[Clinical analysis of 4 children with cryptogenic organizing pneumonia].

Objective: To analyze the clinical features of children with cryptogenic organizing pneumonia (COP) confirmed by pathology. Methods: The clinical manifestations, imaging, pathology, treatment and outcome data of 4 children with COP confirmed by thoracoscopic lung biopsy were retrospectively analyzed, who were hospitalized at Respiratory Department of Shenzhen Children's Hospital from January 2004 to December 2022. Results: All of the 4 patients were male, the age ranged from 1 year 3 months to 14 years. The time from onset to diagnosis was 3 months to 3 years. The follow-up duration was 6 months to 6 years. All the 4 cases had cough, 2 cases had tachypnea and wheezing, 1 case had expectoration, 1 case had chest pain, 1 case had decreased activity tolerance and weight loss. Rales in 2 cases and hypoxemia in 1 case. Pulmonary high resolution CT showed diffuse distribution, involvement of both lungs in 3 cases, and single lung combined migration in 1 case.Three cases showed ground-glass opacity, consolidation, patchy or fibrous strips, and 1 case presented air bronchogram and "reversed halo sign". All the 4 cases were performed thoracoscopic lung biopsy, and the pathological findings showed cellulose exudate or small nodules filled with granulation tissue or fibroblasts in the alveolar cavity and small airways, and 1 case was Masson corpuscle positive. Three patients achieved remission after glucocorticoid therapy. Spontaneous remission without treatment was seen in 1 patient.Two cases were followed up for 17 months and 6 years, respectively, who had excellent outcome. Conclusions: The manifestations of COP in children include cough, expectoration and chest pain. Infants and young children may have tachypnea and wheezing. The most common chest CT findings are diffuse distribution of ground-glass opacity, patchy and consolidation in both lungs. Diagnosis should depend on pathological examination. The effect of glucocorticoid therapy is good.

[Immunodeficiency diseases with interstitial lung disease as major clinical manifestations: report of six cases].

Objective: To summarize the clinical features of immunodeficiency diseases with interstitial lung disease (ILD) as major clinical manifestations and to improve understanding etiology of ILD. Methods: The clinical features and clinical clues for diagnosis of six cases with immunodeficiency presented with ILD in Shenzhen Children's Hospital from January 2014 to December 2016 were retrospectively analyzed. Results: The patients' age ranged from 3 months to 5 years and 9 months, 5 cases were male. All cases had cough and tachypnea, 3 cases had lung infection and respiratory failure, 2 cases had chronic hypoxia and one had clubbing. Three cases had skin rashes; 5 cases had failure to thrive. Chest CT scan showed diffuse ground glass opacity in all the 6 cases, and 2 cases had cystic changes and one had "crazy-paving" pattern. Five patients were suspected to have surfactant dysfunction and genetic testing was performed before diagnosis of immunodeficiency, of which the results were negative. With human immunodeficiency virus antibody test or immunologic laboratory testing and/or immune genetic panel, acquired immune deficiency syndrome was confirmed in one case, hyper-IgM syndrome was confirmed in two cases and hyper-IgE syndrome in one case, Wiskott-Aldrich syndrome in one and STAT3 gain of function genetic mutation in another. All cases had clinical clues indicative of underlying immunocompromise. Conclusions: The clinical features of immunodeficiency diseases with ILD are cough, tachypnea or hypoxia, respiratory failure with infection, diffuse ground glass opacity in Chest CT imaging. With thorough medical history and immunology screening, there would be clinical clues indicative of underlying immunocompromise. Screening for immunodeficiency disease should be emphasized in the differential diagnosis of ILD, otherwise it may lead to misdiagnosis or unnecessary testing.

[A novel compound heterozygous mutation in ABCA3 gene in a child with diffuse parenchymal lung disease].

