Patient preferences and shared decision making for the traditional Chinese medicine treatment of lung cancer: A discrete choice experiment study.

Background: Traditional Chinese Medicine (TCM), integrating patient preferences into decision-making process, has been widely used in the multimodality therapy of lung cancer. This study aimed to estimate patient preferences for treatment and shared decision-making (SDM) modes concerning inpatient TCM treatment of lung cancer in Shanghai in order to provide a basis for clinical decision-making process on TCM therapy for lung cancer. Methods: This study was conducted among patients (n = 347) from nine tertiary hospitals in Shanghai by discrete-choice experiment (DCE) survey and Shared Decision-Making Questionnaire-patient version (SDM-Q-9) survey. The DCE was developed with the inclusion of the most relevant attributes at appropriate levels for the TCM treatment of lung cancer. The empirical data analyses of patients were performed using mixed logit models. Additionally, subgroup analysis was conducted. Results: In total, 347 respondents completed the questionnaire. All attributes' coefficients were statistically significant for patients' preferences. Patients showed strong preferences for increasing disease control rate, relieving nausea and vomiting, reducing the risk of side effects, and were concerned about monthly out-of-pocket costs. Subgroup analysis indicated that patients with a lower SDM-Q-9 score and those who were satisfied with medical services emphasized more importance of higher disease control rate. Furthermore, most of the patients (90.20%) self-reported a high willingness to use SDM during the decision-making process. Conclusion: In Shanghai, patients mainly preferred SDM and considered disease control rate as the most essential attribute in the TCM treatment of lung cancer. The study findings could underscore the importance of considering patients' preferences and promote SDM.

Preparation, characteristics and cytotoxicity of green synthesized selenium nanoparticles using Paenibacillus motobuensis LY5201 isolated from the local specialty food of longevity area.

Selenium is an essential micronutrient element. For the extremely biotoxic of selenite, Selenium nanoparticles (SeNPs) is gaining increasing interest. In this work, a selenium-enriched strain with highly selenite-resistant (up to 173 mmol/L) was isolated from the local specialty food of longevity area and identified as Paenibacillus motobuensis (P. motobuensis) LY5201. Most of the SeNPs were accumulated extracellular. SeNPs were around spherical with a diameter of approximately 100 nm. The X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy showed that the purified SeNPs consisted of selenium and proteins. Our results suggested that P. motobuensis LY5201could be a suitable and robust biocatalyst for SeNPs synthesis. In addition, the cytotoxicity effect and the anti-invasive activity of SeNPs on the HepG2 showed an inhibitory effect on HepG2, indicating that SeNPs could be used as a potential anticancer drug.

Deoxyelephantopin Suppresses Pancreatic Cancer Progression In Vitro and In Vivo by Targeting linc00511/miR-370-5p/p21 Promoter Axis.

Objectives: Deoxyelephantopin (DET) is a kind of natural active ingredient extracted from the Chinese herbal medicine Elephantopus scaber L. Many studies have revealed the potential antitumor effect on multiple malignancies. However, the detailed mechanism of its antitumor effect in pancreatic cancer remains unclear. Recently, studies have confirmed that noncoding RNA (ncRNA) plays an important regulatory role in malignancies. This research was performed to explore the relationship between ncRNA and DET-induced tumor inhibition in pancreatic cancer. Methods: Microarray profiling was applied to identify the candidate ncRNAs associated with DET-induced tumor inhibition. Quantitative real-time PCR was used to evaluate the expression of linc00511 in pancreatic cancer cells and tissues. The influence of DET on the cell proliferation, migration, and invasion was assessed by CCK-8, colony formation, wound healing, and Transwell assays. The relationship between lncRNAs, miRNAs, and p21 promoter region was analyzed by bioinformatics and verified by luciferase reporter gene and western blotting. The effect of linc00511 on nuclear translocation of miR-370-5p was explored by cytoplasmic and nuclear RNA purification. Moreover, the effect of DET on tumor growth and metastasis, and the prophylactic effect were investigated by establishing subcutaneous and lung metastatic tumor models. Results: Microarray assay indicated linc00511 was a potential target gene. The antitumor effect of DET in pancreatic cancer depended on downregulating linc00511 expression, and linc00511 might be an oncogene in pancreatic cancer. Silencing linc00511 enhanced the antitumor function of DET; conversely, linc00511 overexpression antagonized the DET cytotoxic effect. Additionally, miR-370-5p could bind to p21 promoter to exert the RNA activation and then promote p21 expression. P21 was a downstream gene of linc00511 and associated with pancreatic cancer progression. Linc00511 regulated p21 expression by blocking miR-370-5p nuclear translocation. Conclusions: To sum up, the present finding confirmed that DET suppressed the malignant biological behavior of pancreatic cancer via linc00511/miR-370-5p/p21 promoter axis.

