Objective To investigate the regulatory effect of tumor necrosis factor-α-induced protein-8-like factor 2 (TIPE2) on the phenotype of lung cancer tumor-associated macrophages (TAM) and its influence on the stemness of lung cancer cells. Methods Mouse macrophage cell line RAW264.7 was cultured and infected with either LV-TIPE2 lentivirus or negative control LV-NC lentivirus. The TIPE2 expression in infected cells was assessed by real-time quantitative PCR (RT-qPCR) and Western blotting to verify transfection efficiency. The infected RAW264.7 cells were co-cultured with lung cancer cell line A549, and were divided into four groups: control group (RAW264.7 cells or A549 cells cultured alone), TAM group (RAW264.7 cells co-cultured with A549 cells), LV-NC group (RAW264.7 cells infected with LV-NC and co-cultured with A549 cells), LV-TIPE2 group (RAW264.7 cells infected with LV- TIPE2 and co-cultured with A549 cells). The RAW264.7 cells were collected after co-culture, and the expression of mannose receptor (CD206) protein of M2 macrophages was detected by cellular immunofluorescence staining. The proportions of M1 and M2 macrophages were detected by flow cytometry. After co-culture, A549 cells were collected, and their activity was assessed by CCK-8 assay. Self-renewal ability was evaluated using tumor cell pelleting experiment. The expression of stemness marker proteins-including cluster of differentiation 133 (CD133), transmembrane adhesion molecule (CD44), sex-determining region Y-box protein 2 (SOX2) and octamer-binding transcription factor 4 (OCT4)-was detected by Western blot. Results Compared with the control group or LV-NC group, the relative mRNA and protein expression levels of TIPE2 in RAW264.7 cells from the LV-TIPE2 group were significantly upregulated. Compared with the control group, the fluorescence intensity of M2-type macrophage marker CD206 protein in RAW264.7 cells from the TAM group was significantly increased, the proportion of M1-type macrophages was significantly decreased, and the proportion of M2-type macrophages was significantly increased. In contrast, compared with the TAM group, the fluorescence intensity of CD206 protein in RAW264.7 cells from the LV-TIPE2 group was significantly decreased, the proportion of M1-type macrophages was significantly increased, and the proportion of M2-type macrophages was significantly decreased. Compared with the control group, the proliferation activity of A549 cells in TAM group was significantly increased, the number of tumor pellet formation was significantly increased, and the relative expression levels of CD133, CD44, SOX2 and OCT4 were significantly up-regulated. However, compared with the TAM group, the proliferation activity of A549 cells from the LV-TIPE2 group was significantly decreased, the number of tumor pellet formation was significantly decreased, and the relative expression levels of CD133, CD44, SOX2 and OCT4 were significantly decreased. Conclusion TIPE2 can suppress the stemness of lung cancer cells by inhibiting the polarization of macrophages to M2-type, thereby exerting an anticancer effect.
Animals ; Mice ; Humans ; Tumor-Associated Macrophages/metabolism* ; Lung Neoplasms/genetics* ; Intracellular Signaling Peptides and Proteins/metabolism* ; RAW 264.7 Cells ; A549 Cells ; Phenotype ; Coculture Techniques ; Receptors, Cell Surface/metabolism* ; Neoplastic Stem Cells/metabolism* ; Mannose Receptor ; Mannose-Binding Lectins/metabolism* ; Lectins, C-Type/metabolism* ; Cell Polarity ; Macrophages/metabolism*

The cross regional loose medical alliance is an important carrier in the current integrated development process of medical services in the Yangtze River Delta region. Smith policy implementation process model was used to analyze the development difficulties of cross regional loose medical alliances from idealized policies, policy implementation institutions, policy target groups, and policy implementation environment. Such medical alliances were formed under the background of integrated development in the Yangtze River Delta, with Shanghai′s tertiary public hospitals as leading units and medical institutions in Jiangsu, Zhejiang, and Anhui provinces as member units. Analysis showed that the policies for such medical alliances development had not yet clearly defined the organizational management mode, operational mechanism, and implementation path, and the corporate governance structure of medical alliance was immature; The policy implementation agencies were relatively lagging behind in the support of special funds and the formulation of related supporting policies; Participation of policy target groups was insufficient and their incentive mechanisms was imperfect; There were problems in the policy implementation environment, namely inconsistent medical and health service regulations and systems in different regions, different health financing capabilities of local governments, insufficient coordination of medical institution management concepts, and a lack of unified standards in information systems. Based on the above difficulties, this study proposed to strengthen the development planning and layout of cross regional loose medical alliances, and improve the corporate governance structure; To strengthen the government′s main responsibility and improving policy implementation capabilities; To improve the internal cooperation and operation mechanism of cross regional loose medical alliances, and enhance the sense of identity of the target group; To optimize the policy implementation environment and implement various support measures, so as to provide references for further promoting the coordinated development of high-quality medical resources in the Yangtze River Delta region.

