Cystathionine-γ-lyase contributes to tamoxifen resistance, and the compound I194496 alleviates this effect by inhibiting the PPARγ/ACSL1/STAT3 signalling pathway in oestrogen receptor-positive breast cancer.

Tamoxifen (TAM) resistance is a major challenge in treating oestrogen receptor-positive (ER+) breast cancers. It is possible that the H2S synthase cystathionine-γ-lyase (CSE), which has been previously shown to promote tumour growth and metastasis in other cancer cells, is involved in this resistance. Therefore, we investigated CSE's role and potential mechanisms in TAM-resistant breast cancer cells. First, we examined the effect of CSE expression on TAM sensitivity and resistance in MCF7 (breast cancer) cells. The findings revealed that CSE was directly associated with TAM sensitivity and involved in TAM resistance in ER+ breast cancer cells, indicating that it may be useful as a biomarker. Next, we wanted to determine the molecular mechanism of CSE's role in TAM resistance. Using cell migration, co-immunoprecipitation, western blotting, and cell viability assays, we determined that the CSE/H2S system can affect the expression of PPARγ by promoting the sulfhydrylation of PPARγ, which regulates the transcriptional activity of ACSL1. ACSL1, in turn, influences STAT3 activation by affecting the phosphorylation, palmitoylation and dimerization of STAT3, ultimately leading to the development of TAM resistance in breast cancer. Finally, we examined the effect of CSE inhibitors on reducing drug resistance to determine whether CSE may be used as a biomarker of TAM resistance. We observed that the novel CSE inhibitor I194496 can reverse TAM resistance in TAM-resistant breast cancer via targeting the PPARγ/ACSL1/STAT3 signalling pathway. Overall, our data indicate that CSE may serve as a biomarker of TAM resistance and that the CSE inhibitor I194496 is a promising candidate for combating TAM resistance.

Utility of contrast-enhanced MRI radiomics features combined with clinical indicators for predicting induction chemotherapy response in primary central nervous system lymphoma.

PURPOSE: To assess the utility of combining contrast-enhanced magnetic resonance imaging (CE-MRI) radiomics features with clinical variables in predicting the response to induction chemotherapy (IC) for primary central nervous system lymphoma (PCNSL). METHODS: A total of 131 patients with PCNSL (101 in the training set and 30 in the testing set) who had undergone contrast-enhanced MRI scans were retrospectively analyzed. Pyradiomics was utilized to extract radiomics features, and the clinical variables of the patients were gathered. Radiomics prediction models were developed using different combinations of feature selection methods and machine learning models, and the best combination was ultimately chosen. We screened clinical variables associated with treatment outcomes and developed clinical prediction models. The predictive performance of radiomics model, clinical model, and combined model, which integrates the best radiomics model and clinical characteristics, was independently assessed and compared using Receiver Operating Characteristic (ROC) curves. RESULTS: In total, we extracted 1598 features. The best radiomics model we selected as the best utilized T-test and Recursive Feature Elimination (RFE) for feature selection and logistic regression for model building. Serum Interleukin 2 Receptor (IL-2R) and Eastern Cooperative Oncology Group (ECOG) Score were utilized to develop a clinical predictive model for assessing the response to induction chemotherapy. The results of the testing set revealed that the combined prediction model (radiomics and IL-2R) achieved the highest area under the ROC curve at 0.868 (0.683, 0.967), followed by the radiomics model at 0.857 (0.681, 0.957), and the clinical prediction model (IL-2R and ECOG) at 0.618 (0.413, 0.797). The combined model was significantly more accurate than the clinical model, with an AUC of 0.868 compared to 0.618 (P < 0.05). While the radiomics model had slightly better predictive power than the clinical model, this difference was not statistically significant (AUC, 0.857 vs. 0.618, P > 0.05). CONCLUSIONS: Our prediction model, which combines radiomics signatures from CE-MRI with serum IL-2R, can effectively stratify patients with PCNSL before high-dose methotrexate (HD-MTX) -based chemotherapy.

iPSC-Derived Airway Epithelial Cells: Progress, Promise, and Challenges.