Physician Preferences and Shared-Decision Making for the Traditional Chinese Medicine Treatment of Lung Cancer: A Discrete-Choice Experiment Study in China.

Background: With progress being made in the treatment of cancer, various clinical and treatment options are being pursued. In China, Traditional Chinese Medicine (TCM) is used widely in the treatment of cancer. Objective: To estimate TCM treatment preferences and SDM mode of physicians in China. Methods: This study was conducted among physicians (n=185) from nine tertiary hospitals in China by discrete-choice experiment (DCE) survey and Shared Decision-Making Questionnaire-physician version (SDM-Q-Doc) survey. The DCE was developed with the inclusion of the most relevant attributes at appropriate levels for the TCM treatment of lung cancer. The empirical data analyses of physicians were performed using mixed logit models. Additionally, subgroup analysis was conducted. Results: In total, 185 respondents completed the questionnaire. All attributes were statistically significant except out-of-pocket costs. Physicians showed the strongest preferences for increasing disease control rate, relieving nausea and vomiting, and reducing the risk of side effects. Most of the physicians (78.38%) self-reported a high willingness to use SDM during the decision-making process. The physicians with a higher SDM-Q-Doc score had more preference for improving all three attributes than those with a lower score. Little variation was found in preferences among the physicians with other sociodemographic characteristics. Conclusion: In China, physicians considered disease control rate as the most essential attribute in the TCM treatment of lung cancer. The physicians in China mainly preferred SDM, and the preference was different according to SDM mode when involving the TCM therapy for patients with lung cancer. The study findings could inform future TCM therapy for lung cancer and promote SDM.

Health-Related Quality of Life and Utility Scores of Lung Cancer Patients Treated with Traditional Chinese Medicine in China.

PURPOSE: To assess health-related quality of life (HRQoL) and utility scores of lung cancer patients treated with traditional Chinese medicine (TCM) in China. METHODS: This cross-sectional study included lung cancer patients treated with TCM in seven tertiary hospitals in Shanghai, China. The HRQoL and utility scores of these patients were measured using the five-level EQ-5D (EQ-5D-5L). The EQ-5D-5L utility scores were derived from the Chinese EQ-5D-5L Value Set. The relationships between HRQoL and the socio-demographic and clinical characteristics of these patients were further explored by Tobit regression. RESULTS: This study included a total of 347 patients. Their mean ± SD and median EQ-5D-5L utility scores were 0.851 ± 0.198 and 0.893, respectively. The highest proportion of participants reporting problems was observed in pain/discomfort dimension (57.9%) and anxiety/depression (45.5%). Lung cancer patients treated with TCM had poor HRQoL, influenced by cancer clinical stage. CONCLUSION: Lung cancer patients treated with TCM have poor HRQoL, with many patients reporting problems in the pain/discomfort and anxiety/depression dimensions. The information on health utility scores and HRQoL of lung cancer patients treated with TCM could be useful for future supportive care, economic evaluations and decision-making in China.

Optimal PET-based radiomic signature construction based on the cross-combination method for predicting the survival of patients with diffuse large B-cell lymphoma.

