Background and aims:Liver fibrosis is a prevalent pathological stage of various chronic liver diseases and has the potential to progress to liver cirrhosis and hepatocellular carcinoma.However,experimental models for in vivo research are limited.Unexpectedly,increased liver inflammation and fibrosis were previously observed in mice treated with aluminum adjuvant(commercial Imject Alum,a mixture of Al(OH)3 and Mg(OH)2).Our study aimed to reveal the pathogenesis and pathological features of Imject Alum-induced liver injury and evaluate its potential as an experimental model of fibrotic liver disease.Methods and materials:C57BL/6J mice were randomly divided into the following four groups:(ⅰ)control group,which received phosphate-buffered saline injections on days 1,12,26,40,and 54;(ⅱ)Imject Alum(Al(OH)3 160 mg/kg)D26 group,which was administered with Imject Alum(Al(OH)3 160 mg/kg)on days 1,12,and 26;(ⅲ)Imject Alum(Al(OH)3 80 mg/kg)D54;and(ⅳ)Imject Alum(Al(OH)3 160 mg/kg)D54 groups,which were treated with 80 mg/kg and 160 mg/kg of Imject Alum(Al(OH)3),respectively,on days 1,12,26,40,and 54.All reagents were delivered by intraperitoneal injection.Serum biochemical pa-rameters,liver pathology,and expression of genes related to inflammation and fibrogenesis were eval-uated.Transcriptome sequencing was performed.The genetic characteristics of the Imject Alum-induced liver lesions in the existing fibrosis model and patients with cirrhosis were determined.Results:Administration of Imject Alum(Al(OH)3 160 mg/kg)at certain points for 54 days led to extensive hepatic inflammation and fibrosis,accompanied by disturbed bile acid metabolism in mice.Moreover,Imject Alum aggravated liver inflammation and injury by activating the pyroptosis-related inflamma-some pathway.Transcriptome analysis revealed that Imject Alum-induced liver lesions had differentially expressed genes that were significantly enriched in pathways related to inflammation,fibrogenesis,and multiple metabolic processes.Moreover,Imject Alum-induced liver lesions exhibited gene signatures similar to those of existing fibrosis models and patients with cirrhosis.Conclusions:Aluminum adjuvant(Imject Alum;Al(OH)3 160 mg/kg)administration at certain points for 54 days resulted in notable liver injury,inflammation,and fibrosis.This model had similar gene expression characteristics with existing fibrosis models and liver samples from patients with cirrhosis.Overall,aluminum adjuvant(Imject Alum)-induced mouse model may be a novel approach for estab-lishing a liver fibrosis animal model.

Objective:To construct a postoperative nursing plan for liver transplant recipients using the NANDA international, nursing outcomes classification, nursing intervention classification (NANDA-I-NOC-NIC) link (referred to as NNN-link) as the theoretical framework, so as to optimize the nursing process after liver transplantation and improve the quality of nursing.Methods:This study retrospectively collected nursing diagnoses with a postoperative usage rate of over 50% from 300 liver transplant recipients at Shulan (Hangzhou) Hospital from January 2019 to December 2021, and matched nursing outcomes and measures based on the NNN-link theory framework. After two rounds of Delphi expert consultation and group discussion, the entry content was rated, discussed, and modified to form the final version of the postoperative NNN-link for liver transplant recipients.Results:In two rounds of expert consultation, the recovery rates were 96.67% (29/30) and 100.00% (29/29) , respectively. The expert authority coefficients were 0.83 and 0.84, respectively. The Kendall harmony coefficients for the second round were 0.50, 0.38, 0.35. The final postoperative NNN-link for liver transplant recipients included 15 nursing diagnoses, 42 nursing outcomes, and 106 nursing measures.Conclusions:The process of constructing the postoperative NNN-link for liver transplant recipients is scientific and reasonable, and the entries are highly specialized, which can provide reference for clinical nursing after liver transplantation.

