[Preparation and evaluation of blank and doxorubicin loaded poly (acrylic acid) microspheres for embolization].

OBJECTIVE: To prepare ion exchange doxorubicin-loaded poly (acrylic acid) microspheres (DPMs) and evaluate the properties of these chemoembolic agents. METHODS: Poly (acrylic acid) microspheres (PMs) without drug were prepared by inverse suspension polymerization method and then doxorubicin was loaded by ion exchange mechanism to prepare DPMs. Optical microscope was used to investigate the morphology and particle size distribution of PMs and DPMs; fluorescence microscope and confocal microscope were used to observe the distribution of doxorubicin after drug loading. Elasticities of both the microspheres were evaluated by texture analyzer. High performance liquid chromatography (HPLC) method was established to determine the drug loading behavior of PMs and releasing behavior of DPMs. The in vivo embolic property was evaluated by embolizing the hepatic artery of a rabbit with 0.1 mL of DPMs. RESULTS: PMs and DPMs were both spherical in shape, smooth in surface and dispersed well. Doxorubicin was mainly in the outer area inside of DPMs and distributed evenly. The average particle size of PMs and DPMs were (283±136) µm and (248±149) µm, respectively. PMs and DPMs both had good compression ability with the Young's modulus of (62.63±1.65) kPa and (93.94±1.10) kPa separately. PMs reached the drug loading balance at 12 h, and the entrapment efficiency was greater than 99%. Drug loading of PMs in doxorubicin solution at the concentration of 5.0 g/L and 12.5 g/L was (19.78±0.27) g/L and (49.45±0.37) g/L, respectively. Doxorubicin released slowly from DPMs in PBS and the accumulative release percentages of DPMs with corresponding drug loading were 6.82%±0.02% and 2.83%±0.10% after 24 h, respectively. Arterial angiograms showed that the hepatic artery of the rabbit was successfully embolized with DPMs. CONCLUSION: DPMs with good performance of loading doxorubicin could be a potential embolic agent for transcatheter arterial chemoembolization.

[Development of Markov models for economics evaluation of strategies on hepatitis B vaccination and population-based antiviral treatment in China].

Objective: To construct the Markov models to reflect the reality of prevention and treatment interventions against hepatitis B virus (HBV) infection, simulate the natural history of HBV infection in different age groups and provide evidence for the economics evaluations of hepatitis B vaccination and population-based antiviral treatment in China. Methods: According to the theory and techniques of Markov chain, the Markov models of Chinese HBV epidemic were developed based on the national data and related literature both at home and abroad, including the settings of Markov model states, allowable transitions and initial and transition probabilities. The model construction, operation and verification were conducted by using software TreeAge Pro 2015. Results: Several types of Markov models were constructed to describe the disease progression of HBV infection in neonatal period, perinatal period or adulthood, the progression of chronic hepatitis B after antiviral therapy, hepatitis B prevention and control in adults, chronic hepatitis B antiviral treatment and the natural progression of chronic hepatitis B in general population. The model for the newborn was fundamental which included ten states, i.e. susceptiblity to HBV, HBsAg clearance, immune tolerance, immune clearance, low replication, HBeAg negative CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC) and death. The susceptible state to HBV was excluded in the perinatal period model, and the immune tolerance state was excluded in the adulthood model. The model for general population only included two states, survive and death. Among the 5 types of models, there were 9 initial states assigned with initial probabilities, and 27 states for transition probabilities. The results of model verifications showed that the probability curves were basically consistent with the situation of HBV epidemic in China. Conclusion: The Markov models developed can be used in economics evaluation of hepatitis B vaccination and treatment for the elimination of HBV infection in China though the structures and parameters in the model have uncertainty with dynamic natures.

[Cost-effectiveness and affordability of strategy for preventing mother-to-child transmission of hepatitis B in China].