PURPOSE: To develop and externally validate models incorporating a PET radiomics signature (R-signature) obtained by the cross-combination method for predicting the survival of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 383 patients with DLBCL from two medical centres between 2011 and 2019 were included. The cross-combination method was used on three types of PET radiomics features from the training cohort to generate 49 feature selection-classification candidates based on 7 different machine learning models. The R-signature was then built by selecting the optimal candidates based on their progression-free survival (PFS) and overall survival (OS). Cox regression analysis was used to develop the survival prediction models. The calibration, discrimination, and clinical utility of the models were assessed and externally validated. RESULTS: The R-signatures determined by 12 and 31 radiomics features were significantly associated with PFS and OS, respectively (P<0.05). The combined models that incorporated R-signatures, metabolic metrics, and clinical risk factors exhibited significant prognostic superiority over the clinical models, PET-based models, and the National Comprehensive Cancer Network International Prognostic Index in terms of both PFS (C-index: 0.801 vs. 0.732 vs. 0.785 vs. 0.720, respectively) and OS (C-index: 0.807 vs. 0.740 vs. 0.773 vs. 0.726, respectively). For external validation, the C-indices were 0.758 vs. 0.621 vs. 0.732 vs. 0.673 and 0.794 vs. 0.696 vs. 0.781 vs. 0.708 in the PFS and OS analyses, respectively. The calibration curves showed good consistency, and the decision curve analysis supported the clinical utility of the combined model. CONCLUSION: The R-signature could be used as a survival predictor for DLBCL, and its combination with clinical factors may allow for accurate risk stratification.

[Lingnan fire needling combined with 0.1% sodium hyaluronate eye drops in the treatment of xerophthalmia: a randomized controlled trial].

OBJECTIVE: To observe the effect of Lingnan fire needling combined with artificial tears in the treatment of xerophthalmia. METHODS: A total of 86 xerophthalmia patients were equally and randomly divided into treatment group and control group. The patients of both groups were received treatment with 0.1% sodium hyaluronate eye drops in their eyes 3 times a day, one drop in each eye. In addition, the patients of treatment group also treated by Lingnan fire needling on bilateral Shaoze (SI1), Neichengqi and beside lacrimal puncta once a week. The treatment was conducted for 4 consecutive weeks. Before and after 4 weeks of treatment, the clinical efficacy, visual acuity, intraocular pressure, ocular symptom score, OSDI score, fluorescence staining （FL） score, schemer I, tear menisci height, tear film break-up time (BUT) and eye redness index were recorded and evaluated. RESULTS: After the treatment, self-comparison showed that the symptom score, OSDI score, FL score and eye redness index were significantly decreased (P<0.05), and BUT was notably increased in both groups (P<0.05) in comparison with their own pre-treatment. The tear menisci height in the treatment group was higher than that before the treatment (P<0.05). Comparison between the two groups showed that the symptom score, OSDI score and eye redness index were obviously lower in the treatment group than in the control group (P<0.05), whereas the BUT and tear menisci height were evidently higher (P<0.05). The total effective rate of the treatment group was 84.88% (73/86), better than 76.74% (66/86) of the control group (P<0.05). CONCLUSION: Lingnan fire needling combined with 0.1% sodium hyaluronate eye drops is more effective than simple sodium hyaluronate eye drops for xerophthalmia patients, with significant curative effect and no adverse reactions.

The Effect of Shenyi Capsule on Non-Small-Cell Lung Cancer Combined with Chemotherapy from the Yin-Yang Perspective.

As an example of Shenyi capsule on non-small-cell lung cancer combined with chemotherapy, this review discusses the synergistic effect and mechanism of natural drugs in oncotherapy from the yin-yang perspective in ancient Chinese philosophy, so as to reflect the therapeutic principle of natural drugs for tumor more comprehensively. The major focuses of this review are on the philosophical thinking of yin-yang as a tool which can not only explain the effect of Shenyi capsule in NSCLC combined with chemotherapy but also explore the mechanism of Shenyi capsule at the cellular and molecular level. Learning from the "yin-yang" thinking of ancient Chinese philosophy will bring more enlightenment to the research and development of traditional Chinese drugs in the future.

Value of total lesion glycolysis and cell-of-origin subtypes for prognostic stratification of diffuse large B-cell lymphoma patients.

