[Phase â ¡ clinical trial of PD-1 inhibitor combined with chemotherapy for locally advanced resectable oral squamous cell carcinoma].

Objective: To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma. Methods: This study was a randomized controlled phase Ⅱ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1∶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis. Results: A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups (P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group (P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ2=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ2=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death (P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion: The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.

[Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study].

Objective: To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications. Methods: This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression. Results: The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion: Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

[A multicenter retrospective study on the efficacy of different anti-reflux reconstruction methods after proximal gastrectomy for gastric cancer].

Objective: To examine the clinical efficacy of 3 anti-reflux methods of digestive tract reconstruction after proximal gastrectomy for gastric cancer. Methods: The clinical data and follow-up data of gastric cancer patients who underwent anti-reflux reconstruction after proximal gastrectomy in 11 medical centers of China from September 2016 to August 2021 were retrospectively collected, including 273 males and 65 females, aging of (63±10) years (range: 28 to 91 years). Among them, 159 cases were performed with gastric tube anastomosis (GTA), 107 cases with double tract reconstruction (DTR), and 72 cases with double-flap technique (DFT), respectively. The duration of operation, length of postoperative hospital stay and early postoperative complications (referring to Clavien-Dindo classification) of different anti-reflux reconstruction methods were assessed. Body mass index, hemoglobin and albumin were used to reflect postoperative nutritional status. Reflux esophagitis was graded according to Los Angeles criteria based on the routinely gastroscopy within 12 months after surgery. The postoperative quality of life (QoL) was evaluated by Visick score system. The ANOVA analysis, Kruskal-Wallis rank sum test, χ2 test and Fisher's exact test were used for comparison between multiple groups, and further comparison among groups were performed with LSD, Tamhane's test or Bonferroni corrected χ2 test. The mixed effect model was used to compare the trends of Body mass index, hemoglobin and albumin over time among different groups. Results: The operation time of DFT was significantly longer than that of GTA and DTR ((352±63) minutes vs. (221±66) minutes, (352±63) minutes vs. (234±61) minutes, both P<0.01). The incidence of early complications with Clavien-Dindo grade Ⅱ to Ⅴ in GTA, DFT and DTR groups was 17.0% (27/159), 9.7% (7/72) and 10.3% (11/107), respectively, without significant difference among these three groups (χ2=3.51, P=0.173). Body mass index decreased more significantly in GTA than DFT group at 6 and 12 months after surgery (mean difference=1.721 kg/m2, P<0.01; mean difference=2.429 kg/m2, P<0.01). body mass index decreased significantly in DTR compared with DFT at 12 months after surgery (mean difference=1.319 kg/m2, P=0.027). There was no significant difference in hemoglobin or albumin fluctuation between different reconstruction methods perioperative. The incidence of reflux esophagitis one year after surgery in DTR group was 12.9% (4/31), which was lower than that in DFT (45.9% (17/37), χ2=8.63, P=0.003). Follow-up of postoperative quality of life showed the incidence of Visick grade 2 to 4 in DFT group was lower than that in GTA group (10.4% (7/67) vs. 34.6% (27/78), χ2=11.70, P=0.018), while there was no significant difference between DFT and DTR group (10.4% (7/67) vs. 22.2% (8/36, P>0.05). Conclusions: Compared with GTA and DTR, DFT is more time-consuming, but there is no significant difference in early complications among three methods. DFT reconstruction is more conducive to maintain postoperative nutritional status and improve QoL, especially compared with GTA. The risk of reflux esophagitis after DTR reconstruction is lower than that of DFT.

The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma.

