Objective To study the curative effectiveness of Itraconazole in the treatment of invasive pulmonary aspergillosis following bilateral lung transplantation.Methods One patients undergoing bilateral lung transplantation was readmitted at 8-month postoperatively due to cough, sputum, and fever. Sputum culture reported positive Aspergillus flavus. Chest X-ray manifested bilateral lung infiltration. Chest CT scan showed multiple small cavities. Itraconazole (Sporanox) therapy was performed.Results Sputum smear and culture reported negative aspergillus at sixth of Itraconazole therapy. Patient’s symptoms after Itraconazole treatment for 10 days were improved obviously. Chest CT scan showed the lung lesion still existed. After treatment by Itraconazole, FK506 dosage was decreased from 3 mg, twice a day to 0.5 mg, once a day.Conclusion Pulmonary aspergillosis is an important complication following lung transplantation. Itraconazole therapy can effectively treat invasive pulmonary aspergillosis following bilateral lung transplantation. Blood drug concentration monitoring indicated the dosage of FK506 was significantly decreased after Itraconazole therapy.

Objective To explore the surgical indications and safety of bilateral sequential lung transplantation in 9 cases.Methods Between Jan.2003 to June 2005,9 bilateral sequential lung transplantations were performed in Shanghai Chest Hospital.In 2 cases,the resection and re-transplantation of the second lung was done after ventilation and perfusion in the first lung transplantation.In 6 cases,after the first lung was transplanted,ECMO was established with heparin-bonded circuitry and centrifugal pump and the second lung was transplanted.In 1 case,CPB was used during the transplantation of the second lung.Meanwhile,inhaled nitric oxide(INO) therapy(40 ppm) was performed in 7 cases.Results Severe lung edema occurred in 2 cases,and the patients survived only 12 and 36 h respectively.Six cases with ECMO thereafter rided out the operation successfully.Postoperative days ventilated were 36 to 72 h(mean 48 h).Four patients of them discharged in good conditions and have survived 16,14,11,9 months respectively.One patient died of pulmonary infection and emptysis one month after operation.Another patient died of acute renal failure 3 weeks after operation.The operation performed under the support of CPB was unsuccessful because of heavy hemorrhage and severe acidosis.Conclusions Bilateral sequential lung transplantation is a high risk procedure.ECMO can reduce the risk significantly. Inhaled nitric oxide during and after operation is of benefit to stabilization of hemodynamics and reduce ischemic reperfusion injury.

ObjectiveTo investigate the effects of imatinib mesylate as a tyrosine kinase inhibitor on the biological activity of and Wnt/β-catenin pathway in Hs294T melanoma cells.MethodsAfter Hs294T cells were incubated with imatinib mesylate at various concentrations(4,8,10,16,20 and 24 μmol/L) for 24 hours or imatinib mesylate at 10 μmol/L for 24,48 and 72 hours,methyl thiazolyl tetrazolium (MTT) assay was performed to estimate the proliferation of cells and to determine the effects of imatinib mesylate on the proliferation of Hs294T cells.Then,Hs294T cells were treated with imatinib mesylate at 10 μmol/L or dimethyl sulfoxide (DMSO) for different durations,followed by the detection of cell apoptosis with flow cytometry,localization of β-catenin with annexin V/propidium iodide-double staining and laser confocal microscopy,quantification of β-catenin and cyclin D1 protein with Western blot,and measurement of LEF1 and C-myc mRNA expression with real time fluorescence-based quantitative PCR.Matrigel invasion assay was performed to evaluate the invasiveness of Hs294T cells after treatment with imatinib mesylate at 5 μmol/L or DMSO for 24 hours.ResultsImatinib mesylate at 4-10 μmol/L elicited a dose-dependent decline in the proliferation of Hs294T cells (F =125.3,P ＜ 0.05),and imatinib mesylate at 10 μmol/L induced a time-dependent decrease from 24 to 72 hours(F =714.6,P ＜ 0.01 ).The percentage of early and late apoptotic cells was markedly increased,while the invasiveness was decreased by about 48％(P ＜ 0.01 ),together with a downregulation in the expression of LEF1,C-myc and Cyclin D1 in imatinib mesylate-treated Hs294T cells compared with the DMSO-treated cells.No obvious changes were observed in the protein expression of β-catenin,but a decline in the nuclear localization of β-catenin was noted in Hs294T cells after being treated with imatinib mesylate.ConclusionImatinib mesylate may suppress the proliferation and invasion of,but promote the apoptosis in,melanoma cells,by downregulating the Wnt/β-catenin pathway.

