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The microbiological diagnosis of infection for hematological malignancy patients receiving chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients relies primarily on standard microbial culture, especially blood culture, which has many shortcomings, such as having low positive rates, being time-consuming and having a limited pathogenic spectrum. In this prospective observational self-controlled test accuracy study, blood, cerebrospinal fluid (CSF), and bronchoalveolar lavage fluid (BALF) samples were collected from chemotherapy or allo-HSCT patients with clinical symptoms of infections who were hospitalized at Peking University First Hospital. Possible pathogens were detected by the method based on recombinant mannan-binding lectin (MBL) magnetic bead enrichment (M1 method) and simultaneously by a standard method. The analytical sensitivity of M1 method was close to that of standard culture method. Besides, the turn-around time of M1-method was significantly shorter than that of standard culture method. Moreover, the M1 method also added diagnostic value through the detection of some clinically relevant microbes missed by the standard method. M1 method could significantly increase the detection efficiency of pathogens (including bacteria and fungi) in immunocompromised patients. KEY POINTS: ⢠The detection results of M1-method had a high coincidence rate with that of standard method ⢠M1 method detected many pathogens which had not been found by standard clinic method.
Subject(s)
Mannose-Binding Lectin , Humans , Bronchoalveolar Lavage Fluid , Bacteria , Immunocompromised Host , Magnetic Phenomena , High-Throughput Nucleotide SequencingABSTRACT
Metadherin (MTDH) is a well-established oncogene in various cancers including Hepatocellular Carcinoma (HCC). However, the precise mechanism through which MTDH promotes cancer-related signaling pathways in HCC remains unknown. In this study, we identified DDX17 as a novel binding partner of MTDH. Furthermore, MTDH increased the protein level of DDX17 by inhibiting its ubiquitination. We confirmed that DDX17 was a novel oncogene, with dramatically upregulated expression in HCC tissues. The increased expression of DDX17 was closely associated with vascular invasion, TNM stage, BCLC stage, and poor prognosis. In vitro and in vivo tests demonstrated that DDX17, a downstream target of MTDH, played a crucial role in tumor initiation and progression. Mechanistically, DDX17 acted as a transcriptional regulator that interacted with Y-box binding protein 1 (YB1) in the nucleus, which in turn drove the binding of YB1 to its target epidermal growth factor receptor (EGFR) gene promoter to increase its transcription. This in turn increased expression of EGFR and the activation of the downstream MEK/pERK signaling pathway. Our results identify DDX17, stabilized by MTDH, as a powerful oncogene in HCC and suggest that the DDX17/YB1/EGFR axis contributes to tumorigenesis and metastasis of HCC.
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Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Cell Adhesion Molecules/metabolism , Cell Transformation, Neoplastic/genetics , ErbB Receptors/genetics , ErbB Receptors/metabolism , Transcription Factors/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Membrane Proteins/genetics , Membrane Proteins/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , DEAD-box RNA Helicases/geneticsABSTRACT
Objective: To establish a nested recombinant enzyme-assisted polymerase chain reaction (RAP) technique combined with recombined mannose-binding lectin protein (M1 protein)-magnetic beads enrichment for the detection of Candida albicans (C. albicans) and Candida tropicalis (C. tropicalis) in blood samples for the early diagnosis of candidemia albicans and candidiemia tropicalis. Methods: The primer probes for highly conserved regions of the internal transcribed spacerregions of C. albicans and C. tropicalis were deigned to establish RAP assays for the detections of C. albicans and C. tropicalis; The sensitivity and reproducibility of nucleic acid tests with gradient dilutions of standard strains and specificity of nucleic acid tests with common clinical pathogens causing bloodstream infection were condcuted. M1 protein-magnetic bead enriched plasma C. albicans and C. tropicalis were used for RAP and PCR in with simulated samples and the results were compared. Results: The sensitivity of the established dual RAP assay was 2.4-2.8 copies/reaction, with higher reproducibility and specificity. M1 protein-magnetic bead enrichment of pathogen combined with the dual RAP assay could complete the detections of C. albicans and C. tropicalis in plasma within 4 hours. Fie the pathogen samples at concentration <10 CFU/ml, the number of the samples tested by RAP was higher than that tested by PCR after enrichment. Conclusion: In this study, a dual RAP assay for the detections of C. albicans and C. tropicalis in blood sample was developed, which has the advantages of accuracy, rapidity, and less contaminants and has great potential for rapid detection of Candidemia.
