A study on the identification of factors related to depression in a population with an increasing number of chronic diseases in the short term in China based on a health ecology model.

BACKGROUND: The rapid increase in the number of patients with chronic diseases and depression, as well as the rapid spread of their effects, have led to these two health problems gradually developing into major public health issues in China and around the world. Currently, many individuals with chronic diseases are experiencing depressive symptoms one after another. Therefore, it is imperative to conduct research on how to prevent depression in this growing population of individuals with chronic diseases in a timely manner. METHODS: Based on the data of the 2015 and 2018 national follow-up surveys of the China Health and Elderly Care Longitudinal Survey, a total of 7641 patients with short-term increase in the number of chronic diseases were selected as the study objects, and a binary logistic regression model was constructed according to the five dimensions of the health ecology model. The neural network model was used to explore the main (first two) factors affecting the increase in the number of chronic diseases in China in the short term, and the random forest and extreme value gradient lifting algorithm were used to verify them, and effective suggestions were put forward. RESULTS: The detection rate of depression in the population with increasing number of chronic diseases from 2015 to 2018 was 42.13 %. The model was established based on five dimensions of the health ecology model: Model 1 (Personal trait layer), Model 2 (Personal trait layer plus Behavioral feature layer), Model 3 (Personal trait layer plus Behavioral feature layer plus Living and working conditions layer), Model 4 (Personal trait layer plus Behavioral feature layer plus Living and working conditions layer plus Networking layer) and Model 5 (Personal trait layer plus Behavioral feature layer plus Living and working conditions layer plus Networking layer plus Policy environment layer).The prediction accuracy of the five models was 66.4 %, 68.3 %, 70.7 %, 71.6 % and 71.6 %, respectively, and Model 5 showed that the P values of gender, self-rated health, night's sleep time (h), disability, life satisfaction, child satisfaction, place of residence and highest level of education were all <0.05, life satisfaction and self-rated health importance were 0.249 (100 %) and 0.226 (90.8 %). CONCLUSION: Gender, self-rated health, night sleep duration, disability, satisfaction with life, satisfaction with children, place of residence and highest level of education were the main influencing factors for the increase of depressive symptoms in the population with chronic diseases in the short term, among which life satisfaction and self-rated health have the greatest impact on depressive symptoms, and there is an interaction between the two.

Enhancing psychological well-being in college students: the mediating role of perceived social support and resilience in coping styles.

BACKGROUND: The prevalence of depression among college students is higher than that of the general population. Although a growing body of research suggests that depression in college students and their potential risk factors, few studies have focused on the correlation between depression and risk factors. This study aims to explore the mediating role of perceived social support and resilience in the relationship between trait coping styles and depression among college students. METHODS: A total of 1262 college students completed questionnaires including the Trait Coping Styles Questionnaire (TCSQ), the Patient Health Questionnaire-9 (PHQ-9), the Perceived Social Support Scale (PSSS), and the Resilience Scale-14 (RS-14). Common method bias tests and spearman were conducted, then regressions and bootstrap tests were used to examine the mediating effects. RESULTS: In college students, there was a negative correlation between perceived control PC and depression, with a significant direct predictive effect on depression (ß = -0.067, P < 0.01); in contrast, negative control NC showed the opposite relationship (ß = 0.057, P < 0.01). PC significantly positively predicted perceived social support (ß = 0.575, P < 0.01) and psychological resilience (ß = 1.363, P < 0.01); conversely, NC exerted a significant negative impact. Perceived social support could positively predict psychological resilience (ß = 0.303, P < 0.01), and both factors had a significant negative predictive effect on depression. Additionally, Perceived social support and resilience played a significant mediating role in the relationship between trait coping styles and depression among college students, with three mediating paths: PC/NC → perceived social support → depression among college students (-0.049/0.033), PC/NC→ resilience → depression among college students (-0.122/-0.021), and PC/NC → perceived social support → resilience → depression among college students (-0.016/0.026). CONCLUSION: The results indicate that trait coping styles among college students not only directly predict lower depression but also indirectly influence them through perceived social support and resilience. This suggests that guiding students to confront and solve problems can alleviate their depression.

Relationship between social participation and depressive symptoms in patients with multimorbidity: the chained mediating role of cognitive function and activities of daily living.

