Design, synthesis and evaluation of 2-pyrimidinylindole derivatives as anti-obesity agents by regulating lipid metabolism.

Obesity, a global pandemic posing a growing threat to human health, necessitates the development of effective and safe anti-obesity agents. Our previous studies highlighted the lipid-lowering effects of indolylquinazoline Bouchardatine and its derivatives. In this study, we employed scaffold hopping and simplification strategies to design and synthesize two new series derivatives by modifying the D ring. Extensive discussions have been conducted regarding the structure-activity relationship between lipid-lowering activity and the new compounds. These discussions have resulted in the discovery of 2-pyrimidinylindole derivatives as a promising scaffold for anti-obesity treatment. The new 2-pyrimidinylindole derivatives exhibited comparable lipid-lowering activity to the previously reported indolylquinazoline derivatives, including SYSU-3d and R17, with reduced toxicity. The most potent compound, 5a, demonstrated a larger therapeutic index, improved aqueous solubility and oral bioavailability compared to the previous lead compounds. In vivo evaluation indicated that 5a effectively reduced lipid accumulation in adipose tissue, improved glucose tolerance, and mitigated insulin resistance and liver function damage caused by a high-fat and high-cholesterol diet. Mechanism studies indicated that 5a may regulate lipid metabolism through the modulation of the PPARγ signaling pathway. Overall, our study has identified a highly active compound 5a, and provided the basis for further development of 2-pyrimidinylindole as a promising scaffold for obesity treatment.

Biomimetic triumvirate nanogel complexes via peptide-polysaccharide-polyphenol self-assembly.

Self-assembled peptide and polysaccharide nanogels are excellent candidates for bioactive delivery vectors. However, there are still significant challenges in the application of nanogels as delivery tools for bioactive elements. This study aims to deliver, and control the release of a hydrophobic bioactive flavonoid hesperidin. Using the self-assembling peptide (SAP) Fmoc-FRGDF, extracellular matrix mimicking nanofibrils were fabricated, which were decorated and bolstered with immunomodulatory polysaccharide strands of fucoidan and infused with hesperidin. The mechanical properties, secondary structure, and microscopic morphologies of the composite hydrogels were characterized using rheometer, FTIR, XRD, and TEM, etc. The encapsulation efficiency (EE) and release behavior of hesperidin were determined. Coassembly of the SAP with fucoidan improved the mechanical properties (from 9.54 Pa of Fmoc-FRGDF hydrogel to 7735 Pa of coassembly hydrogel at 6 mg/mL fucoidan concentration), formed thicker nanofibril bundles at 4 and 6 mg/mL fucoidan concentration, improved the EE of hesperidin from 72.86 % of Fmoc-FRGDF hydrogel to over 90 % of coassembly hydrogels, and showed effectively controlled release of hesperidin in vitro. Intriguingly, the first order kinetic model predicted an enhanced hydrogel retention and release of hesperidin. This study revealed a new approach for bioengineered nanogels that could be used to stabilize and release hydrophobic payloads.

The impacts of spatio-temporal variation of natural and agricultural influences on the environmental water quality in a fluvial-lacustrine watershed in China.

Despite the significant impacts of natural factors such as rainfall, topography, soil type, and river network as well as agricultural activities on the environmental water quality, little is known about the influence of their temporal and spatial variations in a fluvial-lacustrine watershed. In this study, a whole process accounting method based the export coefficient model (WP-ECM) was first developed to quantify how natural factors and agricultural activities distribution influenced water quality. A case study was performed in a typical fluvial-lacustrine area - Dongting basin, China. The simulated results indicated that the natural factors can promote and inhibit the migration and transformation of agricultural pollutants generated from the watershed and the spatial distribution of the natural factors displayed high variability. It should be priority to monitor the areas with greater natural impact in the basin. Moreover, the cultivated land area and the number of pig-breeding were positively correlated with the pollutant discharge. From the perspective of the spatial distribution of comprehensive influence, the comprehensive high-impact areas are mainly distributed in the Dongting Lake district in 2005-2010 and in Xiang River watershed in 2010-2020. A key strategy for controlling or reducing the cultivated land area and the intensity of livestock breeding in these high-impacts areas is recommended to reduce the impact of the environmental water quality for the entire basin.