BACKGROUND: This study aimed to explore the added prognostic value of baseline metabolic volumetric parameters and cell of origin subtypes to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in nodal diffuse large B-cell lymphoma (DLBCL) patients. METHODS: A total of 184 consecutive de novo nodal DLBCL patients who underwent baseline positron emission tomography/computed tomography (PET/CT) were included in this study. Kaplan-Meier estimates were generated to evaluate the clinical, biological, and PET/CT parameters' prognostic value. The Cox proportional hazards model was performed to examine the potential independent predictors for progression-free survival (PFS) and overall survival (OS). RESULTS: With a median follow-up of 35 months, the 3-year PFS and OS were 65.2% and 73.0%, respectively. In univariate analysis, total lesion glycolysis (TLG), cell-of-origin subtypes, and NCCN-IPI were both PFS and OS predictors. High TLG (≥1,852), non-germinal center B (non-GCB), as well as high NCCN-IPI (≥4), were shown to be independently significantly associated with inferior PFS and OS after multivariate analysis. Based on the number of risk factors (high TLG, non-GCB, and high NCCN-IPI), a revised risk model was designed, and the participants were divided into four risk groups with very different outcomes, in which the PFS rates were 89.7%, 66.2%, 51.7%, and 26.7% (χ2=30.179, P<0.001), and OS rates were 93.1%, 73.8%, 56.7%, and 43.3%, respectively (χ2=23.649, P<0.001), respectively. Compared with the NCCN-IPI alone, the revised risk model showed a stronger ability to reveal further discrimination among subgroups, especially for participants with very unfavorable survival outcomes (PFS: χ2=9.963, P=0.002; OS: χ2=4.166, P=0.041, respectively). CONCLUSIONS: The TLG, cell-of-origin subtypes, and NCCN-IPI are independent prognostic survival factors in DLBCL patients. Moreover, the revised risk model composed of the number of risk factors (high TLG, non-GCB, and high NCCN-IPI) can stratify patients better than the NCCN-IPI, especially for patients at high risk, which suggests its potential integration into decision making for personalized medicine.

Laser Speckle Contrast Imaging for the Objective Assessment of Blood Perfusion in Keloids Treated With Dual-Wavelength Laser Therapy.

BACKGROUND: Most of the widely used methods for the assessment of keloid treatment are subjective grading scales based on the opinion of an individual clinician or patient. There is a growing need for objective methods to evaluate keloid treatment. OBJECTIVE: This study aimed to evaluate the value of laser speckle contrast imaging (LSCI) as an objective method for the assessment of dual-wavelength laser therapy for keloids. METHODS: This prospective study included 21 patients with 54 keloids. All patients were treated with a combined 585-nm pulsed dye laser and 1,064 nm neodymium-doped yttrium aluminum garnet dual-wavelength laser at 4 weeks to 6 weeks intervals. Keloids were assessed using the Vancouver Scar Scale (VSS) and LSCI. RESULTS: The total VSS score significantly decreased after 4 sessions of treatment (p < .05). Blood perfusion in keloids as measured by LSCI was significantly reduced after treatment (p < .05). The improvement of chest keloids in terms of the total VSS score and blood perfusion was significantly greater than that of scapular keloids (p < .05). There was a positive correlation between decreased perfusion and reduced total VSS score (R2 = 0.84). CONCLUSION: Blood perfusion in keloids significantly decreased after dual-wavelength laser therapy. Laser speckle contrast imaging is a promising objective method for assessing the improvement of keloids treated with laser therapy.

Will Baseline Total Lesion Glycolysis Play a Role in Improving the Prognostic Value of the NCCN-IPI in Primary Gastric Diffuse Large B-Cell Lymphoma Patients Treated With the R-CHOP Regimen?

PURPOSE: The aim was to explore whether baseline total lesion glycolysis (TLG) can improve the prognostic value of the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in primary gastric diffuse large B-cell lymphoma (PG-DLBCL) patients treated with an R-CHOP-like regimen. MATERIALS AND METHODS: Ninety-four PG-DLBCL patients who underwent baseline PET/CT between July 2010 and May 2019 were included in this retrospective study. FDG-avid lesions in each patient were segmented to calculate the SUVmax, total metabolic tumor volume (TMTV), and TLG. Progression-free survival (PFS) and overall survival (OS) were used as end points to evaluate prognosis. RESULTS: During the follow-up period of 5 to 108 months (35.3 ± 23.5 months), high TLG and a high NCCN-IPI were significantly associated with poor PFS and OS. Total lesion glycolysis and the NCCN-IPI were independent predictors of PFS and OS. Patients were stratified into 3 groups according to the combination of TLG and the NCCN-IPI for PFS (P < 0.001) and OS (P < 0.001): high-risk group (TLG > 1159.1 and NCCN-IPI 4-8) (PFS and OS, 57.7% and 61.5%, respectively, n = 42), intermediate-risk group (TLG > 1159.1 or NCCN-IPI 4-8) (PFS and OS, both 76.9%, n = 26), and low-risk group (TLG ≤ 1159.1 and NCCN-IPI 0-3) (PFS and OS, 97.6% and 100.0%, respectively, n = 26). CONCLUSIONS: Both TLG and the NCCN-IPI are independent predictors of PG-DLBCL patient survival. Moreover, the combination of TLG and the NCCN-IPI improved patient risk stratification and might help personalize therapeutic regimens.