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Humans , Lectins , Candida , Candidemia , Reproducibility of Results , Polymerase Chain Reaction , Nucleic Acids , Magnetic PhenomenaABSTRACT
The Coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (⩾ 245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528-29.523; P < 0.001) and coagulation-related biomarker D-dimer (⩾ 0.5 µg/mL, HR = 4.321, 95% CI = 1.443-12.939; P = 0.009) and decreased albumin (< 35 g/L, HR = 0.131, 95% CI = 0.048-0.361; P < 0.001) and albumin/globulin ratio (< 1.5, HR = 0.123, 95% CI = 0.017-0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.
Subject(s)
Humans , COVID-19 , Cohort Studies , Hepatitis B, Chronic/epidemiology , Retrospective Studies , Risk FactorsABSTRACT
Objective To study the effect of type 2 diabetes mellitus (T2DM) on the cerebral blood vessels in Alzheimer's disease (AD), and to explore its mechanism of influence on the pathogenesis of Alzheimer's disease. Methods To generate a mouse model with AD complicated with long-term T2DM, forty 6-month-old APP/PS1 transgenic mice were fed with high-sugar and high-fat diet for 6 months, that was, when mice at 12 months of age, they were intraperitoneally injected with 1% streptozotocin solution for 4 consecutive days. Then, mice were randomly divided into 4 groups: the normal control group, AD model group, T2DM model group and AD complicated with T2DM model group, 10 mice were used in each group. The learning and memory ability of the mice were tested by the mouse step-down assay, and the vascular morphology of the mice's hippocampal CAI area was observed by ink perfusion. Then oil red 0 staining and immunofluorescent staining were applied to test the pathological indices of the hippocampal area in the model. Results Compared with the control group, AD combined with T2DM mice showed decreasing significantly abilities in the learning and memory (P<0.05), and the blood vessels in the hippocampus became thinner and the vascular density decreased. Moreover, T2DM promoted lipid deposits and vascular leak in the hippocampus of the model. Additionally, the expression of β-site amyloid precursor protein cleaving enzyme-1 (BACE-1), nuclear factor (NF)-κB and matrix metalloproteinase (MMP) -9 were increased compared with the controls in the hippocampal CAI region. Conclusion T2DM plays a negative regulatory role on learning and memory functions of mice, accelerates the onset of AD and result in cerebrovascular lesions. In addition, the abnormal expression of MMP-9 may also be one of the causes of AD vascular lesions.
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Objective To investigate the effects of the development of Purkinje cells and expression of cerebellin in postnatal mice with intrauterine hypoxia. Methods Twenty healthy adult Kunming mice were randomly divided into two groups : control group and hypoxia group, with 10 mice in each group. Mice in the hypoxia group were placed in the hypoxia chamber of the animal since the 14th day of gestation to make an animal model of intrauterine hypoxia. After the mother gave birth, the experimental animals were divided into hypoxia group and control group. There were 6 age groups including postnatal day (P)0, P5, P9, P14, P21 and P30 in each group, and 5 mice in each age group. The cerebellum tissue was taken for vibrating sectioning. The developmental changes of calbindin-positive Purkinje cells were detected by immunofluorescence technique. The expression of cerebellin in Purkinje cell protuberances was detected by cerebellin (CBLN)l, CBLN4 and calbindin double labeling. Finally, Western blotting was used to semi-quantitatively analyze the protein expression of cerebellar peptide in cerebellum at each time point. Results Compared with the control group of the same age, the number of cerebellar Purkinje cells in the hypoxic group decreased, the dendritic branches decreased, and the arrangement was disordered, and the expression of CBLN1 and CBLN4 in the cortex were significantly reduced. Conclusion Intrauterine hypoxia leads to abnormal development of the cerebellar Purkinje cells and synaptic changes.