Induced pluripotent stem cells (iPSCs) generated from somatic cell sources are pluripotent and capable of indefinite expansion in vitro. They provide an unlimited source of cells that can be differentiated into lung progenitor cells for potential clinical use in pulmonary regenerative medicine. This review gives a comprehensive overview of recent progress toward the use of iPSCs to generate proximal and distal airway epithelial cells and mix lung organoids. Furthermore, their potential applications and future challenges for the field are discussed, with a focus on the technological hurdles that must be cleared before stem cell therapeutics can be used for clinical treatment.

Circadian clock disruptions link oxidative stress and systemic inflammation to metabolic syndrome in obstructive sleep apnea patients.

Objectives: Obstructive sleep apnea (OSA) is an independent risk factor for metabolic syndrome (MetS). Recent studies have indicated that circadian clock genes were dysregulated in OSA. In addition, it is clear that the impairment of circadian clocks drives the progression of MetS. Therefore, we hypothesized that circadian rhythm disruption links OSA with MetS. Methods: A total of 118 participants, who underwent polysomnography (PSG) and were diagnosed as healthy snorers (control, n = 29) or OSA (n = 89) patients based on the apnea-hypopnea index (AHI), were enrolled in the present study. General information, anthropometric data, blood biochemical indicators, clock gene expressions, and levels of oxidative and inflammatory indicators were collected, determined, and compared in all the participants. Results: We found that Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) and Differentiated embryo chondrocyte 1 (Dec1) were upregulated, while Period 1 (Per1) was reduced in OSA patients. In addition, these changing trends were closely associated with the hypoxia indicator of AHI and have a significant impact on the presence of MetS components, such as hyperglycemia (Dec1 and Per1, p < 0.05 and 0.001, respectively), hypertension (Bmal1 and Dec1, p < 0.001 and 0.01, respectively), hyperlipidemia (Dec1, p < 0.01), and obesity (Dec1, p < 0.05). Notably, expressions of Dec1 correlated with IR and predicted the presence of MetS in OSA patients. Finally, we also observed that Dec1 expression was interrelated with levels of both oxidative indicators and inflammatory biomarkers (IL-6) in OSA. Conclusion: This study concluded that circadian clock disruptions, especially Dec1, link OSA with MetS in an oxidative and inflammatory-related manner. Circadian clock Dec1 can be used as a specific biomarker (p < 0.001) and therapeutic target in OSA combined with Mets patients.

Activation of DDX58/RIG­I suppresses the growth of tumor cells by inhibiting STAT3/CSE signaling in colon cancer.

Some patients with colon cancer eventually develop metastasis during treatment, and the 5­year survival rate of patients with metastatic colon cancer remains relatively low, which is most likely due to the ineffectiveness of the current standard treatment. Systemic treatment for patients with colon cancer has expanded from chemotherapy to targeted therapy and immunotherapy. Immunotherapy holds promise in the treatment of colon cancer. The present study revealed the role of innate immune receptor helicase DExD/H­box helicase 58 (DDX58), which encodes retinoic acid­inducible gene­I (RIG­I), in colon cancer. It was demonstrated that colon cancer patients with a low protein expression of DDX58/RIG­I had a worse 5­year survival rate of patients compared with patients with a high expression of DDX58/RIG­I. The activation of DDX58/RIG­I inhibited the proliferation, migration and invasion of colon cancer cells, as well as tumor growth in a nude mouse xenograft model of colon cancer. To investigate the mechanisms of action of DDX58/RIG­I in colon cancer, the role of signal transducer and activator of transcription 3 (STAT3)/cystathionine­Î³­lyase (CSE) signaling in the up­ or downregulation of DDX58 was examined. The data demonstrated that DDX58 regulated the STAT3/CSE signaling pathway by interacting with STAT3 and consequently affecting the proliferation of tumor cells in colon cancer. In addition, the RIG­I agonist, SB9200, induced proliferation, migration and invasion of human colon cancer. On the whole, the present study demonstrates that DDX58/RIG­I affects the proliferation of tumor cells by regulating STAT3/CSE signaling in colon cancer. The findings presented herein suggest that DDX58/RIG­I activation may be an effective treatment strategy, and DDX58/RIG­I agonists may be potential therapeutic candidates for colon cancer.