Objective To study the survival rate,cause of death and the incidence of complications of extremely low birth weight (ELBW) infants.Method Clinical data of the ELBW infants admitted in our hospital between December 2013 and November 2016 were retrospectively analyzed.The cases were assigned into five groups based on gestational age (GA) or birth weight (BW) to further analyze the survival rates among each group.According to the time of death,the cases were assigned into two groups (death within 7 days or after 7 days) to analyze their direct death causes.ELBW infants were categorized into three groups according to GA (＜ 26 weeks,26-27 weeks and ≥ 28 weeks) or into two groups according to birth weight (＜ 750 g and ≥ 750 g) to analyze the incidence of complications within 14 days or after 14 days.Result A total of 122 ELBW infants were enrolled in this study.The mean GA was 27.6 ± 2.1 (range of 22-33) weeks,mean birth weight was 849 ± 112 (range of 525-995) g.GA and BW were both positively correlated with the survival rate.Among all the studied cases,43 were dead cases.Within these 43 cases,13 of them died within 7 days.The top 3 causes of death of them were neonatal respiratory distress syndrome (RDS),severe asphyxia and pulmonary hemorrhage of neonatal.The other 30 cases died after 7 days,while the top 3 causes of death of them were sepsis,bronchopulmonary dysplasia (BPD) combined with pneumonia and neonatal necrotizing enterocolitis (NEC).The incidences of complications of all 122 ELBW infants within 14 days of hospitalization were as follow:ELBW infants with BW ＜ 750 g had higher morbidity of neonatal severe asphyxia and neonatal blood glucose disorder than ELBW infants with BW ≥ 750 g (37.0％ vs.8.4％,51.9％ vs.24.2％,P ＜0.05);ELBW infants with GA ＜ 26 weeks and 26-27 weeks had higher morbidity of neonatal RDS than ELBW infants with GA≥28 weeks (86.5％ and 94.3％ vs.59.4％,P ＜ 0.05).99 cases of ELBW infants whose duration of hospitalization were more than 14 days were analyzed.The incidences of retinopathy of prematurity (ROP) in GA ＜ 26 weeks group was higher than that in GA between 26-27 weeks group and GA ≥ 28 weeks group (40.7％ vs.18.2％ and 14.3％,P ＜ 0.05).The incidences of BPD and anemia in GA ＜ 26 weeks group and GA between 26-27 weeks group were higher than that in GA≥28 weeks group (BPD:70.4％ and 68.2％ vs.35.7％;anemia:88.9％ and 84.1％ vs.57.1％;P ＜ 0.05).The incidence of sepsis in GA ＜ 26 weeks was higher than that in GA ≥ 28 weeks group (74.1％ vs.39.3％,P ＜0.05).The differences of the incidences of all the complications between BW ＜ 750 g group and BW ≥750 g showed no significance statistically (all P ＞ 0.05).Conclusion As the increasing of GA and BW,the survival rates of ELBW infants increase significantly,and the incidence of complications decline significantly.The complications related to ELBW infants during hospitalization should be prevented to improve the early survival quality of them.

Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9 basal cells (BCs) located at airway epithelium rugae can regenerate adult human lung. Human SOX9 BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9 BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient's lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9 BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3-12 months after cell transplantation. Altogether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future.
Bronchiectasis ; genetics ; metabolism ; Humans ; Pulmonary Alveoli ; cytology ; metabolism ; SOX9 Transcription Factor ; genetics ; metabolism ; Stem Cell Transplantation ; methods ; Stem Cells ; cytology ; metabolism

OBJECTIVE:To observe clinical efficacy and safety of tegafur combined with three dimensional conformal radio-therapy for advanced esophageal carcinoma. METHODS:Totally 88 cases of advanced esophageal carcinoma admitted into Xuchang central hospital during Aug. 2013-Mar. 2016 were selected and divided into control group and observation group according to random number table,with 44 cases in each group. On the basis of anti-inflammatory,relieving asthma and other symptomatic treatment,two groups accepted three dimensional conformal radiotherapy. Control group was given fluorouracil 80 mg/m2,ivgtt,d1+nadeplatin 70 mg/m2,ivgtt,d1-d5. Observation group was given Tegafur capsules 60 mg,bid,continuous use 5 days,rest for 2 days. A treatment course lasted for 3 weeks,and they received 3 courses of treatment. Clinical efficacies of 2 groups were observed as well as serum inflammatory factors(TNF-α,IL-6,IL-8),lab indexes(VEGF,CA125,CA199,CEA),QLQ-C30 scores be-fore and after treatment. The occurrence of ADR was recorded in 2 groups. RESULTS:The total response rate of observation group was 88.64%,which was significantly higher than 68.18%,with statistical significance(P<0.05). Before treatment,there was no statistical significance in serum inflammatory factor levels,lab index levels and QLQ-C30 scores between 2 groups(P>0.05). Af-ter treatment,serum inflammatory factor levels and lab index levels of 2 groups were significantly decreased,while QLQ-C30 scores were decreased significantly;the observation group was significantly better than control group,with statistical significance (P<0.05). There was no statistical significance in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS:Tegafur combined with three dimensional conformal radiotherapy shows good therapeutic efficacy for advanced esophageal carcinoma,can significantly reduce serum inflammatory factor levels and lab index levels and improve life quality but do not increase the occur-rence of ADR.

