Embracing the Future of Health Care: Investigating Medical Students' Willingness to Become Online Doctors.

Purpose: With the rapid advancement of technology, online health care services are becoming increasingly prominent. This study aims to investigate medical students' perceptions, attitudes, and readiness to adopt online health care services. Methods: Based on a literature review, this study constructed a conceptual model describing the relationships among medical students' perception, personality traits, and usage intention, grounded in the Technology Acceptance Model and Technology Readiness Index (TRI). The data for this study were collected from January to February 2023 through a questionnaire survey at Wenzhou Medical University, China. The proposed hypotheses were tested using structural equation modeling through AMOS software. Results: Out of the 340 respondents, 281 (82.6%) validly responded. Among these, 58.4% of medical students agreed and strongly agreed with the intention to become an online doctor. Within the TRI's motivational factors, optimism positively and significantly affected perceived usefulness (PU) and perceived ease of use (PEOU). Innovativeness also significantly enhanced PEOU. Among the inhibitory factors, insecurity was found to have a negative and statistically significant influence on PU. The rest of the dimensions did not have a significant effect on either PU or PEOU. Importantly, both PU and PEOU demonstrated a direct and substantial effect on usage intention. Conclusions: This study emphasizes the significance of comprehending medical students' readiness to adopt the role of online doctors in shaping the future of health care. By equipping medical students with the necessary skills and competencies, health care institutions can effectively leverage the full potential of online health care services while ensuring the provision of high-quality, accessible, and patient-centered care in the digital era.

A Survey of Myopia Correction Pattern of Children and Parent's Attitudes in China.

SIGNIFICANCE: This survey provides information about Chinese children's myopia correction status and parents' attitudes toward myopia correction. PURPOSE: Under the background of a guideline of appropriate techniques for the prevention and control of children's myopia, this study aimed to investigate the current myopia correction pattern of children and parents' attitudes. METHODS: Two self-administered questionnaires were distributed to 684 children with myopia corrections and 450 parents (384 mothers and 66 fathers) to explore children's myopia correction patterns and parental attitudes. The questionnaire investigated the pattern of children's myopia correction, prescribing of children's myopia correction, the incidence of high myopia, parental attitudes toward various myopia corrections methods, and preferred initial age for contact lens usage. RESULTS: Single-vision spectacles (n = 600; 88.2 ± 7.4%) are widely used in China because of their comfort and affordability. More than 80% of children use single-vision spectacles prescribed by ophthalmologists and opticians. Children who used single-vision spectacles at an earlier age had more incidence of high myopia (18.4 ± 4.2%) than those who used single-vision spectacles at a later age (0.7 ± 0.9%). Effective myopia control was the primary reason parents preferred to choose different optical corrections, followed by safety, convenience, clarity, affordability, comfort, and other reasons. The survey indicated that 52.4% of parents whose children used orthokeratology lenses would have preferred safe and convenient options if available. In addition, 50% of the parents preferred delaying their children's use of orthokeratology lenses and other contact lenses to an older age. CONCLUSIONS: Single-vision spectacles are still a popular option to correct myopia in children. There was a demonstrated increase in myopia in children who used single spectacles at an earlier age. Parents' attitudes were important factors for selecting myopia corrections in children.

Associations of self-reported vision impairment with depression symptoms among middle-aged and older Chinese.

BACKGROUND: Vision impairment (VI) and depression are highly prevalent among adults. However, few nationally representative studies from China on the self-reported VI and its association with depression symptoms. AIMS: This study re-estimated the relationship between self-reported VI and depression symptoms. METHODS: In this analysis, 62,525 respondents from the China Health and Retirement Longitudinal Study 2011-2018 were included. Based on self-reports, respondents with VI were allocated to distance VI (DVI), near VI (NVI), both distance and near VI (DNVI), or a blindness group. Multivariable pooled logistic regression models were used to evaluate the groups' odds ratios (ORs) for depression symptoms and self-reported VI. RESULTS: Overall, 35.9% of the respondents were self-reported VI. DVI (OR: 1.51, 95% confidence interval [95% CI]: 1.28-1.79) and DNVI (OR: 1.51, 95% CI: 1.21-1.88) showed the highest ORs for depression symptoms, followed by NVI (OR: 1.31, 95% CI: 1.11-1.54). Depression symptoms were associated with a significantly increased risk of DVI (OR: 1.49, 95% CI: 1.26-1.76), DNVI (OR: 1.49, 95% CI: 1.20-1.86), and NVI (OR: 1.29, 95% CI: 1.10-1.52), respectively. However, these associations between self-reported blindness and depression symptoms were not significant. All models provided similar results by excluding respondents aged 45-59 years. CONCLUSION: Self-reported DVI, NVI, and DNVI are associated with depression symptoms. A strong reverse association was found between depression and self-reported DVI, NVI, and DNVI, but not for blindness. Our findings emphasize the urgent need for depression screening for self-reported VI among Chinese adults.