Multiple myeloma is the second most common hematological malignancy. Despite significant advances in treatment, relapse is common and carries a poor prognosis. Thus, it is critical to elucidate the genetic factors contributing to disease progression and drug resistance. Here, we carry out integrative clinical sequencing of 511 relapsed, refractory multiple myeloma (RRMM) patients to define the disease's molecular alterations landscape. The NF-κB and RAS/MAPK pathways are more commonly altered than previously reported, with a prevalence of 45-65% each. In the RAS/MAPK pathway, there is a long tail of variants associated with the RASopathies. By comparing our RRMM cases with untreated patients, we identify a diverse set of alterations conferring resistance to three main classes of targeted therapy in 22% of our cohort. Activating mutations in IL6ST are also enriched in RRMM. Taken together, our study serves as a resource for future investigations of RRMM biology and potentially informs clinical management.

A novel risk prediction model of pyroptosis-related genes for the prognosis and immunotherapy response of endometrial cancer.

OBJECTIVE: This study aims to develop a risk prediction model of pyroptosis-related genes based on its impact on immunotherapy sensitivity of uterine corpus endometrial carcinoma (UCEC), one of the most common and threatening gynecological malignancies. PATIENTS AND METHODS: Through multiple bioinformatics analysis, we obtained raw counts of RNA-sequencing data and corresponding clinical information related to UCEC from The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) to investigate the potential mechanisms of differentially expressed pyroptosis-related genes (DEPRGs), including the correlation between DEPRGs and prognosis, tumor immune microenvironment and the immunotherapy sensitivity of UCEC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment Analysis were used to figure out the functional differences. Furthermore, a mRNA-miRNA-lncRNA network was constructed to identify potential impact of pyroptosis on tumor progression. RESULTS: In this study, we achieved six DEPRGs (CASP3, GPX4, GSDMD, NOD2, PYCARD and TIRAP) and constructed a 6-gene signature which classified UCEC patients in the TCGA cohort into a low-risk group or a high-risk group. Patients in the low-risk group showed significantly longer survival time (p=0.000373). The risk score was also confirmed as an independent prognostic factor combining with the clinical characteristics. GO and KEGG functional analysis revealed the possible molecular mechanisms by which six DEPRGs influence anti-tumor immunity in UCEC patients. In addition, we found that two DEPRGs (GPX4, TIRAP) were not only significantly associated with tumor mutational burden (TMB) or microsatellite Instability (MSI), but also involved in regulating the number and function of CD8+ cells. CONCLUSIONS: Upon comprehensive bioinformatics analysis, it was concluded that pyroptosis-related genes (PRGs) could predict the prognosis of EC patients and be affected in modulating the anti-tumor immune responses for patients with EC.

The Association Between Socioeconomic Factors and Incident Peripheral Artery Disease in the Chronic Renal Insufficiency Cohort (CRIC).

BACKGROUND: The association between socioeconomic factors and development of peripheral artery disease (PAD) has not been as well characterized compared to other cardiovascular diseases. We sought to define how annual income, sex, race, and education level are associated with newly diagnosed PAD in a well-characterized, diverse set of adults with CKD. METHODS: The Chronic Renal Insufficiency Cohort Study (CRIC) is a multicenter, prospective cohort study designed to examine risk factors for progression of CKD and cardiovascular disease. Demographic and clinical data including ankle brachial index (ABI) and interventions were collected at baseline, as well as yearly during follow-up visits. Annual income was categorized as: <$25,000, $25,000-50,000, $50,000-100,000, or above $100,000. We excluded those with pre-existing PAD, defined as enrollment ABI of <0.9 or >1.4, or missing income data. Cox proportional hazards regression was used to estimate the risk for incident PAD during CRIC enrollment, defined as a drop in ABI to <0.90 or a confirmed PAD intervention, including revascularization or amputation. RESULTS: A total of 3,313 patients met inclusion criteria, the mean age was 58.7 years, 56% were male, and 42% were Black. Over a median follow-up of 10.1 years, 639 participants (19%) were newly diagnosed with PAD. After adjusting for cardiovascular risk factors, all lower levels of annual household income were associated with increased incidence of PAD (income <$25,000 HR 1.7, 95% CI 1.1-2.4, P = 0.008; income $25,000-50,000 HR 1.5, 95% CI 1.1-2.3, P = 0.009; income $50,000-100,000 HR 1.6, 95% CI 1.2-2.4, P = 0.004), relative to a baseline annual income of >$100,000 (overall P-value = 0.02). In the multivariable model, there was no association between education level and PAD incidence (P = 0.80). Black race (HR 1.2, 95% CI 1.0-1.5, P = 0.023) and female sex (HR 1.7, 95% CI 1.4-2.0, P < 0.001) were independently associated with PAD incidence. Multiple imputation analysis provided similar results. CONCLUSIONS: In the CRIC, a multi-center cohort of prospectively followed CKD patients undergoing yearly CVD surveillance, lower annual household income, female sex, and Black race were significantly associated with the PAD incidence. In contrast, level of education was not independently associated with incident PAD.

