Background The senescence of alveolar type II epithelial cells is an important driving factor for the progression of silicotic fibrosis, and the regulatory effects of oxamate on the senescence of alveolar type II epithelial cells is still unclear. Objective To explore whether lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting senescence of alveolar type II epithelial cellsMethods This study was divided into two parts: in vivo experiments and in vitro experiments. In the first part, forty SPF C57BL/6J male mice were randomly divided into four groups with 10 in each group: control group, silicosis model group, low-dose oxamate treatment group, and high-dose oxamate treatment group. The silicotic mouse model was established by intratracheal instillation of 50 μL SiO₂ suspension (100 mg·mL⁻¹). The treatment models were prepared by intraperitoneal injection of 100 μL oxamate (225 mmol·L⁻¹ and 1125 mmol·L⁻¹). In the second part, induction of MLE-12 mouse alveolar type II epithelial cells was conducted with SiO₂. The in vitro experimental groups were ① SiO₂ induction groups: control group, 50 μg·mL⁻¹ SiO₂ group, 100 μg·mL⁻¹ SiO₂ group, and 200 μg·mL⁻¹ SiO₂ group, and ② oxamate treatment groups: control group, SiO₂ group (100 μg·mL⁻¹), low-dose oxamate (25 mmol·L⁻¹) treatment group, and high-dose oxamate (50 mmol·L⁻¹) treatment group. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after sirius red staining; positive co-expression of prosurfactant protein C (Pro-SPC) and β-galactosidase was detected by immunofluorescence staining; positive expression of β-galactosidase in MLE-12 cells was detected by immunofluorescence staining. The protein expression levels of collagen type I (CoL I), fibronectin1 (FN1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), lactate dehydrogenase A (LDHA), p-ataxia telangiectasia and Rad3-related kinase (ATR), and cyclin-dependent kinase inhibitors p21, and p16 were detected by Western blotting. Results Compared with the control group, the protein expression levels of HK2, PKM2, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group and the SiO₂-induced MLE-12 cells (P＜0.05). The in vivo studies showed that, compared with the control group, the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the protein expression levels of CoL I, FN1, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group (P＜0.05). Compared with the silicosis model group, the oxamate treatment groups showed significant downregulation of the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the the CoL I, FN1, LDHA, p-ATR, p21, and p16 protein expression levels, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). The in vitro studies showed that, compared with the control group, the proportion of β-galactosidase positive cells and the protein expression levels of p-ATR, p21, and p16 were significantly upregulated in the SiO₂-induced group (P＜0.05). Compared with the SiO₂ group, the proportion of β-galactosidase positive cells and the LDHA, p-ATR, p21 and p16 protein expression levels were significantly downregulated in the oxamate treatment groups, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). Conclusion Lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting the senescence of alveolar type II epithelial cells.

Objective To discuss the imaging features of pulmonary lophomonas blattarum infecfiom Methods Seventeen patients with renal homotransplantations presented fever without congh.dyspnea and shortness of breath in 1-4 months after the transplantation were included.Chest X-ray abnormalities were comfirmed as pulmonary lophomonag blattarum infection through fiberoptic bronchoscopy (FOB)and bronchoalveolar lavage(BAL).The X-ray and CT films were reviewed and the imaging features were summarized.Results X-ray appearances:Bilateral pulmonary shadows were seen in 16 patients.of which 9 cases presented patchy and cord shadows,and 7 cases presented large area of pathy shadows.Lung marking increase Wag seen in 1 case.CT appearances:CT abnormalities presented bilaterally and involved more than two lobes in all 16 patients.15 eases displayed ground-glass opacity.11 cases displayed patchy consolidation,14 cases displayed bandlike attenuation,and 8 cases displayed nodular opacity.Ground-glass opacity,consolidation and bandlike attenuation were seen simultaneously in 11 cases.Lymph node enlargement in mediastinum Wag presented in 10 cages.Conclusion Pulmonary lophomonas blattarum infection should be suspected in immunosuppressed patients combining the CT appearances and clinical information.