Value of 18F-FDG PET/CT for prognostic stratification in patients with primary intestinal diffuse large B cell lymphoma treated with an R-CHOP-like regimen.

PURPOSE: The prognostic value of 18F-FDG PET/CT for primary intestinal diffuse large B-cell lymphoma (PI-DLBCL) patients has not been determined. This prompted us to explore the value of 18F-FDG PET/CT for prognostic stratification in patients with PI-DLBCL treated with an R-CHOP-like regimen. MATERIALS AND METHODS: Seventy-three PI-DLBCL patients who underwent baseline PET/CT between January 2010 and May 2019 were included in this retrospective study. Total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) were computed using the 41% SUVmax thresholding method. Progression-free survival (PFS) and overall survival (OS) were used as endpoints to evaluate prognosis. RESULTS: During the follow-up period of 3-117 months (29.0 ± 25.5 months), high TLG, non-germinal center B-cell-like (non-GCB) and high National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) were significantly associated with inferior PFS and OS. TLG, cell-of-origin and NCCN-IPI were independent predictors of PFS, and both TLG and NCCN-IPI were independent predictors of OS. The grading system was based on the number of risk factors (high TLG, non-GCB, high NCCN-IPI) and patients were divided into 4 risk groups (PFS: χ2 = 33.858, P < 0.001; OS: χ2 = 29.435, P < 0.001): low-risk group (none of the 3 risk factors, 18 patients); low-intermediate risk group (1 risk factor, 24 patients); high-intermediate risk group (2 risk factors, 16 patients); and high-risk group (all 3 risk factors, 15 patients). CONCLUSIONS: High TLG, non-GCB and high NCCN-IPI can identify a subset of PI-DLBCL patients with inferior survival outcomes. Furthermore, the grading system can identify PI-DLBCL patient groups with markedly different prognoses, which might contribute to the adjustment of the therapeutic regime.

[Effects of vitamin D supplementation in early pregnancy on high-risk groups of gestational diabetes mellitus].

OBJECTIVE: To investigate the effect of vitamin D supplementation(VD) in early pregnancy on the serum 25-hydroxyvitamin D(25-OH-D) level and the risk of gestational diabetes mellitus(GDM). METHODS: From October to December 2017, a total of 101 pregnant women with high risk factors for GDM were enrolled in the first pregnancy consultation at the nutrition clinic of Haidian Maternal and Child Health Hospital, and were randomly divided into intervention group and control group. The intervention group was supplemented with 700 U VD and 100 mg of calcium at the beginning of pregnancy, and the control group was supplemented with 100 U VD and 100 mg of calcium at the same time, and the intervention time was until delivery. RESULTS: After intervention, the mean serum 25-OH-D level in the intervention group was(92. 08±29. 69) nmol/L, and that in the control group was(69. 99±25. 10) nmol/L. The serum levels of 25-OH-D in the pregnant women, gestational age and cord blood were higher than those in the control group(P<0. 05). The incidence of GDM in the intervention group was 18. 37%, and the incidence rate in the control group was 28. 85%(P>0. 05). Compared with the control group, the OR value of the risk of GDM in the intervention group was 0. 56(95% CI 0. 22-1. 42)( P<0. 05). CONCLUSION: The supplementation of VD in early pregnancy can significantly improve the VD nutrition level of pregnant women, but does not significantly reduce the incidence of GDM.

Comparative Effectiveness of Pemetrexed-platinum Doublet Chemotherapy With or Without Bevacizumab as First-line Therapy for Treatment-naive Patients With Advanced Nonsquamous Non-small-cell Lung Cancer in China.

