Access to anticancer medicines in public hospitals of Northwestern China.

Objective: We aimed to evaluate the accessibility of anticancer medicines in public hospitals of Shaanxi, a representative province of Northwestern China. Methods: Thirty-one anticancer medicines were investigated in 146 designated public hospitals in 10 cities of Shaanxi Province. We used medicine procurement data from the Shaanxi Drug Centralized Purchasing Platform during 2019-2021. Primary outcomes included the availability, drug utilization, and affordability of anticancer medicines. Results: The mean availability of 31 anticancer medicines increased significantly from 5.45% in 2019 to 14.72% in 2021. The mean availability of nationally negotiated medicines was significantly lower than that of Class B medicines (8.72% vs. 12.85%, p = 0.048), whilst the availability of injectable medicines was significantly greater than that of oral medicines (13.66% vs. 8.77%, p = 0.007). In 2019-2021, the annual mean amount purchased increased significantly from CNY 6.51 million to CNY 18.56 million (p = 0.007). The mean defined daily doses of 31 medicines significantly rose from 225.50 to 1019.50 (p = 0.008) whereas their defined daily drug cost significantly decreased from CNY 551.15 to CNY 404.50 (p < 0.001). The percentage of catastrophic health expenditure decreased from 71.0 to 51.65% and from 90.30 to 80.60% for urban and rural residents, respectively. The affordability of nationally negotiated medicines was significantly lower than that of Class B medicines (p = 0.032), and the affordability of injectable medicines had no significant difference compared to that of oral medicines (p = 0.124) for both urban and rural residents. Conclusion: The accessibility of anticancer medicines improved dramatically in public hospitals of Northwestern China during the period 2019-2021.

Cost-Effectiveness of Recombinant Zoster Vaccine for Adults Aged ≥50 Years in China.

INTRODUCTION: Adjuvanted recombinant zoster vaccine (RZV) was the first vaccine made available for herpes zoster in China. Authors aimed to evaluate its economic and health impacts on Chinese adults aged ≥50 years. METHODS: A lifetime Markov model was developed to compare the cost-effectiveness of RZV with that of no vaccination from a societal perspective. Model inputs were derived from published literature and analyzed in 2022. Outcomes included total costs, quality-adjusted life-years, incremental cost-effectiveness ratio, and number of herpes zoster and herpes zoster-related cases. Sensitivity analyses were performed to examine the robustness of the model results. RESULTS: RZV was more costly than no vaccination by $2.78 billion with an additional 65,008 quality-adjusted life-years gained and could avoid 1,893,530 herpes zoster cases, 295,761 postherpetic neuralgia cases, 51,734 other complications, and 229 herpes zoster-related deaths. Incremental cost-effectiveness ratios of RZV varied in a range of $34,465.5-$51,002.7 per quality-adjusted life-year. RZV for the entire cohort would be cost-effective when discount rate was <2.4%, a waning rate of 2-dose RZV efficacy decreased to <0.8%, the utility of postherpetic neuralgia was <0.496, duration of postherpetic neuralgia was >12.86 months, or the cost of RZV per dose decreased to <$229.6. In a probabilistic sensitivity analysis, the probability of RZV being cost-effective was 43.95%, 59.32%, 45.27%, and 39.50% for people aged 50-59, 60-69, 70-79, and ≥80 years, respectively, with threefold gross domestic product per capita (37,654.5 per quality-adjusted life-year) as the willingness-to-pay threshold. CONCLUSIONS: RZV was most likely to be cost-effective in people aged 60-69 years. A slight decrease in vaccine cost would result in RZV being cost-effective in all people aged ≥50 years.

Impact of video-led educational intervention on uptake of influenza vaccine among the elderly in western China: a community-based randomized controlled trial.