Objective: To evaluate the cost effectiveness of nationwide prevention of mother to child transmission (PMTCT) strategy for hepatitis B, and estimate the willing to pay and budget impacts on the PMTCT. Methods: The decision analytic Markov model for the PMTCT was constructed and a birth cohort of Chinese infants born in 2013 was used to calculate the cost-effectiveness of the PMTCT among them compared with those receiving no intervention. The parameters in the model were obtained from literatures of national surveys or Meta-analysis. The costs, cases of HBV-related diseases and quality-adjusted life-years (QALYs) were obtained from the societal and payer perspectives, respectively. The incremental cost-effectiveness ratio (ICER) was used as measures of strategy optimization. One-way and probability sensitivity analysis were performed to explore the uncertainty of the primary results. In addition, cost-effectiveness acceptability curve and cost-effectiveness affordability curves were drawn to illustrate the cost effectiveness threshold and financial budget of the PMTCT strategy. Results: The lifetime cost for PMTCT strategy was 4 063.5 yuan (RMB) per carrier, which was 37 829.7 yuan (RMB) lower compared with those receiving no intervention. Due to the strategy, a total of 24.516 1 QALYs per person would be gained, which was higher than that in those receiving no intervention. From societal perspective, the ICER was -59 136.6 yuan (RMB) per additional QALYs gained, indicating that the PMTCT is cost effective. The results were reliable indicated by one-way, multi-way and probability sensitivity analyses. By the CEAC, the willing to pay was much lower than the cost-effectiveness threshold. From the affordability curve of the PMTCT strategy, the annual budget ranged from 590.4 million yuan (RMB) to 688.8 million yuan (RMB), which was lower than the financial ability. Based on the results of cost-effectiveness affordability curves, the higher annual budget was determined, the higher probability of affordability for the PMTCT would be obtained under the same willing to pay state. Only when the annual budget reaches 688.8 million yuan (RMB), the goal of PMTCT would be fully realized. Conclusions: The PMTCT strategy in China was cost effective, and the cost is not beyond the financial budget needed and the willing to pay. The strategy, which is consistent with the global hepatitis B elimination efforts, should be conducted widely in China.

[Cost-effectiveness of community-based treatment of chronic hepatitis B in China].

Objective: Since eliminating hepatitis B in China would need considerable public health resources, the economics problem of the strategy of community-based antiviral treatment for chronic hepatitis B (CHB) has become an important issue. The cost-effectiveness and affordability of the strategy were evaluated in this study. Methods: According to the advocacy on eliminating hepatitis B by WHO and the comprehensive protocol of community based prevention of major infectious diseases and the guideline for CHB prevention and treatment in China, the decision analytic Markov model was constructed with the parameters from national surveys or Meta-analysis. A cohort population aged 20-59 years was used as study subjects. The strategy of CHB antiviral treatment was compared with the strategies of hepatitis B vaccination and non-intervention, respectively. The costs and disability-adjusted life years (QALYs) of the strategies were calculated from the societal and payer perspectives. The incremental cost-effectiveness ratio (ICER) and the cost-effectiveness ratio (CER) were calculated for the comparison of the strategies. One-way and probability sensitivity analysis were performed for uncertainty of the results. And the cost-effectiveness and affordability curves were introduced to estimate the budget impact on the strategies. Results: In the Chinese aged 20-59 years, the ICER of CHB antiviral treatment was 37 598.6 yuan (RMB) per QALYs and the ICERs were smaller in the low age groups, indicating that the antiviral treatment strategy is cost-effective and low age groups should be the priority population. The ICER of hepatitis B vaccination was -64 000.0 yuan (RMB) per QALYs, indicating that hepatitis B vaccination is cost saving. The CER of CHB antiviral treatment ranged from 731.8 to 1 813.3 yuan (RMB) per QALYs compared with hepatitis B vaccination, and the CER of CHB antiviral treatment was higher than that of hepatitis B vaccination in all age groups, indicating that hepatitis B vaccination would be more cost-effective than CHB antiviral treatment. The price of antiviral drug, entercavir, can influence the cost effectiveness of CHB antiviral treatment. If the price of entercavir declined half, CHB antiviral treatment would be cost-saving. The probability sensitivity analysis showed that people's willing to pay for CHB antiviral treatment should not be ignored, although the results of economics evaluation of CHB antiviral treatment were reliable. The results of affordability analysis indicated that the antiviral treatment strategy could not be implemented with the budget lower than 30 million yuan (RMB), the probability of implementing the strategy was 42.6% if the budget reaches 127 million yuan (RMB), and only when the budget reaches 269 million yuan (RMB), the goal of CHB antiviral treatment strategy can be fully realized. Conclusions: Although the strategy of CHB antiviral treatment as prevention in Chinese aged 20-59 years is cost-effective, it is not an appropriate public health measure due to the high cost. The cost effectiveness would be higher by conducting hepatitis B vaccination and then antiviral treatment in susceptible population.

[Survey of economic burden of hepatitis B-related diseases in 12 areas in China].