Objective:To analyze the difference of clinical characteristics and outcomes of infants with moderate and severe pediatric acute respiratory distress syndrome(PARDS)diagnosed according to baseline oxygenation index(OI) in pediatric intensive care unit(PICU).Methods:Second analysis of the data collected from the "Efficacy of pulmonary surfactant (PS) in the treatment of children with moderate and severe ARDS" program.Retrospectively compare of the differences in clinical data such as general condition, underlying diseases, OI, mechanical ventilation, PS administration and outcomes among infants with moderate and severe PARDS divided by baseline OI who admitted to PICUs at 14 participating tertiary hospitals from 2016 to December 2021.Results:Among the 101 cases, 55 cases (54.5%) were moderate and 46 cases (45.5%) were severe PARDS.The proportion of male in the severe group (50.0% vs.72.7%, P=0.019) and the pediatric critical illness score(PCIS)[72 (68, 78) vs.76 (70, 80), P=0.019] were significantly lower than those in the moderate group, while there was no significant difference regarding age, body weight, etiology of PARDS and underlying diseases.The utilization rate of high-frequency ventilator in the severe group was significantly higher than that in the moderate group (34.8% vs.10.9%, P=0.004), but there was no significant difference in PS use, fluid load and pulmonary complications.The 24 h OI improvement (0.26±0.33 vs.0.04±0.34, P=0.001) and the 72 h OI improvement[0.34 (-0.04, 0.62) vs.0.15 (-0.14, 0.42), P=0.029)]in the severe group were significantly better than those in the moderate group, but there was no significant difference regarding mortality, length of hospital stay and intubation duration after diagnosis of PARDS between the two groups. Conclusion:In moderate and severe(divided by baseline OI) PARDS infants with invasive mechanical ventilation, children in severe group have better oxygenation improvement in the early stage after PARDS identified and are more likely to receive high frequency ventilation compared to those in moderate group.Baseline OI can not sensitively distinguish the outcomes and is not an ideal index for PARDS grading of this kind of patient.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by progressive lung fibrogenesis and histological features of usual interstitial pneumonia. IPF has a poor prognosis and presents a spectrum of disease courses ranging from slow evolving disease to rapid deterioration; thus, a differential diagnosis remains challenging. Several biomarkers have been identified to achieve a differential diagnosis; however, comprehensive reviews are lacking. This review summarizes over 100 biomarkers which can be divided into six categories according to their functions: differentially expressed biomarkers in the IPF compared to healthy controls; biomarkers distinguishing IPF from other types of interstitial lung disease; biomarkers differentiating acute exacerbation of IPF from stable disease; biomarkers predicting disease progression; biomarkers related to disease severity; and biomarkers related to treatment. Specimen used for the diagnosis of IPF included serum, bronchoalveolar lavage fluid, lung tissue, and sputum. IPF-specific biomarkers are of great clinical value for the differential diagnosis of IPF. Currently, the physiological measurements used to evaluate the occurrence of acute exacerbation, disease progression, and disease severity have limitations. Combining physiological measurements with biomarkers may increase the accuracy and sensitivity of diagnosis and disease evaluation of IPF. Most biomarkers described in this review are not routinely used in clinical practice. Future large-scale multicenter studies are required to design and validate suitable biomarker panels that have diagnostic utility for IPF.
Humans ; Idiopathic Pulmonary Fibrosis/diagnosis* ; Biomarkers ; Lung Diseases, Interstitial ; Lung ; Bronchoalveolar Lavage Fluid ; Disease Progression ; Prognosis