Involvement of microRNAs-MMPs-E-cadherin in the migration and invasion of gastric cancer cells infected with Helicobacter pylori.

It has been found that Helicobacter pylori （H. pylori）is not only the main cause of gastric cancer, but also closely related to its metastasis. E-cadherin cleavage induced by matrix metalloproteinases (MMPs) plays an important role in the tumor metastasis. In the present study, we investigated the role of microRNAs-MMPs-E-cadherin in migration and invasion of gastric cancer cells treated with H. pylori. The results showed that H. pylori induced migration and invasion of SGC-7901 cells with a down-regulation of E-cadherin expression, which were abolished by MMPs knock down, E-cadherin overexpression, mimics of miR128 and miR148a. MiR128/miR148a inhibitors restored MMP-3/MMP-7 expression, down-regulated E-cadherin level, and accelerated cellular migration and invasion. This study suggests that H. pylori induces migration and invasion of gastric cancer cells through reduction of E-cadherin function by activation of MMP-3, - 7. The present results also suggest that the activated MMPs/E-cadherin pathway is related with down-regulation of miR128/miR148a in the human gastric cancer cells infected with H. pylori.

CCR4 Expression Is Associated With Poor Prognosis in Patients With Early Stage (pN0) Oral Tongue Cancer.

PURPOSE: Chemokine receptors are involved in tumor metastasis and can predict poor prognosis; however, the expression and clinicopathologic relevance of chemokine receptors in early-stage cancer remain largely unknown. This study measured the association between chemokine (C-C motif) receptor-4 (CCR4) expression and prognosis in patients with histologically node-negative (pN0) oral tongue cancer. MATERIALS AND METHODS: A retrospective analysis of CCR4 expression data from a consecutive case series of patients with pN0 oral cancer tongue was conducted. The expression of CCR4 by immunohistochemistry was investigated and the association between CCR4 expression and clinicopathologic variables and overall and disease-free survivals was evaluated using Kaplan-Meier analysis and a Cox regression model. RESULTS: CCR4 expression was examined in 128 human tongue cancerous samples (109 tongue squamous cell carcinomas [TSCCs] and 19 other types) and 10 normal tongue samples and was found to be highly expressed in tumor tissues compared with normal tissues. CCR4 expression was observed in 64.2% of patients with TSCC and showed a significant association with tumor stage (P = .037). Patients with CCR4-positive expression exhibited poorer overall and disease-free survivals compared with those with CCR4-negative expression (P < .001 and P = .001), and CCR4-positive expression was an independent factor of unfavorable overall and disease-free survivals (P = .002 and P = .007). CONCLUSIONS: This study identified CCR4 as a potential prognostic biomarker for recurrence and survival of patients with pN0 oral tongue cancer. Thus, CCR4 might be a possible therapeutic target for patients with early-stage cancer.

Inequality trends in the demographic and geographic distribution of health care professionals in China: Data from 2002 to 2016.

China has long been negatively affected by a shortage and maldistribution of health workers. This study aimed to examine the national and regional trends in the demographic and geographic distribution inequality of health care professionals in China from 2002 to 2016. Based on data from the China Health and Family Planning Statistical and China Statistical Yearbooks, we calculated the Gini coefficient and the Theil T and Theil L indices based on the number of health care professionals per capita and per geographic area to measure the inequalities in their demographic and geographic distribution, respectively. The contributions by intra-regional and inter-regional differences on total inequality were explored within and among East, Central, and West China via Theil index decomposition. We found that the national demographic distribution of health care professionals maintained in an absolute equality level, and the inequality indices decreased gradually, whereas the corresponding geographic inequalities were severe and presented a worsening trend. Compared with nurses, physicians not only maintained higher densities but also maintained a more equal distribution. Intra-regional disparities within the east, central, and western regions were the main cause for overall demographic inequality, whereas both intra-regional and inter-regional disparities significantly contributed to overall geographic inequality. To conclude, the distribution equality of health care professionals by population was satisfactory, whereas the corresponding distribution inequality by area was severe. Different types of distribution inequality of health care professionals existed regionally and nationally despite their increasing quantities and densities. Factors beyond population size should be considered when the government introduces health workforce allocation policies.

