Impacts of COVID-19 pandemic on the collection and use of blood and blood components in Taiwan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the supply and transfusion of blood components. This study aims to evaluate changes in blood collection and transfusions during the period following the nationwide Level 3 alert (May-July 2021). METHODS: We retrieved usage data for red blood cells (RBC) from the Taiwan National Health Insurance (NHI) database 2019-2021. RESULTS: During the Level 3 alert period, approximately 85% of COVID-19 cases (11,455/13,624) were in Taipei. In Taipei, blood collection declined by 26.34% and RBC transfusions decreased by 17.14% compared to pre-pandemic levels. RBC usage decreased across all service types, with a significant decrease observed in hematology/oncology by 15.62% (-483 patients, -2,425 units). In non-Taipei regions, blood collection declined by 12.54%, rebounding around one month earlier than in Taipei. The decline in RBC transfusions occurred one month later than in Taipei, with a much lower magnitude (4.57%). Strain on the blood supply occurred in May and June in both Taipei and non-Taipei regions. Among 7,532 hospitalized COVID-19 patients, approximately 6.9% patients required a total of 1,873 RBC transfusions. The rapid increase in COVID-19 inpatients did not significantly increase the burden of blood demands. SUMMARY: During the Level 3 alert, the most significant decline in both RBC collection and transfusions was observed in Taipei. In non-Taipei regions, the decrease in RBC use was only marginal. Notably, there was a significant decrease in RBC use in hematology/oncology in Taipei. This study supports transfusion specialists in seeking efficient ways to address similar future challenges.

The Reduction of PSMB4 in T24 and J82 Bladder Cancer Cells Inhibits the Angiogenesis and Migration of Endothelial Cells.

Bladder cancer (BC) is a malignant tumor of the urinary system with high mortality and recurrence rates. Proteasome subunit type 4 (PSMB4) is highly expressed and has been identified as having oncogenic properties in a variety of cancer types. This study aimed to explore the effect of PSMB4 knockdown on the survival, migration, and angiogenesis of human bladder cancer cells with different degrees of malignancy. We analyzed the effects of PSMB4 knockdown in bladder cancer cells and endothelial cells in the tumor microenvironment. PSMB4 was highly expressed in patients with low- and high-grade urothelial carcinoma. Inhibition of PSMB4 reduced protein expression of focal adhesion kinase (FAK) and myosin light chain (MLC), leading to reduced migration. Furthermore, the suppression of PSMB4 decreased the levels of vascular endothelial factor B (VEGF-B), resulting in lower angiogenic abilities in human bladder cancer cells. PSMB4 inhibition affected the migratory ability of HUVECs and reduced VEGFR2 expression, consequently downregulating angiogenesis. In the metastatic animal model, PSMB4 knockdown reduced the relative volumes of lung tumors. Our findings suggest the role of PSMB4 as a potential target for therapeutic strategies against human bladder cancer.

Dengue Virus Ribonucleic Acid Detection Rates in Blood Donors Correlate With Local Infection Incidences During a Dengue Outbreak in Taiwan.

BACKGROUND: Evidence for mitigation of transfusion-transmitted dengue informed by surveillance data is lacking. In this study, we evaluated the risk of positive dengue viral (DENV) ribonucleic acid (RNA) from blood transfusions during a large outbreak in Taiwan. METHODS: Serum collected from blood donors living in districts experiencing the dengue epidemic were tested for DENV RNA using a qualitative transcription-mediated nucleic acid amplification assay (TMA). The TMA-reactive specimens were further tested for immunoglobulin (Ig)M and IgG antibodies, nonstructural protein 1 (NS1) antigen, and viral RNA by reverse-transcription polymerase chain reaction. We estimated DENV RNA prevalence and the number of DENV infections among blood donors. RESULTS: A total of 4976 specimens were tested for DENV RNA, and 21 were TMA-reactive. The detection rate was 0.84 (95% confidence interval [CI], 0.15-4.73), 3.36 (95% CI, 1.31-8.60), and 6.19 (95% CI, 3.14-12.17) per 1000 donors in districts where the weekly dengue incidence was 5-50, 50-200, and 200 or more per 100 000 residents, respectively. Alanine aminotransferase screening only detected 4.4% of TMA-reactive donations. A total of 143 transfusion-transmitted DENV infections probably occurred during this outbreak, accounting for 9.2 in 10 000 dengue infections. CONCLUSIONS: Approximately 0.5%-1% of blood donations were DENV RNA positive in epidemic districts. The correlation of DENV RNA rates with dengue incidence may inform the design of effective control measures.