Dandelion Seed Extract Affects Tumor Progression and Enhances the Sensitivity of Cisplatin in Esophageal Squamous Cell Carcinoma.

Like dandelion, dandelion seed also have anti-inflammatory activity. Therefore, in this article, we intend to explore the anti-cancer availability of aqueous dandelion seed extract (DSE) in esophageal squamous cell carcinoma (ESCC). Firstly, the effects of DSE on cell proliferation, apoptosis, migration, invasion and angiogenesis were investigated. Then to explore the mechanism of DSE against ESCC, the levels of proliferation-associated proteins (PI3K, Akt and pAkt), apoptosis-associated proteins (survivin, Bcl-2, Bax, caspase3 and caspase9), metastasis-associated proteins (MMP2, MMP9, VEGF) and EMT progression-associated proteins (Snail, E-cadherin and Vimentin) were analyzed. Next, we further explored the effect of DSE on the sensitivity of cisplatin (DDP) in ESCC cells and investigated the effect of DSE combined with DDP on DNA damage repair-associated proteins (MSH2, MLH1 and ERCC1) and drug resistant target protein STAT3. The results indicated that DSE selectively inhibited cell growth, proliferation, migration, invasion, angiogenesis and induced cell apoptosis in ESCC cells. It was observed the decreased PI3K, Akt and pAkt proteins levels in KYSE450 and Eca109 cells administrated with DSE. The data also showed that the application of DSE decreased the level of survivin and the ratio of Bcl-2/Bax, while increased the levels of caspase3 and caspase9. We also observed that DSE significantly decreased the levels of MMP2, MMP9 and VEGF proteins and inhibited the EMT progression in KYSE450 and Eca109 cells. In addition, survivin plays a critical role in DSE against ESCC followed with the application of survivin inhibitor YM155 impairing the inhibitory abilities of DSE in ESCC cells. Meanwhile, it was observed that DSE enhances the sensitivity of DDP to human ESCC cells via promoting DNA damage and inhibiting phosphorylation of STAT3. Therefore, DSE may affect ESCC progression and enhance the sensitivity of cisplatin, and consequently become an effective anti-cancer option for human ESCC treatment.

The effects of obstructive sleep apnea-hypopnea syndrome (OSAHS) on learn and memory function of 6-12 years old children.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a sleep disorder causing cognitive impairments. AIMS: We use the auditory verbal learning test (AVLT), clock drawing test (CDT), Wechsler intelligence scale for children (WISC) and Montreal cognitive assessment (MoCA) to evaluate the memory and spatial impairments of OSHAS in 6-12 years old children patients with different severity. MATERIAL AND METHODS: A total of 137 children of snoring were enrolled following the inclusion criteria of this study. According to the apnea-hypopnea indices (AHI), they were divided into three groups. The AVLT, CDT, WISC and MoCA tests were executed by physicians. The self-rating depression scale (SDS) test was performed for depression screening. RESULTS: Compared with the children in the primary snoring group, the other two groups had higher body mass index (BMI), longer periods of snoring and older age. The AHI, oxygen desaturation index (ODI) and 90% oxygen saturation (TS90%) showed increasing trends whereas the lowest blood oxygen saturation (LSaO2) showed a decreasing trend. Besides, compared with the primary snoring group, the two groups had lower immediate recall scores in AVLT. CONCLUSION: AVLT had clinical values for evaluation of impaired memory function in OSAHS children, suggesting a correlation between cognitive impairments and nocturnal hypoxia.

Cervical Vestibular Evoked Myogenic Potentials in Benign Paroxysmal Positional Vertigo: A Systematic Review and Meta-Analysis.