Objective To explore the therapeutic effects and adverse reaction of high-dose Diazepam (DZP) in patients with electrical status epilepticus during sleep (ESES).Methods Nine patients in the Outpatient of the Department of Pediatrics,Peking University First Hospital from October 2016 to May 2017 with ESES were treated with high-dose DZP.Oral DZP was administered in a dose of 0.75-1.00 mg/kg(maximum:40 mg) during the first night followed by 0.5 mg/(kg · d) (maximum:20 mg) from the second night for 1-3 months and tapered over next 1-3 months.The seizures,electroencephalogram (EEG) changes and adverse reactions were observed before and after DZP treatment.Results Six of 9 patients were male and 3 were female.The age of onset was ranged from 1 year and 6 months to 10 years.Benign childhood epilepsy with central temporal spike was diagnosed in 5 cases,epileptic encephalopathy with continuous spike-and-wave during sleep in 1 case,and ESES related epilepsy in 3 cases.Age of onset DZP treatment ranged from 4 years and 4 months to 12 years,and the duration of DZP treatment was ranged from 1 to 5 months (1 case only for the first night).The follow-up interval was 6-12 months.The efficiency of DZP on seizures:intent effective in 5 patients,effective in 2 patients and ineffective in 2 patients,and the effective rate was 78％ (7/9 cases).The efficiency of DZP on EEG (1 month after DZP treatment):intent effective in 2 patients (EEG normalized),effect in 3 patients and no effect in 2 patients,and the effective rate was 71％ (5/7 cases),while 2 patients did not receive EEG examination.Four of 7 patients (57％) with intent effect and effective of DZP on seizures had seizures relapse during drug reduction and after drug withdrawal,and the EEG deteriorated simultaneously.Adverse reactions of DZP included 3 patients (33％) with adverse reactions,bed-wetting in 2 patients and snoring on the first night in 1 patient who withdrew DZP later.Conclusions The high-dose of DZP has a certain effect on seizures control and ESES suppression in patients with ESES,but also has a certain recurrence rate.The adverse reactions are mild and self-limiting.High-dose DZP treatment could be a choice for refractory patients with ESES to alleviate disease.

Objective To test the effect of bone marrow mesenehymal stem cells (MSCs) transplantation on oxidative stress and the development of pulmonary emphysema in rats. Methods SD rats (n=26) were randomly divided into three groups:normal control group (group A, n=8),emphysema group (group B, n=8) and emphysema+MSCs transplantation group (group C, n=10).Rat models of emphysema was established by exposing rats to cigarette smoking for 14 weeks. Then rats of group C received MSCs transplantation. At the 14th and 28th days after 4 course of MSCs transplantations, one rat in group C was sacrificed at each time point and their lungs were preserved in frozen sections. Survival of MSCs in the lung tissues were observed by fluorescence microscopy. Eight weeks after transplantations, lung sections were stained by hematoxylin and eo?sin (HE) to observe the morphological alterations.Mean linear intercept (MLI) and mean alveolar numbers (MAN) were also measured. Serum and lung malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were also examined. Re?sults At the 14th day and 28th day after transplantations of MSCs, MSCs successfully localized to lung and survived in rat models of emphysema. Emphysematous changes of lung tissues were observed in both group B and group C. MLI was higher while MAN was lower in group B and C than those in group A (P<0.05). MLI and MDA levels in serum and lung were high?er while MAN level and SOD activity were lower in group B than those in group C (P<0.05).MDA levels in serum and lung was higher while SOD activity was lower in group B and C than those in group A (P<0.05). Conclusion MSCs transplanta?tions can effectively alleviates pulmonary emphysema in rat models which might through reducing oxidative stress .

Objetive To investigate a method of collecting lung cancer cells with bronchofibroscopic biopsy for primary culture and to improve the success rate of primary culture. Methods Thirty lung cancer specimens were obtained through bronchoscopic biopsy for primary culture. The correlation of cancer morphology under bronchofi-broscopy and success rate of primary culture was analyzed. Results Among the lung cancer specimens obtained through bronchoscopic biopsy, primary culture was successful in 17 of 30 cases (56.67%) . The success rate of cauliflower-like tumor mass under bronchofibroscopy was 84.62% (11/13) . The success rate of infiltrating tumor mass under bronchial mucosa with luminal stenosis with or without cristate were 66.67% (2/3) and 37.5%(3/8), respectively. The primary culture of a globular and stiff tumor mass was successful only 1 in 6 cases (16.67%) .Conclusions The primary culture of lung cancer cells obtained from bronchofibroscopic biopsy is simple and effective with a total success rate of 56.67%. Furthermore, the success rate of primary culture is signifi-cantly correlated with the cancer morphology under bronchofibroscopy.

