[Identification the key factor of pulmonary fibrosis following silica nanoparticles exposure based on bioinformatics analysis].

Objective: To investigate the main mechanisms of pulmonary fibrosis following silica nanoparticles (SiNPs) exposure through constructing the macrophage-fibroblast model in vitro, which simulated the process of pulmonary fibrosis. Methods: In January 2021, human mononuclear leukemia cells (THP-1) were treated with 0, 25, 50, 100 µg/ml SiNPs for 24 h. The supernatant of THP-1 cells was collected and applied to human embryonic lung fibroblast cells (MRC-5) which divided into control and low, medium and high dose groups at the logarithmic growth stage for 24 h. MRC-5 cell viability was detected by CCK8. The hydroxyproline (Hyp), interleukin 6 (IL-6), interleukin 1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) expression were detected in the supernatants of MRC-5. The changed proteins were detected by liquid-phase mass spectrometry in high dose group. GeneCard database were applied to identity the differential pulmonary fibrosis proteins in high dose group. Gene Ontology (GO) was performed to identity the key biological process in differential pulmonary fibrosis proteins of high dose group. The String database was used to construct the protein-protein interactions (PPI) network of differential pulmonary fibrosis proteins. The APP of CytoHubba was applied to calculate the key protein of differential pulmonary fibrosis proteins in PPI network. Correlation coefficients between key differential pulmonary fibrosis proteins were calculated using Pearson correlation analysis. Western blotting was applied to detect the expression of key proteins of differential pulmonary fibrosis proteins in different groups. Results: CCK8 results showed that MRC-5 cell viability was increasing in low, medium and high dose groups compared with control group (P<0.05). The expression levels of Hyp and IL-1ß in different group were increased compared with control group, the expression levels of IL-6 and TNF-α were increased in high dose group compared with control group (P<0.05). GeneCard database identified 26 differential pulmonary fibrosis proteins, which were mainly involved in extracellular matrix hydrolysis, cell inflammatory response, tissue repair, cell proliferation, inflammation response by GO analysis. The APP of CytoHubba was calculated that matrix metalloproteinase 9 (MMP9) and tissue inhibitor metalloproteinase 1 (TIMP1) played an important role in PPI network. The results of correlation analysis showed that MMP9 was correlated with the expression of matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3), TIMP1 and epidermal growth factor receptor (EGFR) (r=0.97, 0.98, 0.94, 0.93, P<0.05). Western blotting results showed that TIMP1 protein expression was increased in low, medium and high dose groups, while MMP9 protein expression was increased only in high dose group (P<0.05) . Conclusion: Differential expression proteins related with pulmonary fibrosis in MRC-5 cells mainly regulate biological processes of extracellular matrix hydrolysis, tissue repair, and cellular inflammation response following SiNPs exposure. MMP9 and TIMP1 may be the key proteins, which affected the fibrosis process in vitro pulmonary fibrosis model.

[Randomized controlled clinical trials of a quick screening model for symptomatic bacterascites for guided antibiotic therapy].

Objective: To investigate the clinical significance of a quick screening model for symptomatic bacterascites for guided antibiotic therapy. Methods: Data were collected prospectively from 24 cases of cirrhotic ascites who were newly admitted to Nanchang Ninth Hospital between September 2016 and February 2017. No clear indication for antibiotic treatment was used when the number of polymorphonuclear cells in ascites was <250 cells/mm3. A quick screening model for symptomatic bacterascites was determined by positivity and was randomly divided into the experimental (12 cases) and the control group (12 cases). The experimental group was given antibiotic treatment during the whole process, while the control group did not receive antibiotic treatment. The 10th day of treatment was the end point of the study. The treatment responses of the two groups were compared. The treatment response results were divided into three categories: complete response, partial response, and no response. The sum of complete and partial response rates was used to determine the response rate. The Mann-Whitney U test and Fisher's exact test were used to compare the treatment responses between groups. Results: The baseline conditions of gender, age, screening score, and disease severity were consistent between the two groups (P>0.05). On the 10th day of treatment, the number of complete responses between the experimental group and the control group was 1 to 0, the number of partial responses was 7 to 2, and the number of non-responses was 4 to 10, Z=-2.467, P=0.014. The response rate was significantly better in the experimental group than in the control group [66.7% (8/12) vs. 16.7% (2/12), P=0.036]. Conclusion: Guided antibiotic therapy is somehow important for the quick screening model for symptomatic bacterascites, and patients with cirrhotic ascites who test positive in this model can benefit from antibiotic therapy.

[CART therapy followed by allo-HSCT for patients with B-cell acute lymphoblastic leukemia relapsing after the first hematopoietic stem cell transplantation].