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OBJECTIVE@#To summarize and analyze the clinical characteristics of primary hyperpara-thyroidism (PHPT) with normocalcemic parathormone elevation (NPE) after surgical treatment, so as to improve the therapeutic ability and standardized post-operative follow-up of PHPT patients.@*METHODS@#Nine patients who were diagnosed with PHPT in the Department of Endocrinology of China-Japan Friendship Hospital from August 2017 to November 2019 were selected as the subjects. They all developed NPE within 6 months after surgical treatment. The clinical features and outcomes were collected and analyzed retrospectively, in addition, the related literature was reviewed.@*RESULTS@#Clinical features: among the 9 patients, 6 were middle-aged and elderly females and 3 were male. The main clinical manifestations were bone pain, kidney stones, nausea and fatigue except for one case of asymptomatic PHPT. Pre-operative examination showed high serum calcium [(3.33±0.48) mmol/L], low serum phosphorus [0.76 (0.74, 0.78) mmol/L], high 24-hour urinary calcium [8.1(7.8, 12.0) mmol/24 h], obviously elevated intact PTH [(546.1±257.7) ng/L], vitamin D deficiency [25-hydroxyvitamin D3 (21.0±5.7) nmol/L]. Serum levels of bone alkaline phosphatase [7 patients 41.3(38.6, 68.4) μg/L, 2 patients >90 μg/L] and N-terminal midcourse osteocalcin (>71.4 μg/L) were significantly elevated. The estimated glomerular filtration rate decreased in 2 patients. Imaging examination: 7 patients had osteoporosis. Renal calculi were found in 3 patients by renal ultrasound. Imaging examination of parathyroid glands found definite lesions in all the patients, including 2 cases of multiple lesions and 7 cases of single lesions.@*TREATMENT AND OUTCOME@#two patients underwent parathyroidectomy, while other patients were treated with microwave thermal ablation. PTH increased 1 month after therapy [(255.0±101.4) ng/L], and no recurrent lesions were found by parathyroid ultrasound. After combined treatment with cal-cium and vitamin D for six months, PTH decreased significantly and the level of serum calcium remained normal at anytime during the follow-up period.@*CONCLUSION@#The occurrence of postoperative NPE may be related to the higher pre-operative PTH, vitamin D deficiency and lower creatinine clearance. However, NPE may not predict recurrent hyperthyroidism or incomplete parathyroidectomy. Adequate calcium and vitamin D supplementation after surgery seems to be beneficial for patients with NPE. Post-operative follow-up of PHPT patients should be standardized to prevent and treat post-operative NPE.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Calcium , China , Hyperparathyroidism, Primary/surgery , Parathyroid Hormone , Parathyroidectomy , Retrospective StudiesABSTRACT
Patients with cancer are at increased risk of severe infections. From a cohort including 3060 patients with confirmed COVID-19, 109 (3.4%) cancer patients were included in this study. Among them, 23 (21.1%) patients died in the hospital. Cancer patients, especially those with hematological malignancies (41.6%), urinary carcinoma (35.7%), malignancies of the digestive system (33.3%), gynecological malignancies (20%), and lung cancer (14.3%), had a much higher mortality than patients without cancer. A total of 19 (17.4%) cancer patients were infected in the hospital. The clinical characteristics of deceased cancer patients were compared with those of recovered cancer patients. Multivariate Cox regression analysis indicated that a Nutritional Risk Screening (NRS2002) score ⩾ 3 (adjusted hazard ratio (HR) 11.00; 95% confidence interval (CI) 4.60-26.32; P < 0.001), high-risk type (adjusted HR 18.81; 95% CI 4.21-83.93; P < 0.001), tumor stage IV (adjusted HR 4.26; 95% CI 2.34-7.75; P < 0.001), and recent adjuvant therapy (< 1 month) (adjusted HR 3.16; 95% CI 1.75-5.70; P < 0.01) were independent risk factors for in-hospital death after adjusting for age, comorbidities, D-dimer, and lymphocyte count. In conclusion, cancer patients showed a higher risk of COVID-19 infection with a poorer prognosis than patients without cancer. Cancer patients with high-risk tumor, NRS2002 score ⩾ 3, advanced tumor stage, and recent adjuvant therapy (< 1 month) may have high risk of mortality.
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Humans , COVID-19 , Hospital Mortality , Neoplasms , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2ABSTRACT
Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.