[Cost-effectiveness analysis of Chaiyin Granules in treatment of influenza].

This study aimed to evaluate the cost-effectiveness of Chaiyin Granules compared with Oseltamivir Phosphate Capsules in the treatment of influenza(exogenous wind-heat syndrome). Based on a randomized, double-blind, positive drug parallel control clinical trial, this study evaluated the pharmacoeconomics of Chaiyin Granules with cost-effectiveness analysis method. A total of 116 patients with influenza from eight hospitals(grade Ⅱ level A above) in 6 cities were selected in this study, including 78 cases in the experimental group with Chaiyin Granules and Oseltamivir Phosphate Capsules placebo, and 38 cases in the control group with Oseltamivir Phosphate Capsules and Chaiyin Granules placebo. The total cost of this study included direct medical cost, direct non-medical cost, and indirect cost. The remission time of clinical symptoms, cure time/cure rate, antipyretic onset time/complete antipyretic time, viral nucleic acid negative rate, and traditional Chinese medicine(TCM) syndrome curative effect were selected as the effect indicators for cost-effectiveness analysis. Four-quadrant diagram was used to estimate the incremental cost-effectiveness ratio. The results showed that Chaiyin Granules were not inferior to Oseltamivir Phosphate Capsules in the remission time of clinical symptoms of influenza(3.1 d vs 2.9 d, P=0.360, non-inferiority margin was 0.5 d). Compared with Oseltamivir Phosphate Capsules, Chaiyin Granules would delay the remission time of clinic symptoms of influenza for 1 d, but could save 213.9 yuan. 1 d delay in cure time could save 149.3 yuan; 1% reduction in the cure rate could save 8.2 yuan; 1 d delay in antipyretic onset time could save 295.4 yuan; 1 d delay in complete antipyretic time could save 114.3 yuan; 1% reduction in the 5-day cure rate of TCM syndrome could save 19.2 yuan. Different from other indicators, there was no statistically significant difference between two groups in the effect of negative conversion rate of viral nucleic acid, but the cost was lower and the effect was superior, and the pharmacoeconomics was not different from that of Oseltamivir Phosphate Capsules in the field of influenza treatment.

The efficacy of ethnic specific blood groups genotyping for routine donor investigation and rare donor identification in Taiwan.

BACKGROUND: Large-scale single nucleotide variation (SNV)-based blood group genotyping assays have been made available for over a decade. Due to differences in ethnic groups, there is much diversity in clinically important blood group antigens and genetic variants. Here, we developed a robust matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)-based blood group genotyping method on MassARRAY system. STUDY DESIGN AND METHODS: A total of 1428 donors were enrolled into three groups: (a) reagent red cell donors; (b) rare donor or common antigen-negative donors; and (c) group O, R1 R1 /R2 R2 donors. Forty-two SNVs were designed for determining nine blood groups, with X/Y chromosome in two multiplex reactions, on MassARRAY 96-well format system. Further targeted sequence analyses were performed by Sanger sequencing. RESULTS: WHO reference reagent (NIBSC code: 11/214) was tested for concordance with the provided genotype results. Among the donors, concordance rate was over 99%. Alleles of important phenotypes such as Mi(a+), Di(a+), and Asian-type DEL and alleles of rare blood groups such as Fy(a-), Jk(a-b-) and s- were screened. Three types of discrepancies were found. Serologically, the 'N' antigen was expressed on genetically MM with GYP*Mur red blood cells and caused genuine discrepancies (9.5%). Genetically, allele dropout (ADO) was caused by rare SNV in the primer for Ss genotype (2.1%) and partial insertion of RHD genes (0.9%) led to difficulties in predicting phenotypes. CONCLUSION: Hemo panel module and MassARRAY System in 96-well format showed good performance in terms of large-scale blood group genotyping and phenotype predictions. Implementation of this method is effective for routine blood group genotype screening of donors.

The continued decline of plasma transfusions in Taiwan: An 11-year population-based study.