Objective: To study the clinical efficacy of chimeric antigen receptor T-cell (CART) treatment followed by a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (ALL) who relapsed following the first HSCT. Methods: Retrospective analysis of the clinical characteristics and prognosis of 41 patients with B-cell ALL who received a second allo-HSCT from October 2015 to June 2020 in Hebei Yanda Lu Daopei Hospital. After the first HSCT, all patients received CD19-CART, or CD22-CART treatment following a relapse of bone marrow morphology or extramedullary leukemia. Results: A total of 41 patients (male, 21; female, 20) were included in this study. The median age at the second HSCT was 16 (3-46) years. There were 31 cases of bone marrow recurrence (75.6%) , 5 cases of extramedullary recurrence (12.2%) , and 5 cases of bone marrow and extramedullary recurrences (12.2%) . After relapse, 35 patients (85.4%) received CD19-CART treatment, 2 patients received CD22-CART treatment (4.9%) , and 4 patients received CD19-CART and CD22-CART treatments (9.8%) . The expected 3-year overall survival (OS) , leukemia-free survival, cumulative relapse incidence, and non-relapse mortality (NRM) of patients after the second HSCT were 48.9% (95%CI 23.0%-70.6%) , 41.8% (95%CI 17.3%-64.9%) , 8.8% (95%CI 2.9%-26.4%) , and 51.1% (95%CI 31.2%-83.6%) , respectively. The 1-year OS of patients who relapsed ≤6 months and >6 months after the first HSCT were 45.0% (95%CI 12.7%-73.5%) and 75.0% (95%CI 51.4% -88.8%) (P=0.017) , respectively. Conclusion: CART bridging in the second HSCT enables some B-cell ALL patients who relapsed after the first HSCT to achieve long-term survival. However, because of the high NRM, further modifications could help improve the outcome.

[Comparison of the clinical outcomes of haploidentical and matched-sibling donor stem cell transplantation for T cell acute lymphoblastic leukemia in complete remission].

Objective: To compare the efficacy of haplotype hematopoietic stem cell transplantation (HIDT) and sibling matched hematopoietic stem cell transplantation (MSDT) in the treatment of complete remission (CR) acute T-lymphoblastic leukemia (T-ALL) . Methods: We retrospectively analyzed the clinical characteristics and outcomes of 98 patients who underwent HSCT in Hebei Yanda Ludaopei hospital with HID (n=81) or ISD (n=17) between May 2012 and May 2016. Results: The incidence of grades 2-4 and 3-4 acute-versus-host disease 100 days after HSCT were 51.9% (95% Confidence interval [CI] 42.0%-64.0%) vs 29.4% (95% CI 14.1%-61.4%) (P=0.072) and 9.8% (95% CI 5.1%-19.1%) vs 11.8% (95% CI 3.2%-43.3%) (P=1.000) for HIDT and MSDT. The 100-day cumulative incidences of CMV and EBV viremia were 53.1% (95% CI 43.3%-65.2%) vs 29.4% (95% CI 14.1%-61.4%) (P=0.115) and 35.8% (95% CI 26.8%-47.9%) vs11.8% (95% CI 3.2%-43.3%) (P=0.048) . The 5-year overall survival, leukemia-free survival, cumulative incidences of relapse, and no-relapse mortality were 60.5% (95% CI 5.4%-49.0%) vs 68.8% (95% CI 11.8%-40.0%) (P=0.315) , 58.0% (95% CI 5.5%-46.5%) vs 68.8% (95% CI 11.8%-40.0%) (P=0.258) , 16.1% (95% CI 9.8%-26.4%) vs 11.8% (95% CI 3.2%-43.3%) (P=0.643) , 25.9% (95% CI 17.9%-37.5%) vs 19.4% (95% CI 6.9%-54.4%) (P=0.386) for HIDT and MSDT, respectively. Conclusion: HID could be a valid alternative donor for patients with T-ALL in CR lacking an identical donor.

[The effect of TP53 mutations on the clinical outcomes of Ph-negative B-acute lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation].

