[Preliminary study on the role and mechanism of IL-6 receptor antagonists in improving post-infarction ventricular arrhythmia].

Objective: To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism. Methods: The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining. Results: Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP (P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower (P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group (P all<0.05). Conclusions: TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.

[Analysis of the effect of gene mutations on the efficacy of ruxolitinib in patients with myelofibrosis based on second-generation sequencing technology].

Objective: To assess the effect of gene mutations on the efficacy of ruxolitinib for treating myelofibrosis (MF) . Methods: We retrospectively analyzed the clinical data of 56 patients with MF treated with ruxolitinib from July 2017 to December 2020 and applied second-generation sequencing (NGS) technology to detect 127 hematologic tumor-related gene mutations. Additionally, we analyzed the relationship between mutated genes and the efficacy of ruxolitinib. Results: ①Among the 56 patients, there were 36 cases of primary bone marrow fibrosis (PMF) , 9 cases of bone marrow fibrosis (ppv-mf) after polycythemia vera, and 11 cases of bone marrow fibrosis (PET-MF) after primary thrombocytosis (ET) . ②Fifty-six patients with MF taking ruxolitinib underwent NGS, among whom, 50 (89.29%) carried driver mutations, 22 (39.29%) carried ≥3 mutations, and 29 (51.79%) carried high-risk mutations (HMR) . ③ For patients with MF carrying ≥ 3 mutations, ruxolitinib still had a better effect of improving somatic symptoms and shrinking the spleen (P=0.001, P<0.001) , but TTF and PFS were significantly shorter in patients carrying ≥ 3 mutations (P=0.007, P=0.042) . ④For patients carrying ≥ 2 HMR mutations, ruxolitinib was less effective in shrinking the spleen than in those who did not carry HMR (t= 10.471, P=0.034) , and the TTF and PFS were significantly shorter in patients carrying ≥2 HMR mutations (P<0.001, P=0.001) . ⑤Ruxolitinib had poorer effects on spleen reduction, symptom improvement, and stabilization of myelofibrosis in patients carrying additional mutations in ASXL1, EZH2, and SRSF2. Moreover, patients carrying ASXL1 and EZH2 mutations had significantly shorter TTF [ASXL1: 360 (55-1270) d vs 440 (55-1268) d, z=-3.115, P=0.002; EZH2: 327 (55-975) d vs 404 (50-1270) d, z=-3.219, P=0.001], and significantly shorter PFS compared to non-carriers [ASXL1: 457 (50-1331) d vs 574 (55-1437) d, z=-3.219, P=0.001) ; 428 (55-1331) d vs 505 (55-1437) d, z=-2.576, P=0.008]. Conclusion: The type and number of mutations carried by patients with myelofibrosis and HMR impact the efficacy of ruxolitinib.

[Correlation between nUGT1A1 gene polymorphisms and adverse events of irinotecan plus S-1 for patients with recurrent or metastatic esophageal squamous cell carcinoma: a prospective, open-label, randomized controlled trial (ESWN 01)].

Objective: To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients. Methods: A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m(2)) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results: Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%). Conclusions: The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m(2)) plus S-1 regimen for 2 weeks. However, it's still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.

[Anatomical recognition of pancreatic membrane and its application in surgery].

With the rise of domestic membrane anatomy and preliminary establishment of theoretical framework, the operation concepts supported by membrane anatomy are gaining popularity in surgery, especially in abdominal surgery. However, on account of a deep location and the complexity of organs and tissues around the pancreas and mesangial membrane, there is no unified understanding about the pancreas mesangial by experts and scholars. Meanwhile, few studies on it have been conducted. In addition, the location and extent of total mesangectomy based on the mesangial pancreatic theory are also controversial. The purpose of this article is to summarize the anatomy of pancreatic membrane and its application in surgery, in order to provide support for current studies on pancreatic mesangial anatomy.

[Analysis of gene mutations and clinic features in 108 patients with myeloproliferative neoplasm].