Cell-free lncRNA expression signatures in urine serve as novel non-invasive biomarkers for diagnosis and recurrence prediction of bladder cancer.

Cell-free long non-coding RNAs (lncRNAs) are stably present in urine and can serve as non-invasive biomarkers for cancer. We aimed to identify signatures of lncRNAs in urine for diagnosis and prognosis of bladder cancer (BC). Screening of lncRNAs by microarray analysis was performed using urine samples of 10 BC patients and 10 controls. Expressions of candidate lncRNAs were evaluated in the training and validation set including 230 BC patients and 230 controls by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A two-lncRNA panel (uc004cox.4 and GAS5) was constructed and provided high diagnostic accuracy of BC with an area under the curve (AUC) of 0.885 (95% CI, 0.836-0.924). The AUCs of the lncRNA panel for Ta, T1 and T2-T4 were 0.843, 0.867 and 0.923, respectively, significantly higher than those of urine cytology (all P < .05). Kaplan-Meier analysis revealed that higher level of uc004cox.4 was associated with poor recurrence-free survival (RFS) of non-muscle invasive BC (NMIBC) (P = .008). Additionally, Cox regression analysis indicated that uc004cox.4 was an independent prognostic factor for RFS of NMIBC (P = .018). Taken together, our findings indicated that urinary lncRNA signatures possessed potential clinical value for BC diagnosis. Moreover, uc004cox.4 could provide prognostic information for NMIBC.

Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer.

Long noncoding RNA HOTTIP plays important roles in the generation and progression of human cancers. Exosomes participate in cellular communication by transmitting moleculars between cells and are regarded as suitable candidates for non-invasive diagnosis. However, the existence of HOTTIP in the circulating exosomes and the potential roles of exosomal HOTTIP in gastric cancer (GC) was poorly understood. This study aims at investigating the clinical roles of exosomal HOTTIP in GC. Serum exosomal HOTTIP from 246 subjects (126 GC patients and 120 healthy people) were detected by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). Our results showed that expression levels of exosomal HOTTIP were typically upregulated in GC than in normal control (P < 0.001). And its expression levels were significantly correlated with invasion depth (P = 0.0298) and TNM stage (P < 0.001). The AUC for exosomal HOTTIP was 0.827, which demonstrated a higher diagnostic capability than CEA, CA 19-9 and CA72-4 (AUC = 0.653, 0.685 and 0.639, respectively) (P < 0.001). The Kaplan-Meier analysis showed a correlation between increased exosomal HOTTIP levels and poor overall survival (OS) (logrank P < 0.001). And univariate and multivariate COX analysis revealed exosomal HOTTIP overexpression was an independent prognostic factor in GC patients (P = 0.027). These findings demonstrated that exosomal HOTTIP may be a potential biomarker for GC in diagnosis and prognosis.

Nested quantitative PCR approach for urinary cell-free EZH2 mRNA and its potential clinical application in bladder cancer.

EZH2 is overexpressed in bladder cancer (BC) and plays important roles in tumor development and progression. Recent studies show cell free (cf) RNAs released from cancer cells can reflect tissues changes and are stable and detectable in urine. Although conventional quantitative real-time PCR (qPCR) is highly sensitive, low abundances of urinary cf-RNAs usually result in false-negatives. Thus, this study develops a nested qPCR (nqPCR) approach to quantify cf-EZH2 mRNA in urine and further assess its clinical significance for BC. Forty urine samples were first selected to evaluate feasibility of nqPCR. Then, levels of urinary cf-EZH2 mRNA were detected using developed method in an independent cohort of subjects with 91 healthy, 81 cystitis, 169 nonmuscle invasive BC (NMIBC) and 103 muscle-invasive BC (MIBC). In cf-EZH2 mRNA detection, nqPCR method was significantly associated with qPCR, but it could detect more urine samples and increase detection limit three orders of magnitude. Based on nqPCR method, cf-EZH2 mRNA levels have been found to be increased in urine of NMIBC and MIBC patients (p < 0.001). Compared with cytology, cf-EZH2 mRNA showed higher diagnostic ability for MIBC (p < 0.001) while not for NMIBC (p > 0.05). Moreover, it also could distinguish MIBC from NMIBC, with AUC of 0.787. For MIBC patients, high expression of cf-EZH2 mRNA associated with advanced stage and was an independent predictor of reduced disease free survival or overall survival. In conclusion, detection of cf-EZH2 mRNA in urine by nqPCR is a sensitive and noninvasive approach and may be used for diagnosis and prognosis prediction of MIBC.

