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OBJECTIVE To analyze the dose-adjusted concentrations of Posaconazole oral suspension in patients undergoing hematopoietic stem cell transplantation （HSCT） and their influential factors. METHODS Data were collected from hospitalized HSCT patients admitted to the First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital） from January 2021 to April whtwhm@yeah.net 2023 who took Posaconazole oral suspension for the prevention of invasive fungal disease （IFD） and received blood concentration of posaconazole. The rate of concentration attainment and clinical failure rate of posaconazole for the prevention of IFD were evaluated， and one-way and multiple linear regression analyses were performed for the influential factors of dose-adjusted concentrations （C0/D） of posaconazole. RESULTS A total of 44 patients were enrolled； the mean C0 of posaconazole in patients was （0.99±0.94） µg/mL， and 20 patients had a C0≥0.7 μg/mL， with a concentration attainment rate of 45.45% for the prevention of IFD； 13 cases were clinical failures， with a clinical failure rate of 29.55%. Of 24 patients who did not achieve C0/D of posaconazole for IFD prophylaxis， one patient was a clinical failure despite timely dose adjustment of posaconazole in seven patients； seven of the thirteen patients who did not undergo dose adjustment were clinical failures； and the remaining four patients were switched to other antifungal agents. The results of univariate analysis showed that gender， body mass index （BMI）， renal function， combined use of sodium phenytoin， omeprazole and metoclopramide had a significant effect on the C0/D of posaconazole （P＜0.05）； the results of multivariate linear regression analysis showed that gender， BMI and combined use of sodium phenytoin were the independent factors affecting the C0/D of posaconazole （P＜0.05）. CONCLUSIONS Significant individual differences are reflected in the blood concentration of Posaconazole oral suspension； gender， BMI and combined use of sodium phenytoin are independent factors affecting the C0/D of posaconazole.
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IgG4-related disease (IgG4-RD) is a recently recognized disorder characterized by elevated serum IgG4 levels and infiltration of IgG4 positive blood cells in the affected organs. However, other conditions like malignancy as well as connective tissue diseases, may show similar findings. A 56-year-old male patient visited Second Xiangya Hospital, Central South University for recurrent fever and chest pain for more than 1 month. Preliminary tests diagnosed as IgG4-related lung disease (IgG4-RLD). However, the improvement of symptoms was absent after the treatment with methylprednisolone. The patient underwent the second biopsy and the result eventually demonstrated lung adenocarcinoma. The role of IgG4 in the pathogenesis or prognosis for lung adenocarcinoma remains unclear. Therefore, a thorough evaluation of symptoms, test of specific serum markers and eventually pathological confirmation are required to avoid misdiagnosis.
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Objective To explore the molecular mechanism underlying the anti-apoptotic activity of pORF5 plasmid protein of Chlamydia trachomatis,so as to provide an experimental basis for further clarifying the pathogenesis of Chlamydia trachomatis.Methods HeLa cells were divided into two groups:carbonyl cyanide m-chlorophenyl hydrazone (CCCP,an apoptosis inducer) group was stimulated by CCCP for 30 minutes,and pORF5 + CCCP group was pretreated with pORF5 plasmid protein for 18 hours followed by CCCP for 30 minutes.Then,Western blot analysis was performed to determine the expression of apoptosisrelated proteins Bcl-2,Bax and caspase-3,JC-1 fluorescent probe was used to detect changes in the mitochondrial membrane potential in HeLa cells,and cytochrome c release from mitochondria was analyzed by indirect immunofluorescence assay.To analyze whether high-mobility group box 1 (HMGB1) protein participated in the anti-apoptotic role of pORF5 plasmid protein,HMGB 1 shRNA and control RNA were separately transfected into the HeLa cells,which were then stimulated by pORF5 plasmid protein and CCCP.Then,the protein expression of Bcl-2,Bax,activated caspase-3 was determined,and cytochrome c release was analyzed.Data were compared between two groups by using paired t test.Results pORF5 plasmid protein could antagonize the CCCP-induced decrease of mitochondrial membrane potential,and the red/green fluorescence intensity ratio was significantly lower in the CCCP group (0.4 ± 0.1) than in the pORF5 + CCCP group (1.7 ± 0.3;t =6.95,P ＜ 0.01).The protein expression of Bcl-2 in the HeLa cells in the pORF5 + CCCP group was 5.3 ± 0.6 times more than that in the CCCP group (t =8.62,P ＜ 0.01),while the protein expression of Bax and activated caspase-3 in the pORF5 + CCCP group significantly decreased by 79％ ± 10％ (t =9.23,P ＜ 0.01) and 75％ ± 8％ (t =4.26,P ＜ 0.05) respectively compared with the CCCP group.Compared with the control RNA transfection group,the HMGB1 shRNA transfection group showed significantly decreased mitochondrial membrane potential in the HeLa cells (t =11.23,P ＜ 0.01),increased cytochrome c release,decreased Bcl-2 expresson (t =7.19,P ＜ 0.05) and increased Bax expression (t =13.06,P ＜ 0.01) after stimulation with pORF5 and CCCP.Conclusion Chlamydia trachomatis plasmid protein pORF5 plays an anti-apoptosis role by blocking the mitochondrial apoptotic pathway through HMGB1 protein.
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Kawasaki disease (KD) is an acute systemic small and medium vasculitis syndrome,which is most commonly found in children under the age of 5 years.The most severe complications of KD are coronary artery lesions (CAL),which will lead to coronary artery dilatation,myocardial infarction and sudden death.In the acute stage,severe clinical manifestations are associated with shock,and all organs could be involved,which is called severe Kawasaki disease (SKD),sometimes requiring treatment in the pediatric intensive care unit (PICU) have been reported.Although the clinical symptoms of children with SKD are severe,most patients can survive without any sequelae as long as they can be diagnosed accurately and treated rapidly.In recent years,scholars at home and abroad have paid more and more attention to SKD.Based on these,we take SKD as the research object,try to explain the progress of clinical diagnosis and treatment,which is beneficial to pediatric clinicians to accurately judge and treat related diseases.
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Clinical data of 28 cases of childhood bronchiolitis obliterans treated from September 2008 to November 2010 were retrospectively analysis.Pulmonary high-resolution CT (HRCT) showed that bronchial wall thicken was seen in all 28 patients,the mosaic pattern in 26 cases,patchy shadows in 18 cases,bronchiectasis with typical signet ring sign in 2 cases,atelectasis in 2 cases without pleural effusion.Pulmonary function tests and flexible bronchofiberscopy were performed in 6 cases,which showed the inflammation in bronchial tunica intima and obstruction of small airway.Blood routine,blood sedimentation,c-reaction protein,TORCH,hepatic function,renal function and immune function were normal.Patients received comprehensive treatment with methylprednisolone,clarithromycin and montelukast.The clinical conditions of 28 cases were improved with varying degrees after treatment and no significant side effects were observed.
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Objective To discuss adhesion blocking experiment of vascular endotelial cells with platelets.Methods The expression,regulation and adhesion of CD226 on vascular endothelial cells incubated by sera from 10 PIH patients and 10 normal pregnant women repectively was detected by flow cytometry,then incubated with interacted platelets by PTA1/Ig protein.Results The positive rate of CD226 in PIH group was significantly higher than that in normal pregnant woman group(P