Objective: The objective of our study was to investigate the potential association between the occurrence of benign paroxysmal positional vertigo (BPPV) and saccular dysfunction using cervical vestibular evoked myogenic potentials (cVEMP) testing. Methods: The databases including Pubmed, Embase, and CENTRAL were systemically searched for case-control literatures investigating saccular dysfunction using cVEMP testing in BPPV patients compared with healthy controls. The literatures were published up to 16 April 2019 and were limited to the English language. All statistical processes were carried out using software Review Manager, version 5.3. Subgroup analysis and sensitive analysis were performed simultaneously. Results: Of the 12 case-control studies confirmed for meta-analysis, p13 latency of cVEMP was assessed in 8 studies, n23 latency in 6 studies, amplitude in 5 studies, asymmetry ratio (AR) in 3 studies, proportion of absent response in 9 studies, and abnormal cVEMP in 8 studies. Compared with healthy controls, the p13 mean latency of cVEMP was longer (MD = 0.88, 95% CI = 0.64-1.12, p < 0.00001), the mean amplitude was lower (SMD = -0.60, 95% CI = -0.80 to -0.41, p < 0.00001), and the proportions of absent response (OR = 8.76, 95% CI = 2.28-33.61, p = 0.002), and abnormal cVEMP (OR = 7.47, 95% CI = 4.65-12.01, p < 0.00001) were higher in BPPV patients. But there was no significant difference in the n23 mean latency (MD = 0.37, 95% CI = -0.23-0.98, p = 0.22) and the AR of cVEMP (MD = 3.95, 95% CI = -4.75-12.65, p = 0.37) between BPPV patients and healthy controls. In the sub-group analysis based on age, only the result of the proportion of absent response of cVEMP indicated a significant difference existed (p = 0.002) between the studies with age-matched controls (OR = 2.78, 95% CI = 1.09-7.10, p = 0.03) and the studies without age-matched controls (OR = 53.85, 95% CI = 10.09-287.13, p < 0.00001). In the sub-group analysis of the proportion of abnormal cVEMP according to the diagnostic criteria of abnormal cVEMP, the result indicated no significant difference existed between the four groups (p = 0.61, I 2 = 0%). In the sensitivity analysis, we obtained the consistent results after removing each study sequentially. Conclusion: The meta-analysis reveals that saccular dysfunction may be associated with BPPV occurrence, and neural degeneration in the saccular macula may be a potential pathogenesis for BPPV.

Treatment and recurrence of traumatic versus idiopathic benign paroxysmal positional vertigo: a meta-analysis.

Background: So far, there has been a controversy surrounding repositioning difficulty and recurrence rate between traumatic benign paroxysmal positional vertigo (t-BPPV) and idiopathic BPPV (i-BPPV). Objectives: This meta-analysis was aimed to explore whether or not the differences between t-BPPV and i-BPPV in the repositioning difficulty and recurrence rate existed. Material and methods: A literature search was performed in the databases including Pubmed, Embase, CENTRAL, which completed in 21 January 2019, with no restriction of publication language. Relative risk (RR) of number of repositioning maneuvers and the recurrence rate was calculated with its 95% confidence interval. Sensitive analysis was performed simultaneously. Results: Six retrospective cohort studies were included in our meta-analysis, including 865 t-BPPV patients and 3027 i-BPPV patients. All studies were high quality according to Newcastle-Ottawa Scale (NOS) assessment. Patients with t-BPPV required more repositioning maneuvers for resolution than those with i-BPPV (RR = 3.27, 95% CI = 1.88-5.69, p < .0001), and the recurrence rate of t-BPPV was higher than that of i-BPPV (RR = 2.91, 95% CI = 2.04-4.14, p < .00001). Conclusions and significance: Compared with i-BPPV, patients with t-BPPV require more repositioning maneuvers to resolve, and the recurrence of t-BPPV was more frequent.

Otolith dysfunction in recurrent benign paroxysmal positional vertigo after mild traumatic brain injury.