Design and Synthesis of Bouchardatine Derivatives as a Novel AMP-Activated Protein Kinase Activator for the Treatment of Colorectal Cancer.

Metabolic reprogramming is a crucial hallmark of tumorigenesis. Modulating the reprogrammed energy metabolism is an attractive anticancer therapeutic strategy. We previously found a natural product, bouchardatine, modulated aerobic metabolism and inhibited proliferation in the colorectal cancer cell (CRC). Herein, we designed and synthesized a new series of bouchardatine derivatives to discover more potential modulators. We applied the dual-parametric high-content screening (HCS) to evaluate their AMP-activated protein kinase (AMPK) modulation and CRC proliferation inhibition effect simultaneously. And we found their antiproliferation activities were highly correlated to AMPK activation. Among them, 18a was identified with nanomole-level antiproliferation activities against several CRCs. Interestingly, the evaluation found that 18a selectively upregulated oxidative phosphorylation (OXPHOS) and inhibited proliferation by modulating energy metabolism. Additionally, this compound effectively inhibited the RKO xenograft growth along with AMPK activation. In conclusion, our study identified 18a as a promising candidate for CRC treatment and suggested a novel anti-CRC strategy by AMPK activating and OXPHOS upregulating.

Extraction Optimization, UHPLC-Triple-TOF-MS/MS Analysis and Antioxidant Activity of Ceramides from Sea Red Rice Bran.

As a new type of salt-tolerant rice, sea red rice contains more minerals, proteins, and lipid compounds, and, in particular, its by-product rice bran may be used to replace other commercial rice brans as the main source of ceramides (Cers). However, the extraction rate of Cers is generally low, and it is crucial to seek an efficient extraction method. This study optimized the ultrasonic-assisted extraction of Cers from sea red rice bran using response surface methodology (RSM) and obtained a Cers yield of 12.54% under optimal conditions involving an extraction temperature of 46 °C, an extraction time of 46 min, and a material-to-liquid ratio of 5 g/mL. The Cers content in sea red rice bran was preliminarily analyzed using thin-layer chromatography, and the Cers content was determined via UHPLC-Triple-TOF-MS/MS after purification and separation using silica column chromatography. Forty-six different types of Cers were identified in sea red rice bran, of which Cer 18:0/24:0 (2OH), Cer 18:0/26:0, Cer 18:0/26:0 (2OH), and Cer 18:0/24:0 accounted for 23.66%, 17.54%, 14.91%, and 11.96%. Most of the Cers structures were mainly composed of sphingadienine. A biological activity assay indicated that Cers extracted from sea red rice bran had significant antioxidant and anti-aging properties. These findings indicate that the extracted Cers show great potential for applications in the cosmetic and pharmaceutical industries.

Chitosan/Alginate Nanoparticles for the Enhanced Oral Antithrombotic Activity of Clam Heparinoid from the Clam Coelomactra antiquata.

Chitosan/alginate nanoparticles (DG1-NPs and DG1/Cur-NPs) aiming to enhance the oral antithrombotic activity of clam heparinoid DG1 were prepared by ionotropic pre-gelation. The influence of parameters, such as the concentration of sodium alginate (SA), chitosan (CTS), CaCl2, clam heparinoid DG1, and curcumin (Cur), on the characteristics of the nanoparticles, were investigated. Results indicate that chitosan and alginate can be used as polymer matrices to encapsulate DG1, and nanoparticle characteristics depend on the preparation parameters. Nano-particles should be prepared using 0.6 mg/mL SA, 0.33 mg/mL CaCl2, 0.6 mg/mL CTS, 7.2 mg/mL DG1, and 0.24 mg/mL Cur under vigorous stirring to produce DG1-NPS and DG1/Cur-NPS with small size, high encapsulation efficiency, high loading capacity, and negative zeta potential from approximately -20 to 30 mV. Data from scanning electron microscopy, Fourier-transform infrared spectrometry, and differential scanning calorimetry analyses showed no chemical reaction between DG1, Cur, and the polymers; only physical mixing. Moreover, the drug was loaded in the amorphous phase within the nanoparticle matrix. In the acute pulmonary embolism murine model, DG1-NPs enhanced the oral antithrombotic activity of DG1, but DG1/Cur-NPs did not exhibit higher antithrombotic activity than DG1-NPs. Therefore, the chitosan/alginate nanoparticles enhanced the oral antithrombotic activity of DG1, but curcumin did not further enhance this effect.