Objective: To analyze the genetic mutations and clinical features of the subtypes of classical BCR-ABL-negative myeloproliferative neoplasm (MPN) . Methods: Mutations of 108 newly diagnosed BCR-ABL-negative MPN patients [including 55 patients with essential thrombocytopenia (ET) , 24 with polycythemia vera (PV) , and 29 with primary myelofibrosis (PMF) ] were identified using next-generation sequencing with 127-gene panel, and the relationship between gene mutations and clinical features were analyzed. Results: Total 211 mutations in 32 genes were detected in 100 MPN patients (92.59% ) , per capita carried (1.96±1.32) mutations. 85.19% (92/108) patients carried the driver gene (JAK2, CALR, MPL) mutations, 69.56% (64/92) of these patients carried at least 1 additional gene mutation. In descending order of mutation frequency, the highest frequency was for activation signaling pathway genes (42.2% , 89/211) , methylation genes (17.6% , 36/211) , and chromatin-modified genes (16.1% , 34/211) . There was a significant difference in the number of mutations in the activation signaling pathway genes, epigenetic regulatory genes, spliceosomes, and RNA metabolism genes among the three MPN subgroups. The average number of additional mutations in PMF patients was higher than that in ET and PV patients (1.69±1.39, 0.67±0.70, 0.87±1.22, χ(2)=13.445, P=0.001) . MPN-SAF-TSS (MPN 10 score) (P=0.006) and myelofibrosis level (P=0.015) in patients with ≥ 3 mutant genes were higher and the HGB level (P=0.002) was lower than in those with<3 mutations. Twenty-six patients (24.1% ) carried high-risk mutation (HMR) , and patients with HMR had lower PLT (P=0.017) , HGB levels (P<0.001) , and higher myelofibrosis level (P=0.010) and MPN10 score (P<0.001) . The frequency of ASXL1 mutations was higher in PMF than in PV patients (34.5% vs. 4.2% , P=0.005) . PMF patients with ASXL1 had lower levels of PLT and HGB (P=0.029 and 0.019) . Conclusion: 69.56% of MPN patients carry at least one additional mutation, and 24.1% patients had HMR. Each subgroup had different mutation patterns. PMF patients had a higher average number of additional gene mutations, especially a higher frequency of ASXL1 mutation; PLT and HGB levels were lower in ASXL1 mutation PMF patients.

[Value of dynamic MRI in monitoring the microenvironmental changes of anti-vascular therapy in a xenograft model].

Objective: To explore the feasibility of dynamic-enhanced magnetic resonance imaging (DCE-MRI) and blood oxygen level-dependent MRI (BOLD-MRI) in assessing the hemodynamics and tumor aggressiveness during treatment. Methods: The colon cancer xenograft model was established in BALB/C nude mice with HCT116 cell line. Sixteen nude mice were randomly divided into treatment and control groups (aged 6 to 8 weeks, weighted 15 to 18 g, Certificate No. 11400700325797), which were treated with bevacizumab and saline by intraperitoneal injection on the 1st, 4th, 7th, 10th and 13th day. DCE-MRI and BOLD-MRI were performed before and on the 3th, 6th, 9th, 12th, and 15th day after treatment. The vascular maturity and microenvironment hypoxia were confirmed by pathology. Results: The tumor volume of treatment group was significantly smaller than that of control group after 15 days ((712±43) vs (1 051±112) mm(3),P<0.01).The measurements of K(trans) were (0.135±0.005),(0.147±0.006),(0.175±0.009),(0.161±0.006), (0.140±0.005),(0.116±0.008)/min (F=81.386, P<0.01); K(ep) were (0.788±0.030),(0.804±0.036),(0.983±0.059), (1.105±0.091),(0.840±0.047),(0.786±0.041)/min(F=45.901,P<0.01);Ve were (0.652±0.006), (0.559±0.026), (0.466±0.016), (0.286±0.027), (0.363±0.020), (0.246±0.033) (F=384.290, P<0.01) and R2* values were (24.813±0.961), (24.675±1.070), (21.425±1.371), (17.850±0.885), (24.613±0.640), (27.013±0.734)/s (F=89.323, P<0.01) showed different trends with time in the treatment group, and the differences were statistically significant. The K(trans) values and tumor vessel maturity index (VMI) were higher than baseline values during 3-12 d after treatment. CD31 positive staining rate and VMI had the strongest correlations with K(trans) values (r=0.854 and 0.795), followed by AUC(180) (r=0.750 and 0.808), Ve (r=0.744 and 0.712) and K(ep) values (r=0.729 and 0.758), all P<0.05. R2* value positively correlated with the positive staining rate of HIF-1α and fibronectin (r=0.810 and 0.816), all P<0.05. Conclusion: DCE-MRI and BOLD-MRI are adequate to observe the tumor perfusion and hypoxia during anti-vascular treatment, and the R2* value can predict the tumor metastatic potential during the process of vascular normalization.

Circular RNA circHIPK3 serves as a prognostic marker to promote chronic myeloid leukemia progression.