MicroRNA-218 is a prognostic indicator in colorectal cancer and enhances 5-fluorouracil-induced apoptosis by targeting BIRC5.

One major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to fluoropyrimidine (FU)-based chemotherapy. Various reports showed that ectopic expression and function of microRNAs (miRNAs) played key roles to mediate apoptosis at the post-transcriptional level. To further explore the possible mechanisms, we evaluated the prognostic effect of miR-218 in patients with CRC receiving 5-FU-based treatment and investigated the proapoptotic role of miR-218 in vitro. Primary tumour specimens and adjacent non-tumour sites were used to determine miR-218 expression distribution and explore its potential prognostic value in response to 5-FU-based treatment in patients with CRC. HCT116 and HT29 cells were transfected with precursor miR-218 or negative control, followed by assays to investigate its influence on apoptosis, cell proliferation and pathways involved in molecular mechanisms of chemoresistance to 5-FU. Results showed that high miR-218 expression was associated with positive response to firstline 5-FU treatment in CRC patients. MiR-218 promoted apoptosis, inhibited cell proliferation and caused cell cycle arrest in CRC cells by suppressing BIRC5 expression. Furthermore, miR-218 enhanced 5-FU cytotoxicity in CRC cells by suppressing the 5-FU targeted enzyme, thymidylate synthase (TS). In conclusion, we demonstrated that high miR-218 expression had a positive prognostic value in 5-FU-based treatments for CRC patients and discovered a novel mechanism mediated by miR-218 to promote apoptosis and to function synergistically with 5-FU to promote chemosensitivity by suppressing BIRC5 and TS in CRC. These suggest the unique potential of miR-218 as a novel candidate for developing miR-218-based therapeutic strategies in CRC.

Serum microRNA expression signatures identified from genome-wide microRNA profiling serve as novel noninvasive biomarkers for diagnosis and recurrence of bladder cancer.

Recent advantages of serum microRNAs (miRNAs) open a new realm of possibilities for noninvasive diagnosis and prognosis of bladder cancer (BC). The aim of our study was to identify serum miRNA expression signatures in patients with BC and establish new models for the diagnosis of BC and recurrence prediction. We performed genome-wide serum miRNA analysis by Miseq sequencing followed by evaluations in the training and validation sets with reverse transcription quantitative real-time PCR assays from serum samples of 250 patients with BC and 240 controls. A six-miRNA panel (miR-152, miR-148b-3p, miR-3187-3p, miR-15b-5p, miR-27a-3p and miR-30a-5p) for the diagnosis of BC was finally developed by multivariate logistic regression model with an area under the receiver operating characteristic curve of 0.899. The corresponding sensitivities of this panel for Ta, T1 and T2-T4 were 90.00, 84.85 and 89.36%, significantly higher than those of urine cytology, which were 13.33, 30.30 and 44.68%, respectively (all at p<0.001). In addition, Kaplan-Meier analysis showed that patients with nonmuscle-invasive BC (NMIBC) with high miR-152 level and low miR-3187-3p level had worse recurrence-free survival (p=0.023 and 0.043, respectively). In multivariate Cox regression analysis, miR-152 was independently associated with tumor recurrence of NMIBC (p=0.028). Our results suggested that a serum miRNA signature may have considerable clinical value in diagnosing BC. Furthermore, expression level of serum miR-152 could provide information on the recurrence risk of NMIBC.

Downregulation of urinary cell-free microRNA-214 as a diagnostic and prognostic biomarker in bladder cancer.