International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials.

Minimal residual disease (MRD) assessment is incorporated in an increasing number of multiple myeloma (MM) clinical trials as a correlative analysis, an endpoint or even as a determinant of subsequent therapy. There is substantial heterogeneity across clinical trials in how MRD is assessed and reported, creating challenges for data interpretation and for the design of subsequent studies. We convened an international panel of MM investigators to harmonize how MRD should be assessed and reported in MM clinical trials. The panel provides consensus on which MM trials should include MRD, the recommended time points for MRD assessment, and expected analytical validation for MRD assays. We subsequently outlined parameters for reporting MRD results implementing the intention-to-treat principle. The panel provides guidance regarding the incorporation of newer peripheral blood-based and imaging-based approaches to detection of residual disease. Recommendations are summarized in 13 consensus statements that should be followed by sponsors, investigators, editors, and reviewers engaged in designing, performing, and interpreting MM trials.

Structural difference analysis of adult's intestinal flora basing on the 16S rDNA gene sequencing technology.

OBJECTIVE: Through 16S rDNA technology, we aimed at separating adults aging 20-50 years old into a few groups and processing the high-throughput sequencing analysis, in order to explore the features and differences of intestinal flora in each age group in a microcosmic perspective. PATIENTS AND METHODS: 120 stool specimens were collected strictly in accordance with acceptance criteria and exclusion criteria. 49 subjects aging 20-29 years old (Group AGE1), 51 subjects aging 30-39 years old (Group AGE2), and 20 subjects aging 40-49 years old (Group AGE3) were divided into 3 groups. Bacteria DNA from fresh stool specimens of 3 groups were abstracted. Illumina MiSeq high-throughput sequencing platform was applied to process 16S rDNA sequencing in Area 338F_806R for intestinal flora detection. I-Sanger Bio-cloud platform was applied for the analysis of intestinal flora structure changes in phylum level and genus level. RESULTS: Among the age of 20-50, with older age, the abundance of intestinal flora decreased among healthy adults more than 40 years old. In addition, the diversity and sample dispersion of intestinal flora is significantly different from people among 20-40 years old. The decrease ratio of Firmicutes/Bacteroidetes indicated that as the age grows, glucose tolerance might decrease. Comparing with people among 20-40 years old, the amount of Bifidobacterium and Eubacterium in people over 40 years old have significantly decreased. The decrease of Bifidobacterium and Eubacterium may increase the risks of cognitive impairment and lower the anti-inflammation and anti-cancer efficacy in human body, respectively. Subdoligranulum relates to poor metabolism and chronic inflammation and it happens more in people aged over 40 than young people who are among 20-40 years old. CONCLUSIONS: There are differences in the intestinal flora of healthy adults aged 20-50. Effective intervention of the intestinal flora may play a role in delaying aging and preventing diseases.

Combined Tumors in Hematolymphoid Neoplasms: Case Series of Histiocytic and Langerhans Cell Sarcomas Arising From Low-Grade B-Cell Lymphoma.