OBJECTIVE: The potential mechanisms linking social participation and depressive symptoms in Chinese individuals with multimorbidity are not yet fully understood. This study aims to explore how cognitive function and activities of daily living (ADLs) mediate the relationship between social participation and depressive symptoms in individuals with multimorbidity. METHODS: We selected 3782 participants with multimorbidity from the 2018 China Health and Retirement Longitudinal Study. Data related to social participation, cognitive function, ADLs, and depressive symptoms were extracted. Regression and Bootstrap analyses were used to explore the sequential mediating effects of social participation, cognitive function, ADLs, and depressive symptoms. RESULTS: (1) There was a significant correlation between social participation, cognitive function, activities of daily living, and depressive symptoms (p < 0.01). (2) Social participation directly affected depressive symptoms (ß = -0.205, p < 0.05). (3) Cognitive function (ß = -0.070, p < 0.01) and activities of daily living (ß = -0.058, p < 0.01) played separate mediating roles in the effect of social participation on depressive symptoms. (4) Cognitive function and activities of daily living had a chain-mediated role in the relationship between social participation and depressive symptoms in patients with multimorbidity (ß = -0.020, p < 0.01). CONCLUSION: A chained mediating effect was found between cognitive function, ADLs, social participation, and depressive symptoms in patients with multimorbidity. Social participation was found to improve the cognitive function of patients with multimorbidity, which in turn enhanced their daily life activities and ultimately alleviated their depressive symptoms.

Classification of high-risk depressed mood groups in cancer patients based on Health Ecology Model.

BACKGROUND: Depressed mood affects a significant number of patients with cancer, and can impair their quality of life and interfere with successful treatment. Our study aims to create a predictive model for identifying high-risk groups of depressed mood in cancer patients, offering a theoretical support for preventing depressed mood in these individuals. METHODS: The China Health and Retirement Longitudinal Study (CHARLS) provided the data for this research, which used CES-D as a tool to identify individuals with depressed mood. Influencing factors of depressed mood in cancer patients was analyzed using a binary logistic regression model. Using the Harvard Cancer Index, we classified the high-risk patients for depressed mood. RESULTS: In present study, 52.96 % of cancer patients met criteria for depressed mood based on the CES-D. Significant correlations were found between depressed mood and factors such as gender, self-rated health, sleep duration, exercise, satisfaction with family, residence, education, life satisfaction, and medical insurance. Utilizing the Harvard Cancer Index, we classified patients into five risk levels for depressed mood, revealing a significant variation in the number of depressive patients across these levels (x2=99.82, P < 0.05). Notably, the incidence of depressed mood increased with the risk level among cancer patients (x2=103.40, P < 0.05). LIMITATIONS: Lack of data on tumor typing and subgroups makes it unlikely to explore the specifics of depressed mood in patients with various types of cancer. CONCLUSION: The determinants of depressed mood in cancer patients are multi-dimensional. The Harvard Cancer Index may be helpful in identifying high-risk populations.

The value of TDI combined with myocardial strain parameters in quantitative evaluation of left heart function in parturient with pregnancy-induced hypertension.

This study aimed to investigate the value of tissue doppler imaging (TDI) and 4D myocardial strain parameters in evaluating left heart function of pregnant women with hypertension and the association between these parameters and relevant factors. Forty-five pregnant women with hypertensive disorder, including 20 with hypertension, 15 with mild preeclampsia, and 10 with severe preeclampsia, were recruited, and their cardiac functions were compared with those of 30 healthy pregnant women as controls. High Left ventricular end-systolic volume (LVESV), Left atrial volume index (LAVI), E/e were observed in hypertensive disorder, while Mitral peak diastolic velocity(E), Early diastolic peak velocity(e), E/A, Left ventricularglobal longitudinal strain (LVGLS), Left ventricularglobal area strain (LVGAS), and Left atrialglobal longitudinal strain (LAGLS) were decreased; for pre-eclampsia, Left ventricular end-systolic diameter (LVESD), Left atrial anteroposterior diameter (LAD-ap), LVESV, LAVI were significantly increased, LVGLS, LAGLS were significantly decreased, Left ventricular end-diastolic diameter (LVEDD), Left ventricular end-diastolic volume (LVEDV), A peak, E/e were increased, while E peak, E/A, e, Left ventricle global radial strain (LVGRS), Left ventricle global circumferential strain (LVGCS), LVGAS were decreased but not significantly; for severe preeclampsia, Left ventricular end diastolic diameter (LVEDD), LVESD, LAD-ap, Left ventricular end-diastolic volume (LVEDV), LVESV, LAVI, A, and E/e were significantly increased, while LVGLS, LVGRS, LVGCS, LVGAS, LAGLS, E peak, E/A, and e were significantly reduced. TDI combined with 4D myocardial strain parameters can detect early changes in cardiac function of hypertensive disorders in pregnancy, with LVGLS, LVGAS, and LAGLS being the most sensitive indicators for early changes. Such findings provide a basis for effective clinical treatment of these symptoms.