PURPOSE: Bevacizumab plus platinum-based doublet chemotherapy is recommended by the National Comprehensive Cancer Network as a category 1 regimen and is widely used in patients with advanced nonsquamous non-small-cell lung cancer (NS-NSCLC). In China, a common first-line chemotherapy for NS-NSCLC is the pemetrexed-platinum doublet regimen (Pem-Pt). However, limited evaluation exists to show the effectiveness of the Pem-Pt + bevacizumab (Bev) regimen in advanced NS-NSCLC. This study describes the treatment patterns, effectiveness, and safety profile of Pem-Pt + Bev in patients with NS-NSCLC in China in clinical practice. METHODS: Data from eligible patients with advanced NS-NSCLC who received Pem-Pt with (136 patients) or without (97 patients) bevacizumab from January 2012 to March 2017 were retrospectively evaluated. The effectiveness outcomes included the assessment of progression-free survival (PFS) and objective response rate (ORR) in the overall population, the percentage of patients with pleural effusion or brain metastasis, as well as the percentage of patients receiving maintenance therapy. Moreover, the intracranial remission rate in patients with brain metastasis was estimated. Finally, the adverse events with the 2 treatments were addressed. FINDINGS: Compared with the Pem-Pt regimen, the Pem-Pt + Bev regimen was associated with a significantly longer median PFS and a higher ORR in the overall population (P = 0.0002). An improvement in ORR was observed in Pem-Pt + Bev-treated patients with brain metastasis (P = 0.0045). Moreover, patients receiving Pem-Pt + Bev and maintenance therapy not only showed a longer median PFS than that in those whose treatment was interrupted after induction but also a longer median PFS than that in patients who received Pem-Pt and maintenance therapy. The safety profile was acceptable in all groups, with no observations of hypertension, proteinuria, severe bleeding (1 case of grade I epistaxis was reported with Pem-Pt + Bev), or any unexpected findings reported. IMPLICATIONS: These results from clinical practice further support the concept that pemetrexed-platinum doublet plus bevacizumab could be an effective and tolerable regimen in patients with advanced NS-NSCLC in China.

[Concentration of red blood cell folate and the analysis of folic acid supplement optimum time and dose in first trimester].

OBJECTIVE: To have a knowledge of prevalent red blood cell folate concentration in Beijing and analyzes optimum time and dose of folic acid supplement. To provide the basis data for making public health policy and clinical consultation. METHODS: This study included 3458 pregnant women who visited nutrition outpatient of the Haidian Maternal and Child Health Hospital in Beijing in first trimester. Their last menstrual period is between 1st Feb 2014 and 31 st Jan 2016. Using the method of cross sectional study to collect their demographic information, folic acid supplementation, clinical information and venous blood samples. Competitive binding receptor assay was used for detecting the red blood cell folate concentration. RESULTS: The mean of red blood cell folate concentration was( 806. 5 ± 273. 7) ng/mL. The red blood cell folate concentration differences between age groups were significant( P < 0. 001). Women with graduate and above had higher red blood cell folate concentration than others( P = 0. 030). Women whose family income > 10000 had higher red blood cell folate concentration than other groups( P < 0. 001). Red blood cell folate concentration in summer and autumn higherthan other season( P < 0. 001). Red blood cell folate concentration level increased with folic acid supplementation dose and time. 84. 3% the pregnant women reached 1180nmol/L( 521 ng/mL) and 90. 0% could reach the reference if used 400 µg folic acid supplemented for 16 weeks or ≥600 µg more than 8 weeks. CONCLUSION: Age, education level and family income are associated with red blood cell folate concentration. Depending on red blood cell folate concentration to advise the time and dose of folic acid supplementation.

Early initiation of fluorouracil-based adjuvant chemotherapy improves survival in patients with resectable gastric cancer.