Objective: To evaluate the association of TP53 mutations with the clinical outcomes of Ph-negative B-ALL following allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Total 300 patients with Ph-negative B-ALL who underwent allo-HSCT at the Hebei Yanda Ludaopei Hospital from May 2012 to May 2017 were retrospectively analyzed; their clinical characteristics, TP53 gene mutation type, and association between TP53 mutations and transplantation outcomes, including leukemia-free survival (LFS) , overall survival (OS) , non-relapse mortality (NRM) , relapse, and GVHD, were evaluated. Results: Total 23 patients had TP53 mutations; all the TP53 mutations affected P53'DNA-binding domain. The 5-year-LFS, OS, and RI were 34.8% and 62.3% (P=0.001) , 41.9% and 65.1% (P=0.020) , and 47.8% and 14.8% (P=0.000) , respectively, for TP53 mutations and wild-type TP53 patients. However, there were no significant differences in NRM and GVHD. Multivariate analysis showed that TP53 mutations remained adverse prognostic factors for LFS, OS, and RI after allo-HSCT. Conclusion: Some patients with TP53 mutations can achieve long-term survival with allo-HSCT. TP53 mutations are adverse prognostic factors for Ph-negative B-ALL patients who undergo allo-HSCT.

[Clinical characteristics of 10 patients with uremic tumoral calcinosis].

Objective: To analyze the clinical characteristics of patients with uremic tumoral calcinosis (UTC). Methods: A total of 10 patients with UTC were enrolled in this study, who were admitted in the Department of Nephrology, China-Japan Friendship Hospital and Beijing Chuiyangliu Hospital from March 2013 to February 2019. Results: The average age of 4 male and 6 female patients on regular hemodialysis was (39.90±8.57) years. The average dialysis duration was(5.90±2.57) years. Three patients presented as single lesion of one joint, the other 7 patients as involvement of multiple large joints. Serum calcium was elevated in 2 patients,both over 2.75 mmol/L. Serum hyperphosphatemia was seen in all patients with average level 2.22 (1.94,2.44) mmol/L. Serum intact parathyroid hormone (iPTH) was remarkably increased in 9 patients with average level 1 348.0(854.8,1 800.0) ng/L, while only 1 patient reported slight elevation (92.4 ng/L).High-sensitivity C-reactive protein increased in all 10 patients with average 35.81 (17.60,74.20) mg/L. The imaging findings before treatment suggested that a large number of irregular masses of calcification shadows deposited in the soft tissue adjacent to the joints. The outlines of calcification were clear without significant bone absorption. Nine patients with severe secondary hyperparathyroidism (SHPT) were treated with parathyroidectomy, resulting in lesions diminishing or even disappearing. A total of 32 parathyroid glands were resected, and pathological results showed that 7 parathyroids were diffuse hyperplasia, 11 as diffuse/nodular hyperplasia, the rest 14 as nodular hyperplasia. At least one hyperplastic parathyroid gland was seen in each patient. Only 1 patient received medical therapy yet no obvious improvement was observed. Conclusion: UTC is a rare complication in patients on regular hemodialysis, which is usually associated with severe SHPT. Parathyroid surgery may improve the clinical outcome.

[Prognostic analysis of allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in complete remission in the era of tyrosine kinase inhibitors].

Objective: To study the clinical results and prognostic factors for allo-HSCT of Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in complete remission (CR) in the era of tyrosine kinase inhibitors (TKI) . Methods: We performed a retrospective analysis of the clinical characteristics of 116 patients with Ph(+)ALL who underwent allo-HSCT while in CR. Results: The study population included 72 men and 44 women. The median patient age was 20 years (4-64 years) . The patients received sibling-identical donor (n=21) , haplo (n=77) , and unrelated donor (n=18) HSCT. The overall survival (OS) rate at 5 years was 73.2% (95% CI 63.8% -80.5% ) . In particular, the 5-year OS can reach 87.5% when the time from diagnosis to transplant is <180 days. The 5-years DFS was 61.4% (95% CI 51.8% -69.7% ) , the 5-year molecular and morphology cumulative relapse incidence was 18.5% (95% CI 12.6% -27.3% ) , and the 5-year TRM was 19.9% (95% CI 13.8% -28.7% ) . A multivariate analysis showed that an age range of 15-39 years (HR=2.730, P=0.044) , time from diagnosis to HSCT ≥ 180 days (HR=4.534, P=0.010) , and Ⅲ-Ⅳgrade aGVHD (HR=7.558, P=0.000) were significantly associated with an inferior overall survival. Limited cGVHD subgroup had better OS (HR=0.300, P=0.034) . Sex, WBC count at diagnosis, type of BCR-ABL fusion genes, somatic gene mutations, CR(1) or >CR(1), MRD negative or positive, conditioning regimen based on TBI or Bu, conditioning intensity, donor source, GVHD prophylactic proposal using cyclosporine or tacrolimus, presence/absence of CMV viremia, and presence/absence of EBV viremia were not significantly different in terms of the OS and DFS. Conclusion: Factors influencing the overall survival of Ph(+) ALL patients who underwent allo-HSCT in CR in the TKI era include age, time form diagnosis to HSCT, and aGVHD severity.

COVID-19 and chronic renal disease: clinical characteristics and prognosis.