Quality assessment of transperineal ultrasound in Chinese tertiary medical centers: a multicenter study.

Background: Transperineal ultrasound (TPUS) is a vital examination method for diagnosing pelvic floor diseases. However, the quality of TPUS largely relies on the operator's experience, and there is a lack of studies on the evaluation of TPUS quality. Therefore, the objective of this study was to assess the quality of TPUS examinations in Chinese tertiary medical centers. Methods: This multicenter study conducted in 44 Chinese tertiary medical centers recruited postpartum women between September 2020 and September 2021. All participants underwent a standardized inquiry and TPUS examination. The participating centers were required to submit 5 parts of ultrasound data to the National Ultrasound Quality Control Center: 2-dimensional images at rest, 2-dimensional images at strain; 4-dimensional images of the levator ani hiatus; 4-dimensional images of the levator ani muscle; and 4-dimensional images of the anal sphincter. Quality assessment was performed by 2 experts with more than 5 years of experience in TPUS, and the reasons for nonqualification were stated. Results: In this study, 31 hospitals that were distributed across 20 provinces in China were included, submitting 2,251 cases in total. The overall qualified rate ranged from 12.00% to 86.92%. In each part, the qualified rate of 2-dimensional images at rest, 2-dimensional images at straining, levator ani hiatus, levator ani muscle, and anal sphincter was 94.27% (2,122/2,251), 78.54% (1,768/2,251), 85.52% (1,925/2,251), 93.03% (2,094/2,251), and 88.09% (1,983/2,251), respectively. Most of the nonqualified images belonged to 2-dimensional images at strain, and the errors in image acquisition (221/483, 45.76%) and measurement (262/483, 54.24%) were the main reasons for nonqualification. For levator ani hiatus images, error in image acquisition (275/326, 84.36%) was the main reason for nonqualification. Reconstruction error was the most common reason for nonqualification for levator ani muscle (133/157, 84.71%) and anal sphincter images (133/268, 49.63%). Conclusions: This multicenter study assessed the quality of TPUS in tertiary medical centers in China and identified the common reasons for nonqualification in each part. These findings can aid in forming the basis for quality control management and training for TPUS.

MnO2 nanosheets and gold nanoparticles supported electrochemical detection of circulating tumor cells.

The concentration of circulating tumor cells (CTCs) in peripheral blood is strongly correlated with the progress of certain metastatic cancers. In this study, we have developed a novel and facile electrochemical biosensor for the detection of CTCs based on the use of manganese dioxide nanosheets (MnO2 NSs) and gold nanoparticles (AuNPs). Aptamer sequence of target cell is modified on the surface of AuNPs for specifical recognition. With low-speed centrifugation, numerous AuNPs@DNA can be removed from the supernatant. On the other hand, MnO2 NSs are modified on the electrode surface to capture unreacted AuNPs@DNA. The declined electrochemical signal intensity can be used to reflect the level of CTCs. This biosensor achieves a wide linear range from 10 to 104 cells mL-1 and a limit of detection as low as 3 cells mL-1. Due to the specific aptamer as the recognition element, interfering cells can be successfully distinguished and this method performs satisfactorily in clinical samples. Therefore, it has great potential to be used as a powerful tool benefiting rare cells analysis and the investigation of dynamics of cellular interactions.

A hydrophobic Cu/Cu2O sheet catalyst for selective electroreduction of CO to ethanol.