PURPOSE: Several clinical trials have suggested that adjuvant chemotherapy improves the survival of patients with resected gastric cancer, but the optimal time at which to initiate post-operative adjuvant chemotherapy has not been studied. This study investigated the association between time to adjuvant chemotherapy and survival in gastric cancer. METHODS: We retrospectively identified 266 patients with stage IB-IIIC gastric cancer who received fluorouracil-based adjuvant chemotherapy after radical gastrectomy. Overall survival (OS) was compared between patients grouped according to time from surgery to adjuvant chemotherapy (<45 and ≥45 days). The Cox proportional hazards model was used to analyze the effects of time to initiation of chemotherapy and other clinical covariates on survival. RESULTS: Of 266 patients, 141 (53%) started adjuvant chemotherapy within 45 days after surgery and 125 (47%) started adjuvant chemotherapy more than 45 days after surgery. The 3-year OS rates were 81.2 and 65.8% for patients starting chemotherapy within 45 days and after 45 days, respectively (p=0.006). Multivariate analysis identified early initiation of adjuvant chemotherapy, completion of the planned chemotherapy, and early-stage disease as favorable prognostic factors in terms of OS (p<0.05). Subgroup analysis suggested that starting chemotherapy within 45 days after surgery was associated with significant OS benefit compared with initiation of chemotherapy after 45 days from surgery in most subgroups. CONCLUSIONS: This retrospective analysis suggests that delaying adjuvant chemotherapy for longer than 45 days after surgery may be associated with poorer survival in patients with resected gastric cancer.

YY1 suppresses FEN1 over-expression and drug resistance in breast cancer.

BACKGROUND: Drug resistance is a major challenge in cancer therapeutics. Abundant evidence indicates that DNA repair systems are enhanced after repetitive chemotherapeutic treatments, rendering cancers cells drug-resistant. Flap endonuclease 1 (FEN1) plays critical roles in DNA replication and repair and in counteracting replication stress, which is a key mechanism for many chemotherapeutic drugs to kill cancer cells. FEN1 was previously shown to be upregulated in response to DNA damaging agents. However, it is unclear about the transcription factors that regulate FEN1 expression in human cancer. More importantly, it is unknown whether up-regulation of FEN1 has an adverse impact on the prognosis of chemotherapeutic treatments of human cancers. METHODS: To reveal regulation mechanism of FEN1 expression, we search and identify FEN1 transcription factors or repressors and investigate their function on FEN1 expression by using a combination of biochemical, molecular, and cellular approaches. Furthermore, to gain insights into the impact of FEN1 levels on the response of human cancer to therapeutic treatments, we determine FEN1 levels in human breast cancer specimens and correlate them to the response to treatments and the survivorship of corresponding breast cancer patients. RESULTS: We observe that FEN1 is significantly up-regulated upon treatment of chemotherapeutic drugs such as mitomycin C (MMC) and Taxol in breast cancer cells. We identify that the transcription factor/repressor YY1 binds to the FEN1 promoter and suppresses the expression of FEN1 gene. In response to the drug treatments, YY1 is dissociated from the FEN1 promoter region leading over-expression of FEN1. Overexpression of YY1 in the cells results in down-regulation of FEN1 and sensitization of the cancer cells to MMC or taxol. Furthermore, we observe that the level of FEN1 is inversely correlated with cancer drug and radiation resistance and with survivorship in breast cancer patients. CONCLUSION: Altogether, our current data indicate that YY1 is a transcription repressor of FEN1 regulating FEN1 levels in response to DNA damaging agents. FEN1 is up-regulated in human breast cancer and its levels inversely correlated with cancer drug and radiation resistance and with survivorship in breast cancer patients.

Protective effects of water fraction of Fructus Ligustri Lucidi extract against hypercalciuria and trabecular bone deterioration in experimentally type 1 diabetic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait, is a commonly prescribed herb to nourish the endocrine and renal systems and to strengthen the bones in Traditional Chinese Medicine. This study was aimed to determine the effects of water fraction of FLL ethanol extract (WF-EE) on urinary calcium excretion and trabecular bone properties in type 1 diabetic mice. MATERIALS AND METHODS: The DBA/2J mice with type 1 diabetes induced by streptozotocin injection were orally administered with WF-EE. After 6 weeks of treatment, the level of biomarkers, including serum calcium, parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF-23) and urine calcium, was measured. Micro-CT was performed to detect trabecular bone properties of the proximal tibial metaphysis. The expression of active calcium transporting proteins in kidney and duodenum was determined by RT-PCR, immunoblotting and immunostaining. RESULTS: Type 1 diabetes induced hypercalciuria and trabecular bone deterioration. The WF-EE could significantly inhibit hypercalciuria and ameliorate the micro-structure of trabecular bone as well as increase serum PTH and FGF-23 levels in type 1 diabetic mice. The gene expressions of active calcium transporting proteins in duodenum were up-regulated, and the gene and protein expressions of calcium-sensing receptor (CaSR) in kidney were dramatically down-regulated in diabetic mice in response to the treatment with WF-EE. CONCLUSIONS: The present study demonstrated the protective effects of the water fraction of Fructus Ligustri Lucidi ethanol extract against hypercalciuria and trabecular bone deterioration in experimentally type 1 diabetic mice, and the underlying mechanism may be attributed to its regulations on duodenal calcium transporting proteins and renal CaSR.