Increasing evidence demonstrate that circular RNAs (circRNAs) play critical role in regulation of gene expression, which participate in the pathogenesis of cancer, including chronic myeloid leukemia (CML). In this study, we aimed to investigate the expression profiling of circHIPK3 in CML. We found that circHIPK3 was significantly upregulated in peripheral blood mononuclear cells (PBMC) and serum samples from CML compared with healthy controls. High circHIPK3 expression predicted a poor outcome of CML patients. Further loss-function experiments suggested the oncogenic role of circHIPK3 in CML. Our findings provide insights on the role of circHIPK3 in the development and treatment of CML.

Cost-effectiveness analysis of capecitabine plus bevacizumab versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer from Chinese societal perspective.

PURPOSE: The aim of the study was to evaluate the cost-effectiveness of capecitabine plus bevacizumab compared with capecitabine alone in elderly patients with metastatic colorectal cancer (CRC) from a Chinese societal perspective. METHODS: A decision-analytic Markov model was conducted to simulate the process of metastatic CRC. Three distinct health states: progression-free survival (PFS), progressive disease and death were included. Clinical data were derived from the AVEX trial. Health effectiveness was denoted in quality-adjusted life years (QALYs) and health utilities were derived from previously published studies. Incremental cost-effectiveness ratio (ICER) was regarded as the primary endpoint and willingness-to-pay (WTP) threshold was set at $26,753.37/QALY (3 × per capita GDP of China, 2017). One-way sensitivity analyses and probabilistic sensitivity analysis were also performed to explore the parameters uncertainty in the study. RESULTS: Over a 10-year life horizon, capecitabine plus bevacizumab gained 1.14 QALYs at an average cost of $21,609.48, while the effectiveness and cost of capecitabine group were 0.99 QALYs and $7274.83, respectively. The ICER between the two groups was $95,564.33/QALY. Parameters that mostly influenced the results of the model were utility of PFS state, duration of PFS state for capecitabine plus bevacizumab, total cost of PFS state for capecitabine plus bevacizumab and price of bevacizumab. The probabilities of capecitabine plus bevacizumab and capecitabine as the dominant option were 0% and 100% at the WTP threshold of $26,753.37/QALY. CONCLUSIONS: The results of the study showed that capecitabine plus bevacizumab is unlikely to be a cost-effective treatment option for elderly patients with metastatic CRC.

LncRNA SNHG16 predicts poor prognosis in ESCC and promotes cell proliferation and invasion by regulating Wnt/ß-catenin signaling pathway.

OBJECTIVE: Increasing evidence indicated that small nucleolar RNA host gene 16 (SNHG16) acted as a key regulator in the proliferation and metastasis of several cancers, including esophageal squamous cell carcinoma (ESCC). In this research, we aimed to explore biological functions, clinical significance and the underlying molecular mechanisms of SNHG16 in ESCC. PATIENTS AND METHODS: qRT-PCR was performed to examine the expression of SNHG16 in ESCC cell lines and clinical ESCC tissue samples. The association of SNHG16 expression with clinicopathological factors and prognosis was statistically analyzed. Cell Counting Kit-8, flow cytometry, and transwell invasion assays were performed to determine the effect of SNHG16 in the regulation of biological behaviors of ESCC cells. Luciferase assay and Western blot were performed to determine the activation of Wnt/ß-catenin signaling pathway RESULTS: We observed that SNHG16 expression levels were significantly upregulated in ESCC tissues and cell lines compared with the corresponding normal tissues and normal esophageal cell line, respectively. In addition, increased expression of SNHG16 were strongly linked to tumor stage (p = 0.019), lymph nodes metastasis (p = 0.007) and clinical stage (p = 0.026). Kaplan-Meier assay showed that the survival time of patients with high SNHG16 expression was significantly shorter than those with low SNHG16 expression (p = 0.0017). Univariate and multivariate analyses showed that high SNHG16 expression in ESCC was an independent predictor of poor survival. Loss-of-function experiments revealed that knockdown of SNHG16 suppressed proliferation and invasion and induced apoptosis of ESCC cells. Mechanistically, Wnt/ß-catenin signaling pathways were actively modulated by SNHG16 in ESCC cells. CONCLUSIONS: Our findings reveal that SNHG16 plays an important role in ESCC proliferation/metastasis via modulating Wnt/ß-catenin signaling pathways and could represent a novel biomarker for predicting poor survival as well a promising therapeutic target.