BACKGROUND: Patients on dialysis were susceptible to coronavirus disease 2019 (COVID-19) and were prone to severe clinical characteristics after infection; acute kidney injury was related to mortality in COVID-19 cases. Limited is known about the characteristics of COVID-19 patients with end-stage renal disease not requiring renal replacement therapy (RRT). AIM: Evaluate clinical characteristics, course and outcomes of COVID-19 patients with chronic kidney disease (CKD) who did not require RRT and those on dialysis. DESIGN: A two-center retrospective study. METHODS: A total of 836 adult patients with COVID-19 (24 CKD not on dialysis; 15 dialysis-dependent CKD) were included. The study includes no patients with renal transplantation. Risk factors were explored. RESULTS: CKD not requiring RRT is an independent risk factor for in-hospital death [adjusted odds ratio (aOR) 7.35 (95% CI 2.41-22.44)] and poor prognosis [aOR 3.01 (95% CI 1.23-7.33)]. Compared with COVID-19 cases without CKD, those with CKD not requiring RRT showed similar percentage of initial moderate cases (75.00% vs. 73.65%) but higher incidence of in-hospital neutrophilia (50.00% vs. 27.30%) or death (50.00% vs. 9.03%). The odds ratio of dialysis associated to mortality in CKD patients was 2.00 (95% CI 0.52-7.63), suggesting COVID-19 patients with dialysis-dependent CKD were at greater risk of in-hospital death. For COVID-19 patients with CKD not requiring RRT, statins reduced the risk of neutrophilia [OR 0.10 (95% CI 0.01-0.69)] while diuretics increased the risk of neutrophilia [OR 15.4 (95% CI 1.47-160.97)], although both showed no association to mortality. CONCLUSION: COVID-19 patients with CKD presented high incidence of neutrophilia, poor prognosis and in-hospital death, with dialysis patients being more vulnerable.

[Molecular identification of Tricula spp. and the parasitized trematode cercariae in schistosomiasis-endemic areas of Yunnan Province].

OBJECTIVE: To characterize a species of the genus Tricula and parasitized trematodes in schistosomiasis-endemic areas of Yunnan Province using a molecular analysis, so as to understand their taxonomic positions. METHODS: Tricula spp. and Oncomelania snails were collected from Xiangyun County, Yunnan Province, and cercaria parasitizing snails were observed using crushing followed by microscopy. Cercaria parasitizing Tricula snails at various morphologies were sampled using a shedding method. Genomic DNA was extracted from snail soft tissues and cercariae, and the 16S rRNA, COI, 28S rDNA genes in snails and the ND1 and 28S rDNA genes in cercariae were amplified using a PCR assay and sequenced. The species of Tricula snails and their parasitized trematodes was characterized using sequence alignment and phylogenetic analysis. RESULTS: Among 382 Tricula snails detected, there were three types of trematode cercariae found, including the non-forked (20.94%, 80/382), double-forked (3.40%, 13/382) and swallow shapes (7.07%, 27/382). Sequence and phylogenetic analyses showed that the 16S rRNA, COI and 28S rDNA gene sequences of this species of Tricula had high homology to those in Delavaya dianchiensis, and were clustered in a branch. Sequencing analysis of the ND1 and 28S rDNA genes revealed that the non-forked cercariae belonged to the family Pleu- rogenidae, the swallow-shaped cercariae belonged to the family Opecoelidae, and the double-forked cercariae belonged to another species of the genus Schistosoma that was different from S. sinensium and S. ovuncatum. CONCLUSIONS: The species and taxonomy of Triculla spp. and their parasitized trematodes are preliminarily determined in schistosomiasis-endemic areas of Yunnan Province; however, further studies are required to investigate the more definite taxonomy and pathogenicity.

A common variant rs2272804 in the 5'UTR of RIBC2 inhibits downstream gene expression by creating an upstream open reading frame.