Optimal duration of fluorouracil-based adjuvant chemotherapy for patients with resectable gastric cancer.

BACKGROUND: Although several clinical trials have suggested that postoperative adjuvant chemotherapy can improve survival of patients with gastric cancer, the optimal treatment duration has not been studied. This retrospective analysis evaluated the outcomes of patients with gastric cancer treated with six cycles of fluorouracil-based treatment compared with a cohort treated with four or eight cycles. METHODS: We retrospectively identified 237 patients with stage IB-IIIC gastric cancer who received four, six, or eight cycles of fluorouracil-based adjuvant chemotherapy administered every 3 weeks after radical gastrectomy. The endpoint was overall survival (OS). Factors associated with prognosis were also analyzed. RESULTS: The estimated 3-year OS rates for the four-, six-, and eight-cycle cohorts were 54.4%, 76.1%, and 68.9%, respectively; and the estimated 5-year OS rates were 41.2%, 74.0%, and 65.8%, respectively. Patients who received six cycles were more likely to have a better OS than those who received four cycles (P = 0.002). Eight cycles failed to show an additional survival benefit (P = 0.454). In the multivariate analysis, the number of chemotherapy cycles was associated with OS independent of clinical covariates (P<0.05). Subgroup analysis suggested that among patients in all age groups examined, male patients, and subgroups of fluorouracil plus oxaliplatin combined chemotherapy, stage III, poor differentiation, and gastrectomy with D2 lymphadenectomy, six cycles of adjuvant chemotherapy were associated with a statistically significant benefit of OS compared with four cycles (P<0.05). CONCLUSIONS: Six cycles of adjuvant chemotherapy might lead to a favorable outcome for patients with gastric cancer, and two further cycles could not provide an additional clinical benefit.

Cost-effectiveness analysis of neonatal hearing screening program in China: should universal screening be prioritized?

BACKGROUND: Neonatal hearing screening (NHS) has been routinely offered as a vital component of early childhood care in developed countries, whereas such a screening program is still at the pilot or preliminary stage as regards its nationwide implementation in developing countries. To provide significant evidence for health policy making in China, this study aims to determine the cost-effectiveness of NHS program implementation in case of eight provinces of China. METHODS: A cost-effectiveness model was conducted and all neonates annually born from 2007 to 2009 in eight provinces of China were simulated in this model. The model parameters were estimated from the established databases in the general hospitals or maternal and child health hospitals of these eight provinces, supplemented from the published literature. The model estimated changes in program implementation costs, disability-adjusted life years (DALYs), average cost-effectiveness ratio (ACER), and incremental cost-effectiveness ratio (ICER) for universal screening compared to targeted screening in eight provinces. RESULTS AND DISCUSSION: A multivariate sensitivity analysis was performed to determine uncertainty in health effect estimates and cost-effectiveness ratios using a probabilistic modeling technique. Targeted strategy trended to be cost-effective in Guangxi, Jiangxi, Henan, Guangdong, Zhejiang, Hebei, Shandong, and Beijing from the level of 9%, 9%, 8%, 4%, 3%, 7%, 5%, and 2%, respectively; while universal strategy trended to be cost-effective in those provinces from the level of 70%, 70%, 48%, 10%, 8%, 28%, 15%, 4%, respectively. This study showed although there was a huge disparity in the implementation of the NHS program in the surveyed provinces, both universal strategy and targeted strategy showed cost-effectiveness in those relatively developed provinces, while neither of the screening strategy showed cost-effectiveness in those relatively developing provinces. This study also showed that both strategies especially universal strategy achieve a good economic effect in the long term costs. CONCLUSIONS: Universal screening might be considered as the prioritized implementation goal especially in those relatively developed provinces of China as it provides the best health and economic effects, while targeted screening might be temporarily more realistic than universal screening in those relatively developing provinces of China.