Objective: Less surveys on the economic burden of hepatitis B (HB)-related diseases have been conducted in China, so the socioeconomic harm caused by the diseases is not clear and the key parameters for economic evaluation of hepatitis B prevention and treatment are lacking. This study aimed to analyze the direct, indirect and intangible expenditures of hospitalized patients with HB-related diseases during hospitalization and during a year in different areas of China. Methods: The hospitals for infectious diseases and the large general hospitals in 12 areas in China were selected in the study. All the inpatients with HB-related diseases were surveyed by cluster sampling of consecutive cases. The direct expenditure included direct medical cost and direct non-medical cost. The indirect expenditure, including work loss of patients and caregivers, were calculated by using human capital method for urban and rural populations in 12 areas. The intangible expenditure were reflected by willing to pay and stochastic tournament. The influencing factors of direct and indirect costs were identified by stepwise linear multi-variation regression analysis. Results: A total of 27 hospitals in 12 areas were included in the survey. A total of 4 718 cases were surveyed, the overall response rate was 77.7%. The average hospital stay was 29.2 days (27-34) and the hospitalization expenditure was averagely 16 832.80 yuan (RMB) per case, in which the highest proportion (61.2%) was medicine fees [10 365.10 yuan (RMB)]. The average direct expenditure and indirect expenditure were consistent with the severity of illness, which were 18 336.10 yuan (RMB) and 4 759.60 yuan (RMB) respectively, with the ratio of 3.85 ∶ 1. The direct medical expenditure [17 434.70 yuan (RMB)] were substantially higher than the direct non-medical expenditure [901.40 yuan (RMB)]. It was found that the hospitalization expenses was highest in direct medical expenditure and the transportation expenses was highest in direct non-medical expenditures. Among the average indirect expenditure, the loss of income for the patients [3 832.50 yuan (RMB)] was higher than that for the caregivers [927.20 yuan (RMB)]. The total direct and indirect expenditure was highest for liver transplantation, followed by severe hepatitis, hepatocellular carcinoma and decompensated cirrhosis, acute hepatitis B, compensated cirrhosis and chronic hepatitis B. The influencing factors for both direct and indirect expenditure were high hospital level, severity of hepatitis B, living in urban area, antiviral therapy, long hospitalization and monthly income of family. For average 3.74 outpatient visits and 1.51 hospitalization, the average annual direct, indirect and intangible expenditure for HB-related diseases were 30 135.30, 6 253.80 and 44 729.90 yuan (RMB) [totally 81 119.00 yuan (RMB)], accounting for 37.3%, 7.7% and 55.0%, respectively. Of the annual direct medical expenditure [28 402.80 yuan (RMB)], which were much higher than non-medical expenditure [1 732.50 yuan (RMB)], hospitalization expenditure [26 074.20 yuan (RMB)] was higher than outpatient visit expenditure [4 061.10 yuan (RMB)]. The annual indirect expenditures for outpatient visit and hospitalization were 763.60 and 5 490.10 yuan (RMB), respectively. Of the annual intangible expenditure, the highest was that for primary hepatocellular carcinoma, followed by cirrhosis, chronic hepatitis B, severe hepatitis B, liver transplantation and acute hepatitis B. Conclusions: A heavy economic burden has been caused by HB-related diseases in China, and patients are more likely to rely on medical service rather than non-medical service. It is necessary to take effective treatment measures to prevent the adverse outcome of HB related diseases and achieve significant economic benefits. The influence of HB related diseases on mental health of the people can be reflected by an economics term, intangible expenditure.

MicroRNA-9 promotes the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.

PURPOSE: The objective of the study was to investigate the role of microRNA-9 (miR-9) targeting forkhead box O1 (FOXO1) in the proliferation, migration, and invasion of breast cancer cells. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expressions of miR-9 and FOXO1 mRNA in breast cancer tissues, normal breast tissues, breast cancer cell lines, and normal breast epithelial cells. After the up-regulation of miR-9 expression, qRT-PCR and Western blotting were used to determine the expression of FOXO1. The luciferase reporter gene assay was used to validate the target gene. The CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay were used to investigate the changes in the proliferation, migration, and invasion of breast cancer cells, respectively. RESULTS: MicroRNA-9 expression was significantly up-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). FOXO1 mRNA and protein expressions were substantially down-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). There can be a negative correlation between miR-9 and FOXO1 mRNA in breast cancer. Luciferase reporter gene assay indicated that miR-9 can down-regulate FOXO1 expression at a post-transcriptional level through binding specifically to FOXO1 3'UTR. The results of CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay revealed that the inhibition of miR-9 can suppress MCF7 cell proliferation, migration, and invasion. Additionally, the expression of miR-9 increased significantly whilst that of FOXO1 decreased substantially as the disease progressed (P < 0.05). CONCLUSIONS: Our study provides evidence that miR-9 can promote the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.