Objective To evaluate the development of fetal cerebellar vermis using 3D transabdominal ultrasound,and provide evidence for prenatal screening fetal cerebellar vermis anomalies.Methods Totally 387 normal fetuses at 20～36 gestation weeks were examined by three-dimensional extended imaging(3DXI) to observe the fetal cerebellar vermis.The width,anteroposterior diameter,craniocaudal diameter of the cerebellar vermis,the angle between brain stem and vermis,a ratio between the area of anterior vermis and posterior vermis were measured,and the relationship between the gestational age and parameters mentioned above were analyzed.Results The multi slice view of 3DXI and 3D reconstructed sagittal section well evaluated the integrity of vermis morphous and vermis size,identified characteristic signs of vermis:the fourth ventricle apex and vermis crack.In normal fetus,brain stem and vermis were almost parallel,the angle between them was 3.97°±1.65°.There was no significant correlation between the angle and the gestational age.The area of the anterior vermis was smaller than that of posterior vermis,with a ratio of 0.76±0.06,which was also not related to gestational age.The width,anteroposte rior diameter and craniocaudal diameter of the cerebellar vermis were positively correlated with gestational age.Conclusions The multi slice view of 3DXI and 3D reconstructed sagittal section should help evaluate the development of the cerebellar vermis,accurately show the cerebellar vermis and its surrounding strutures,and provide a new way to evaluate the fetal cerebellar vermis.

Objective:To study the clinical effect and safety of ubenimex capsules and SOX chemotherapy on the advanced gastric cancer.Methods:90 patients with advanced gastric cancer who were treated in our hospital from September 2013 to September 2015 were selected and randomly divided into the observation group (n=45) and the control group (n=45).The patients in the control group were treated with SOX chemotherapy,while the patients in the observation group were treated with ubenimex capsules on the basis of control group.Then the serum levels of MMP-2 and MMP-9,the immune functions,the clinical efficacy,the adverse reactions and survival rate of two groups were observed and compared before and after the treatment.Results:After treatment,the CD4+,CD4+/CD8+ in the observation group were higher than those of the control group (P＜0.05);The levels of MMP2 and MMP-9 in the observation group were lower than those of the control group (P＜0.05);The total effective rate of the observation group was higher than that of the control group [68.89％(31/45) vs 48.89％(22/45)] (P＜0.05);The incidence of thrombocytopenia,leukopenia,nausea and vomiting and abnormal liver functions in the observation group was lower than that of the control group (P＜0.05);The survival rate of the observation group was higher than that of the control group at 6 months and 12 months [93.33％ (42/45) vs 77.78％ (35/45),82.22％ (37/45) vs 57.78％ (26/45)](P＜0.05).Conclusion:Compared with SOX chemotherapy alone,ubenimex capsules and SOX chemotherapy could effectively improve the immune function,enhance the long-term survival rate with high safety of patients with advanced gastric cancer.

OBJECTIVEDehydroandrographolide (DP) from Andrographis paniculata (Burm. F.) Nees is a potential anticancer agent. This study aimed to investigate the oral bioavailability and intestinal disposition of DP to provide useful information for the development of DP as a new candidate anticancer drug.

METHODSThe pharmacokinetics of DP was evaluated in rats, and its intestinal disposition was determined using cultured Caco-2 cells and a single-pass rat intestinal perfusion model.

RESULTSThe oral bioavailability of DP was 11.92% in rats. The apparent permeability coefficient (P(app)) of DP from the basolateral side (B) to the apical side (A) (5.37×10(-5) cm/s) of the Caco-2 model was roughly equal to that from A to B (4.56×10(-5) cm/s), suggesting no involvement of the efflux transporter(s). In the perfusion model, no significant difference was found in the effective permeability (P*(eff)) of DP between the 4 segments of the intestine. No significant metabolism of DP was detected in the intestinal perfusates. The amount of DP found in the bile was only about 0.1% of the absorbed amount. The P*(eff) and bile amounts of DP were not significantly increased by P-glycoprotein (P-gp) inhibitor or breast cancer resistant protein (BCRP) inhibitor (P>0.05).

CONCLUSIONThe bioavailability of DP was 11.92% in rats. DP has good absorption and metabolism stability in the intestine. The efflux transporters such as P-gp and BCRP do not participate in DP transport.

Administration, Oral ; Animals ; Biological Availability ; Biological Transport ; Caco-2 Cells ; Diterpenes ; administration & dosage ; pharmacokinetics ; Humans ; Intestinal Absorption ; Intestines ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo perform a comparative proteomic analysis for identification of pulmonary proteins related to the progression of silicosis and anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP).