OBJECTIVE: The RIB43A domain with coiled-coils 2 (RIBC2) encodes an uncharacterized vertebrate protein exhibiting similarity with Chlamydomonas protofilament ribbon proteins, required for ciliary motility. To date, no functional variants capable of triggering a change in the expression of RIBC2 have been reported. PATIENTS AND METHODS: The genotypes of rs2272804 in 30 individuals were identified with Sanger sequencing to estimate allele frequencies. Dual-Luciferase and mutagenesis assays were carried out to investigate the impact of rs2272804 on transcriptional and translational levels. The microarray data of 7 types of cancer were obtained from the Gene Expression Omnibus (GEO) to explore the role of rs2272804 in those diseases. RESULTS: In this study, we identified a common variant in the 5'UTR of RIBC2, rs2272804, which can create an upstream open reading frame (uORF) in the 5'UTR significantly inhibiting the expression of its host gene. Using Dual-Luciferase constructs, we found that this variant leads to an 85% reduction in translational efficiency, but only a 20% decrease was observed at the transcriptional level. In terms of population studies, mRNA levels of RIBC2 varied according to their rs2272804 genotypes. The "A" allele homozygotes, which created a uORF, showed the lowest transcriptional levels while the transcriptional activity of the "C" allele homozygotes without an uORF was the highest, consistent with the in-vitro studies. Furthermore, we explored its role in 7 types of cancer and identified RIBC2 as a significantly differentially expressed gene (DEG) in breast cancer (BRCA), ovarian serous cystadenocarcinoma (OV), and kidney renal clear cell carcinoma (KIRC). Finally, we showed that the overexpression of RIBC2 enhanced the expression of TRIM37 and down-regulated TRAF2. TRIM37 is a member of the tripartite motif (TRIM) family involved in developmental patterning and oncogenesis while TRAF2 is associated with the signal transduction from members of the TNF receptor superfamily. CONCLUSIONS: Our reports identified a common variant that exerts a dramatic impact on expression efficiency and provides further functional insight into RIBC2.

Prevalence of smoking among adolescents in China: an updated systematic review and meta-analysis.

OBJECTIVES: Smoking is a major public health problem worldwide. Estimates for smoking prevalence among adolescents in different regions and in the whole of China are important for the development of public health policies. We conducted a systematic review and meta-analysis to estimate the prevalence of smoking among youth in China. STUDY DESIGN: This is a meta-analysis study. METHODS: English (PubMed, EMBASE) and Chinese (China National Knowledge Internet, WANFANG Data, and CBM) databases were independently searched by two investigators from inception to May 2019. Random effects meta-analysis was conducted to estimate the pooled prevalence of smoking. Subgroup analysis and meta-regression were performed to investigate sources of heterogeneity. This study is registered with PROSPERO, number CRD42019130803. RESULTS: In total, 131 articles were included in the meta-analysis, with a total of 146 studies, involving 684,370 Chinese participants. The total prevalence of smoking among youth in mainland China was 8.17% (95% confidence interval: 6.97-9.45). Subgroup analysis showed that the geographic location and gender could significantly influence the prevalence of smoking. Meta-regression analyses revealed study year, sex ratio (male, %), and response rates did not contribute to the heterogeneity of the results (P-value >0.05). Sensitivity analysis showed that the results were statistically stable. CONCLUSION: This meta-analysis indicates that smoking is common among adolescents in China, and the rate varies between different regions. More practical and effective policies targeting adolescents are urgently needed.

[Analysis of risk factors and consequences for concurrent obstructive sleep apnea in chronic obstructive pulmonary disease patients].

Objective: To compare clinical characteristics between patients with chronic obstructive pulmonary disease (COPD) and COPD -OSA overlap, and to analyze the risk factors for OSA in patients with COPD. Methods: A total of 431 patients with COPD were divided into a COPD-OSA group with AHI>15 events/h or a COPD group with AHI ≤ 15 events/h according to the results of polysomnography, and their clinical characteristics were summarized. Risk factors for OSA overlap in COPD patients were identified by univariate and multivariate logistic regression analyses. Results: There were no significant differences in gender composition, dyspnea scale (mMRC) score, the numbers of acute exacerbations and hospitalizations in the last year, prevalence of coronary heart disease, or cor pulmonale or diabetes mellitus in the two groups (all P>0.05). Age, BMI, neck circumference, smoking index, COPD assessment test (CAT) score, the values of FEV(1) or FEV(1)%, FEV(1)/FVC ratios, and the prevalence of hypertension in the COPD-OSA group with AHI>15 events/h were significantly higher than in the COPD group with AHI ≤15 events/h, while the duration of COPD and the proportion of severe COPD were lower than the COPD group with AHI≤ 15 (P<0.05). The scores of Charlson Comorbidity Index, Epworth Sleepiness Scale (ESS) and Sleep Apnea Clinical Score (SACS) in the COPD-OSA group were significantly higher than in the COPD group with AHI≤ 15, with all P values<0.05. Risk factors for AHI>15 OSA coinciding in patients with COPD included BMI, neck circumference, ESS, SACS and CAT (P<0.05). Furthermore, BMI, ESS and CAT were independent risk factors for OSA in COPD patients (P<0.05). Compared with mild or moderate COPD cases, patients with severe COPD (FEV(1)%<50%) had a lower risk of having OSA (ß=-0.459, OR=0.632, 95% CI 0.401-0.997, P=0.048). Conclusions: Compared to COPD patients with AHI ≤ 15 events/h, OSA-COPD overlap patients (AHI>15 events/h) had a worse quality of life, more daytime sleepiness and higher prevalence of hypertension. BMI, ESS and CAT were independent risk factors for AHI>15 OSA in patients with COPD. The risk of having OSA in severe COPD patients was lower than cases with mild or moderate COPD.