We report an index case of histiocytic sarcoma arising in a 70-year-old patient with long-standing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The patient presented in 2017 with painful, enlarging swelling of the left neck. He had remote history of cutaneous squamous cell carcinoma with no sign of recurrence, and his CLL/SLL was thought to be in remission. Computed tomography showed mild splenomegaly and multifocal lymphadenopathy including a 3-cm left neck mass. Biopsy of the left neck mass showed CLL/SLL with associated histiocytic sarcoma. Flow cytometry demonstrated a B cell neoplasm with CLL/SLL phenotype. Despite radiation therapy, he expired 3 months after presentation. Two similar cases (CLL/SLL and histiocytic sarcoma, follicular lymphoma and Langerhans cell sarcoma) from another institution are also illustrated. The pathological features of combined tumors in lymphoid neoplasms, a general framework to the work-up to determine interrelatedness of tumor components, and the clinical relevance are discussed.

Temperature-dependent optical constants of liquid isopropanol, n-butanol, and n-decane.

Liquid isopropanol, n-butanol, and n-decane are combustible organic compounds that are frequently used in theoretical and experimental researches on fuel combustion. In this work, the temperature-dependent optical constants of liquid isopropanol, n-butanol, and n-decane in the region 500-5500 cm-1 at ambient pressure are measured using the combined ellipsometry-transmission method. In the combined method, the optical constants are first measured by a modified ellipsometry method, and then the absorption indices for weak absorption regions are obtained by the transmission method using the refractive indices measured by the modified ellipsometry method. The refractive indices of liquid isopropanol, n-butanol, and n-decane are within the range from 1.3 to 1.45 in the studied wavelength and temperature region. The absorption indices of these liquids range from 10-5 to 10-1. In the temperature range studied, the refractive indices decrease with increasing temperature in an approximately linear manner, but the effects of the temperature on the absorption indices are much smaller. The characteristic wavenumbers of the main absorption peaks are consistent with the vibrational frequencies of major functional groups.

The application of illite supported nanoscale zero valent iron for the treatment of uranium contaminated groundwater.

In this study, nanoscale zero valent iron I-NZVI was investigated as a remediation strategy for uranium contaminated groundwater from the former Cimarron Fuel Fabrication Site in Oklahoma, USA. The 1 L batch-treatment system was applied in the study. The result shows that 99.9% of uranium in groundwater was removed by I-NZVI within 2 h. Uranium concentration in the groundwater stayed around 27 µg/L, and there was no sign of uranium release into groundwater after seven days of reaction time. Meanwhile the release of iron was significantly decreased compared to NZVI which can reduce the treatment impact on the water environment. To study the influence of background pH of the treatment system on removal efficiency of uranium, the groundwater was adjusted from pH 2-10 before the addition of I-NZVI. The pH of the groundwater was from 2.1 to 10.7 after treatment. The removal efficiency of uranium achieved a maximum in neutral pH of groundwater. The desorption of uranium on the residual solid phase after treatment was investigated in order to discuss the stability of uranium on residual solids. After 2 h of leaching, 0.07% of the total uranium on residual solid phase was leached out in a HNO3 leaching solution with a pH of 4.03. The concentration of uranium in the acid leachate was under 3.2 µg/L which is below the EPA's maximum contaminant level of 30 µg/L. Otherwise, the concentration of uranium was negligible in distilled water leaching solution (pH = 6.44) and NaOH leaching solution (pH = 8.52). A desorption study shows that an acceptable amount of uranium on the residuals can be released into water system under strong acid conditions in short terms. For long term disposal management of the residual solids, the leachate needs to be monitored and treated before discharge into a hazardous landfill or the water system. For the first time, I-NZVI was applied for the treatment of uranium contaminated groundwater. These results provide proof that I-NZVI has improved performance compared to NZVI and is a promising technology for the restoration of complex uranium contaminated water resources.

Zebrafish models of leukemia.