BACKGROUND AND OBJECTIVES: In Taiwan, plasma use per capita ranks among the highest in the world. We aimed to describe the trends in usage after the introduction of new hospital accreditation standards that evaluate compliance with institutional plasma transfusion guidelines. MATERIALS AND METHODS: We identified hospitalizations receiving plasma between 2007 and 2017 from the national health insurance database. We estimated plasma transfusions per thousand capita. The risk ratio of transfusion rates among hospitalizations in 2017 compared to 2007 was estimated using logistic regression. RESULTS: The total number of plasma transfusions declined from 964,408 in 2007 to 659,828 in 2017, yielding a rate of 28.00 per thousand capita. The proportion of hospitalizations receiving plasma declined by 38%, from 3.89% (95% confidence interval: 3.86%-3.91%) to 2.62% (2.61%-2.64%). Gastroenterology (16.4%) and general surgery (15.3%) accounted for the largest proportions of plasma usage. Within these two services, liver diseases were the top diagnoses needing plasma use. For hospitalized patients with liver diseases, approximately 40% of plasma units were administered to patients with neither noticeable bleeding nor red blood cells transfusions. Among these patients, almost 50% received plasma with an international normalized ratio trigger of less than 1.50. The use of potential alternative therapies or anticoagulants remained quite low during this period. CONCLUSION: Plasma utilization rates during hospitalizations continuously declined over 11 years. However, inappropriate plasma use remained high, while the use of alternative therapies remained low in services such as gastroenterology. To improve the appropriateness of plasma transfusions, patient blood management should be implemented in the near future.

Determining programmed cell death ligand 1 expression in circulating tumor cells of patients with clear cell renal cell carcinoma and its correlation with response to programmed cell death protein 1 inhibitors.

OBJECTIVE: There is a great interest in determining whether the expression of the programmed cell death ligand 1 is correlated with the efficacy of immune checkpoint inhibitors in patients with clear cell renal cell carcinoma; however, primary tumor biopsies can only provide limited information. Therefore, we explored the expression of programmed cell death ligand 1 on circulating tumor cells, which is a potential predictor of therapeutic response. METHODS: Circulating tumor cells were isolated from 20 clear cell renal cell carcinoma patients based on cell surface markers targeting clear cell renal cell carcinoma using IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. Programmed cell death ligand 1 expression status and clinical correlations were also analyzed. RESULTS: Before treatment with programmed cell death protein 1 inhibitors, circulating tumor cells were detected in all patients, ranging from 1 to 22 (median 7), with 75% (15/20) of the patients having programmed cell death ligand 1 + circulating tumor cells. Circulating tumor cell programmed cell death ligand 1 expression did not correlate with the immunohistochemical staining of programmed cell death ligand 1 in primary tumors. During treatment with programmed cell death protein 1 inhibitors, the disease control rate was much higher in the patients harboring programmed cell death ligand 1 + circulating tumor cells (73%, 11/15) than others (20%, 1/5). We also found that changes in total circulating tumor cell numbers and programmed cell death ligand 1 + circulating tumor cell counts correlated well with the disease outcome. CONCLUSION: We showed that the presence of programmed cell death ligand 1 + circulating tumor cells before programmed cell death protein 1 inhibition treatment could be a prognosis predictive factor and that the dynamic changes in circulating tumor cell numbers may be used to monitor the therapeutic response. Our study confirms the possibility of programmed cell death ligand 1 + circulating tumor cell detection in clear cell renal cell carcinoma patients' blood samples, which can potentially be used as an individualized immunotherapy molecular biomarker for real-time exploration.

An imbalance in blood collection and demand is anticipated to occur in the near future in Taiwan.

Due to excessive clinical blood usage and a rapidly aging population, an impending blood shortage in Taiwan is inevitable. This study aimed to determine the potential blood deficit in Taiwan in 2030. The numbers of units of whole blood (WB) donated and red blood cells (RBC) transfused will increase from 1,182,973 to 1,115,803 in 2018 to 1,230,500 and 1,250,760 in 2030, respectively. Considering the gap between donation and transfusion, we estimate a deficit of 97,633 units of WB in 2030. Blood collection will increasingly rely on donors over the age of 40. Moreover, we observed a large decline in units of WB donated among people less than 25 years old. A growing demand for RBC is attributed to the aging population and limited decreases in age-specific units of RBC transfused per capita. Scrutinizing and forecasting changes in blood collection and transfusion are necessary for generating strategies to mitigate blood shortages.