METHODSBronchial instillation of SiO₂powder (for 4 or 8 weeks) was applied in rats to establish a silicosis model. Ac-SDKP treatment was performed before (prevention group) or after (treatment group) SiO₂instillation. The control group was treated by bronchial instillation of sodium chloride solution of the same volume as SiO₂powder for 4 or 8 weeks. Proteins in lung tissue were separated by two-dimensional gel electrophoresis and stained with colloidal Coomassie brilliant blue. The gel images were scanned with the Lab Scan III system and analyzed with Imagemaster 6.0. The protein spots with significant differences between two groups (i.e., P value was less than 0.05 in One-way ANOVA) and with a change in volume over 30% were defined as differential proteins. Comparison was performed between the silicosis group and control group after 4 or 8 weeks, between the Ac-SDKP treatment group and silicosis group after 8 weeks, and between the Ac-SDKP prevention group and silicosis group after 8 weeks. The differentially expressed proteins were subjected to in-gel digestion with trypsin and MALDI-TOF-MS and Mascot search engine analysis to identify these proteins.

RESULTSThirty-three differential proteins were identified. In comparison with the control group (4 weeks), the silicosis group (4 weeks) had 17 up-regulated proteins and 11 down-regulated proteins. In comparison with the control group (8 weeks), the silicosis group (8 weeks) had 16 up-regulated proteins and 12 down-regulated proteins. In comparison with the silicosis group (8 weeks), the Ac-SDKP treatment group had 5 up-regulated proteins and 6 down-regulated proteins, and the Ac-SDKP prevention group had 8 up-regulated proteins and 10 down-regulated proteins.

CONCLUSIONCritical regulatory proteins related to silicotic fibrosis and anti-silicotic effect of Ac-SDKP have been identified. These proteins may play an important role in proliferation, apoptosis, inflammation, epithelial-mesenchymal transition, and signal transduction in silicosis.

Animals ; Disease Models, Animal ; Lung ; metabolism ; Male ; Oligopeptides ; therapeutic use ; Proteome ; metabolism ; Rats ; Rats, Wistar ; Silicosis ; drug therapy ; metabolism

OBJECTIVETo explore the inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on myofibroblast differentiation of MRC-5 human fetal lung fibroblasts induced by angiotensin (Ang) II.

METHODSThe study was divided into 2 step: (1) MRC-5 human fetal lung fibroblasts was induced for 48 h at different dose of Ang II and at different time point by 100 nmol/L Ang II. Then the expression of collagen type I and α-smooth muscle actin (α-SMA) were mesaured by western blot. (2) MRC-5 human fetal lung fibroblasts were divided into 4 group: (1) control, (2) Ang II, (3) Ang II+Ac-SDKP, (4) Ang II+8-Me-cAMP (a specific activator of Epac). The α-SMA expression was observed by immnocytochemical stain. The protein expression of collagen type I, α-SMA, serum response factor (SRF), myocardin-related transcription factor (MRTF)-A, exchange protein directly activated by cAMP (Epac) 1, 2 were measured by Westen blot.

RESULTSMyofibroblast differentiation could be induced by Ang II from MRC-5 cells with a dose- and time-dependent manner. The up-regulation of SRF and MRTF-A were observed in MRC-5 cells induced by Ang II and accompanied with collagen I and α-SMA increased. Pre-treatment with 8-Me-cAMP or Ac-SDKP could attenuated all this changes induced by Ang II, and promoted the expression of Epac1.

CONCLUSIONAc-SDKP can inhibit the myofibroblast differentiation of MRC-5 cells induced by Ang II via Epac1 activating.

Actins ; Angiotensin II ; Cell Differentiation ; drug effects ; Collagen ; Collagen Type I ; Cyclic AMP ; analogs & derivatives ; Fetus ; cytology ; Fibroblasts ; cytology ; Guanine Nucleotide Exchange Factors ; Humans ; Lung ; cytology ; Myofibroblasts ; drug effects ; Oligopeptides ; pharmacology ; Serum Response Factor ; Trans-Activators