A novel HSF1 activator ameliorates non-alcoholic steatohepatitis by stimulating mitochondrial adaptive oxidation.

BACKGROUND AND PURPOSE: Non-alcoholic steatohepatitis (NASH) is the more severe form of metabolic associated fatty liver disease (MAFLD) and no pharmacological treatment as yet been approved. Identification of novel therapeutic targets and their agents is critical to overcome the current inadequacy of drug treatment for NASH. EXPERIMENTAL APPROACH: The correlation between heat shock factor 1 (HSF1) levels and the development of NASH and the target genes of HSF1 in hepatocyte were investigated by chromatin-immunoprecipitation sequencing. The effects and mechanisms of SYSU-3d in alleviating NASH were examined in relevant cell models and mouse models (the Ob/Ob mice, high-fat and high-cholesterol diet and the methionine-choline deficient diet-fed mice). The actions of SYSU-3d in vivo were evaluated. KEY RESULTS: HSF1 is progressively reduced with mitochondrial dysfunction in NASH pathogenesis and activation of this transcription factor by its newly identified activator SYSU-3d effectively inhibited all manifestations of NASH in mice. When activated, the phosphorylated HSF1 (Ser326) translocated to nucleus and bound to the promoter of PPARγ coactivator-1α (PGC-1α) to induce mitochondrial biogenesis. Thus, increasing mitochondrial adaptive oxidation and inhibiting oxidative stress. The deletion of HSF1 and PGC-1α or recovery of HSF1 in HSF1-deficiency cells showed the HSF1/PGC-1α pathway was mainly responsible for the anti-NASH effects of SYSU-3d independent of AMP-activated protein kinase (AMPK). CONCLUSION AND IMPLICATIONS: Activation of HSF1 is a practical therapeutic approach for NASH treatment via the HSF1/PGC-1α/mitochondrial pathway and SYSU-3d can be considered as a potential candidate for the treatment of NASH.

Medical expenditure for lung cancer in China: a multicenter, hospital-based retrospective survey.

BACKGROUND: Lung cancer is the most prevalent cancer, and the leading cause of cancer-related deaths in China. The aim of this study was to estimate the direct medical expenditure incurred for lung cancer care and analyze the trend therein for the period 2002-2011 using nationally representative data in China METHODS: This study was based on 10-year, multicenter retrospective expenditure data collected from hospital records, covering 15,437 lung cancer patients from 13 provinces diagnosed during the period 2002-2011. All expenditure data were adjusted to 2011 to eliminate the effects of inflation using China's annual consumer price index. RESULTS: The direct medical expenditure for lung cancer care (in 2011) was 39,015 CNY (US$6,041) per case, with an annual growth rate of 7.55% from 2002 to 2011. Drug costs were the highest proportionally in the total medical expenditure (54.27%), followed by treatment expenditure (14.32%) and surgical expenditure (8.10%). Medical expenditures for the disease varied based on region, hospital level, type, and stage. CONCLUSION: The medical expenditure for lung cancer care is substantial in China. Drug costs and laboratory test are the main factors increasing medical costs.

Clinical characteristics, medical service utilization, and expenditure for colorectal cancer in China, 2005 to 2014: Overall design and results from a multicenter retrospective epidemiologic survey.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

Health-related quality of life of patients with colorectal neoplasms in China: A multicenter cross-sectional survey.