MicroRNA-24 attenuates vascular remodeling in diabetic rats through PI3K/Akt signaling pathway.

BACKGROUND AND AIMS: The vascular remodeling plays a crucial role in pathogenesis of diabetic cardiovascular complications. In this study, we intended to explore the effects and potential mechanisms of microRNA-24 (miR-24) on vascular remodeling under diabetic conditions. METHODS AND RESULTS: MiR-24 recombinant adenovirus (Ad-miR-24-GFP) was used to induce miR-24 overexpression either in carotid arteries or high glucose (HG)-induced vascular smooth muscle cells (VSMCs). Cell proliferation was analyzed using CCK-8 method. Cell migration was examined using wound-healing and transwell assay. mRNA and protein expressions of critical factors were, respectively, measured by real-time PCR and western blot as follows: qRT-PCR for the levels of miR-24, PIK3R1; western blot for the protein levels of PI3K (p85α), Akt, p-Akt, mTOR, p-mTOR, 4E-BP1, p-4E-BP1, p70s6k, p-p70s6k, MMP 2, MMP 9, collagen Ⅰ, as well as collagen Ⅲ. Carotid arteries in diabetic rats suffered balloon injury were harvested and examined by HE, immunohistochemical and Masson trichrome staining. The expression of miR-24 was decreased in HG-stimulated VSMCs and balloon-injured carotid arteries of diabetic rats, accompanied by increased mRNA expression of PIK3R1. The up-regulation of miR-24 suppressed VSMCs proliferation, migration, collagen deposition not only induced by HG in vitro, but also in balloon-injured diabetic rats, which were related to inactivation of PI3K/Akt signaling pathway. CONCLUSION: The up-regulation of miR-24 significantly attenuated vascular remodeling both in balloon-injured diabetic rats and HG-stimulated VSMCs via suppression of proliferation, migration and collagen deposition by acting on PIK3R1 gene that modulated the PI3K/Akt/mTOR axes.

Crohn's disease with positive Ziehl-Neelsen stain: Three case reports.

Because of the similarity of the clinical symptoms, endoscopic, and pathological features, the differential diagnosis between Crohn's disease (CD) and intestinal tuberculosis (ITB) remains difficult, especially in a high-incidence area of tuberculosis (TB). Here we reported three patients with positive Ziehl-Neelsen stain in endoscopic mucosal biopsy specimens. They had a poor response to anti-TB therapy but a good response to immunosuppresses, infliximab, or surgery, and were finally diagnosed as CD. It was not clear that they were CD concomitant with mycobacteria infection or CD induced by mycobacteria infection. Further studies including more clinical cases and related animal models are needed. Our cases highlight the importance of considering the presence of CD in patients with positive Ziehl-Neelsen stain, which were failure to respond to anti-TB treatment.

[5-HT(2A) receptor/protein kinase C pathway in mediating long-term facilitation of carotid sinus nerve discharge in chronic intermittent hypoxia rats].

Objective: To explore the role of 5-HT(2A)R/PKC pathway in mediating long-term facilitation (LTF) of carotid sinus nerve (CSN) discharge in chronic intermittent hypoxia (CIH) rats. Methods: With number table, 24 adult SD rats were randomly divided into saline control group (group A, n=6), 5-HT(2A)R antagonist (ketanserin) group (group B, n=6), PKC inhibitor (PKC θ-pseudosubstrate) group (group C, n=6) and combined ketanserin with PKC θ-pseudosubstrate group (group D, n=6). All rats were placed into the animal chambers for CIH treatment, 8 h per day (from 9: 00 to 17: 00) for 4 consecutive weeks. 28 days later, 5 min × 3 times of stimulation with acute intermittent hypoxia (AIH) were given, after that, stable CSN discharge activities were recorded and compared before and after intravenous injection of saline (group A), ketanserin (group B), PKC θ-pseudosubstrate (group C) or ketanserin + PKC θ-pseudosubstrate (group D), respectively. Results: There were no significant difference in the baseline (before AIH stimulation) average peak amplitude of CSN discharge among the four groups (P>0.05). In group A, the amplitude of CSN discharge at 30 min and 60 min after AIH were (5.01 ± 0.53) µV and (4.95 ± 0.34) µV respectively, which were significantly higher than that before AIH (P<0.01). The results implied that the CSN LTF could be induced by AIH in CIH pre-treatment rats. In group B, the amplitude of CSN discharge at 30 min and 60 min after AIH were (3.79 ± 0.42) µV and (3.73 ± 0.46) µV, respectively, which were still significantly higher than that before AIH (P<0.01), showing that carotid sinus nerve LTF couldn't be completely blocked by 5-HT(2A)R antagonist in rats. After injection of PKC θ-pseudosubstrate or ketanserin + PKC θ-pseudosubstrate in group C or D, there were no significant differences in CSN discharge amplitude before and after AIH (P>0.01), suggesting that inhibition of PKC alone or 5-HT(2A)R/PKC pathway could completely block the LTF of CSN. Conclusion: 5-HT(2A)R/PKC pathway was involved in mediating long-term facilitation of carotid sinus nerve discharge in CIH rats.