Electrocatalytic reduction of carbon monoxide into fuels or chemicals with two or more carbons is very attractive due to their high energy density and economic value. Herein we demonstrate the synthesis of a hydrophobic Cu/Cu2O sheet catalyst with hydrophobic n-butylamine layer and its application in CO electroreduction. The CO reduction on this catalyst produces two or more carbon products with a Faradaic efficiency of 93.5% and partial current density of 151 mA cm-2 at the potential of -0.70 V versus a reversible hydrogen electrode. A Faradaic efficiency of 68.8% and partial current density of 111 mA cm-2 for ethanol were reached, which is very high in comparison to all previous reports of CO2/CO electroreduction with a total current density higher than 10 mA cm-2. The as-prepared catalyst also showed impressive stability that the activity and selectivity for two or more carbon products could remain even after 100 operating hours. This work opens a way for efficient electrocatalytic conversion of CO2/CO to liquid fuels.

Risk factors and diagnostic markers for Escherichia coli bloodstream infection in older patients.

OBJECTIVE: To investigate risk factors for Escherichia coli (E. coli) bloodstream infection (BSI) in older patients and the diagnostic accuracy of laboratory parameters. METHODS: The electronic medical records of patients aged 60 years and above who were admitted with a serious condition were extracted. Propensity score matching (PSM) was used to ensure that the included patients had similar baseline clinical features. Multiple regression analysis was used to identify risk factors for E. coli BSI and extended-spectrum ß-lactamase (ESBL)-producing E. coli BSI. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic utility of relevant laboratory indicators. RESULTS: After PSM, 508 patients were included: 254 patients with E. coli BSI and 254 control patients. Bile duct stone (adjusted odds ratio [aOR] 5.131), kidney stone (aOR 3.678), and urinary system infection (aOR 3.173) were independent risk factors for E. coli BSI. Prior exposure to cephems (aOR 3.782) and drainage tube placement (aOR 2.572) were independent risk factors for ESBL-producing E. coli BSI. Serum procalcitonin (PCT) yielded the highest area under the curve (0.783) and the best cut-off value (1.3 ng/ml). CONCLUSION: Bile duct stone, kidney stone, and urinary system infection must be detected and treated early, in order to prevent E. coli BSI in older patients. Further, administration of cephems and invasive procedures must be undertaken with caution, in order to reduce the risk of BSI with ESBL-producing E. coli. Finally, serum PCT level has potential as diagnostic marker for E. coli BSI in older individuals.

Diagnostic Role of Carotid Intima-Media Thickness for Coronary Artery Disease: A Meta-Analysis.

BACKGROUND: The present meta-analysis was conducted to confirm whether carotid intima-media thickness (IMT) could serve as an accurate diagnostic method for coronary artery disease (CAD). METHODS: Databases of PubMed, Google Scholar, and Embase were searched for potential articles. The articles were selected according to inclusion criteria. Pooled sensitivity and specificity with corresponding 95% confidence interval (CI) were used to confirm the diagnostic role of IMT for CAD. I 2 and P value were used to assess the existence of heterogeneity. I 2 and P value were used to assess the existence of heterogeneity. RESULTS: 22 eligible articles were selected in the present meta-analysis. Pooled sensitivity and specificity of IMT for diagnosing CAD were 0.68 (0.57-0.77) and 0.70 (0.64-0.75), respectively. The corresponding AUC was 0.74 (0.70-0.78). Subgroup analyses based on cutoff value of IMT were performed. A cutoff value of 1 mm was demonstrated to be much more accurate diagnostic criteria for CAD (sensitivity: 0.66; specificity: 0.79; AUC: 0.80). Sensitivity analysis indicated that the pooled results were robust. Deek's funnel plot indicated no significant publication bias (P value were used to assess the existence of heterogeneity. CONCLUSION: Carotid IMT may serve as an accurate diagnostic tool. A cutoff value of 1 mm seems to provide much more accurate diagnostic results for CAD.

Hypertension and physical activity in middle-aged and older adults in China.