Acute kidney injury (AKI) is the complex clinical syndrome attributed to multiple causes and risk factors, which is characterized by an abrupt loss of renal function. Metabonomics, recently advances in the field of omics, is the nontargeted measurement of all of the low-molecularweight compounds that appear in a particular cell, tissue, organ or biofluid in a living organism. Compared to genomics, transcriptomics and proteomics,metabonomics has its unique advantages, including fewer metabolites than genes, transcripts and proteins, the most accurate predictors of the signature of the actual processes, easy access to biofluids. Thus, metabonomics makes it possible to find new biomarkers for AKI on early diagnosis, identifying new metabolic pathways, finding new targets for drug therapy and individual medical treatment.

Objective To observe the expression profiles of miR-200b/c and their targets ZEB1/2 in early pulmonary fibrosis caused by acute lung injury induced by lipopolysaccharide in mice.Methods Early pulmonary fibrosis caused by acute lung injury is built via a lipopolysaccharide three-hit regimen.Mice were sacrificed at post-injective day 3,7,14,21 respectively and the lung tissue specimens were collected.The lung tissue sections were stained with HE and Masson staining and pathological changes were observed by optical microscope.The expression profiles of miR-200b,miR-200c,ZEB1 mRNA and ZEB2 mRNA were detected by real-time PCR.Western blot was utilized to detect the levels of ZEB1,ZEB2,E-cadherin,Vimentin,α-SMA proteins.Results (1) pathological findings:compared with the control group,the collagen fibers deposited on on the third day after LPS treatment and pulmonary fibrosis gradually worsened;(2) Real time-PCR results:With the aggravation of pulmonary fibrosis,miR-200b and miR-200c levels were declined and the levels of miR-200b/c at post-injective day 7,14,21 were significantly lower than that of control group (P＜0.01).ZEB1 mRNA and ZEB2 mRNA levels were gradually increased in the process of pulmonary fibrosis and the increased magnitude of ZEB2 mRNA was more significant than that of ZEB1 mRNA;(3) Western blot results:ZEB1 and ZEB2 protein levels were also gradually increased,consistent with their mRNA levels and the expression of E-cadherin protein was decreased while Vimentin and oα-SMA protein levels increased with the evolution of pulmonary fibrosis caused by acute lung injury.Conclusion miR-200b and miR-200c promote epithelial-mesenchymal transition by inhibiting their targets ZEB1/2 in early pulmonary fibrosis caused by acute lung injury induced by LPS.

Subclinical hypothyroidism is a metabolic disease, defined by increased thyroid-stimulating hormone (TSH) and accompanied by normal thyroid hormone levels. Recent years, many domestic and foreign studies have showed that sub?clinical hypothyroidism may be related with atherosclerosis and left ventricular diastolic dysfunction, which increasing the risk and mortality of cardiovascular diseases. Subclinical hypothyroidism may be associated with lipid metabolic disorders, hypertension, coagulation dysfunction, endothelial dysfunction, abnormal glucose metabolism, homocysteine, C-reactive pro?tein and lipoprotein. At present, controversy persists on the subclinical hypothyroidism. The aim of this study is to review the correlation between cardiovascular diseases and subclinical hypothyroidism.

Preterm infants are often significantly growth retarded at the time of hospital discharge.They often in the nutritional crisis after hospital discharge,and should be carefully follow up evaluated.Preterm formula and fortified breast milk may improve the growth of preterm infants and is a reasonable option for preterm infants.Preterm formula and fortified breast milk are recommended for preterm infants with weights below the 10th percentile for age at the time of hospital discharge and those birth weights below 1 500 g.After hospital discharge,exclusively human milk-fed preterm infants are at increased risk for suboptimal growth compared to formula-fed infants.Infants with BPD are at increased risk of growth retardation after hospital discharge.Protein and mineral enriched formula may provide short-term growth catch-up.

Objective To investigate the expression of TIPE2 in splenic lymphocytes derived from the mouse model of cattle collagen Ⅱ-induced rheumatoid arthritis (CIA) and from peripheral blood of patients with rheumatoid arthritis (RA) for its role in the pathogenesis of RA.Methods The CIA mouse model was established by immunization of DBA-1/J mice with cattle collagen Ⅱ.Peripheral blood lymphocytes were collected from RA patients and healthy donors.The TIPE2 mRNA and protein expression in splenocytes of CIA and control mice were measured by semi-quantitative RT-PCR and Western blot,respectively.In addition,fluorescence quantitative RT-PCR and Western blot were used to determine the TIPE2 mRNA and protein expression in peripheral blood lymphocytes derived from patients with RA and healthy donors.Results Both mRNA and protein expression of TIPE2 were higher in splenocytes of CIA mice and lymphocytes of peripheral blood from RA patients compared with corresponding controls.Furthermore,the mRNA and protein expression of TIPE2 increased significantly in patients with active RA.TIPE2 expression were positively correlated with DAS28 scores (P＜0.001).Conclusion Our results suggest that TIPE2 plays a role in the RA pathogenesis.The level of TIPE2 may also indicate the severity of rheumatoid arthritis.