Enhancement of Farnesoid X Receptor Inhibits Migration, Adhesion and Angiogenesis through Proteasome Degradation and VEGF Reduction in Bladder Cancers.

(1) Background: Bladder cancer is a malignant tumor mainly caused by exposure to environmental chemicals, with a high recurrence rate. NR1H4, also known as Farnesoid X Receptor (FXR), acts as a nuclear receptor that can be activated by binding with bile acids, and FXR is highly correlated with the progression of cancers. The aim of this study was to verify the role of FXR in bladder cancer cells. (2) Methods: A FXR overexpressed system was established to investigate the effect of cell viability, migration, adhesion, and angiogenesis in low-grade TSGH8301 and high-grade T24 cells. (3) Results: After FXR overexpression, the ability of migration, adhesion, invasion and angiogenesis of bladder cancer cells declined significantly. Focal adhesive complex, MMP2, MMP9, and angiogenic-related proteins were decreased, while FXR was overexpressed in bladder cancer cells. Moreover, FXR overexpression reduced vascular endothelial growth factor mRNA and protein expression and secretion in bladder cancer cells. After treatment with the proteosome inhibitor MG132, the migration, adhesion and angiogenesis caused by FXR overexpression were all reversed in bladder cancer cells. (4) Conclusions: These results may provide evidence on the role of FXR in bladder cancer, and thus may improve the therapeutic efficacy of urothelial carcinoma in the future.

DNA Hypomethylation Is Associated with the Overexpression of INHBA in Upper Tract Urothelial Carcinoma.

Urothelial carcinoma includes upper urinary tract cancer (UTUC) and bladder cancer. Although nephroureterectomy is the standard treatment for UTUC, the recurrence rate is approximately half and the tumor is associated with poor prognoses. Metastases are the most devastating and lethal clinical situation in urothelial carcinoma. Despite its clinical importance, few potential diagnostic biomarkers are suitable for early UC detection. We compared high-stage/high-grade urothelial carcinoma tissues to adjacent normal urothelial tissues using methyl-CpG binding domain protein capture for genome-wide DNA methylation analysis. Based on our findings, inhibin ßA (INHBA) might be associated with carcinogenesis and metastasis. Further, clinical UC specimens had significant INHBA hypomethylation based on pyrosequencing. INHBA was detected by real-time PCR and immunohistochemistry staining, and was found to be highly expressed in clinical tissues and cell lines of urothelial carcinoma. Further, INHBA depletion was found to significantly reduce BFTC-909 cell growth and migration by INHBA-specific small interfering RNA. Interestingly, a positive correlation was found between SMAD binding and extracellular structure organization with INHBA using gene set enrichment analysis and gene ontology analysis. Together, these results are the first evidence of INHBA promoter hypomethylation and INHBA overexpression in UTUC. INHBA may affect urothelial carcinoma migration by reorganizing the extracellular matrix through the SMAD pathway.

Fatty Acid Binding Protein 6 Inhibition Decreases Cell Cycle Progression, Migration and Autophagy in Bladder Cancers.

Bladder cancer (BC) has a high recurrence rate worldwide. The aim of this study was to evaluate the role of fatty acid binding protein 6 (FABP6) in proliferation and migration in human bladder cancer cells. Cell growth was confirmed by MTT and colony formation assay. Western blotting was used to explore protein expressions. Wound healing and Transwell assays were performed to evaluate the migration ability. A xenograft animal model with subcutaneous implantation of BC cells was generated to confirm the tumor progression. Knockdown of FABP6 reduced cell growth in low-grade TSGH-8301 and high-grade T24 cells. Cell cycle blockade was observed with the decrease of CDK2, CDK4, and Ki67 levels in FABP6-knockdown BC cells. Interestingly, knockdown of FBAP6 led to downregulation of autophagic markers and activation of AKT-mTOR signaling. The application of PI3K/AKT inhibitor decreased cell viability mediated by FABP6-knockdown additionally. Moreover, FABP6-knockdown reduced peroxisome proliferator-activated receptor γ and retinoid X receptor α levels but increased p-p65 expression. Knockdown of FABP6 also inhibited BC cell motility with focal adhesive complex reduction. Finally, shFABP6 combined with cisplatin suppressed tumor growth in vivo. These results provide evidence that FABP6 may be a potential target in BC cells progression.