Objective To study the effects of anti-keratin autoantibody (AK auto Ab) on apoptosis of human keratinocytes. Methods Light and electron microscopy were used to observe morphological changes, flow cytometry (FCM) to analyze cell cycle, and electrophoresis to analyze DNA profiles of cultured keratinocytes. Results Typical morphological changes with apoptotic characteristics such as karyopyknosis, chromatin agglutination and apoptosis bodies were found. The subdiploid peaks due to apoptosis were also found in cell cycle analyses. DNA electrophoresis of keratinocytes showed characteristic ladder. Conclusions AK auto Ab could induce apoptosis in cultured human keratinocytes.

Objective To detect the proliferation of and production of interferon-γ by drug-specific peripheral T cells from patients with severe drug eruption.Methods Peripheral blood mononuclear cells (PBMCs) were isolated from 10 patients with severe drug eruption,10 patients with mild or moderate drug eruption and 10 normal human controls,stimulated with causative drugs to obtain drug-specific T cells.Then,both PBMCs and drug-specific T cells were stimulated with causative drugs or unrelated drugs followed by the detection of secretion levels of IFN-γ with ex vivo enzyme-linked immunodotting (ELISpot) assay and cultured ELlSpot assav respectively.Results After stimulation with causative drugs,a higher level of IFN-γ was secreted by PBMCs and drug-specific T cells from patients with severe drug eruption compared with those from normal human controls (both P<0.01).and by drug-specific T cells than by PBMCs (P<0.01).The culture with unrelated drugs could neither induce the generation of drug-specific T cells nor promote the secretion of IFN-γ by PBMCs from the patients.Drug-specific T cells still existed in the peripheral blood of 3 patients within 1 to 3 years after recovery of drug eruption.Conclusions There are drug-specific T cells in peripheral blood of patients with severe drug eruption,and they may persist for a certain period of time after recovery of drug eruption.Ex vivo ELISpot combined with cultured ELISpot may be applied to the identification of causative drugs in vivo.

BACKGROUNDTo determine the value of preoperative cardiopulmonary risk index (CPRI) in predicting the short-term prognosis after lung resection in patients with lung cancer.

METHODSPreoperative clinical data were used to generate a cardiac risk index (CRI) and a pulmonary risk index (PRI). And the value of cardiopulmonary risk index (CPRI) consisting of CRI and PRI in predicting postoperative prognosis was estimated in patients who underwent lung resection at Shanghai Chest Hospital in 1999.

RESULTSA total of 625 consecutive patients were studied. Postoperative complications occurred in 49 patients (7.8%), including 8 deaths within 30 days of operation. In the total group, CRI, PRI and CPRI scores ranged from 1 to 3, 0 to 5 and 1 to 7, respectively. There were 489 patients with CPRI < 4, and 136 with CPRI≥4. Using CPRI≥4 as a threshold for predicting postoperative complications, the sensitivity, specificity and accuracy rate were 75.5%, 82.8% and 82.2% respectively.

CONCLUSIONSThe preoperative CPRI is one of the important indexes in predicting the short-term postoperative prognosis for patients with lung cancer. However, it can not completely predict all of postoperative risks, and should be used together with other factors.

BACKGROUNDTo detect dendritic cells (DC)in the peripheral blood and plasma concentration of vascular endothelial growth factor (VEGF) of patients with non-small cell lung cancer (NSCLC) and to evaluate their relationship.

METHODSThe quantitation of DC in the blood was performed in 55 patients with NSCLC, 13 patients with pulmonary benign diseases, and 12 healthy volunteers by a novel flow cytometric assay. The concentration of VEGF in the plasma was measured by ELISA kit.