BACKGROUND: Influenza vaccination coverage rate among the elderly is low in China. We aimed to evaluate the impact of video-led educational intervention on influenza vaccine uptake among the Chinese elderly. METHODS: A randomized controlled trial was conducted in 8 communities of Xi'an, a representative city in western China. Elderly aged over 60 years were randomized to the control group and intervention group (12-minute video education on influenza and its vaccination). Participants' knowledge, attitudes, and practices (KAP) of influenza was assessed by using a questionnaire survey before and after the intervention. The primary outcomes were participants' willingness to get influenza vaccinated and their actual uptake rates in the 2020-21 flu season. Secondary outcomes were the variations of pre- and post-intervention KAP scores. Intention-to-treat analysis was performed to analyze the data, and sensitivity analyses were conducted to examine the robustness of the results. RESULTS: A total of 350 people were enrolled, with 175 individuals for each group. Participants in the intervention group were more willing to receive influenza vaccination than those in the control group (64.6% vs. 51.4%, p<0.05). The influenza vaccination uptake rate occurred in 10.3% of participants in the intervention group and 3.4% in the control group (odds ratio, 3.23; 95% CI 1.25-8.32, p<0.001). The post-intervention KAP scores in the intervention group were significantly higher compared to those in the control group (p<0.001). CONCLUSION: Video-led education was an effective and feasible approach to improve old people's willingness and uptake of influenza vaccination in western China.

Parental Preferences of Influenza Vaccination for Children in China: A National Survey with a Discrete Choice Experiment.

The influenza vaccination coverage among children is low in China. We aimed to conduct a nationwide survey to quantify parental preferences and willingness to pay (WTP) for influenza vaccination for their children. Parents with children aged six months to 18 years from six provinces in China were investigated by a discrete choice experiment regarding six influenza vaccination attributes. Mixed logit models were used to estimate the relative importance of vaccine attributes and parents' WTP. Interaction analysis and subgroup analysis were conducted to explore preference heterogeneity. A total of 1206 parents were included in the analysis. Parents reported vaccine effectiveness as the most important vaccine attribute. The mode of vaccine administration had no significant impact on parents' preferences. Parents aged over 30 years with higher education or income levels were more likely to prefer no influenza vaccination for their children. The largest marginal WTP (CNY 802.57) for vaccination and the largest increase in vaccine uptake (41.85%) occurred with improved vaccine effectiveness from 30% to 80%. Parents from central regions or mid-latitude areas had a relatively lower WTP than those from other regions. No significant difference in the relative importance of vaccine attributes were observed among parents from various regions of China.

Knowledge, attitudes, and practices towards influenza among Chinese adults during the epidemic of COVID-19: a cross-sectional online survey.

The epidemic of coronavirus disease 2019 (COVID-19) broke out during the peak season of influenza in China. We aimed to assess the knowledge, attitudes, and practices (KAP) of influenza among Chinese adults during this special season. A cross-sectional online questionnaire survey was performed by recruiting 4822 participants. There were 76.09% of the participants reporting that they learned more knowledge of influenza during the COVID-19 epidemic. The mean knowledge score of participants was 5.51 ± 1.55 (78.7% correct rate), and participants who received influenza vaccination in the past year scored the highest (6.06 ± 1.30, p< .001). Nearly half of the participants (49.63%) agreed the threat to the functioning of society by influenza was far less than the COVID-19. 73.04% of the participants knew influenza vaccination was the most effective way to prevent influenza infection, while 54.18% did not know the vaccination location. The proportion of participants who were willing to get vaccinated would increase from 62.53% to 85.82% if clinicians recommended the vaccination. For influenza-like illness, merely 36.11% of participants would seek medical care from the hospital, and 60.53% agreed or showed a neutral attitude toward antibiotic use for influenza treatment. Regression analyses showed that the medical profession and history of influenza vaccination were both associated with higher knowledge or attitude score and participants' use of face masks in previous seasons and their willingness to receive influenza vaccination. In conclusion, the awareness of influenza vaccination among adults in China should be reinforced and educational campaigns were warranted to increase the coverage of influenza vaccination.

Cost-effectiveness analysis of aspirin for primary prevention of cardiovascular events among patients with type 2 diabetes in China.