BACKGROUND AND AIM: This study aimed to clarify health-related quality of life (HRQoL) of patients with colorectal precancer and colorectal cancer (CRC) in China and to better understand related utility scores. METHODS: A hospital-based cross-sectional survey was conducted in precancer and CRC patients from 2012 to 2014, covering 12 provinces in China. HRQoL was assessed with EuroQol 5-Dimensions 3-Levels. Utility scores were derived using Chinese value set. A multivariate regression model was established to explore potential predictors of utility scores. RESULTS: A total of 376 precancer (mean age 58.7 years, 61.2% men) and 2470 CRC patients (mean age 58.6 years, 57.6% men) were included. In five dimensions, there was a certain percentage of problem reported among precancer (range: 12.0% to 36.7%) and CRC (range: 32.4% to 50.3%) patients, with pain/discomfort being the most serious dimension. Utility scores of precancer and CRC patients were 0.870 (95% confidence interval [CI], 0.855-0.886) and 0.751 (95% CI, 0.742-0.759), both of which were lower than those of general Chinese population (0.960 [95% CI, 0.960-0.960]). Utilities for patients at stage I to stage IV were 0.742 (95% CI, 0.715-0.769), 0.722 (95% CI, 0.705-0.740), 0.756 (95% CI, 0.741-0.772), and 0.745 (95% CI, 0.742-0.767), respectively. Multivariate analysis showed that therapeutic regimen, time point of the interview, education, occupation, annual household income, and geographic region were associated with utilities of CRC patients. CONCLUSION: Health-related quality of life of both precancer and CRC patients in China declined considerably. Utility scores differed by sociodemographic and clinical characteristics, and findings of these utilities may facilitate implementation of further cost-utility evaluations.

Discovery of a promising agent IQZ23 for the treatment of obesity and related metabolic disorders.

Discovery of novel anti-obesity agents is a challenging and promising research area. Based on our previous works, we synthesized 40 novel ß-indoloquinazoline analogues by altering the skeleton and introducing preferential side chains, evaluated their lipid-lowering activity and summarized the structure-activity relationships. In combination with an evaluation of the lipid-lowering efficacies, AMP-dependent activated protein kinase (AMPK) activating ability and liver microsomal stability, compound 23 (named as IQZ23) was selected for further studies. IQZ23 exerted a high efficacy in decreasing the triglyceride level (EC50 = 0.033 µM) in 3T3-L1 adipocytes. Mechanistic studies revealed the lipid-lowering activity of IQZ23 was dependent on the AMPK pathway by modulating ATP synthase activity. This activation was accompanied by mitochondrial biogenesis and oxidation capacity increased, and insulin sensitivity enhanced in pertinent cell models by various interventions. Correspondingly, IQZ23 (20 mg/kg, i.p.) treatment significantly reversed high fat and cholesterol diet (HFC)- induced body weight increases and accompanying clinical symptoms of obesity in mice but without indicative toxicity. These results indicate that IQZ23 could be a useful candidate for the treatment of obesity and related metabolic disorders.

Short-term impact of breast cancer screening intervention on health-related quality of life in China: A multicentre cross-sectional survey.

OBJECTIVE: The impact of participating in breast cancer screening programmes on health-related quality of life (HRQoL)is poorly understood. METHODS: Based on a national breast cancer screening programme in China, a multicentre cross-sectional survey was conducted covering 12 provinces from September 2013 to December 2014. HRQoL of participants in the screening population and general population was evaluated by the three-levelEuroQol-five-Dimensions (EQ-5D-3L) instrument, and utility scores were generated through the Chinese value set. Univariate and multivariate regression analyses were performed to explore determinants of utility scores and anxiety/depression problems. RESULTS: For screening group and general population (n = 4756, mean age = 51.6 year old), the corresponding utility scores were 0.937 (95% CI, 0.933-0.941) and 0.953 (0.949-0.957) (P < .001). Pain/discomfort and anxiety/depression were the most common reported in both groups (51.4% and 34.3%, P < .001). Utility scores at prescreening, in-screening, and postscreening interview timings were 0.928 (0.921-0.935), 0.958 (0.948-0.969), and 0.938 (0.933-0.943), respectively (P < .001); the corresponding proportions of anxiety/depression reporting were 25.9%, 16.3%, and 21.1%, respectively (P = .004). Interview timing, geographical region, and insurance status were associated with HRQoL and anxiety/depression in women at high-risk of breast cancer. CONCLUSIONS: Utility scores of screening participants were significantly lower than that of general population in China, but the difference may be clinically insignificant. Further cohort studies using HRQoL measurements are needed.