Association between socioeconomic status and severity of oral epithelial dysplasia using a Taiwanese Nationwide Oral Mucosal Screening Program: a retrospective analysis.

BACKGROUND: The study aimed to investigate the association between socioeconomic status and severity of oral epithelial dysplasia (OED) using current data from the Taiwanese Nationwide Oral Mucosal Screening Program (TNOMSP). METHODS: This retrospective analysis was conducted in the Department of Oral and Maxillofacial Surgery at a general hospital in Taipei, Taiwan. A total of 134 participants were analysed from a previous study database of 150 patients. The inclusion criteria included age > 20 years and a history of either tobacco or betel nut use. Background information, including para-habits such as betel and tobacco use, was analysed using the Pearson chi-square (χ2) test; furthermore, the correlation of background information with OED severity was investigated using logistic regression (mild or moderate/severe). RESULTS: High school education level (P < 0.001), poor self-awareness (P = 0.002), current betel use (P < 0.001), and tobacco use (P = 0.003) were highly correlated with moderate- and severe OED (P < 0.05). The odds ratio (OR) of education status above senior high school was 0.03 (95% confidence interval [CI] 0.01-0.15, P < 0.001), while that of junior high school was 1. Current betel chewing (OR 6.57 [95% CI 1.17-37.0], P = 0.033) was significantly associated with OED severity compared with never or ex-use of betel. CONCLUSIONS: We found a strong correlation between the severity of OED and current betel use and low education status. The current study revealed that the socioeconomic status, poor self-awareness, and para-habit history of the patients with OED should be evaluated to identify high-risk individuals using TNOMSP.

Demethoxycurcumin induces apoptosis in HER2 overexpressing bladder cancer cells through degradation of HER2 and inhibiting the PI3K/Akt pathway.

Bladder cancer is the most common malignancy of the urinary tract and arising from the epithelial lining of the urinary bladder. Resistance to cytotoxic therapies is associated with overexpression of oncogenic proteins; including HER2, and Akt in chemotherapy resistance of bladder cancer. Various studies demonstrated that curcuminoids, the most important active phenolic compounds of turmeric (Curcuma longa), have anti-tumor activities in a wide range of human malignant cell lines. The aim of this study is to evaluate whether curcuminoids (curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin) could repress the expression of HER2 in HER2-overexpressing bladder cancer cells. Among the test compounds, DMC significantly suppressed the expression of HER2, and preferentially inhibited cell proliferation and induced apoptosis in HER2-overexpressing bladder cancer cells. DMC decreases HER2 level through inhibiting the interaction of HER2 and Hsp90. Our study also indicated that DMC showed additive activity in combination with chemotherapeutic agents, including paclitaxel and cisplatin. These findings show that DMC should be developed further as a new antitumor drug candidate for treatment of HER2-overexpressing bladder cancer.

Inflammatory Regulation by TNF-α-Activated Adipose-Derived Stem Cells in the Human Bladder Cancer Microenvironment.

Mesenchymal stem cells (MSCs), such as adipose-derived stem cells (ADSCs), have the most impressive ability to reduce inflammation through paracrine growth factors and cytokines that participate in inflammation. Tumor necrosis factor (TNF)-α bioactivity is a prerequisite in several inflammatory and autoimmune disease models. This study investigated the effects of TNF-α stimulate on ADSCs in the tumor microenvironment. The RNAseq analysis and cytokines assay demonstrated that TNF-α stimulated ADSCs proliferation and pro-inflammatory genes that correlated to leukocytes differentiation were upregulated. We found that upregulation of TLR2 or PTGS2 toward to IRF7 gene-associated with immunomodulatory and antitumor pathway under TNF-α treatment. In TNF-α-treated ADSCs cultured with the bladder cancer (BC) cell medium, the results showed that apoptosis ratio and OCT-4 and TLR2 genes which maintained the self-renewal ability of stem cells were decreased. Furthermore, the cell survival regulation genes including TRAF1, NF-kB, and IRF7 were upregulated in TNF-α-treated ADSCs. Additionally, these genes have not been upregulated in BC cell medium. A parallel study showed that tumor progressing genes were downregulated in TNF-α-treated ADSCs. Hence, the study suggests that TNF-α enhances the immunomodulatory potential of ADSCs during tumorigenesis and provides insight into highly efficacious MSC-based therapeutic options for BC.