Objective: To summarize the clinical characteristics of the diffuse parenchymal lung diseases in a child caused by a novel compound heterozygous ABCA3 mutation and explore the association between the phenotype and ABCA3 mutation. Method: The clinical material of a patient diagnosed with diffuse parenchymal lung disease with ABCA3 mutation in December 2016 in Shenzhen Children's Hospital was analyzed. The information about ABCA3 gene mutation updated before April, 2017 was searched and collected from the gene databases (including 1000Genomes, HGMD, EXAC) and the literatures (including Wanfang Chinese database and Pubmed). Result: The girl was one year and nine months old. She presented with chronic cough, tachypnea, cyanosis and failure to thrive since she was one year and three months old. Her condition gradually deteriorated after she was empirically treated. Physical examination showed malnutrition, tachypnea and clubbed-fingers. Her high resolution computed tomography (HRCT) revealed diffused ground-glass opacities, thickened interlobular septum, and multiple subpleural small air-filled lung cysts. The second generation sequencing study identified a novel compound heterozygous mutation (c.1755delC+c.2890G>A) in her ABCA3 gene, which derived respectively from her parents and has not been reported in the database and the literatures mentioned above. Conclusion: c.1755delC+c.2890G>A is a new kind of compound heterozygous mutation in ABCA3, which can cause children's diffuse parenchymal lung disease. Its phenotype is related to its genotype.

Antioxidant enzyme levels in pathogenesis of oral squamous cell carcinoma (OSCC).

Increased oxidative stress and altered anti-oxidant defense systems have been implicated in the pathogenesis of several diseases including cancer. Therefore, the aim of our study is to evaluate the antioxidant enzyme levels such as superoxide dismutase (SOD) and catalase in blood samples and tissues collected from oral squamous cell carcinoma patients and compared with healthy controls.The collected blood samples and tumor tissues from the diseased individuals and the normal controls are analyzed for malondialdehyde (MDA) and nitric oxide (NO), which is the indicator of oxidative and nitrosative stress respectively. The anti-oxidant enzymes SOD and catalase levels are measured by UV visible spectrophotometer. Subsequently, immuno-histostaining for antioxidant enzymes were performed in oral squamous cell carcinoma biopsies and sections were analyzed.The levels of MDA and NO were significantly elevated in the blood and tissue samples of OSCC patients. The antioxidant enzymes SOD and catalase were significantly reduced in OSCC tissues; while in erythrocytes catalase level is reduced whereas the SOD level is increased. Further, the reduced immuno-histostaining was observed for catalase and SOD in OSCC tissues when compared to normal oral epithelium.The enhanced levels of MDA and NO revealed that increased oxidative stress in conjunction with the reduced antioxidant defense mechanism in OSCC patients, might be involved in cancer progression. Our results suggest that detection of reactive oxygen species (ROS) and antioxidant enzymes levels might be a valuable marker in cancer prognosis and for improving therapeutic strategies in oral cancer.

Protocatechuic acid suppresses MPP+ -induced mitochondrial dysfunction and apoptotic cell death in PC12 cells.

Protocatechuic acid (PCA), a phenolic compound isolated from the kernels of Alpinia (A.) oxyphylla, showed antioxidant neuroprotective effect in our previous study. Here, we investigated the effect of PCA on the MPP(+)-induced mitochondrial dysfunction and apoptotic cell death in PC12 cells. The apoptosis in MPP(+)-induced PC12 cells was associated with loss of mitochondrial membrane potential, the formation of reactive oxygen species (ROS), GSH depletion, activation of caspase-3 and down-regulation of Bcl-2. In contrast, treatment of PC12 cells with PCA significantly prevented the above-mentioned mitochondrial dysfunction. Our data pointed to the potential clinical application/use of PCA to overcome neurodegenerative diseases such as Parkinson's disease.

Protocatechuic acid from Alpinia oxyphylla against MPP+-induced neurotoxicity in PC12 cells.