Objective:To investigate the serum measles antibody in children with tumor and to provide the clinical evidence for measles vaccination strategy for this special population.Methods:From January 2016 to December 2018, the blood samples of children who were diagnosed with hematological malignancy or solid tumors and received chemotherapy in the Department of Hematology or Oncology Surgery of Children′s Hospital of Fudan University were collected. Enzyme-linked immunosorbent assay was used to quantitatively detect the level of measles IgG antibody, and dynamically monitor the changes of measles antibody level during chemotherapy. Kruskal-Wallis test and chi-square test were used for statistical analysis.Results:A total of 441 children with tumors were enrolled, with the positive rate of measles antibody of 79.1%(349/441), and only 43.3%(191/441) of children had the protective level of IgG antibody. There was a statistically significant difference of the antibody protection rate in children aged0.05). The protection rate of serum measles antibody in children with hematological malignancy and solid tumor were 45.6%(78/171) and 41.9%(113/270), respectively, and there was no statistically significant ( P>0.05). There were 16.3%(16/98) of children who were observed to lose the pre-existing protective antibody during chemotherapy. There was no statistically significant difference of the protection rate of serum among children who had finished chemotherapy 0.05). Conclusions:Serum measles antibody is below the protective level in more than 50% of children with malignancy after chemotherapy. Chemotherapy can compromise the protective antibody against measles. It is recommended for this special population to re-schedule measles vaccine after individualized evaluation to acquire the immuneprotection against measles.

Objective To understand the regional epidemiology and antibiotic resistance pattern of diarrheagenic E .coli infection in children ,and to clarify the pathogenic association between diarrheagenic E .coli infection and childhood diarrhea .Methods Totally 680 diarrheal children in the outpatient setting and 680 non-diarrheal control children were enrolled prospectively .The stool samples were collected and the potential enteric pathogens were detected .Minimal inhibitory concentration (MIC) method was used to determine the antimicrobial susceptibility for diarrheagenic E .coli isolates .Results The isolation rates of diarrheagenic E .coli in diarrhea group and control group were 15 .6％ and 13 .1％ ,respecitvely ,and diarrheagenic E .coli was the most commonly detected enteric bacteria .Multivariate logistic regression analysis adjusted for age suggested no clinical association between diarrhea and infection with enteropathogenic E .coli (EPEC) (aOR=1 .2 ,95％ CI:0 .8-1 .8) ,enteroadhesive E .coli (EAEC) (aOR=1 .1 ,95％ CI:0 .7 -1 .6) and enterotoxigenic E .coli (ETEC) (aOR= 1 .8 ,95％ CI:0 .5 -6 .2) . Among 199 diarrheagenic E .coli strains ,the rates of resistance to ampicillin ,tetracycline ,trimethoprim-sulfamethoxazole ,azithromycin ,and ceftriaxone were 63 .8％ ,55 .8％ ,48 .2％ ,34 .2％ and 26 .6％ , respectively ,while the rates of resistance to ciprofloxacin , amoxicillin-clavulanate and cefoxitin were 4 .5％ ,1 .5％ and 0 .5％ ,respectively .Conclusions Diarrheagenic E .coli is the most common enteric bacteria detected in the stool samples from children with and without diarrhea in this study . The pathogenic role of infections with EPEC ,EAEC and ETEC in childhood diarrhea is not determined .EHEC and EIEC are rarely detected and further studies are needed to clarify the pathogenic association between infection with EHEC ,EIEC and childhood diarrhea .

Objective To investigate the short-term clinical effect of CT guided 125Ⅰ radioactive particle therapy in superficial malignant tumor. Methods The clinic data of 28 patients with metastatic superficial malignant tumor in our hospital were analyzed retrospectively.All patients were treated with CT guided 125Ⅰ radioactive particle therapy.The short-term effects,1 year survival rate and 1 year progression free survival rate of the patients were compared.Results Objective remission rate(ORR)and disease control rate(DCR)after 6 months were 92.86% and 100.00%.1 year overall survival and 1 year progression free survival were 96.43%(27/28)and 82.14%(23/28), respectively.The median overall survival and median progression free survival were 26.978 months (95%CI:22.558-31.399)and 16.932 months (95 % CI:14 .471-19.393).There were 27 cases of 0-Ⅱ degree adverse reactions,1 case of grade Ⅲ adverse reactions and no grade Ⅳ adverse reactions.No signs of 125Ⅰ radioactive particle translocation,vascular embolism and vascular rupture were found. Conclusion 125Ⅰ radioactive particle treatment of superficial malignant tumor has a definite short-term curative effect,with overall survival and progression free survival longer and higher safety,which can be considered in clinical application.