Evaluation of left atrial function by speckle tracking echocardiography in patients with systemic lupus erythematosus.

Left atrial (LA) function plays a key role in maintaining optimal cardiac output. Left ventricular diastolic dysfunction (LVDD) has been reported in systemic lupus erythematosus (SLE), but whether LA functional abnormalities also occur in patients with SLE is unknown. Toward this aim we evaluated left atrial function and volume by strain and strain rate derived from speckle tracking echocardiography (STE) and their associations with LVDD. Sixty SLE patients were compared with age- and gender-matched normal controls. The LA strain (S) and strain rate (SR) during systole, early diastole and late diastole (SRs, SRe and SRa, respectively) were measured by STE. The LA volume index (LAVI), traditional parameters of LA and left ventricular diastolic function also were analysed. Global strain and positive SRe were significantly reduced in the SLE group compared with the control group (26.2% ± 9.5% vs 32.5% ± 9.8% and -2.4 ± 1.0 s(-1) vs -3.1 ± 1.2 s(-1), both p < 0.05). The SRs in the SLE and control groups were not significantly different (2.1 ± 0.7 s(-1) vs 2.4 ± 0.8 s(-1), p = 0.2). The positive SRa was increased in the SLE group compared with the control group (-2.1 ± 0.8 s(-1) vs -1.6 ± 0.5 s(-1), p < 0.05) and the LAVI was larger in the SLE group than in the control group (32.4 ± 8.0 vs 25.8 ± 7.1 ml/m(2), p < 0.001). Patients with SLE exhibiting varying grades of LVDD displayed significant differences in LA parameters, including LAVI, SRs, SRe and SRa (all p < 0.05). Multivariate linear analysis additionally revealed that SLICC/ACR damage index (SDI) was independently and inversely associated with global strain, SRs and positive SRe. LA functions were changed in SLE patients, demonstrating impairment in conduit function, decrease in storage function and increase in pump function. Meanwhile, the magnitude of this impairment was predictively associated with the severity of LVDD. The results from this study demonstrate that STE is capable of detecting various aspects of LA functional impairment during SLE progression, and should be further explored as a diagnostic tool for improving the outcomes of SLE patients.

Genetic affinities of central China populations.

Hunan locates in the south-central part of China, to the south of the middle reaches of the Yangtze River and south of Lake Dongting. According to the historical records, the peopling of Hunan by modern human ancestors can ascend to 40 thousand years ago. Thus, to trace the ancient maternal components can offer further insight into the origin of south-central China. In this study, we investigated the mitochondrial DNA of 114 individuals from Hunan Province (including 34 Han, 40 Tujia and 40 Miao). Hypervariable regions I and II of the mtDNA control region were sequenced, and the relative diagnostic variations in coding region according to the updated worldwide phylogeny tree were selected and typed by restriction fragment length polymorphism analysis or direct sequencing. All individuals were classified into specific (sub)haplogroups. By comparison with the surrounding populations, southern China-prevalent haplogroups were detected with relative higher frequency in the Tujia and Miao ethnic populations, such as haplogroup B, with more than 20%, lacking in the Han population, which illustrated its southern origin characters. In addition, we also detected northern of East Asia prevalent haplogroups with a relative higher frequency in Tujia populations than in the Miao and Yao ethnic groups, implying a gene flow from Han populations. However, the language-clustering tendency was supported by our principal component analysis and further genetic estimation results. Han and ethnic groups in central China exhibited specific ancestors related to their closer language affinity, although there was extensively genetic admixture between Han and ethnic groups.

Normal hearing after trauma with completely ectopic incus -- how possible?.

OBJECTIVES: To report the rare case of a patient with complete incus dislocation after trauma showing normal hearing. METHODOLOGY: Physical examination, audiometry, CT of temporal bone, and detection during operation. RESULTS: The incus had become remotely located in the mastoid cavity, but the patient showed normal hearing because fibrous connections had preserved bony continuity. CONCLUSION: This case demonstrates that disruption of the ossicular chain does not always require ossicular reconstruction.