Objective To observe the numerical characteristics of dendritic cells (DC),the DC subsets(myeloid dendritic cell,MDC; plasmacytoid dendritic cell,PDC) and CD4+ CD25 + CD127low/-Tr cells in peripheral blood of Graves disease (GD) patients.Methods According to the clinical manifestations and serum FT3,FT4 and TSH,the GD patients were divided into the untreated-group,the clinical remission group and the clinical stable group,and set normal control group as well.The flow cytometry was used to detect DC and CD4+CD25+CD127low/-Tr cells of the percentage of CD4+ T cells in subjects peripheral blood(EDTA-K2 anticoagulated).The indicators were compared among various groups,and the correlation between the indicators with serum FT3,FT4 and TSH were observed.Results (1) In the untreated-group,the clinical remission group,the clinical stable group,and normal control group,total DCs,MDCs and MDC/PDC gradually declined,untreated-group has a significant difference from the other three groups also the significant difference was found among other three groups; (2) In the untreated-group,the clinical remission group,the clinical stable group,and normal control group,PDCs declined successively,but only the difference was found between untreated-group and normal control group; (3)In the untreated-group,the clinical remission group,the clinical stable group,and normal control group,CD4+CD25+CD127low/-Tr cells gradually raised,but only the difference between untreated-group and normal control group make sense; (4)In the untreated-group,PDCs and CD4+CD25+CD127low/-Tr cells have a certain relevance; (5)There was good correlation between DCs and serum FT3,FT4 and TSH,but CD4+CD25+CD127low/-Tr cells only have correlation with FT3 and FT4.Conclusion DC,MDC,MDC/PDC increased in the untreated-GD patients,and decreased after the therapy of anti-thyroid.Therefore,DCs and the DC subsets are expected to be used to monitor GD in the course of disease.CD4+CD25+CD127low/-Tr cells can be used as a new indicator of the onset of GD.

Objective To establish a new technique of isolating pancreatic islet of langerhans and glueoeortieoid-free immunosuppressive regimen and to evaluate the clinical efficacy and safety of simultaneous adult islet-kidney transplantation in the treatment of type 1 diabetes mellitus with endstage renal failure.Methods Pancreases were stored using the"2-layer method"of the oxygenated perfluoroehemieal and UW solution.The pancreases were digested by Liberase collagenase enzyme and purified using continuous gradients of Ficoll-diatrizoic acid on a refrigerated COBE 2991 centrifuge to separate the islets.Cadaver kidney was transplanted by conventional method and cultured islets were infused by surgical approach to the liver via portal vaseulature using glucocorticoid-free immunosuppressive regimen.Clinical metabolic data such as blood glucose,dose of insulin,C-peptide,HbAlc,liver function and renal function,were determined and compared with the pre-transplant data.ResuitsIslets of langerhans were isolated successfully in 23 pancreases.The average islet yield was 300000 islet equivalents(IEQ).Islet purity and viability were 91.6%,94.6%,respectively.The stimulation index as assessing function of human islet was 3.16 and etiology results in vivo were negative.Twelve islet transplant infusions were carried out in 7 patients after kidney transplantation.Three recipients received 2 islet infusions,1 patient had 3 transplants,and 3 patients received 1 transplant only.The average islet mass for infusion was 1 1 820 IEQ/kg.The immunosuppressive regimen glucocorticoid.During 18 months to 3 yearg follow-up,4 recipients had insulin independence,the dosage of insulin decreased by 70%in 3 patients.The level of blood glucose and H bAlc,liver and renal function were normal throughout follow-up period.C-peptide of all patients was positive after islet transplantation.No adverse effects and complications related to islet infusion procedure were found.Conclusions New technique has proved tO be suitable for isolating pancreatic islet of langerhans.Simuhaneous adult islet-kidney transplantation could be used as an effective and safe way for treating type 1 diabetes mellitus with end-stage renal failure.