Investigation of transfusion associated hepatitis C virus infection in Taiwan, 2015-2018.

Continuous strengthening of the safety of blood products to reduce the risk of transfusion-transmitted HCV in recipients is an important issue of Taiwanese government concern. Since 2013, highly sensitivity serology and NAT assays were simultaneously used for blood donation screening to shorten the window period of HIV, HBV and HCV infections. 15 cases of suspected transfusion-transmitted HCV infection were analyzed in 2015-2018. No HCV nucleic acid was detected among a total 91 bags of donated blood. Eleven cases among the 15 suspected recipients were positive for HCV nucleic acid, and 9 recipients had genotype results. Of these 9 recipients, five for genotype 1b (5/9, 55.6%), three for genotype 2a (3/9, 33.3%) and one for genotype 2b (1/9, 11.1%). We will continuously monitor the blood safety of recipients. There have been no confirmed cases of acute hepatitis C (AHC) infection due to transfusions of HCV contaminated blood product in 2015-2018 in Taiwan.

Activities of Ca2+-related ion channels during the formation of kidney stones in an infection-induced urolithiasis rat model.

Bacterial infection has long been recognized to contribute to struvite urinary stone deposition; however, its contribution to the development of chronic kidney stones has not been extensively investigated. In the present study, we hypothesized another possible method of bacteria contributing to the formation of calcium oxalate (CaOx) that accounts for the biggest part of the kidney stone. Bacteria may play important roles by influencing renal Ca2+-related ion channel activities, resulting in chronic inflammation of the kidney along with rapid aggregation of stones. We examined the correlation among infection-promoted CaOx kidney stones and alterations in Ca2+-related ion channels in an animal model with experimentally induced Proteus mirabilis and foreign body infection. After the bladder was infected for 7 days, the data demonstrated that stones were presented and induced severe renal tubular breakage as well as altered levels of monocyte chemoattractant protein-1, cyclooxygenase-2, osteopontin, and transient receptor potential vanilloid member 5 expression, reflecting responses of kidney ion channels. Monocyte chemoattractant protein-1, osteopontin, and transient receptor potential vanilloid member 5 expression was significantly downregulated over time, indicating the chronic inflammation phase of the kidney and accelerated aggregation of CaOx crystals, respectively, whereas cyclooxygenase-2 exhibited no differences. These results indicated that bacterial infection is considerably correlated with an alteration in renal Ca2+-related ion channels and might support specific and targeted Ca2+-related ion channel-based therapeutics for urolithiasis and related inflammatory renal damage.

Health Care Service Utilization After Various Vascular Access Selections.

BACKGROUND: To provide clinicians with sufficient information for selecting optimal access strategies for patients with end-stage renal disease, the utilization of health-care services of patients receiving arteriovenous fistulas (AVFs), arteriovenous grafts (AVGs), and central venous catheters (CVCs) are crucial topics that require investigation. MATERIALS AND METHODS: This study involved 1248, 431, and 323 patients with end-stage renal disease who had received an AVF, AVG, or CVC, respectively. All sampled patients were monitored over the course of a 1-y study period to evaluate their medical utilization. The utilization were further categorized into nephrology and nonnephrology services. This study also performed univariate and multivariate regressions to estimate the effects of vascular accesses. RESULTS: Regarding the utilization of health care services, significant differences were observed for mean outpatient visits (45.30 versus 49.71 versus 48.80), outpatient costs (US$19117 versus US$21015 versus US$19280), inpatient days (9.77 versus 14.41 versus 21.60), inpatient costs (US$2627 versus US$3810 versus US$5238), and total costs (US$21743 versus US$24825 versus US$24518) among patients who had received an AVF, AVG, or CVC, respectively. Furthermore, patients receiving an AVF had lower total costs for all health care services and nonnephrology services than patients undergoing AVG or CVC across the categories of men, women, adults, and elderly individuals. Multiple regressions found that patients undergoing AVF had significantly lower total costs for all health services than patients undergoing other vascular accesses after adjustments. CONCLUSIONS: This study displayed that patients who received an AVF fully used health care and nonnephrology services than patients who received an AVG or CVC.

Secular trends in the distribution of allogeneic blood components in Taiwan.