An ethyl acetate extract of Alpinia oxyphylla was found to possess neuroprotective activity against 1-methyl-4-phenylpyridinium ion (MPP(+)) induced apotosis and oxidative stress in cultured PC12 cells. From the extract, a phenolic compound was isolated through bioassay-guided fractionation and identified as protocatechuic acid (PCA) by IR, MS, and (1)H and (13)C NMR spectroscopy. It was the first time which was isolated from the kernels of A. oxyphylla. Exposure of PC12 cells to 1mM MPP(+) may cause significant viability loss and apoptotic cell death. PCA stimulated PC12 cellular proliferation and markedly attenuated MPP(+)-induced apoptotic cell death in a dose-dependent manner. By observing the nuclear morphological changes and flow cytometric analysis, PCA showed its significant effect on protecting PC12 cells against MPP(+)-induced apoptosis. Meanwhile, PCA enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) in PC12 cells. In addition, PCA also dose-dependently reduced the hydrogen peroxide (H(2)O(2))- or sodium nitroprusside (SNP)-induced cell death in PC12 cells. The results suggest that PCA may be one of the primary active components in the kernels of A. oxyphylla and provide a useful therapeutic strategy for the treatment of oxidative stress-induced neurodegenerative disease such as Parkinson's disease.

Catalpol inhibits apoptosis in hydrogen peroxide-induced PC12 cells by preventing cytochrome c release and inactivating of caspase cascade.

In the present study, using a rat pheochromocytoma (PC12) cell line, the effect of catalpol on H2O2-induced apoptosis was studied. The apoptosis in H2O2-induced PC12 cells was accompanied by down-regulation of Bcl-2, up-regulation of Bax, the release of mitochondrial cytochrome c to cytosol and sequential activation of caspase-1 and caspase-3 then leading to cleavage of poly-ADP-ribose polymerase (PARP). Catalpol not only suppressed the down-regulation of Bcl-2, up-regulation of Bax and the release of mitochondrial cytochrome c to cytosol, but also attenuated caspase-3 activation, PARP cleavage, and eventually protected against H2O2-induced apoptosis. Taken together, these results suggest that treatment of PC12 cells with catalpol can block H2O2-induced apoptosis by the regulation of Bcl-2 family members, as well as suppression of cytochrome c release and caspase cascade activation.

Hydrogen peroxide-induced apoptosis in pc12 cells and the protective effect of puerarin.

In this study, the effect of puerarin on hydrogen peroxide-induced apoptosis in PC12 cells was studied. Exposure of cells to 0.5mM H(2)O(2)may cause significant viability loss and apoptotic rate increase. When c-Myc, Bcl-2 and Bax expression and caspase-3 activity were measured, using Ac-DEVD-AMC as a substrate, the changes in these apoptosis regulatory and effector proteins suggested that the elevation of c-Myc, decrease in Bcl-2:Bax protein ratio, and caspase-3 activation all play a key role in apoptosis. When cells were treated with puerarin prior to 0.5 mM H(2)O(2)treatment, a reduction in viability loss and apoptotic rate was seen. In addition, c-Myc expression decreased and Bcl-2:Bax ratio increased. Puerarin also reduced the H(2)O(2)-induced elevation of caspase-3 activation. These results suggest that puerarin can protect neurons against oxidative stress. It can block apoptosis in its early stages via the regulation of anti- and pro-apoptotic proteins, as well as by the attenuation of caspase-3 activation in H(2)O(2)-induced PC12 cells.

Effect of ischemic preconditioning on hepatic tolerance to cold ischemia in the rat.