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Humans , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic , Chemotherapy, Adjuvant , Hepatectomy , Liver Neoplasms/therapy , Neoplasm Recurrence, Local , Treatment OutcomeSubject(s)
Hepatectomy , Midazolam , Controlled Before-After Studies , Cytochrome P-450 CYP3A , Humans , Prospective StudiesABSTRACT
BACKGROUND@#Resting heart rate (RHR) is considered as a strong predictor of total mortality and hospitalization due to heart failure in hypertension patients. Bisoprolol fumarate, a second-generation beta-adrenoreceptor blockers (β-blocker) is commonly prescribed drug to manage hypertension. The present study was to retrospectively evaluate changes in the average RHR and its association with cardiovascular outcomes in bisoprolol-treated coronary artery disease (CAD) patients from the CAD treated with bisoprolol (BISO-CAD) study who had comorbid hypertension.@*METHODS@#We performed ad-hoc analysis for hypertension sub-group of the BISO-CAD study (n = 866), which was a phase IV, multination, multi-center, single-arm, observational study carried out from October 2011 to July 2015 across China, South Korea, and Vietnam. Multivariate regression analysis was used to identify factors associated with incidence of composite cardiac clinical outcome (CCCO), the results were presented as adjusted odds ratio (OR) along with 95% confidence interval (CI) and adjusted P value.@*RESULTS@#A total of 681 patients (mean age: 64.77 ± 10.33 years) with hypertension from BISO-CAD study were included in the analysis. Bisoprolol improved CCCOs in CAD patients with comorbid hypertension, with RHR <65 and <70 beats/min compared with RHR ≥65 and ≥75 beats/min, respectively, in the efficacy analysis (EA) set. In addition, it lowered RHR in both intent-to-treat (ITT) and EA groups after 6, 12, and 18 months of treatment. Further, RHR 70 to 74 beats/min resulted in significantly higher risk of CCCOs EA set of patients (adjusted OR: 4.34; 95% CI: 1.19-15.89; P = 0.03). Also, events of hospitalization due to acute coronary syndrome were higher when RHR 69 to 74 beats/min compared to RHR <69 beats/min in ITT patients.@*CONCLUSION@#Bisoprolol can effectively reduce RHR in Asian CAD patients with comorbid hypertension and hence, improve CCCO without affecting their blood pressure.
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To investigate the safety and feasibility of longitudinal transpancreatic U-sutures invaginated pancreatojejunostomy (Chen's pancreaticojejunostomy technique) in laparoscopic pancreaticoduodenectomy (LPD). Clinical data of 116 consecutive patients who underwent LPD using Chen's pancreaticojejunostomy technique in Hunan Provincial People's Hospital from May 2017 to December 2018 were retrospectively analyzed. Among these patients, 66 were males and 50 were females. The median age was 58 years old (32-84 yeas old). All 116 patients underwent pure laparoscopic whipple procedure with Child reconstruction method, using Chen's pancreaticojejunostomy technique. The intraoperative and postoperative data of patients were analyzed. All 116 patients underwent LPD successfully. The mean operative time was (260.3±33.5) minutes (200-620 minutes). The mean time of pancreaticojejunostomy was (18.2±7.6) minutes (14-35 minutes). The mean time of hepaticojejunostomy was (14.6±6.3) minutes (10-25 minutes). The mean time of gastrojejunostomy was (12.0±5.5) minutes (8-20 minutes). The mean estimated blood loss was (106.0±87.6) ml (20-800 ml). Postoperative complications were: 11.2%(13/116) of cases had postoperative pancreatic fistula (POPF), including 10.3% (12/116) of biochemical fistula and 0.9%(1/116) of grade B POPF, no grade C POPF occurred; 10.3%(12/116) had gastrojejunal anastomotic bleeding; 3.4%(4/116) had hepaticojejunal anastomotic fistula; 3.4%(4/116) had delayed gastric emptying; 4.3% (5/116) had localized abdominal infection; 12.1%(14/116) had pulmonary infection; postoperative mortality were 0(0/116) and 1.7%(2/116) within 30 days and 90 days, respectively. One patient died of massive abdominal bleeding secondary to Gastroduodenal artery pseudoaneurysm rupture, the other patient died of extensive tumor recurrence and metastasis after surgery. Chen's pancreaticojejunostomy technique is safe and feasible for LPD.It is an option especially for surgeons who have not completed the learning curve of LPD.
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Novel coronavirus pneumonia (NCP) is a highly infectious disease, has a long incubation period and a variety of clinical manifestations, which has a significant impact on public health and life. Afterwards, scientific and standardized work processing during the epidemic is of great significance for prevention and control. In order to implement the central government's decision-making deployment and defeat the NCP as soon as possible, we had focused on the key points in the clinical work of general surgery according to latest relevant guidelines, literature and experience in epidemic prevention. Finally, we drafted the prevention and control strategies and recommendations to make a reference for medical staff of general surgery to fight NCP.