BACKGROUND AND OBJECTIVES: We aimed to investigate potential of urinary cell-free microRNA-214 (miR-214) as a noninvasive biomarker for bladder cancer in this report. METHODS: We screened miR-214 expression in medium from 2 bladder cancer cell lines to determine whether it is secretory. Then we validated expression of cell-free miR-214 in urine samples from an independent set of 192 preoperative bladder cancer patients, 80 matching postoperative patients and 169 healthy controls. RESULTS: miR-214 was secreted from bladder cancer cell lines. Cell-free miR-214 levels were significantly attenuated in preoperative urine from bladder cancer patients, whereas its expression significantly increased in matched postoperative urine. Underexpressed extracellular miR-214 in urine was significantly associated with higher tumor stage, higher lymph node status, higher grade, age and history of non-muscle-invasive bladder cancer (NMIBC). Urinary cell-free miR-214 could forcefully differentiate bladder cancer (area under the curve; AUC = 0.838; 95% CI = 0.796-0.875) patients from healthy controls. Additionally, miR-214 in urine supernatant could serve as an independent prognostic predicator of recurrence-free survival (RFS) and overall survival (OS) for patients with muscle-invasive bladder cancer (MIBC). CONCLUSIONS: Urinary cell-free miR-214 is a hopeful biomarker for tumor stratification, early diagnosis and prognostic assessment of bladder cancer.

Periostin expression and its prognostic value for colorectal cancer.

Integrin is important for cell growth, invasion and metastasis, which are frequently observed in malignant tumors. The periostin (POSTN) gene encodes the ligand for integrin, one of the key focal adhesion proteins contributing to the formation of a structural link between the extracellular matrix and integrins. High expression levels of the POSTN gene are correlated with numerous human malignancies. We examined POSTN protein in colorectal cancer specimens from 115 patients by strictly following up using immunohistochemistry. Cytoplasm immunohistochemical staining showed POSTN protein expression in colorectal cancers. The positive expression rate of POSTN protein (59.13%, 68/115) in colorectal cancers was significantly higher than that in adjacent normal colon mucosa (0.47%, 11/109). POSTN over-expression in colorectal cancers was positively correlated with tumor size, differentiation, lymph node metastasis, serosal invasion, clinical stage and five-year survival rates. Further analysis showed that patients with advanced stage colorectal cancer and high POSTN expression levels had lower survival rates than those with early stage colorectal cancer and low POSTN expression levels. Overall, our results showed that POSTN played an important role in the progression of colorectal cancers.

Involvement of glutamate-cystine/glutamate transporter system in aspirin-induced acute gastric mucosa injury.

Large-dose or long-term use of aspirin tends to cause gastric mucosa injury, which is recognized as the major side effect of aspirin. It has been demonstrated that glutamate exerts a protective effect on stomach, and the level of glutamate is critically controlled by cystine/glutamate transporter (Xc(-)). In the present study, we investigated the role of glutamate-cystine/glutamate transporter system in aspirin-induced acute gastric mucosa injury in vitro and in vivo. Results showed that in human gastric epithelial cells, aspirin incubation increased the activity of LDH and the number of apoptotic cells, meanwhile down-regulated the mRNA expression of Xc(-) accompanied with decreased glutamate release. Similar results were seen in a rat model. In addition, exogenous l-glutamate attenuated the gastric mucosa injury and cell damage induced by aspirin both in vitro and in vivo. Taken together, our results demonstrated that acute gastric mucosa injury induced by aspirin is related to reduction of glutamate-cystine/glutamate transporter system activity.

Regulation of Th1/Th2 polarization by tissue inhibitor of metalloproteinase-3 via modulating dendritic cells.

Tissue inhibitor of metalloproteinase-3 (TIMP-3) is one of a family of proteins inhibiting matrix metalloproteinases, which has also been identified as a mediator for checking inflammation. Meanwhile, it is well known that inflammation causes the activation of the immune response. However, it is not clear whether TIMP-3 plays a role in the immune system. In the present study, we demonstrated a novel function of TIMP-3 in Th1/Th2 polarization through its influence on the antigen-presenting cells. First, TIMP-3 was found strikingly up-regulated by IL-4 during the differentiation of human dendritic cells via the p38MAPK pathway. Second, the expression of costimulatory molecule-CD86 was repressed by TIMP-3. Besides, the induction of IL-12 in matured dendritic cells was significantly inhibited in a PI3K-dependent manner. Furthermore, dendritic cells matured in the presence of TIMP-3 could stimulate allogeneic naive T helper (Th) cells to display a prominent Th2 polarization. Importantly, in an autoimmune disorder-primary immune thrombocytopenia, TIMP-3 showed a statistically positive correlation with IL-4 and platelet count, but a negative correlation with IFN-γ in patient blood samples. Collectively, these in vitro and in vivo data clearly suggested a novel role of TIMP-3 in Th1/Th2 balance in humans.