Recent blood distribution profiles for transfusions in Taiwan have not been comprehensively documented. This study aimed to analyze trends in red blood cell (RBC), platelet, and plasma distribution rates, and compares these profiles with those in other countries. The distribution rates of RBC, platelets, and plasma in Taiwan during 2015 were 47.6, 11.1, and 26.8 units per 1000 population, respectively. At least 1.5 and 2.5-fold higher platelet and plasma distribution rates were observed than other selected countries. During 2007-2015, there was no significant change in RBC distribution. However, we observed a significant increase of 0.20 (95% CI: 0.11-0.30) adult doses of platelets, and a significant decrease of 1.69 (95% CI: 1.45-1.93) units of plasma per 1000 population per annum. Seven other countries showed a general significant decreasing trend of RBC distributions. Higher blood distribution rates were observed in Taiwan. Therefore, the adoption of patient blood management is essential.

Evaluation of the antioxidant and endothelial protective effects of Lysimachia christinae Hance (Jin Qian Cao) extract fractions.

BACKGROUND: Lysimachia christinae Hance is a traditional Chinese medicine with diuretic, detumescent, and detoxifying effects. Our aimed to optimize the extraction protocol to maximize the yield of flavonoids from Lysimachia christinae Hance, and evaluate the pharmacological activities of four fractions, namely, petroleum ether (PE), ethyl acetate (EA), n-butanol (NB), and aqueous (AQ) fractions, of the ethanolic extract of Lysimachia christinae Hance. METHODS: The flavonoid monomers in the crude extract were characterized via high performance liquid chromatography (HPLC), were used as markers for extract quality control and standardization. The total flavonoid, total phenolic, and total polysaccharide contents of each fraction were determined by spectrophotometry. Further, the in vitro free radical (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), superoxide, and hydroxyl radicals) scavenging activities, and antioxidant capacity in endothelial cells were evaluated for each fraction. RESULTS: After optimizing the extraction protocol to maximize the total flavonoid yield from L. christinae Hance, the NB fractions had the highest total flavonoid (39.4 ± 4.55 mg RE/g), total phenolic (41.1 ± 3.07 mg GAE/g) and total polysaccharide (168.1 ± 7.07 mg GE/g); In addition, the NB fraction of the ethanolic extract of L. christinae Hance reveal the strongest radical-scavenging activity, antioxidant activity and protective effects against H2O2-induced injury in HUVECs. CONCLUSIONS: Among the four fractions of L. christinae Hance, the NB fraction showed the most potent antioxidant and endothelial protective effects, which may be attributed to its high flavonoid, phenolic contents and optimal portfolio of different active ingredients of NB fractions of the ethanolic extract of L. christinae Hance. This study might improve our understanding of the pharmacological activities of L. christinae Hance, thereby facilitating its use in disease prevention and treatment.

TNF-α augments CXCR2 and CXCR3 to promote progression of renal cell carcinoma.

Within the tumour microenvironment, a complex network of chemokines and their receptors affects the initiation and progression of tumours. The higher levels of tumour necrosis factor-alpha (TNF-α) are associated with tumour progression and an anti-TNF-α monoclonal antibody has been used successfully to treat patients with renal cell carcinoma (RCC). However, the role of chemokines and their receptors in the TNF-α-promoted progression of RCC remains unclear. In this study, TNF-α was found to enhance the migration, invasion and epithelial-mesenchymal transition (EMT) of RCC cells. To further investigate the molecular mechanism of TNF-α on the progression of RCC, reverse transcription and quantitative PCR was used to screen chemokines and chemokine receptors that were associated with tumorigenesis. The results showed that TNF-α significantly increased the expressions of CXCR2 and CXCR3 and their related ligands in RCC cells. Subsequently, we used a lentiviral shRNA system to knockdown the expression of CXCR2 and/or CXCR3 in RCC cells. CXCR2 and CXCR3 silencing inhibited the induction of Slug and ZEB-1 with TNF-α treatment of RCC cells. In addition, the knockdown of both CXCR2 and CXCR3 resulted in a greater decrease in cell migration, invasion and clonogenic ability compared with either CXCR2 or CXCR3 knockdown alone. Moreover, CXCR2 and CXCR3 silencing significantly reduced the sphere-forming ability of RCC cells. High expression levels of CXCR2 and CXCR3 in cancer tissues correlated with tumour progression of renal cell carcinoma. These findings suggest that TNF-α augments CXCR2 and CXCR3 to promote the progression of renal cell carcinoma leading to a poor prognosis.