BACKGROUND: The pathogenesis of recurrence of traumatic benign paroxysmal positional vertigo (BPPV) is poorly understood by far. OBJECTIVES: To evaluate the value of secondary otolith dysfunction using vestibular evoked myogenic potential (VEMP) test in the pathogenesis of recurrence of BPPV after mild traumatic brain injury (mTBI). MATERIAL AND METHODS: We reviewed 42 patients with BPPV after mTBI. According to recurrence, patients were divided into two groups. Both cervical VEMP (cVEMP) and ocular VEMP (oVEMP) tests were performed on all of them. RESULTS: We detected abnormal cVEMP responses in four (26.7%) patients in the recurrent BPPV group after mTBI and five (18.5%) patients in the non-recurrent BPPV group after mTBI, and there was no significant difference between both groups. We detected abnormal oVMEP responses in nine (60.0%) patients in the recurrent BPPV group after mTBI and six (22.2%) patients in the non-recurrent BPPV group after mTBI, and there was a significant difference between both groups. CONCLUSIONS AND SIGNIFICANCE: Our study shows that oVEMP abnormalities in recurrent BPPV group after mTBI are significantly higher than those in non-recurrent BPPV group after mTBI. Therefore, we can conclude that secondary utricular dysfunction may be a potential pathogenesis of recurrence of traumatic BPPV.

Caveolin-1 is overexpressed in hypopharyngeal squamous cell carcinoma and correlates with clinical parameters.

The present study aimed to identify the role of caveolin-1 (CAV1) in hypopharyngeal squamous cell carcinoma (HSCC) and identify its possible correlation with tumor clinical parameters. Expression of CAV1 was measured using immunohistochemical staining of 66 HSCC samples and 44 samples from morphologically normal tissues adjacent to the carcinomas. Expression of CAV1 in HSCC and paracancerous tissues were 71.2 and 9.5% respectively. Levels of CAV1 expression were significantly associated with tumor differentiation, tumor-node-metastasis stage and lymph nodes metastasis (P<0.05). The present study identified that expression of CAV1 in HSCC is significantly higher than in paracancerous tissues, suggesting that this high expression of CAV1 is associated with tumor invasion and metastasis.

Identification of a subpopulation of nasopharyngeal carcinoma cells with cancer stem-like cell properties by high aldehyde dehydrogenase activity.

OBJECTIVES/HYPOTHESIS: Cancer stem cells have been reported as a new therapeutic target in many cancers, but their existence in nasopharyngeal carcinoma (NPC) is largely unknown. This study was conducted to determine cancer stem-like cells in NPC cell line. STUDY DESIGN: Basic science experimental study. METHODS: Aldehyde dehydrogenase (ALDH) activity, a putative functional marker for cancer stem cells, was assessed in Epstein-Barr virus-associated NPC cell line C666-1 cells. The ability of cells with high and low ALDH activity to proliferate, resist therapy, and initiate tumor formation was compared. RESULTS: Enrichment of cancer stem-like cells (with high ALDH activity) in C666-1 was associated with a significantly greater ability to proliferate, be clonogenic, resist chemotherapy drugs and radiation, reconstitute a heterogeneous population, and express pluripotent markers. Furthermore, subcutaneous injection of these cells into immunodeficient nude mice resulted in a tendency of tumor formation at a higher rate as compared to cells with low ALDH activity. CONCLUSIONS: These results provide evidence for the existence of cancer stem-like cells in the NPC cell line C666-1 cells.

The use of nasal epithelial stem/progenitor cells to produce functioning ciliated cells in vitro.

BACKGROUND: Although epithelial stem/progenitor cells have been isolated from many parts of the human airway epithelium such as lung and trachea, there is limited information in regard to stem cells in nasal epithelium. The aim of this study was to determine if (1) human nasal epithelial stem/progenitor cells (hNESPCs) can be isolated and propagated in vitro and (2) allogeneic adult primary human fibroblasts can serve as a feeder layer for hNESPCs expansion under serum-free conditions. METHODS: Primary cells taken from inferior turbinate biopsy specimens (n = 3) were enzymically dissociated and plated on either allogeneic human fibroblasts or murine NIH 3T3 fibroblasts, in a chemical-defined medium supplemented with growth factors. Self-renewal, proliferation, and differentiation potential were compared. RESULTS: The optimized media were capable of supporting the undifferentiated growth and expansion of hNESPCs on both feeder cells. The doubling time and cloning efficiency of hNESPCs cultured on a human feeder layer were comparable with that cultured on 3T3 feeders. Significantly, the hNESPCs on both feeder layers could be cultured for four passages, and they can differentiate into ciliated columnar cells and goblet cells at the air-liquid interface, resembling the in vivo mucociliary airway epithelium. CONCLUSION: Our results showed the feasibility of expanding hNESPCs for clinical purpose by using human feeder layer, avoiding components of animal source, while preserving their self-renewal and differentiation potential. This study represents an early step toward a better understanding of hNESPCs, and serum -free media plus human feeder potentially would be an ideal method for making clinical grade hNESPCs on a large scale.