Bouchardatine suppresses rectal cancer in mice by disrupting its metabolic pathways via activating the SIRT1-PGC-1α-UCP2 axis.

Cancer metabolism is an attractive target of the therapeutic strategy for cancer. The present study identified bouchardatine (Bou) as a potent suppressor of rectal cancer growth by cycle-arresting independent of apoptosis. In cultured HCT-116 rectal cancer cells, Bou increased glucose uptake/oxidation and capacity of mitochondrial oxidation. These effects were associated with an upregulation of uncoupling protein 2 (UCP2) and the activation of its upstream Sirtuin 1 (SIRT1)/(Liver kinase B1) LKB1- (Adenosine monophosphate-activated protein kinase) AMPK axis. The pivotal role of UCP2 in the cancer-suppressing effect was demonstrated by overexpressing UCP2 in HCT-116 cells with similar metabolic effects to those produced by Bou. Interestingly, Bou activated peroxisome proliferators activated receptor γ coactivator 1α (PGC-1α) and recruited it to the promoter of UCP2 in HCT-116 cells along with deacetylation (thus activation) by SIRT1. The requirement of SIRT1 for the cancer-suppressing effect through the PGC-1α-UCP2 was confirmed by the reciprocal responses to Bou in HCT-116 with defected and overexpressed SIRT1. Whereas knockdown, mutation or pharmacological inhibition of SIRT1 all abolished Bou-induced deacetylation/activation of PGC-1α, the opposing effects were observed after overexpressing SIRT1. In mice, administration of Bou (50 mg/kg) also suppressed the growth of rectal cancer associated with increases the UCP2 expression and mitochondria capacity in the tumor. Collectively, our findings suggest that Bou has a therapeutic potential for the treatment of rectal cancer by disrupting the metabolic path of cancer cells via activating the PGC-1α-UCP2 axis with SIRT1 as its primary target.

Electrochemical Sensor Based on Platinum Nanoparticles Modified Graphite-Like Carbon Nitride for Detection of Phenol.

In this work, platinum nanoparticles were modified on graphite-like carbon nitride (g-C3N4) surface via a simple one-pot deposition reduction method, and the prepared Pt/g-C3N4 was used as electrode materials for phenol sensing. The morphology and crystallographic structure of Pt/g-C3N4 were characterized by Scanning transmission electron microscope (STEM) and X-ray diffraction (XRD). The electrochemical performance of Pt/g-C3N4 toward phenol was investigated in details and the results showed that the Pt/g-C3N4 sensor had favorable sensing ability for phenol detection. Under the optimum parameters, the electrochemical sensor had a wide range of 2 to 20 µM, lower detection limits of 0.667 µM (S/N═3), and higher sensitivity of 1.21084 mA µM-1 in phenol detection, indicating the excellent capability of the newly developed sensor to determine phenol. Moreover, the design of the Pt/g-C3N4 sensor may provide a potential material for actual application in phenol detection due to its merits of simplicity, reliability, sensitivity and low-cost.

Medical expenses of urban Chinese patients with stomach cancer during 2002-2011: a hospital-based multicenter retrospective study.