There are few studies examining the association between levels of physical activity and hypertension in middle-aged and older adults in China. Data were drawn from the Chinese Health and Retirement Longitudinal Study (using four-stage stratified probability-proportional-to-size sampling), involving 7113 individuals aged 45 years and older from 28 provinces of China. Hypertension was defined as a systolic BP ≥ 130 mm Hg, or diastolic BP ≥ 80 mm Hg, or self-reported use of anti-hypertensive medications. The awareness, treatment, and control among hypertensive participants were 53.12%, 43.37%, and 10.03%, respectively. The prevalence of hypertension was 56.12% among all the participants, higher in main city zones (58.68%) than villages (55.52%) and other areas (55.78%, p < 0.0001). Participants who were overweight (BMI ≥ 24: AOR 4.08, 95% CI 3.21-5.20, P < 0.0001; BMI ≥ 28: 10.03, 7.56-13.31, P < 0.0001), and drinking more than once a month (1.28, 1.12-1.46, P < 0.0001) were more likely to have hypertension. The decision tree model was established to analyze the importance of different levels of physical activity on hypertension prevention. Participants who usually participated in moderate-to-vigorous activity for more than 10 minutes (vigorous: 0.82, 0.73-0.91, P = 0.0004; moderate: 0.83, 0.75-0.92, P = 0.0006) were less likely to have hypertension. The results of the decision tree showed that the vigorous physical activity seemed to be more important than moderate and light activity to induce beneficial effects on prevention of hypertension. The strength of our study is in using the decision tree to clearly rank the importance of those key factors affecting hypertension.

Blood pressure and noncommunicable diseases in middle-aged and older adults in China.

BACKGROUND: There are few studies examining the association between blood pressure (BP) and noncommunicable diseases (NCDs) in consideration of the new hypertension guidelines in China. METHODS: Data were drawn from the China Health and Retirement Longitudinal Study. 14 390 eligible participants (aged 45 years and older) were selected through four-stage, stratified, and cluster sampling. Hypertension was considered as a mean systolic blood pressure (SBP) of 130 mm Hg (old definition: 140 mm Hg) or higher, a mean diastolic blood pressure (DBP) of 80 mm Hg (old definition: 90 mm Hg) or higher or taking anti-hypertensive medication. Cochran-Armitage trend test and logistic regression analyses were conducted to test the association between BP level and NCDs. RESULTS: The prevalence of hypertension based on the latest definition was 56.35% (while by old definition: 42.75%). The awareness, treatment, and control among hypertensive participants were 38.62% (51.18%), 43.10% (56.81%), and 9.91% (13.06%), respectively. An increasing rate of NCDs (diabetes, heart disease, stroke, and memory-related disease) among participants were found with the ascending of BP level. After adjusted for demographics and behavioral risks, the following 3 NCDs had been shown to correlate with hypertension: diabetes (adjusted OR 1.15, 0.91-1.45 for elevated BP; 1.20, 0.97-1.49 for hypertension stage 1; 1.55, 1.28-1.86 hypertension stage 2), heart disease (0.94, 0.79-1.12; 1.05, 0.90-1.22; 1.28, 1.12-1.47), and stroke (1.77, 1.25-2.51; 1.32, 0.93-1.87; 1.85, 1.37-2.49). CONCLUSIONS: The association between hypertension and the risk of NCDs is of concern in China. The combined efforts on NCDs prevention and lowered blood pressure should be made by nationally integrated strategies, especially in middle-aged and older adults.

Targeting Notch1 inhibits invasion and angiogenesis of human breast cancer cells via inhibition Nuclear Factor-κB signaling.

Notch-1, a type-1 transmembrane protein, plays critical roles in the pathogenesis and progression of human malignancies, including breast cancer; however, the precise mechanism by which Notch-1 causes tumor cell invasion and angiogenesis remain unclear. Nuclear factor-κB (NF-κB), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) are critically involved in the processes of tumor cell invasion and metastasis, we investigated whether targeting Notch-1 could be mechanistically associated with the down-regulation of NF-κB, IL-8, VEGF, and MMP-9, resulting in the inhibition of invasion and angiogenesis of breast cancer cells. Our data showed that down-regulation of Notch-1 leads to the inactivation of NF-κB activity and inhibits the expression of its target genes, such as IL-8, VEGF and MMP-9. We also found that down-regulation of Notch-1 decreased cell invasion, and vice versa Consistent with these results, we also found that the down-regulation of Notch-1 not only decreased MMP-9 mRNA and its protein expression but also inhibited MMP-9 active form. Moreover, conditioned medium from Notch-1 siRNA-transfected breast cancer cells showed reduced levels of IL-8 and VEGF and, in turn, inhibited the tube formation of HUVECs, suggesting that down-regulation of Notch-1 leads to the inhibition of angiogenesis. Furthermore, conditioned medium from Notch-1 cDNA-transfected breast cancer cells showed increased levels of IL-8 and VEGF and, in turn, promoted the tube formation of HUVECs, suggesting that Notch-1 overexpression leads to the promotion of angiogenesis.We therefore concluded that down-regulation of Notch-1 leads to the inactivation NF-κB and its target genes (IL-8, MMP-9 and VEGF), resulting in the inhibition of invasion and angiogenesis.