A short warm ischemia before reperfusion has been shown to improve the tolerance of the heart and the liver to a prolonged warm ischaemia. The present experimental study was conducted to evaluate the effect of such preconditioning on hepatic tolerance to an extended cold ischemia. In a model of isolated perfused liver, livers from Wistar rats (250-350 g) were stored for 24 h in UW (4 degrees C) immediately after harvesting and reperfused for 3 h at 37 degrees C. Control livers subjected to a 24-h cold ischemia were compared to livers subjected to preconditioning (defined as a 5- or 10-min clamping of the hepatic pedicle followed by a 10-min reperfusion before liver harvesting) prior to the definitive 24-h cold ischemia. While there was no difference in bile production between the preconditioned groups and the controls, transaminases and LDH release was significantly increased, vascular resistance was enhanced, and preservation injury was more extensive in both preconditioned groups as compared to controls. In contrast to the beneficial effect reported on prolonged warm ischaemia, preconditioning has a deleterious effect on hepatic tolerance to an extended cold ischemia.

Effect of extended cold ischaemia with UW solution on graft function after liver transplantation.

Studies in animals on the use of UW solution in liver transplantation have shown an inverse relation between cold ischaemia time (CIT) and graft function. There are few clinical data on this relation in human beings. We have investigated the effect of extended cold ischaemia in a prospective study. We assessed early graft function and subsequent outcome for 306 consecutive elective liver transplantations; for analyses, grafts were grouped according to CIT (< 12 h group A, > or = 12 h group B), since a preliminary study identified 12 h as a significant cut-off point. Initial graft function was better in group A than group B, as shown by maximum alanine aminotransferase activity (mean 623 [805] vs 946 [1148], p = 0.02), bile production on days 1-3 (p < 0.05), maximum serum bilirubin by day 10 (206 [166] vs 244 [163] mumol/l, p = 0.04), and frequencies of primary non-function (1 [0.4%] vs 4 [7%], p = 0.006) and hepatocyte necrosis on routine biopsy sample after reperfusion (18% vs 31%, p = 0.04). Long-term outcome was also better in group A than group B; graft and patient survival rates were higher and fewer retransplantations were needed. These findings suggest that cold ischaemia in UW solution for longer than 12 h is a risk factor for graft function and patient survival. We recommend that the limit of the safe CIT be reconsidered.

Hepatic artery ligation and infusion chemotherapy for unresectable primary liver cancer.

During the period of 1958-1989, 356 patients with pathologically proven primary liver cancer (PLC) were determined by laparotomy to be unresectable. Of the 356 patients, 51 (14.3%) were of subclinical stage, 287 (80.6%) of moderate stage and 18 (5.1%) of late stage. The association of liver cirrhosis was present in 310 patients (87.1%). Treatment modalities in 356 patients were divided into 4 groups: hepatic artery ligation (HAL) (51), hepatic artery infusion (HAI) of chemotherapeutic agents (114), HAL + HAI (117), and HAL + HAI + radiotherapy (74). The 5-year survival rate was zero in the 4 groups in the period of 1958-1977. During 1978-1989, however, the 5-year survival rate was zero in HAL, 7.9% in HAI, 24.4% in HAL + HAI (with second look resection in 10 patients), and 36.5% in HAL + HAI + radiotherapy (with second look resection in 19). The marked improvement in survival in later period was attributable to the accurate site of hepatic artery catheter, longer infusion chemotherapy, and combination treatment, particularly second look resection in some of the patients. These results indicate that HAL + HAI + combination treatment might provide a possible prolongation of survival or even resection in some patients with original unresectable PLC.

Radioimmunotherapy in the multimodality treatment of hepatocellular carcinoma with reference to second-look resection.

Experimental study using nude mice human hepatocellular carcinoma (HCC) xenograft indicated that the combination treatment with iodine 131 (131I)-anti-human HCC isoferritin (131I-isoFtAb), cisplatin, and mixed bacterial vaccine (MBV) yielded better inhibition rate as compared with double combination or 131I-isoFtAb alone. Based on these findings, 25 patients with surgically proven nonresectable and pathologically proven HCC have been treated by radioimmunotherapy using 131I-isoFtAb intrahepatic arterial infusion as a part of multimodality treatment. Of the 25 patients, seven (28.0%) received second-look resection after marked shrinkage of tumor. The 1-year survival was 52.5% (12/23) and 2-year survival 27.7% (five of 18) in the entire series. Of the five patients with 2-year survival, four were in the second-look resection group. Patients with tumor less than or equal to 8 cm showed higher second-look resection rate (62.5% versus 11.8%) and 1-year survival (85.7% versus 37.5%) as compared with tumor greater than 8 cm. Mixed bacterial vaccine as adjuvant immunotherapy seemed effective to prolong survival. The 2-year survival was higher in patients with second-look resection as compared with those without (75.0% versus 14.3%). Thus, radioimmunotherapy using 131I-isoFtAb might be one of the modalities of choice, particularly in the conversion of nonresectable to resectable HCC in a well-designed multimodality treatment regimen.