Airway stem cells: review of potential impact on understanding of upper airway diseases.

Epithelial remodeling is a part of our natural defense mechanisms, and includes migration, proliferation, and differentiation of epithelial cells, as well as the interactions between epithelial and stromal cells. It is not yet possible to distinguish between cause and effect during epithelium remodeling, and are there no clear roles for the many factors involved in respiratory infectious and inflammatory diseases due to a lack of critical information about epithelial cell responses. Most reported data are from lower airway studies or animal models. Therefore, research based on human nasal epithelial stem/progenitor cells can illuminate the pathophysiology of nasal airway disease from a different, more specific perspective. In this review, we discuss epithelial stem/progenitor cell research throughout the airway, with special attention to phenotypes and characterization of these cells from the nasal airway. Recently, we have isolated and cultured P63-positive human epithelial stem/progenitor cells from turbinate biopsies of healthy volunteers and from inflamed mucosa of patients with chronic rhinosinusitis with and without nasal polyposis. These cells propagate in serum-free, growth factor-supplemented, Dulbecco's modified Eagle's medium/F12 media, on either human fibroblast or 3T3 feeder layers. Self-renewal, proliferation, and differentiation potential at an air-liquid interface are being investigated to understand the molecular pathways underlying nasal inflammation. This in vitro culture system for nasal epithelial regeneration will allow molecular studies of human nasal epithelial cell interactions, differentiation, and repair, as well as responses to both environmental agents and to potential anti-inflammatory treatments.

RNA interference of caveolin-1 via lentiviral vector inhibits growth of hypopharyngeal squamous cell carcinoma FaDu cells In Vitro and In Vivo.

OBJECTIVE: To investigate the effects of caveolin-1 (CAV1) on the growth of hypopharyngeal squamous cell carcinoma (HSCC) FaDu cells in vitro and in vivo. METHODS: A CAV1-RNAi-lentivirus construct was transfected into FaDu cells and expression of caveolin-1 was tested by RT-PCR and western blotting analysis. Cell apoptosis was analyzed by transferase-medisated dUTP nick-end labeling (TUNEL) assay. Tumor inhibition effects were investigated by injecting rCAV1-RNAi-lentivirus construct into tumors created with FaDu cells in the HSCC mouse model, with the empty-vector lentivirus as a control. CAV1 expression in xenografts was tested by RT-PCR and immunohistochemistry. RESULTS: RT-PCR and western blot analysis demonstrated successful construction of the CAV1-RNAi-lentivirus construct producing small hairpin RNA. The average weights and volumes of tumor in mice treated with CAV1-RNAi-lentivirus were lower than in mice with control treatment (P < 0.05). RT-PCR revealed weak positive expression of CAV1 in CAV1-construct-treated xenografts and immunohistochemistry confirmed lower CAV1 expression than in controls.(P < 0.05). In addition, downregulation of CAV1 increased cell apoptosis in vitro. CONCLUSION: The growth of HSCCs could be inhibited by recombinant CAV1-RNAi-lentivirus in vitro and in vivo.

Altered expression of miR-21 and PTEN in human laryngeal and hypopharyngeal squamous cell carcinomas.