[Application of three questionnaires in screening obstructive sleep apnea in patients with chronic obstructive pulmonary disease].

Objective: To evaluate the clinical value of three questionnaires [Sleep Apnea Clinical Score (SACS), Berlin Questionnaire (BQ), and Epworth Sleepiness Scale (ESS)] in screening obstructive sleep apnea (OSA) in patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 198 patients with COPD were assessed the likelihood of OSA by using the SACS, BQ, ESS, which was confirmed by the overnight polysomnography (PSG). The receiver operating characteristic curve (ROC) and the calculated likelihood ratios were used to compare the values of three scoring systems in predicting OSA in COPD patients. Results: The patients had an average age of (65.5±9.3) years and 92.9% (184 cases) of which were male, 14 cases (7.1%) were female; 27 cases (13.6%) had a high probability of OSA by SACS assessment, 61 cases (30.8%) had a high probability screened by BQ, and 72 (36.4%) had OSA high probability by ESS. The diagnosis of OSA in 75 patients (37.9%) were confirmed by PSG. OSA did not be accurately predicted by ESS screening in patients with COPD, with a ROC curve area under the curve of 0.592 (95% CI: 0.509-0.674, P=0.053). BQ had an area under the ROC curve of 0.706 (95% CI: 0.626-0.779, P<0.001). However, the prediction of SACS was much better, with an area under the ROC curve of 0.810 (95% CI: 0.737-0.871, P<0.001). Conclusion: SACS is superior to BQ and ESS in predicting OSA in this group of patients with COPD.

The reversal of the spontaneous exchange bias effect and zero-field-cooling magnetization in La1.5Sr0.5Co1-xFexMnO6: the effect of Fe doping.

The crystal structure, electronic structure and magnetic properties were systematically studied in a series of Fe-doped La1.5Sr0.5CoMnO6 double perovskites. The X-ray diffraction patterns of the samples are all refined with a rhombohedral (R3[combining macron]c) structure. The parameters a and c continuously increase with increasing Fe doping concentration x. X-ray photoelectron spectroscopy (XPS) spectra of the Mn, Co, and Fe 2p core levels, consistent with the soft X-ray absorption spectroscopy (XAS) spectra of Mn, Co, and Fe L2,3 edges, indicate that their valence states are Mn3+ and Mn4+, Co2+ and Co3+, and Fe3+, respectively. However, relative to samples with x ≤ 0.1, there is an abrupt change of photon energy in the Co- and Fe-2p XAS spectra for x ≥ 0.2, implying the spin state transition is from high to low. In addition, this is further confirmed by a comparison between the calculated effective spin moment from the paramagnetic data and the theoretical value. Interestingly, we demonstrate the reversal of both zero-field-cooling magnetization and the sign switching of the spontaneous exchange bias (SEB) with the doping concentration from magnetic measurements. The magnetization reverses from positive to negative with the temperature decreasing across the compensation temperature at the critical concentration x = 0.2. Meanwhile, the exchange bias field of the SEB reverses from large negative values to positive ones. Our findings allow us to propose that the spin state transition caused by inhomogeneity is considered to play an important role in the reversal of the magnetization and the SEB effect.

[Comparison of three different types of donor hematopoietic stem cell transplantation for intermediate and high-risk myelodysplastic syndrome].