[Clinical analysis of adult Philadelphia chromosome-positive acute lymphoblastic leukemia with p16 gene deletion].

Objective: To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph(+) ALL patients with p16 deletion. Results: Of 80 adult Ph(+) ALL, the prevalence of p16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts (WBC≥30×10(9)/L) and CD20 expression. The incidence of complex chromosome abnormality in p16 gene deletion group was higher than that in non-deletion group, with alternations in chromosome 7, 8, 19 and der (22) more frequently observed. There was no difference occurred between patients with or without p16 gene deletion in complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs) . However, after three cycles of chemotherapy, the MMR and CMR rate in the p16 gene deletion group was lower than patients with wild-type p16 gene (P=0.034, P=0.036) . The p16 gene deletion patients showed no significant differences in MMR, CMR and relapse rate between Imatinib or Dasatinib plus chemotherapy (P>0.05) . Deletion of p16 gene was significantly associated with poor outcomes including worse overall survival (OS) (37.1% vs 54.1%, P=0.037) , lower disease free-survival (DFS) (12.4% vs 45.9%, P=0.026) , and increased cumulative incidence of relapse (P=0.033) . Among the 25 patients with p16 deletion, 14 underwent allo-HSCT and the median survival was 21 months, better than that of patients received chemotherapy alone (12 months) (P=0.030) . Conclusion: This study indicated that deletion of p16 was associated with poor prognosis in adult Ph(+) ALL, and the utility of second-generation TKI (Dasatinib) does not necessarily have an edge on efficacy over Imatinib, but allo-HSCT has the potential of elongating life expectancy. It is an important significance to define the status of p16 in Ph(+) ALL for predicting prognosis and guiding therapy decision-making.

[Clinical significance of cytogenetic monitoring in chronic myeloid leukemia].

Objective: To analyze the association of cytogenetic abnormalities with the prognosis of chronic myeloid leukemia (CML) patients in tyrosine kinase inhibitors (TKI) era. Methods: Karyotype analysis of chromosome G-banding was carried out in 387 newly diagnosed CML patients by short-term culture of bone marrow cells. The correlation of cytogenetic abnormalities and CML progression was explored in combination with ABL tyrosine point mutations. Result: Of 387 patients with positive BCR-ABL fusion gene assayed by fluorescence in situ hybridization (FISH) technique, 94.1% (364/387) patients were Ph positive and 5.9% (23/387) Ph negative; 320 patients (87.9%) had a translocation t (9;22) (q34;q11) and 5 (1.4%) a variant translocation t (v;22) . Additional cytogenetic aberrations (ACA) at diagnosis were found in 10.7% (39/387) Ph(+) patients, major route ACA in 22 (56.4%) cases and minor route ACA in 15 (38.5%) cases and 2 patients (5.1%) lacked the Y chromosome (-Y) ; 23.4% (71/303) patients occurred ACA during TKI treatment and the most frequent abnormalities were abnormal chromosome numbersd, which were likely associated with high proportion of disease progression (χ(2)=168.21, P<0.001) and ABL tyrosine point mutations (χ(2)=29.04, P<0.001) . Newly diagnosed CML-CP patients with t (9;22) (q34;q11) had a longer event-free survival (EFS) and disease-free survival (DFS) rates than that of patients with ACA (P=0.037; P=0.003) , while the overall survival (OS) had no significant differences (P=0.209) . As for CML-CP patients that occurred ACA during TKI therapy would have a marked low OS, EFS and DFS (all P<0.001) compared with no ACA occurred patients. Survival of advanced patients that occurred ACA were dramatically reduced. Conclusion: ACA often emerged during the disease progress in CML patients, regular and timely detection of chromosomes karyotype and ABL tyrosine point mutations during TKI treatment was important for therapeutic evaluation, progress and prognosis of CML.

[Clinical characteristics and prognosis of 35 patients with therapy-related hematological neoplasms].

