight segments cut with a water-cooled diamond saw were placed side-by-side to yield a 1 cm x 1cm test sample of each wire product for XRD analysis (Rint-Ultima(+), Rigaku) over a 2theta range from 30 degrees to 130 degrees and at successive temperatures of 25, -110, -60, -20, 0 and 25 degrees C. RESULTS: The phases revealed by XRD at the different analysis temperatures were in good agreement with those found in previous TMDSC studies of transformations in these alloys, in particular verifying the presence of R-phase at 25 degrees C. Precise comparisons are not possible because of the approximate nature of the transformation temperatures determined by TMDSC and the preferred crystallographic orientation present in the wires. New XRD peaks appear to result from low-temperature transformation in martensite, which a recent transmission electron microscopy (TEM) study has shown to arise from twinning. SIGNIFICANCE: While XRD is a useful technique to study phases in nickel-titanium orthodontic wires and their transformations as a function of temperature, optimum insight is obtained when XRD analyses are combined with complementary TMDSC and TEM study of the wires.
Subject(s)
Dental Alloys , Orthodontic Wires , Alloys , Calorimetry, Differential Scanning , Copper , Crystallization , Crystallography, X-Ray , Elasticity , Microscopy, Electron, Transmission , Nickel , Phase Transition , Temperature , TitaniumABSTRACT
Objective: To explore the SNP effects of patatin-like phospholipase domain which containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2) gene, environmental effects of smoking, alcohol drinking and interaction between gene-gene, gene-environment and drinking-smoking on hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). Methods: We collected anticoagulant peripheral blood from patients of HBV-HCC, chronic hepatitis B (CHB), liver cirrhosis (LC) and from healthy controls to detect the single nucleotide polymorphism (SNP) of patatin-like phospholipase domain containing 3 (PNPLA3) gene loci rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) gene loci rs58542926, using the flight mass spectrometry method. The optimal assignment value of gene polymorphisms was defined by using the online SNP stats. Hardy-Weinberg (H-W) balance was tested for SNP. Effects of the genetic and environmental factors to HBV-HCC were analyzed by using the multiple classification logistic regression method. The gene-gene, gene-smoking and alcohol drinking interaction effects were investigated by Fork-Life analysis and binary logistic regression methods. Results: The frequency distribution of CHB group rs738409 loci seemed not in conformity with the H-W balance (χ(2)=11.980, P<0.005). Two loci frequency distributions in the other groups were all in accordandce with the H-W balance. After adjusting for influences on age and sex and comparing to the healthy group, the rs58542926 mutation appeared as OR=1.659, 95%CI: 1.026-2.684, P=0.039, in the HBV-HCC group. When comparing to CHB group, the HBV-HCC group presented that drinking as OR=1.680, 95%CI: 1.121-2.519, P=0.012. When comparing to the LC group, the ORs of drinking and smoking were 1.539 (1.071-2.213) and 1.453 (1.005-2.099) respectively, in the HBV-HCC group. When comparing to the CHB+LC group, interactions between the HBV-HCC group were found rs738409 and rs58542926 on additive model OR=1.548 (U=1.885, P=0.029) and OR=1.658 (P=0.024) on logistic regression model while drinking was rs738409 on interaction additive model with OR=1.811(U=1.965, P=0.024). As for drinking and mutation of rs738409, the multiplication model of logistic regression showed no statistically significant differences. Interaction between smoking and drinking appeared as OR=1.756 (P<0.001) in the logistics regression multiplication model. Conclusions: Factors as mutation of TM6SF2, smoking and drinking all appeared as risk factors for HBV-HCC. Mutations of both PNPLA3 and TM6SF2, together with smoking and drinking all served as risk factors for HBV-HCC. However, the mutation of single PNPLA3 appeared as a protective factor on HBV-HCC.
Subject(s)
Alcohol Drinking/adverse effects , Carcinoma, Hepatocellular/genetics , Lipase/genetics , Liver Cirrhosis, Alcoholic/complications , Liver Neoplasms/genetics , Membrane Proteins/genetics , Polymorphism, Single Nucleotide , Smoking/adverse effects , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/virology , Case-Control Studies , Epistasis, Genetic , Gene-Environment Interaction , Genetic Predisposition to Disease , Genotype , Hepatitis B virus , Hepatitis B, Chronic , Humans , Liver Neoplasms/pathology , Liver Neoplasms/virologyABSTRACT
Brucellosis has become a global zoonotic disease, seriously endangering the health of people all over the world. Vaccination is an effective strategy for protection against Brucella infection in livestock in developed countries. However, current vaccines are pathogenic to humans and pregnant animals, which limits their use. Therefore, it is very important to improve the safety and immune protection of Brucella vaccine. In this study, different bioinformatics approaches were carried out to predict the physicochemical properties, T/B epitope, and tertiary structure of Omp2b and Omp31. Then, these two proteins were sequentially linked, and the Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) variable region was fused to the N-terminal of the epitope sequence. In addition, molecular docking was performed to show that the structure of the fusion protein vaccine had strong affinity with B7 (B7-1, B7-2). This study showed that the designed vaccine containing CTLA-4 had high potency against Brucella, which could provide a reference for the future development of efficient brucellosis vaccines.