Objective: To investigate three different types of donor hematopoietic stem cell transplantation (HSCT) for intermediate and high-risk myelodysplastic syndrome (MDS) . Methods: Between August 2001 and May 2015, 167 consecutive patients with MDS in intermediate and high-risk who underwent allogeneic HSCT were analyzed retrospectively. Results: With the median follow up of 60 (12-177) months, The total 5-year DFS was 67.8% (95%CI 60.0%-75.6%) . Among three different types of donor, 5-year DFS rates were 68.0% (95%CI 54.1%-81.9%) in MSD-HSCT vs 77.4% (95%CI 62.1%-92.7%) in MUD-HSCT vs 64.0% (95% CI 52.4%-75.6%) in Haplo-HSCT (P=0.632) , respectively. Univariate analysis showed that median disease course before HSCT was the influencing factor of DFS (P=0.018) . Five-year relapse and TRM had no correlation with the above-mentioned factor. Conclusions: Haplo-HSCT for intermediate and high-risk MDS achieved similar effect produced by MUD or MSD, Haplo-HSCT could be used as an important alternative donor. allo-HSCT must be performed on intermediate and high-risk MDS patients as early as possible after diagnosis.

[Effect of minimal residual disease monitoring by multiparameter flow cytometry pre-conditioning on prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the effect of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) pre-conditioning on prognosis of acute myeloid leukemia in first complete remission (CR(1)-AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and to explore the value of MRD monitoring by MFC in the prognosis evaluation on allo-HSCT in CR(1)-AML. Methods: Between April 2012 and March 2015, consecutive 186 patients with CR(1)-AML who underwent allo-HSCT were analyzed retrospectively. MRD in BM before conditioning was detected by eight-color MFC. Any level of residual disease was considered to be MRD positive. Results: ①Of 186 patients, MRD was negative in 151 patients, positive in 35 patients (<1% in 25 patients and 1% to 3% in 10 patients) . ② With the median follow up of 18 (5-41) months, two-year DFS was 80.0% (95%CI 68.5%-92.3%) . Univariate analysis showed that MRD positive patients had lower DFS[62.9% (95%CI 50.6%-75.2%) vs 88.9% (95%CI 76.6%-100.0%) , P<0.001], higher relapse[11.4% (95%CI 4.1%-29.0%) vs 3.3% (95% CI 0.6%-20.9%) , P=0.003] and higher NRM [25.7% (95% CI 8.1%-43.3%) vs 7.9% (95% CI 1.3%-26.5%) , P=0.001] after HSCT compared with that of MRD negative patients. Secondary AML showed lower DFS than primary AML [60.0% (95% CI 42.4%-76.6%) vs 86.0% (95% CI 68.4%-100.0%) , P=0.004]. ③Multivariate analysis indicated that MRD positive pre-HSCT was the independent risk factor on DFS [HR=4.565 (95%CI 2.918-9.482) , P<0.001], relapse [HR=5.854 (95%CI 1.538-22.288) , P=0.010] and NRM [HR=3.379 (95%CI 1.361-8.391) , P=0.009] after allo-HSCT in CR(1)-AML. Conclusion: MRD positive pre-conditioning was the only negative impact factor for patients with CR(1)-AML after allo-HSCT. MRD by MFC can be used to assess the prognosis of CR(1)-AML after allo-HSCT.

[Effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis of 258 patients with AML in CR (186 cases in CR(1), 72 cases in CR(2)) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk. Results: ①With the median follow up of 18 (5-41) months, two-year disease free surviva (DFS) in 258 patients was 78.0% (95% CI 60.4%-96.6%) . Two-year DFS in AML after transplantation was 78.6% (95% CI 61.0%-96.2%) in low risk, 76.0% (95% CI 84.0%-93.6%) in intermediate risk and 80.3% (95% CI 62.7%-97.9%) (P=0.886) in high risk groups respectively. ②Univariate analysis showed that DFS has no significant difference in patient age, the median disease course before HSCT, the WBC number at the beginning of the disease, blood routine and chromosomes examination before transplantation, extramedullary disease before transplantation, disease status before transplantation, conditioning regimen, donor type, donor and recipient sex, recipient blood type, transfused MNC number, transfused CD34(+) cell number and transfused CD3(+) cell number. DFS was significant lower in primary AML than that in secondary AML (P=0.006) and also lower in MRD positive than that in MRD negative (P=0.003) . The accumulative relapse was significant higher in CR(2) compared to that in CR(1) (P=0.046) . Accumulative non-relapse mortality (NRM) was significanlyt higher in secondary AML compared to that in primary AML (P=0.004) and also higher in MRD positive compared to that in MRD negative (P=0.010) . ③Multivariate analysis showed that MRD positive was the only significant factor in DFS and NRM. Conclusion: Allo-HSCT treatment of AML CR patients could achieve a high efficacy, which is similar between CR(1) and CR(2) patients. There is no significant correlation between NCCN (2015) risk stratification and the prognosis of AML patients with allo-HSCT treatment. Pre-conditioning MRD status monitored by multiparameter flow cytometry was the only impact factor on DFS and NRM in allo-HSCT for CR-AML patients.