OBJECTIVE: To investigate the morbidity, treatment outcomes and prognosis of 35 therapy-related hematological neoplasms patients. METHODS: A total of 35 cases of therapy-related hematological neoplasms were examined genetically and immunologically using flow cytometry, karyotype analysis and FISH, and their clinical data were retrospective analyzed and literatures were reviewed. RESULTS: Among 35 patients, there were 20 cases of therapy-related acute myeloid leukemia (t-AML), 4 cases of therapy-related acute lymphoblastic leukemia (t-ALL), 1 case of acute mixed leukemia, therapy-related non-hodgkin' s lymphoma (t-NHL) in 8 cases and myelodysplastic syndrome (t-MDS) in 2 cases. The median onset of t-HN was 29(16-90) months, the median OS of t-HN was 14(1-60) months, and 3 years of OS was 17.1%. Among therapy-related acute leukemia (t-AL) patients, 40% (10/25) patients had combined complex karyotype, 36% (9/25) patients with MLL gene rearrangement, 12% (3/25) patients with combined AML/ETO fusion gene, 1 case with NPM1 point mutation and 1 case with P16 gene deletion. CONCLUSIONS: Therapy-related hematological neoplasms had a worse prognosis.

[An experimental study of mesenchymal stem cells in tissue engineering scaffolds implanted in rabbit corneal lamellae to increase keratoprosthesis biointegration].

OBJECTIVE: To complete a preliminary evaluation of the feasibility of implanting the complex of mouse bone marrow mesenchymal stem cells (BMSC) and a tissue engineering scaffold into rabbit corneal lamellae, based on which a solution may be proposed to consolidate the keratoprosthesis and the recipient surface, and to reduce the risk of complications. METHODS: This experimental study was composed of two parts. (1) In vitro: some mouse BMSC were marked with red fluorescent proteins (RFP) and integrated with a decellularized pig articular cartilage extracellular matrix (ECM) scaffold. The cell survival was observed under a fluorescence microscope at 4 and 8 weeks. The cell distribution was examined by toluidine blue staining. The pore structure and the cell adhesion were observed under a scanning electron microscope. (2) in vivo: the complex of mouse BMSC and a decellularized scaffold was implanted into the lamellar cornea of 8 rabbit eyes with the fellow eyes as the controls. The eyes were sampled for observation using HE staining under a light microscope at 2, 4 and 8 weeks, respectively. The cell survival was examined under a fluorescence microscope, and the intracorneal cell survival at 8 weeks was observed using in vivo imaging. The conditions of ocular anterior segment of all the experimental animals were recorded. RESULTS: (1) Under the scanning electron microscope, the ECM scaffolds showed satisfactory porosity required for the adhesion and growth of cells and tissues, and the cell distribution over the cell-scaffold complex can be observed by toluidine blue staining. (2) Under the immunofluorescence microscope, cell proliferation was observed in vitro and in the interlamellar space (the maximum observation time was 8 weeks) after the RFP-marked mouse BMSC were integrated in vitro with ECM scaffolds. (3) Under the light microscope (HE staining), the stromal cells were detected to increase at each timepoint. A small number of monocytes and some mouse BMSC were observed in the superficial layer of corneal stroma, with sparsely and orderly arranged collagenous fibers and no neovascularization. All the epithelial cells appeared as mononuclear, columnar and undamaged, and the shape of ECM scaffolds, which were fused with the collagens, became unclear. (4) By in vivo imaging, it was found that the mouse BMSC survived for 8 weeks after being integrated with scaffolds and implanted into the interlamellar space of rabbit cornea. (5) After the implantation of cell-scaffold complex, severe postoperative inflammatory reactions, obvious conjunctival congestion and neovascularization were not observed. The corneal tissues surrounding the recipient area were transparent. One week later, mild inflammatory reactions were barely observed, and the cornea was transparent enough to observe the scaffold in the stromal layers. Four weeks later, the scaffolds became thinner. Eight weeks later, the scaffolds became extremely thin with normal vascular system in the corneal limbus. CONCLUSIONS: The ECM scaffold is a solid and biocompatible carrier for the growth and proliferation of BMSC. The mouse BMSC can grow and proliferate in the microenvironment of the interlamellar space of cornea.

Contribution of chemotherapy mobilization to disease control in multiple myeloma treated with autologous hematopoietic cell transplantation.