Investigation of cell free BIRC5 mRNA as a serum diagnostic and prognostic biomarker for colorectal cancer.

BACKGROUND: BIRC5 (Survivin), a key member of inhibitor of apoptosis family, has been shown in colorectal cancer (CRC) tumorigenesis and progress. This study investigated the expression levels of cell free BIRC5 mRNA in serum of CRC and assess its diagnostic and prognostic potential. METHODS: Levels of cell free BIRC5 mRNA were detected by reverse transcription quantitative real-time PCR in serum of 92 CRC patients and 60 healthy volunteers. RESULTS: Cell free BIRC5 mRNA levels were significantly increased in serum of CRC (P < 0.001), and significantly correlated with tumor differentiation (P = 0.035), regional lymph node metastasis (P < 0.001) and TNM stage (P < 0.001). ROC curve demonstrated an optimal cut-off value of 0.128, providing a sensitivity of 84.8% and a specificity of 80.0% for discriminating CRC from controls. The area under the ROC curve for BIRC5 mRNA was significantly larger than that for CEA (0.855 vs. 0.691, P < 0.001). Furthermore, a significantly higher diagnosis capability was showed when combined BIRC5 mRNA and CEA. High serum BIRC5 mRNA expression has a lower OS, compared with low group (36.4% vs. 73.3%, P = 0.022), and was an independent prognostic factor for CRC. CONCLUSION: Serum cell free BIRC5 mRNA is a promising non-invasive biomarker for diagnosis and prognosis of CRC.

Inequalities in unmet health care needs under universal health insurance coverage in China.

BACKGROUND: Expanding health insurance is a critical step towards universal health coverage due to its positive effect on reducing unmet health care needs and enhancing equitable access to health care. Despite previous studies on the socioeconomic factors associated with unmet health care needs, few studies have analysed the inequalities in such needs and the impact of universal health insurance coverage on addressing them. This study aimed to measure the contribution of social health insurance (SHI) coverage to inequalities in financially and non-financially constrained unmet health care needs among middle-aged and elderly Chinese adults. METHODS: The study data were obtained from the China Health and Retirement Longitudinal Study (2011-2015). A total of 11,592 respondents reporting outpatient care needs and 6320 reporting inpatient care needs were included. The concentration index (CI) was employed to measure the extent of income-related inequalities in unmet health care needs. A decomposition method based on a probit model was used to investigate the contribution of SHI to the inequalities. RESULTS: The incidence rates of unmet outpatient needs due to financial and non-financial constraints were 4.68% and 24.78%, respectively; these rates were 18.69% and 15.73% for unmet inpatient needs. The CIs of unmet outpatient needs due to financial and non-financial constraints were - 0.1872 and 0.0195, respectively; these values were - 0.1558 and 0.0352 for unmet inpatient needs. The percentages of the contribution of SHI to the CIs of financially constrained unmet outpatient and inpatient needs were 0.2639% and 1.8898%, respectively. Moreover, the percentages of the contribution of SHI to the CIs of non-financially constrained unmet outpatient and inpatient needs were - 0.4513% and - 6.4192%, respectively. CONCLUSION: The universal coverage of SHI in China increased pro-poor inequalities in financially constrained unmet health care needs but decreased pro-rich inequalities in non-financially constrained unmet needs. Additionally, the contribution of SHI to inequalities in financially constrained unmet needs for inpatient care was stronger than that for outpatient care. Policy-makers are advised to introduce favourable reimbursement policies for patients with poor socioeconomic conditions and address both financial and non-financial barriers to promote equitable access to health care for the entire population.

Leptin-mediated regulation of MT1-MMP localization is KIF1B dependent and enhances gastric cancer cell invasion.