A comparative study of third-order nonlinear optical properties of silver phenylacetylide and related compounds via ultrafast optical Kerr effect measurements.

A comparative study of the third-order nonlinear optical properties, via the newly developed heterodyned optical Kerr effect (OHD-OKE) measurements, of silver phenylacetylide and related compounds is reported. [AgC[triple bond]CC(6)H(5)](n) (1) was found to exhibit efficient third-order nonlinear optical susceptibility chi((3)) of 2.4 x 10(-14) esu, and second hyperpolarizability gamma of 9.07 x 10(-32) esu. These results are compared with those of two related silver phenylacetylide compounds, namely, a double salt, (silver phenylacetylide).(silver tert-butylthiolate) [AgC[triple bond]CC(6)H(5).AgS(t-C(4)H(9))](n) complex (2), and a cluster, triphenylphosphine silver phenylacetylide tetramer, [(C(6)H(5))(3)PAgC[triple bond]CC(6)H(5)](4) (3), as well as that of the related organic polymer polyphenylacetylene (4). These four compounds represent different types of phenylacetylide derivatives: 1 is an organometallic polymer, 2 a polymeric double salt, 3 a discrete metal cluster, and 4 an organic polymer. It was found that the third-order optical nonlinear response was enhanced by the incorporation of silver d electrons into the delocalized conjugated organic pi system, and its magnitude is highly dependent upon the extent of the pi delocalization. Specifically, the relative magnitudes of chi((3)) and gamma follow the order silver phenylacetylide polymer (1) > (silver phenylacetylide).(silver tert-butylthiolate) double salt (2) > polyphenylacetylene polymer (4) > tetrameric (triphenylphosphine silver phenylacetylide)(4) cluster (3). The observed trend may be attributed to the decreasing length of pi conjugation. It is interesting to note that the incorporation of Ag(I) into the polymeric framework of polyphenylacetylene enhances the chi((3)) by 25-fold for the same degree of polymerization (n = 7). The signs of chi((3)) and gamma, which are related to the response mechanisms, were found to be solvent dependent.

[Research into risk factors of bladder cancer in Heilongjiang].

This article reports a 1:2 matched case-control study on 80 cases of bladder cancer in Heilongjiang province. Multiple logistic regression analysis for risk state suggested that three factors, i.e., cigarette smoking, use of saccharin and reduced intake of vegetables are closely associated with development of bladder cancer. Giving up smoking, using no saccharin and eating more fresh vegetables are main ways to reduce the incidence of bladder cancer.

[Experimental canine hepatic artery embolization with polyvinyl alcohol microspheres].

Polyvinyl alcohol microsphere impregnated with barium sulfate was found to be a good embolizing agent in regard to shape, suspension and distribution in the arteries. Different-phase hepatic artery embolization with microspheres (50 approximately 100 microns, 100 approximately 300 microns) was performed in 20 dogs to evaluate the angiographic and histopathologic changes and hepatic function alterations. Permanent occlusion of the peripheral arterioles was observed on follow-up angiograms one week to six months after embolization. Shrinkage of the embolized segment and focal infarct of the liver were noticed in nearly half of the specimens both grossly and microscopically. The shape and structure of the microspheres were seen unchanged on different-phase specimens, and microspheres as small as 50 microns could reach the corresponding small peripheral arterioles. The liver function alterations were comparable with gelfoam embolization. This study suggested that permanent embolization of small arterioles was possible with such microspheres.

Effect of rhodamine 123 and total glycosides from tripterygium wilfordii (GTW) on ultrastructures, survival and fertilizing capacity of human sperm in vitro.

Human sperms were treated with rhodamine 123 or GTW in vitro. Comparisons were made of survival, fertilizing capacity and ultrastructures of sperms which had been exposed to different concentrations and treatment durations of the agents. The results showed that no prominent change could be observed when treated with lower doses. However, at higher concentrations of rhodamine 123, mitochondria were found to be swollen, vacuolated and deranged instead of surrounding the flagellar axoneme in the normal spiral way, and the mitochondrial cristae were broken or had disappeared. In some sperms, cracks at the flagellar axoneme and concave defects in the acrosome were seen. The sperms lost their fertilizing capacity, though some of them were still alive, whereas the sperms treated with GTW showed no morphological damage and maintained their ability to penetrate the hamster egg. Our results suggest that rhodamine 123 is a prospect in the search for an anti-sperm contraceptive.