The zebrafish, Danio rerio, is a well-established, invaluable model system for the study of human cancers. The genetic pathways that drive oncogenesis are highly conserved between zebrafish and humans, and multiple unique attributes of the zebrafish make it a tractable tool for analyzing the underlying cellular processes that give rise to human disease. In particular, the high conservation between human and zebrafish hematopoiesis (Jing & Zon, 2011) has stimulated the development of zebrafish models for human hematopoietic malignancies to elucidate molecular pathogenesis and to expedite the preclinical investigation of novel therapies. While T-cell acute lymphoblastic leukemia was the first transgenic cancer model in zebrafish (Langenau et al., 2003), a wide spectrum of zebrafish models of human hematopoietic malignancies has been established since 2003, largely through transgenesis and genome-editing approaches. This chapter presents key examples that validate the zebrafish as an indispensable model system for the study of hematopoietic malignancies and highlights new models that demonstrate recent advances in the field.

Review of soluble uranium removal by nanoscale zero valent iron.

Uranium (U) has been released to surface soil and groundwater through military and industrial activities. Soluble forms of U transferred to drinking water sources and food supplements can potentially threaten humans and the biosphere due to its chemical toxicity and radioactivity. The immobilization of aqueous U onto iron-based minerals is one of the most vital geochemical processes controlling the transport of U. As a consequence, much research has been focused on the use of iron-based materials for the treatment of U contaminated waters. One material currently being tested is nanoscale zero-valent iron (nZVI). However, understanding the removal mechanism of U onto nZVI is crucial to develop new technologies for contaminated water resources. This review article aims to provide information on the removal mechanism of U onto nZVI under different conditions (pH, U concentration, solution ion strength, humic acid, presence of O2 and CO2, microorganism effect) pertinent to environmental and engineered systems, and to provide risk or performance assessment results with the stability of nZVI products after removal of U in environmental restoration.

Neuroprotective effects of intravenous transplantation of bone marrow mononuclear cells from 5-fluorouracil pre-treated rats on ischemic stroke.

Our previous findings showed bone marrow mononuclear cells (BMMNCs) from 5- fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats. This study was undertaken to explore the potential mechanisms underlying the neuroprotective effects of BMRMNCs in middle cerebral artery occlusion (MCAO) rat model. Rats were intravenously pre-treated with 5-FU and BMRMNCs were collected at different time points. The contents of growth factors in the supernatant and CXCR4 expression were detected by ELISA and flow cytometry, respectively. MCAO was introduced to rats, and BMMNCs and BMRMNCs collected at 7 days after 5-FU pre-treatment were independently transplanted via the tail vein 24h later. The neurological function was evaluated before cell transplantation and at 24h, 7d and 14d after cell transplantation. Rats were sacrificed at 14d after cell transplantation, the brains were collected for TTC staining, infarct volume detection, NISSL staining, counting of viable cells in the CA1 region, and observation of transplanted cells. BMRMNCs had elevated expressions of growth factors as well as CXCR4 expression. Our results confirmed the better therapeutic effects of BMRMNCs in MCAO rats, demonstrated by reduction in infarct volume, improvement of neurological function and more viable cells in the hippocampus. In addition, more transplanted cells were found after BMRMNCs transplantation at 7 days and 14 days although there was no marked difference at 14 days. These findings indicate that BMRMNCs transplantation may protect ischemic stroke, at least partially, via increasing the secretion of growth factors and migration to the injured site.

Rabbit nucleus pulposus cells facilitate differentiation of adipose-derived stem cells into nucleus pulposus-like cells.