Leptin overexpression is closely correlated with gastric cancer (GC) invasion, but its exact effect and the underlying mechanism in tumorigenesis remain poorly understood. Membrane type 1-matrix metalloproteinase (MT1-MMP), a surface-anchored 'master switch' proteinase, is overexpressed and plays crucial roles in tumor invasion. Here, we characterized the influence of leptin on the generation and surface localization of MT1-MMP in GC and elucidated its molecular mechanisms. Our results revealed that leptin promoted GC cell invasion in vitro by upregulating MT1-MMP expression. Furthermore, cell surface biotinylation assay and flow cytometry demonstrated that the surface expression of MT1-MMP was also enhanced by leptin, and knockdown of kinesin family member 1B (KIF1B, a microtubule plus end-directed monomeric motor protein) by small interference RNA inhibited this process. Notably, coimmunoprecipitation analysis indicated that leptin enhanced the interaction of MT1-MMP with KIF1B in a time-dependent manner, which consequently contributed to GC cell invasion. Moreover, leptin increased MT1-MMP or KIF1B expression by the protein kinase B (AKT) pathway and extracellular signal-regulated kinase 1/2 partially participated in this process. However, only AKT was implicated in the leptin-mediated membrane localization of MT1-MMP. Immunohistochemistry analysis revealed that leptin, MT1-MMP and KIF1B are overexpressed in GC tissues, and they positively correlated with clinical stage and lymph node metastasis. These observations indicate that this regulatory network exists in vivo. Taken together, our findings suggest that leptin is an effective intracellular stimulator of MT1-MMP and that leptin-enhanced cell surface localization of MT1-MMP is dependent on KIF1B, which consequently plays a critical role in GC invasion.

Up-regulation of miR-182 expression in colorectal cancer tissues and its prognostic value.

PURPOSE: Accumulating evidences indicate that dysregulated microRNAs (miRNA) are involved in cancer tumorigenesis and progression. In the present study, we evaluated the expression of miR-182 in colorectal cancer and adjacent noncancerous tissues and explored its associations with clinicopathological characteristics and prognosis. METHODS: Quantitative real-time PCR was used to analyze the expression of miR-182 in 148 pairs of colorectal cancer and adjacent noncancerous tissues. The relationship between miR-182 expression and clinicopathological characteristics in colorectal cancer tissues was estimated using Mann-Whitney U test or Kruskal-Wallis test, as appropriate. We calculated the survival curves and prognostic values of each variable by the Kaplan-Meier method and Cox proportional hazards regression analysis, respectively. RESULTS: The expression of miR-182 was found up-regulated in colorectal cancer tissues compared with adjacent noncancerous tissues (p < 0.001), and its up-regulation was significantly correlated with large tumor size (p = 0.016), positive regional lymph node metastasis (p = 0.008), and advanced tumor-node-metastasis stage (p = 0.020). Furthermore, Kaplan-Meier analysis demonstrated that high miR-182 expression predicted poor survival (p = 0.001), and Cox proportional hazards risk analysis indicated that miR-182 was an independent prognostic factor for colorectal cancer. CONCLUSIONS: MiR-182 was up-regulated in colorectal cancer tissues and correlated with adverse clinical characteristics and poor prognosis, indicating that miR-182 might be involved in colorectal cancer progression and could be used as a potential prognostic biomarker and therapeutic target in the management of colorectal cancer.

Close association of metastasis-associated protein 1 overexpression with increased angiogenesis and poor survival in patients with histologically node-negative gastric cancer.

BACKGROUND: Although metastasis-associated protein 1 (MTA1) has been recently demonstrated as a potent angiogenesis-promoting factor in various malignant tumors, its angiogenic property in gastric cancer (GC) remains unclear. This study has detected the expression of MTA1 protein in surgically resected tissues of pathologic N0 (pN0) GC and further investigated its relation with other clinicopathologic factors and tumor angiogenesis and prognosis. METHODS: MTA1 protein expression was detected immunohistochemically in 111 pN0 GC specimens. Its correlations with clinicopathologic factors and tumor prognosis were evaluated. The intratumoral microvessel density (MVD) was assessed based on CD105 antigen immunoreactivity and analyzed for correlation with MTA1 protein expression. RESULTS: Overexpression of MTA1 was detected in 36.04 % of patients and exhibited a significant association with tumor size and MVD. Survival analysis demonstrated that both overall (OS) and disease-free (DFS) survivals in patients overexpressing MTA1 were significantly poorer than those without MTA1 overexpression 5 years after the operation (both p < 0.001). Multivariate survival analysis demonstrated that MTA1 overexpression was an independent prognosticator for unfavorable OS and DFS (p < 0.001, respectively). CONCLUSIONS: MTA1 overexpression is frequently observed in pN0 GC patients and is significantly associated with increased angiogenesis and poor prognosis. Detection of MTA1 protein expression may help predict the relapse and prognosis of pN0 GC. Also, MTA1 protein may form a novel target for antiangiogenic therapy.