[Comparative study on subcutaneous, intraperitoneal and intrahepatic transplantations in nude rat bearing hepatocellular carcinoma (HCC)].

Biological characteristics of the tumor may be different in various growth sites. Comparison of subcutaneous, intraperitoneal and intrahepatic transplantations in nude rat bearing hepatocellular carcinoma was carried out. The previous characteristics of histologic morphology, cell type and synthesis of AFP were still preserved in those three transplantations. The successful transplantation rate was high, latent stage short and speed of the tumor growth fast in the subcutaneous route. AFP level was the highest in intrahepatic route. Successful transplantation rate was high, latent stage short and speed of the tumor growth fast in the intrahepatic route as compared with intraperitoneal route. Tumor invasion and metastasis were often observed in intraperitoneal and intrahepatic routes. The results indicate that the tumor growth condition provided by body sites is different. Tumor invasion and metastasis are related to the tissue environment besides its potential. Each of the three routes has its advantages and disadvantages which should be selected according to different requirement for cancer research.

[Radioimmunotherapy combined with chemotherapy and immunotherapy for nude mice bearing human hepatocellular carcinoma].

A comparative study of multiple modalities, radioimmunotherapy combined with cisplatin and MBV was made. The tumor size and macrophage activity (acid phosphatase) were measured after treatment. The results showed that the tumor inhibition rates were 48, 55, 74, 76, 79% in radioimmunotherapy, cisplatin, radioimmunotherapy + MBV, radioimmunotherapy + cisplatin and radioimmunotherapy + MBV + cisplatin groups, respectively. Radioimmunotherapy was effective in controlling tumor growth, especially in sequential treatment by two injections. Both cisplatin and MBV could increase therapeutic effect of radioimmunotherapy. Therefore, combination of the three modalities is the best choice for tumor growth control. The effectiveness of MBV may be related to the increase of macrophage activity. Preliminary clinical results were satisfactory. Decline in serum AFP level and shrinkage of tumor were observed in 80% (12/15) and 65% (13/20) of the patients. It is suggested that combination of multiple treatment modalities may provide an important approach to treat moderately advanced liver cancer.

Radioimmunotherapy for hepatocellular carcinoma (HCC) using 131I-anti HCC isoferritin IgG: preliminary results of experimental and clinical studies.

Based on radioimmunoimaging for HCC using 131I-anti HCC isoferritin IgG, the experimental and clinical studies on radioimmunotherapy for HCC were reported. Thirty-six nude mice bearing human HCC were used for the study of labeled IgG, pure 131NaI and pure IgG. In the labeled IgG group, the tumor inhibition rate was significantly higher than that in other groups (81%, 60%, and 18%, respectively, p less than 0.05). The tumor cell DNA analysis showed the tumor cell was inhibited in the S stage of the cell cycle. Twenty pathologically proven unresectable HCC patient were treated by 131I-antihuman HCC isoferritin IgG 20-55mCi monthly for 1-3 times (via hepatic arterial catheter or intravenously). The short-term response was promising, a decline in AFP level and shrinkage of tumor were observed in 80% (12/15) and 65% (13/20) of patients respectively. Sequence resection was successful in five patients (5/20) after radioimmunotherapy. No marked toxic effects were noted in our limited experience, but some problems remain to be discussed.