PURPOSE: The purpose of this study was to examine the expression of mir-21 and phosphatase and tensin homologue (PTEN) in laryngeal squamous cell carcinomas (LSCCs) and hypopharyngeal squamous cell carcinomas (HSCCs), and assess correlations between the two as well as with clinical characteristics of patients. METHODS: The expression of mir-21 in tumor and adjacent non-tumor tissues was investigated by real-time RT-PCR. Immunohistochemistry (IHC) was carried out to analyze PTEN protein levels. RESULTS: Mir-21 was up-regulated in LSCCs and HSCCs compared to adjacent non-tumor tissues (P < 0.05), and the up-regulated expression of mir-21 was associated with clinical stage (P = 0.001), T classification (P = 0.007), pathologic differentiation (P = 0.025), and lymph node positivity (P = 0.002). In contrast, PTEN IHC staining was notably weaker in tumor tissues than in matched non-tumor tissues (P < 0.05), and the down-regulated expression of PTEN was correlated with tumor staging (P = 0.025), the extent of tumor (P = 0.017), and lymph node positivity (P = 0.040). Furthermore, the level of mir-21 was reversely correlated with PTEN expression (P = 0.006). CONCLUSION: mir-21 and PTEN might play important roles in the progression of LSCC and HSCC, the two fcators demonstrating a negative correlation.

MDM2 309T>G polymorphism and risk of squamous cell carcinomas of head and neck: a meta-analysis.

PURPOSE: Several studies have reported influence of the murine double minute 2 (MDM2) 309T>G polymorphism on head and neck squamous cell carcinoma (HNSCC) susceptibility. However, the results remain controversial and ambiguous. We therefore carried out a meta-analysis to explore more precisely the association between MDM2 309T>G variants and the risk of HNSCC. METHODS: Studies on the association between MDM2 309T>G polymorphism and HNSCC were searched in the PubMed database. All relevant studies that met the inclusion criteria were eligible for the analysis. Four genetic models and generalized odds ratios (ORs) and 95% confidence interval (CIs) were used for the assessment. RESULTS: A total of seven articles with 1,629 cases and 2,472 controls were included in our meta-analysis. Overall, significant associations between the MDM2 SNP309T>G and HNSCC risk for TG vs. TT model and the dominant model (TG+GG vs. TT) were observed (OR=0.82, 95%CI=0.70-0.96 and OR=0.83, 95%CI=0.71-0.96, respectively). On subgroup meta-analysis by ethnicity, a negative association was shown in the Caucasian subgroup (for GG vs. TT: OR=0.661, 95%CI=0.455-0.960; for TG vs. TT: OR=0.653, 95%CI=0.496-0.859; for the dominant model GG+TG vs. TT: OR= 0.657, 95%CI=0.463-0.931). However, in the Asian population no significant association was found. Subgroup analysis by the source of controls also yielded non-significant results. None of the results were materially altered in any genetic model after studies which did not fulfill Hardy-Weinberg equilibrium were excluded. CONCLUSION: The present meta-analysis suggested that the MDM2 SNP309 G allele probably acts as an important HNSCC protective factor in Caucasians, but no association exists in Asians.

[An experimental study of polypropylene combined with flap for trachea reconstruction].

OBJECTIVE: Canine model established for tracheal defect reconstruction, to investigate the outcome of tracheal reconstruction with combination of polypropylene and flap. METHODS: About 3.5 to 4 centimeter cervical trachea was resected and replaced with artificial trachea made from monofilament knitted polypropylene and surgical flap. Covered stent was implanted postoperatively. Survival period and quality of life were recorded, bronchofibroscopy, X-ray films and HE sections were performed. RESULTS: Six dogs survived well and another two died. The causes of death were respiratory failure in 1 and infection in another. Stenosis of anastomosis in 1 was recorded during survival period. The dogs started drinking and eating on the second postoperative day, no dyspnea was found. The animals were sacrificed at 2, 4, 8 weeks and 6 months after surgery. Soft tissue growth was found in polypropylene net 2 weeks after surgery and more at 4 weeks. The polypropylene net was covered completely with soft tissue at 8 weeks and 6 months postoperatively, the hardness and sustentation degree were enhanced following the growth and fibrosis of soft tissue. The squamous epithelium and columnar epithelium were observed healing well by HE staining method. CONCLUSIONS: One-stage operative artificial trachea made from monofilament knitted polypropylene which has good histocompatibility and surgical flap is the closer artificial trachea to native trachea. It has a promising prospect in clinical use.