BACKGROUND: In China, stomach cancer is the third most common cancer and the third leading cause of cancer death. Few studies have examined Chinese stomach cancer patients' medical expenses and their associated trends. The Cancer Screening Program in Urban China (CanSPUC) is a Major Public Health Project funded by the central government. Through this project, we have extracted patients' medical expenses from hospital billing data to examine the costs of the first course treatments (which refers to 2 months before and 10 months after the date of cancer diagnosis) in Chinese patients with stomach cancer and the associated trends. METHODS: The expense data of 14,692 urban Chinese patients with stomach cancer were collected from 40 hospitals in 13 provinces. We estimated the inflation-adjusted medical expenses per patient during 2002-2011. We described the time trends of medical expenses at the country-level, and those trends by subgroup, and analyzed the compositions of medical expenses. We constructed the Generalized Linear Mixed (GLM) regression model with Poisson distribution to examine the factors that were associated with medical expenses per patient. RESULTS: The average medical expenses of the first course treatments were about 43,249 CNY (6851 USD) in 2011, more than twice of that in 2002. The expenses increased by an average annual rate of 7.4%. Longer stay during hospitalization and an increased number of episodes of care are the two main contributors to the expense increase. The upward trend of medical expenses was observed in almost all patient subgroups. Drug expenses accounted for over half of the medical expenses. CONCLUSIONS: The average medical expenses of the first course (2 months before and 10 months after the date of cancer diagnosis) treatments per stomach cancer patient in urban China in 2011 were doubled during the previous 10 years, and about twice as high as the per capita disposable income of urban households in the same year. Such high expenses indicate that it makes economic sense to invest in cancer prevention and control in China.

Health-related quality of life and utility scores of patients with breast neoplasms in China: A multicenter cross-sectional survey.

BACKGROUND: Health-related quality of life and utility scores of patients with breast cancer and precancerous lesions are sparse in China. This study aimed to derive utility scores of patients with breast cancer and precancer in China. MATERIAL AND METHODS: An interviewer-administered cross-sectional survey was conducted in 12 provinces across China from 2013 to 2014. The three-level EuroQol-5-Dimension instrument was used to evaluate quality of life, and utility scores were generated using the Chinese value set. Univariate and multivariate analyses were performed to explore the determinants of utility scores. RESULTS: In total, 2626 breast cancer and 471 precancer patients were included. Mean age was 49.1 for breast cancer and 41.4 years for precancer (p < 0.001). Among the five dimensions, pain/discomfort was the most reported problem, 53.9% in breast cancer and 29.3% in precancer patients. Mean (95% CI) utility scores for breast cancer and precancer patients were estimated as 0.887 (0.875-0.899) and 0.781 (0.774-0.788), and the scores of breast cancer at stage-I, stage-II, stage-III and stage-IV were 0.789 (0.774-0.805), 0.793 (0.783-0.802), 0.774 (0.759-0.788) and 0.686 (0.654-0.717), respectively. Mean (95% CI) visual analogue scale scores for breast cancer and precancer were 75.6 (74.0-77.3) and 72.8 (72.3-73.3). Multiple regression showed advanced clinical stage, lower educational level, lower household income, surgery treatment, and undergoing treatment were independently associated with lower utility scores for breast cancer patients. CONCLUSION: The utility scores deteriorate with the severity of breast neoplasms. Detailed utility scores of breast cancer and precancer are fundamental for further cost-utility analysis in China.

Medical expenditure for liver cancer in urban China: A 10-year multicenter retrospective survey (2002-2011).

OBJECTIVE: This study aims to understand the medical expenditure for liver cancer during 2002-2011 in urban areas of China. MATERIALS AND METHODS: This is a retrospective study. Based on a stratified cluster sampling method, a medical expenditure survey collected basic personal information from related medical records. Two-tailed independent sample t-test, variance analysis, and Student-Newman-Keuls Tests were used in cost analysis for the corresponding data types. RESULTS: A total of 12,342 liver cancer patients were included in the analysis. Overall average medical expenditure per case for liver cancer diagnosis and treatment in China has increased from ¥21, 950 to ¥40, 386 over the study period. For each liver cancer patient diagnosed between 2009 and 2011, the average expenditures were 29,332 CNY for stage I, 35,754 CNY for stage II, 34,288 CNY for stage III, and 30,275 CNY for stage IV diseases (P < 0.001). Pharmaceuticals accounted for the biggest part of the medical expenditure and it rose from 48.01% to 52.96% during these ten years, and the share of nursing fee expenses was the lowest (around 1%). Over the entire 10-year data period, the per capita expenditure of the east region (32,983 CNY) was higher than that of the west region (26,219 CNY) and slightly higher than the central region (31,018 CNY, P < 0.001). DISCUSSION: As a major cancer in China, liver cancer accounts for a large portion of health economic burden and its medical expenditure is heavy for families. Early diagnosis and treatment for liver cancer will save medical expenditure. CONCLUSION: The economic burden of liver cancer is high in China and related medical expenditure has increased.