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Objective:To observe the effects of Analgecine (AGC) on middle cerebral artery ischemia-reperfusion injury in rats and its mechanism. Methods:A total of 61 Sprague-Dawley rats were divided into sham group (n = 11), sham-AGC group (n = 11), model group (n = 20) and model-AGC group (n = 19). The model group and the model-AGC group were occluded the middle cerebral arteries for 1.5 hours and reperfused (2 rats in each group unsuccessful). The sham-AGC group and the model-AGC group were injected AGC 20 U/kg through tail-vein, while the sham group and the model group were injected saline of same volume. Four rats in each group were tested heat shock proteins 70 (HSP70), Bcl-2 and Bax in brain with Western blotting 48 hours after injection. The other rats were assessed with Prehensile Traction Test seven days after injection, and then, four of each group were detected ionized calcium binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) expression with immunohistochemistry. Results:The prehensile time increased in the model-AGC group compared with that of the model group (P < 0.01), with the increase of HSP70 and Bcl-2 (P < 0.01) and decrease of Iba1 and GFAP expression (P < 0.05). Conclusion:AGC may promote the recovery of motor function in rats with cerebral ischemia-reperfusion injury, which may associate with inhibiting cell apoptosis and neruoinflammatory response.
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OBJECTIVE@#To analyze the expression and relationship of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR) in local skin tissues of pressure injury and investigate the possible mechanism of stage 3 pressure injury refractory wound.@*METHODS@#Forty male SD rats were randomly divided into normal control group, compressed 3 d, 5 d, 7 d, and 9 d groups. Stage 3 pressure injury animal model were established by magnet compression. The morphology of skin was observed by HE staining. The expression of VEGF was detected by immunohistochemistry. The expression levels of HIF-1α, VEGF and KDR protein in skin tissue were detected by Western blot. One-way analysis of variance and LSD test were performed on the data.@*RESULTS@#①The HE results showed that compared with the normal control group, the epidermis of the compressed group was gradually thickened, the number of blood vessels was decreased, the collagen arrangement disordered and inflammatory cells infiltration were increased. ②Immunohistochemical results showed that the expression of VEGF protein in the 3 d group was significantly higher than that in the normal control group (P<0.01). The expression of VEGF protein in the skin tissue of 5 d, 7 d and 9 d groups was lower than that in normal control group (P<0.05). WB results were consistent with immunohistochemistry results. ③WB results showed that the expression of HIF-1α in the skin tissues of the rats in 3 d, 5 d and 7 d groups was higher than that in the normal control group (P<0.01 or P<0.05). The expression of KDR protein was lower than that of the normal control group (P<0.05 or P<0.01).@*CONCLUSION@#HIF-1α mediated reduction of VEGF and KDR protein expression and decreased tissue angiogenesis may be one of the important causes of chronic dysfunction of stage 3 pressure injury.
Subject(s)
Animals , Male , Rats , Hypoxia-Inducible Factor 1, alpha Subunit , Genetics , Metabolism , Pressure , Random Allocation , Rats, Sprague-Dawley , Skin , Wounds and Injuries , Vascular Endothelial Growth Factor A , Genetics , Metabolism , Vascular Endothelial Growth Factor Receptor-2 , Genetics , MetabolismABSTRACT
AIM:To investigate the expression of IFN-γ,IL-4 and IL-17A in asthmatic mice vaccinated with bacillus Calmette-Guérin(BCG)and hepatitis B(HepB)in the neonatal period.METHODS: BALB/c mice were ran-domly divided into BGG+HepB+ovalbumin(OVA)group(B/H/O group),B/O group,H/O group,B/H group,OVA group,BCG group,HepB group and normal saline(NS)group(n=6).The mice in B/H/O group and B/H group at 0, 7 and 14 d received subcutaneous injection of 1×105CFU BCG for 3 times,while at 0 and 28 d received intramuscular in-jection of 1.5 μg HepB on the hindlimb twice.The mice in other groups were individually vaccinated with BCG or HepB. OVA sensitization and aerosol inhalation were performed to establish the asthma model.The lung tissues were collected for HE staining.Bronchoalveolar lavage fluid(BALF)and peripheral blood(PB)were collected,and the number of eosino-phils(EOS)in BALF was counted.The serum levels of IFN-γand IL-4,and the level of IL-17A in lung tissue homoge-nate were measured by ELISA.RESULTS: The pathological changes of the lung in OVA group, B/O group, B/H/O group and H/O group were observed.There were extensive inflammatory cell infiltration around the bronchus,and epithe-lial cell hypertrophy.Those in B/H/O group and H/O group were worse than those in OVA group, while those in B/O group was better than those in OVA group.Total BALF cell counts in B/H/O group,B/O group and H/O group were de-creased(P<0.05)as compared with OVA group.The BALF EOS count in B/H/O group was higher than that in B/H group,that in B/O group was higher than that in BCG group,and that in H/O group was higher than that in HepB groups (P<0.05).Compared with H/O group, OVA group and NS group, the serum IFN-γ/IL-4 ratio in HepB group was in-creased(P<0.05),and compared with B/H/O group,B/O group,OVA group and NS group,that in B/H group was al-so increased(P<0.05).Compared with OVA group, the level of IL-17A in the lung tissues of B/H/O group and B/O group was decreased(P <0.05), and compared with B/O group, that in B/H/O group was further decreased(P <0.05).CONCLUSION:Combined vaccination of BCG and HepB reduces the inflammotory responses in the lung tissues of asthmatic mice.The mechanism may be related with the decrease in the release of IL-4, the increase in IFN-γ/IL-4, and the inhibition of IL-17A expression.