OBJECTIVE: To investigate the feasibility of inducing adipose-derived stem cells (ADSCs) to nucleus pulposus cells (NPCs). MATERIALS AND METHODS: ADSCs were isolated from rabbit while NPCs were isolated from an allogeneic rabbit. NPCs were co-cultured with the 3rd generation ADSCs in co-cultured system. Only NPCs were cultured in single culturing group. Through the collagen type II collagen immunohistochemistry, we observed NPCs and then identify NPC. Proteoglycan messenger RNA (mRNA) and collagen type II mRNA level were measured by real-time polymerase chain reaction. RESULTS: In two group cells, collagen type II collagen were detected by immunohistochemistry. The amount of proteoglycan mRNA and collagen type II mRNA was both significantly higher in co-cultured group than in single cultured group. CONCLUSIONS: In some condition, ADSCs have the potency to differentiate toward nucleus pulposus-like cells. ADSCs are better seed cells for tissue engineering of artificial nucleus pulposus.

Cytotoxicity of 1-dodecyl-3-methylimidazolium bromide on HepG2 cells.

We evaluated the cytotoxicity of 1-dodecyl-3-methylimidazo-lium bromide ([C12mim][Br]) on HepG2 cells and its influence on plasma membrane permeability. The results showed that [C12mim][Br] inhibited HepG2 cell growth and decreased cell viability in a concentration-depen-dent manner. The results also revealed that [C12mim][Br] exposure induced apoptosis in [C12mim][Br]-treated HepG2 cells. In addition, the results showed that [C12mim][Br] increased membrane permeability in HepG2 cells. These results suggest that plasma membrane permeability may be responsible for apoptosis induced by [C12mim][Br] in HepG2 cells.

Association between interleukin gene polymorphisms and risk of recurrent oral ulceration.

We conducted a case-control study to investigate the association between the functional IL-1ß+3954 (C/T), IL-6-174 (G/C), IL-10-1082 (G/A), and IL-10-819C/T genetic polymorphisms and risk of recurrent oral ulceration (ROU) in a Chinese population. Polymorphisms of IL-1ß+3954C/T, IL-6-174G/C, IL-10-1082A/G and IL-10-819C/T were assessed by polymerase chain reaction-restriction fragment length polymorphism. The genotype distributions of the IL-1ß+3954 C/T and IL-10-819C/T were in Hardy-Weinberg equilibrium in the control group. Conditional logistic regression analyses showed that subjects carrying the IL-1ß+3954CC and IL-10-1082AA genotypes had a significantly increased risk of ROU, with adjusted ORs (95%CI) of 2.86 (1.37-6.33) and 1.72 (1.02-2.89), respectively. In summary, we found that IL-1ß+3954C/T and IL-10-1082A/G polymorphisms are associated with an increased risk of ROU.

The role of testicular nuclear receptor 4 in chemo-resistance of docetaxel in castration-resistant prostate cancer.

Docetaxel-based therapy is one of the first-line options for castration-resistant prostate cancer (CRPC). However, a large proportion of CRPC patients show different extents of docetaxel resistance. The current study aims to investigate the role of testicular nuclear receptor 4 (TR4) in docetaxel resistance in CRPC. TR4 expression level in prostate biopsy samples from CRPC patients treated with docetaxel was measured by immunohistochemistry (IHC). Alternation of TR4 expression in prostate cancer (PCa) cell line PC3 was applied to find out the influence of TR4 on half-maximal inhibitory concentration (IC50), cell viability and cell apoptosis. Patients who failed to achieve prostate-specific antigen (PSA) response (<50% PSA reduction from baseline) after docetaxel-based chemotherapy had a comparatively higher TR4 expression than those who achieved PSA response (⩾50% PSA reduction from baseline). Knocking down TR4 in PC3 cells led to a lower IC50 dose, poorer cell viability and more cell apoptosis when treated with docetaxel, whereas overexpression of TR4 in PC3 led to a higher IC50 dose, better cell viability and less cell apoptosis. TR4 enhances the chemo-resistance of docetaxel in CRPC. It may serve as a biomarker to determine the prognosis of docetaxel-based therapy and as a potential therapy target to combine with docetaxel to better suppress CRPC.

Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy

Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.

Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy.

Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.