Medical and non-medical expenditure for breast cancer diagnosis and treatment in China: a multicenter cross-sectional study.

AIM: We aimed to assess economic burden of breast cancer (BC) diagnosis and treatment in China through a multicenter cross-sectional study, and to obtain theoretical evidence for policy-making. METHODS: This survey was conducted in 37 hospital centers across 13 provinces in China from September 2012 to December 2014. We collected information on the subject characteristics. We then assessed the medical and non-medical expenditure for BC diagnosis and treatment, factors influencing the average case expense, variations between medical and non-medical expenditure at different clinical stages, economic impact of overall expenditure in newly diagnosed course after reimbursement to the patient's family, composition of non-medical expenditure and time loss for the patient and family. RESULTS: Among 2746 women with BC (72.6% were admitted to specialized hospitals), the overall average expenditure was US $8450 (medical expenditure: $7527; non-medical expenditure: $922). Significant differences were found among the overall expenditure in the four clinical stages (P < 0.0001); the expenditure was higher in stages III and IV than that in stages I and II, whereas the stage IV was the highest (P < 0.0001). Moreover, a higher self-reported predicted reimbursement ratio was associated with a less economic impact on the patient's family, and the average time lost was estimated as $1529. CONCLUSIONS: Early detection and treatment of breast cancer might be effective for decreasing the economic burden, because costs escalate as the degree of malignancy increases.

Medical expenditure for esophageal cancer in China: a 10-year multicenter retrospective survey (2002-2011).

BACKGROUND: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. METHODS: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY = 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China. RESULTS: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27% was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage I, 39,302 CNY for stage II, 40,353 CNY for stage III, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02% of the overall expenditure. CONCLUSIONS: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

Expenditure and financial burden for the diagnosis and treatment of colorectal cancer in China: a hospital-based, multicenter, cross-sectional survey.

BACKGROUND: The increasing prevalence of colorectal cancer (CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment. We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China. METHODS: We conducted a multicenter, cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014. Each enrolled patient was interviewed using a structured questionnaire. All expenditure data were inflated to the 2014 Chinese Yuan (CNY; 1 CNY = 0.163 USD). We quantified the overall expenditure and financial burden and by subgroup (hospital type, age at diagnosis, sex, education, occupation, insurance type, household income, clinical stage, pathologic type, and therapeutic regimen). We then performed generalized linear modeling to determine the factors associated with overall expenditure. RESULTS: A total of 2356 patients with a mean age of 57.4 years were included, 57.1% of whom were men; 13.9% of patients had stage I cancer; and the average previous-year household income was 54,525 CNY. The overall average direct expenditure per patient was estimated to be 67,408 CNY, and the expenditures for stage I, II, III, and IV disease were 56,099 CNY, 59,952 CNY, 67,292 CNY, and 82,729 CNY, respectively. Non-medical expenditure accounted for 8.3% of the overall expenditure. The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY, which accounted for 59.9% of their previous-year household income and caused 75.0% of families to suffer an unmanageable financial burden. Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups (P < 0.05), except for sex. Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more, whereas those with a lower household income and those who underwent surgery spent less (all P < 0.05). CONCLUSIONS: For patients in China, direct expenditure for the diagnosis and treatment of CRC seemed catastrophic, and non-medical expenditure was non-ignorable. The financial burden varied among subgroups, especially among patients with different clinical stages of disease, which suggests that, in China, CRC screening might be cost-effective.