In patients with multiple myeloma (MM) undergoing autologous hematopoietic cell transplantation (auto-HCT), peripheral blood progenitor cells may be collected following mobilization with growth factor alone (GF) or cytotoxic chemotherapy plus GF (CC+GF). It is uncertain whether the method of mobilization affects post-transplant outcomes. We compared these mobilization strategies in a retrospective analysis of 968 patients with MM from the Center for International Blood and Marrow Transplant Research database who received an auto-HCT in the US and Canada between 2007 and 2012. The kinetics of neutrophil engraftment (⩾0.5 × 10(9)/L) was similar between groups (13 vs 13 days, P=0.69) while platelet engraftment (⩾20 × 10(9)/L) was slightly faster with CC+GF (19 vs 18 days, P=0.006). Adjusted 3-year PFS was 43% (95% confidence interval (CI) 38-48) in GF and 40% (95% CI 35-45) in CC+GF, P=0.33. Adjusted 3-year OS was 82% (95% CI 78-86) vs 80% (95% CI 75-84), P=0.43 and adjusted 5-year OS was 62% (95% CI 54-68) vs 60% (95% CI 52-67), P=0.76, for GF and CC+GF, respectively. We conclude that MM patients undergoing auto-HCT have similar outcomes irrespective of the method of mobilization and found no evidence that the addition of chemotherapy to mobilization contributes to disease control.

Expression and clinical significance of miR-122 and miR-29 in hepatitis B virus-related liver disease.

MicroRNA molecules have been increasingly regarded as a diagnostic and prognostic marker of certain diseases. The aim of this study was to investigate the expression and clinical significance of miR-122 and miR-29 in liver disease related to hepatitis B virus infection. The serum levels of miR-122 and miR-29 in 20 patients with hepatocellular carcinoma (HCC), 20 patients with liver cirrhosis (LC), 29 patients with chronic hepatitis B (CHB), 20 cases of hepatitis B virus carriers (ASC), and 20 healthy controls (HC) were determined by a fluorescence real-time quantitative PCR method and then evaluated by clinical correlation analysis. Compared with the serum levels of miR-122 in the HC, LC, and ASC groups, those in patients with HCC and CHB were significantly increased. The serum levels of miR-29 in LC patients were lower than those in the healthy controls (P < 0.01). A positive correlation was observed between the expression of miR-122 and miR-29, and HBV DNA in patients with CHB. A negative correlation was found between miR-29 and α-fetoprotein in patients with HCC. The elevation in miR-122 was correlated with liver damage in CHB patients and with the pathogenesis of liver cancer in HCC patients. The decrease in miR-29 expression was related to the incidence of liver fibrosis. The detection of miR-122 and miR-29 may be useful in evaluating the inflammatory liver injury and fibrosis associated with chronic HBV infection.

Clinicopathological significance of cyclooxygenase-2 and cell cycle-regulatory proteins expression in patients with esophageal squamous cell carcinoma.

The aim of this study was to examine the expression of the molecular markers cyclooxygenase-2 (COX-2), Ki-67, cyclin A, and p27 in patients with esophageal squamous cell carcinoma (ESCC), to ascertain the relationship of these makers with the clinicopathological significance of the patients, and to assess the additional prognostic value of the expression profile of these proteins for ESCC patients. The expression levels of COX-2, Ki-67, cyclin A, and p27 proteins of a series of primarily resected ESCC samples were determined by immunohistochemistry method. Clinicopathological and molecular factors affecting survival were analyzed by multivariate analysis. A total of 78 specimens were included in this study. Expression of COX-2 was observed in 43 (55.1%) cases, and high levels of expression of Ki-67, p27, and cyclin A were observed in 57 (73.0%), 33 (42.3%), 43 (55.1%) cases, respectively. The results of univariate survival analysis indicated that more advanced tumor stage, lymph node involvement, systemic dissemination, the levels of expression of COX-2, Ki-67, cyclin A, and p27 were associated with survival (all P-value < 0.05). Multifactorial survival analysis revealed that only lymph node involvement, over-expression of cyclin A, and low p27 expression were associated with the survival of the patients (hazard ratios = 2.83, 4.7, 2.9, respectively; P= 0.025, 0.042, 0.005, respectively). Among the molecular markers assessed, the expression of cell proliferation markers cyclin A and p27 are independent prognostic factors in patients with ESCC, whereas neither COX-2 nor Ki-67 is of independent prognostic value.

Versatile computer-controlled system for characterization of gas sensing materials.

Design of a system used for characterizing gas sensing materials is described. It is distinctive of being able to measure electrical and optical responses of a sample simultaneously, control a number of measurement parameters, perform fast exchange of gaseous environment, and be fully controlled automatically. These features make the system to be versatile in determining most concerned performance indexes of a gas sensing material (e.g., sensitivity, stability, selectivity, response/recovery times, etc.) as functions of various combinations of measurement conditions (e.g., gas concentrations, temperature, total pressure, content of interferants, photo assist, relative humidity, soaking time in a fixed gas concentration, and number of switching cycles in a dynamic test, etc.). Rationales of the designs associated with general gas sensing mechanics are discussed.