Hyper-Cross-Linked Organic Microporous Polymers Based on Alternating Copolymerization of Bismaleimide.

A novel type of hyper-cross-linked organic microporous polymer (HOMP) has been successfully prepared based on the radical copolymerization of bismaleimides and divinylbenzene. In comparison with the HOMPs prepared with cross-linking techniques, the new radical strategy circumvents some intractable problems, such as low atom economy, structure irregularity and corrosive byproducts. The obtained HOMPs have defined molecular structures due to the intrinsic alternating copolymerization properties of the two monomers. A maximum BET surface area of 841 m2 g-1 and high gas capture capacity (CO2, 11.22 wt %, 273 K/1.0 bar; H2, 0.82 wt %, 77.3 K/1.0 bar; benzene, 545 mg g-1, room temperature/0.6 bar; and cyclohexane, 1736 mg g-1, room temperature/0.6 bar) were achieved. In addition, the polymers also displayed good chemical and thermal stability, which is critical for the practical application.

Parathyroid adenoma causing a spontaneous cervical and mediastinal massive hematoma.

Cervical and mediastinal hemorrhaging caused by a spontaneous rupture of a parathyroid adenoma has been rarely reported. Herein, we report a case of a 52-year-old woman who experienced a sudden onset of cervical and mediastinal bleeding related to a parathyroid adenoma. The patient had a history of trauma to the left thorax with a fracture of two ribs. Ultrasonography and computer tomography revealed a nodule in the retrotracheal space and hematoma of the bilateral trachea and thorax. Laboratory examinations revealed significant hypercalcemia, hypophosphatemia, and a high level of intact parathyroid hormone. Surgery was performed and a dark-red, soft tumor was found behind the trachea, which adhered to the surrounding tissues. The pathological diagnosis was a parathyroid adenoma with hemosiderin deposition and fibrosis.

Evaluation of S100A4 mRNA in EUS-FNA specimens for the assessment of chemosensitivity to gemcitabine from patients with unresectable pancreatic cancer.

BACKGROUND/AIMS: Gemcitabine (GEM) is the first-line chemotherapy in patients with unresectable pancreatic cancer. However, the clinical outcomes of this regimen are still unsatisfactory in prolonging survival. Resistant to GEM is one of the reasons for poor prognosis. Therefore, looking for molecular biomarkers to predict chemosensitivity to GEM is important for treatment in unresectable pancreatic cancer patients. The aim of this study was to analyze S100A4 mRNA in tissues of unresectable pancreatic cancer obtained by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA), and to determine the relation between S100A4 mRNA level and chemosensitivity to GEM. METHODS: The analysis was performed on samples from 36 patients with unresectable pancreatic cancer who were treated with gemcitabine alone. The patients were assigned to receive GEM at 1,000 mg/m(2)/wk for weeks 1 to 6, followed by 1 week rest, then for 4 weeks. mRNA was extracted for S100A4 mRNA assay from patients above by EUS-FNA before GEM-treatment. The 36 patients were divided into the following two groups. Patients with partial response and those with stable disease whose tumor markers decreased by 50% or more were classified as the effective group. The rest of patients were classified as the non effective group. The relationship between GEM efficacy and S100A4 mRNA expression was then examined by chi-squared test. RESULTS: S100A4 mRNA showed a significant correlation with GEM efficacy. Patients in the effective group had low S100A4 mRNA expression, whereas patients in non-effective group had high S100A4 mRNA expressions (P = 0.0059). CONCLUSION: S100A4 mRNA level analyzed in EUS-FNA samples is an important molecular biomarker for prediction of chemosensitivity to GEM in unresectable pancreatic cancer.