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Objectives: This study aimed to observe the change of arachidonic acid-induced platelet aggregation rate (AA-Ag) and short-term adverse reactions after taking 50 or 100 mg/d aspirin(enteric-coated sustained-release formulation) or 100 mg/d aspirin (enteric-coated aspirin tablet)in the elderly Chinese population (aged 60 years or older). Methods: A total of 1 194 participants aged 60 or older, who should be recommended to take aspirin therapy due to medical reasons, were recruited and randomly assigned into three groups to receive enteric-coated sustained-release aspirin tablet (50 mg, once daily, group A), or 100 mg, once daily (group B) or enteric-coated aspirin tablet 100 mg once daily (group C), respectively. AA-Ag was measured after (14±3)days of aspirin treatment. Adverse events and bleeding events were recorded during the (28±3)days of follow-up. Results: The AA-Ag in group A (n=347), B (n=338) and C (n=332) post 14-day aspirin therapy were 6.65 (4.03,10.84)%, 5.89(3.22,10.03) % and 6.00(3.68,10.09) %, respectively (P>0.05). During the 28 days follow-up, the adverse events rate of group A (n=388), B (n=387) and C (n=385) was 3.87%,3.36%, and 7.95%, and the mild bleeding events rate was 3.09%, 2.33%, and 6.23%, respectively. Adverse events rate and mild bleeding events rate were significantly higher in group C than in group A and B (P<0.05). Conclusions: Compared with 100 mg-dose aspirin, 50 mg-dose aspirin achieves similar anti-platelet aggregation effect in this elderly Chinese population. The short-term adverse events and mild bleeding risk of aspirin with enteric-coated sustained-release formulation were fewer than that of enteric-coated formulation.
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IDH mutation is prevalent in lower-grade glioma and secondary glioblastoma. Patients bearing IDH mutation are char-acterized by overproduction of 2-HG. 2-HG plays a role in regu-lation of DNA and histone hypermethylation in glioma, thus re-sulting in impaired cell differentiation and tumor formation. As a surrogate marker of mutant IDH, there is increasing interest in development of detection methods for 2-HG. LC-MS is widely used in detecting 2-HG in vitro, and reliable measurement of 2-HG by the non-invasive MRS has been tested in vivo and ex vivo previously. However, whether 2-HG could represent an inde-pendent predictor of patient survival or other clinical features for glioma still needs further study. In this review, we summarize the mechanism adopted by 2-HG in glioma initiation and pro-gression, as well as the detection method tested in clinic. We try to provide guidance to the future combination therapy using mu-tant IDH inhibitors.
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Objective To prepare isophenylcyclopentylamine hydrochloride capsules and evaluate its quality. Methods The suitable excipients were selected by the drug-excipient compatibility test,and after the formulation and preparation process design and screening,the micromeritic property and hygroscopicity of contents of capsules as well as the basic performance and stability of is-ophenylcyclopentylamine hydrochloride capsules were evaluate. Results The selected formulation was composed of isophenylcyclo-pentylamine hydrochloride 10 mg,anhydrous dibasic calcium phosphate 128.7 mg,mannitol 128.7 mg and aerosil 2.7 mg.The angle of repose of intermediate powders was(30.71±1.09)°,aerated and packed bulk densities were(0.76±0.01)and(0.90±0.02)g/ml re-spectively,Hausner value was 1.19±0.01,Carr′s index was(15.86±1.05)%,indicating good flowability and filling property as well as relatively low humidity.The contents,uniformity of contents and dissolution of capsules fulfilled the requirements.The quality of ca-pusles kept well in the 6-month accelerated and long-term stability test.Conclusion The formulation is simple and reasonable,and the preparation process showed a good reproducibility,which might be suitable for industrialization.