RESULTSNo significant difference was found in the levels of DC and VEGF between the patients with pulmonary benign diseases and healthy volunteers (P>0.05). In comparison with subjects of healthy volunteers and pulmonary benign diseases, the level of DC was significantly decreased, while that of VEGF was significantly increased in the patients with NSCLC(P < 0.05 to 0.01). The levels of DC and VEGF in the peripheral blood of NSCLC were closely associated with TNM stages and lymph node metastasis. However, no correlation was found among the levels of DC and VEGF and age, gender, cell differentiation and histologic classification. There was a negative correlation between the VEGF concentration and the DC counts.

CONCLUSIONSThe decline of DC count in peripheral blood and the enhancement of plasma VEGF are remarkably related to the malignancy of NSCLC. And VEGF overexpression may be one of mechanisms of DC maturation and differentiation inhibition in patients with NSCLC.

Objective:To explore the application process, efficacy and safety of MR-guided radiotherapy based on MR-linac in esophageal cancer.Methods:The clinical data of patients with esophageal cancer treated with MR-linac at Shandong Cancer Hospital and Institute from September 2021 to July 2022 were retrospectively analyzed, to investigate the treatment process of esophageal cancer with MR-linac, and to analyze the efficacy and safety of patients. All patients received MR-guided radiotherapy, underwent CT and MR localization, target area delineation, and design of the Monaco treatment planning system plan. Adaptation-to-position adjustment was conducted during the pre-treatment evaluation. The median number of fractions was 25, the median single dose of planning target volume was 1.8 Gy, and the median total dose was 50.2 Gy. Median follow-up was 16 months.Results:Among the 12 patients in the whole group, there were 1 case of cervical esophageal cancer, 3 cases of upper thoracic esophageal cancer, 4 cases of middle thoracic esophageal cancer and 4 cases of lower thoracic esophageal cancer, including 3 cases of neoadjuvant radiotherapy and 9 cases of radical radiotherapy. All patients had a smooth treatment process. The median treatment time was 33 min, and the patients had good compliance. For patients with radical radiotherapy, one month after radiotherapy, the number of objective remission cases was 3, and the number of disease-control cases was 9; six months after radiotherapy, the number of objective remission cases was 3, and the number of disease-control cases was 6. All patients treated with neoadjuvant radiotherapy underwent surgery within 2 months, and one patient achieved pathological complete remission. The most common acute adverse reactions were radiation esophagitis (7 cases) and leukopenia in bone marrow suppression (8 cases), with late-stage adverse reactions being radiation pneumonia (1 case). The adverse reactions to radiotherapy were slight, and no grade 4 or above adverse reactions were observed.Conclusion:The clinical treatment process for esophageal cancer under MR-guided radiotherapy based on MR-linac is feasible, with good curative effects and mild adverse reactions.

Objective To investigate the clinical manifestation and imaging features of diabetic striatopathy(DS).Methods A retrospective analysis was conducted on the clinical,laboratory,and imaging data of 8 patients with DS,which was then summarized in conjunction with relevant literature.Results Random blood glucose(8.39-24.80 mmol/L)and glycated hemoglobin(HbA1c)(9.0%-21.50%)were elevated in 8 patients.One case had positive urine ketone bodies(++),while 7 cases had negative urine ketone bodies(-).Hemichorea was present in 7 cases,while 1 case did not exhibit hemichorea.A total of 7 cases showed unilateral striatum T1WI hyperintensity on MRI,and 8 cases showed iso/hyper-density on CT scans.Following blood glucose control and other related treatments,involuntary movement disappeared in 2 cases,and symptoms improved in 5 cases.Conclusion DS mainly occurs in diabetic patients with poorly controlled blood glucose,presenting with typical clinical manifestation and neuroimaging features.It manifests exclusively in the contralateral striatum of the affected limb.The diagnosis should be based on a combination of clinical,laboratory,and imaging findings to prevent missed or misdiagnoses.

Anemia, Aplastic ; therapy ; Fetal Blood ; transplantation ; Humans ; Mesenchymal Stromal Cells