The use of aspirin for primary prevention of cardiovascular disease (CVD) in patients with diabetes mellitus (DM) is associated with lower rates of cardiovascular events but increased risks of bleeding complications. We aimed to examine the cost-effectiveness of aspirin therapy for primary prevention of CVD in Chinese DM patients. A life-long Markov model was developed to compare aspirin therapy (100mg daily) versus no use of aspirin in DM patients with no history of CVD. Model validation was conducted by comparing the simulated event rates with data reported in a clinical trial. Direct medical costs and quality-adjusted life-years gained (QALYs) were the primary outcomes from the perspective of healthcare system in China. Sensitivity analyses were performed to examine the uncertainty of model inputs. Base-case analysis showed aspirin therapy was more costly (USD1,086 versus USD819) with higher QALYs gained (11.94 versus 11.86 QALYs) compared to no use of aspirin. The base-case results were sensitive to the odds ratio of all-cause death in aspirin therapy versus no use of aspirin. Probabilistic sensitivity analysis found that aspirin therapy gained an additional 0.066 QALYs (95% CI: -0.167 QALYs-0.286 QALYs) at higher cost by USD352 (95% CI: USD130-644)). Using 30,000 USD/QALY as willingness-to-pay threshold, aspirin therapy and no use of aspirin were the preferred option in 68.71% and 31.29% of 10,000 Monte Carlo simulations, respectively. In conclusion, aspirin therapy appears to be cost-effective compared with no use of aspirin in primary prevention of CVD in Chinese DM patients.

Screening anti-tumor compounds from Ligusticum wallichii using cell membrane chromatography combined with high-performance liquid chromatography and mass spectrometry.

Tyrosine 367 Cysteine-fibroblast growth factor receptor 4 cell membrane chromatography combined with high-performance liquid chromatography and mass spectrometry was developed. Tyrosine 367 Cysteine-HEK293 cells were used as the cell membrane stationary phase. The specificity and reproducibility of the cell membrane chromatography was evaluated using 1-tert-butyl-3-{2-[4-(diethylamino)butylamino]-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl}urea, nimodipine and dexamethasone acetate. Then, anti-tumor components acting on Tyrosine 367 Cysteine-fibroblast growth factor receptor 4 were screened and identified from extracts of Ligusticum wallichii. Components from the extract were retained on the cell membrane chromatographic column. The retained fraction was directly eluted into high-performance liquid chromatography with mass spectrometry system for separation and identification. Finally, Levistolide A was identified as an active component from Ligusticum wallichii extracts. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide-formazan colorimetric assay revealed that Levistolide A inhibits proliferation of overexpressing the mutated receptor cells with dose-dependent manner. Phosphorylation of fibroblast growth factor receptor 4 was also decrease under Levistolide A treatment. Flex dock simulation verified that Levistolide A could bind with the tyrosine kinase domain of fibroblast growth factor receptor 4. Therefore, Levistolide A screened by the cell membrane chromatography combined with high-performance liquid chromatography and mass spectrometry can arrest cell growth. In conclusion, the two-dimensional high-performance liquid chromatography method can screen and identify potential anti-tumor ingredients that specifically act on the tyrosine kinase domain of the mutated fibroblast growth factor receptor 4.

Palmitic acid exerts pro-inflammatory effects on vascular smooth muscle cells by inducing the expression of C-reactive protein, inducible nitric oxide synthase and tumor necrosis factor-α.

Atherosclerosis is a chronic inflammatory disease in the vessel, and inflammatory cytokines play an important role in the inflammatory process of atherosclerosis. A high level of free fatty acids (FFAs) produced in lipid metabolism disorders are known to participate in the formation of atherosclerosis through multiple bioactivities. As the main saturated fatty acid in FFAs, palmitic acid stimulates the expression of inflammatory cytokines in macrophages. However, it is unclear whether palmitic acid exerts a pro-inflammatory effect on vascular smooth muscle cells (VSMCs). The purpose of the present study was to observe the effect of palmitic acid on the expression of C-reactive protein (CRP), tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) in VSMCs. Rat VSMCs were cultured, and palmitic acid was used as a stimulant for CRP, TNF-α and iNOS expression. mRNA expression was assayed with reverse transcription-polymerase chain reaction, and protein expression was detected with western blot analysis and immunocytochemistry. The results showed that palmitic acid significantly stimulated mRNA and protein expression of CRP, TNF-α and iNOS in VSMCs in time- and concentration-dependent manners, and therefore, palmitic acid is able to exert a pro-inflammatory effect on VSMCs via stimulating CRP, TNF-α and iNOS expression. The findings provide a novel explanation for the direct pro-inflammatory and atherogenic effects of palmitic acid, and for the association with metabolic syndrome, such as type 2 diabetes mellitus, obesity and atherosclerosis. Therefore, the intervention with anti-inflammatory agents may effectively delay the formation and progression of atherosclerosis in patients with metabolic syndrome.

Homocysteine induces the expression of C-reactive protein via NMDAr-ROS-MAPK-NF-κB signal pathway in rat vascular smooth muscle cells.

OBJECTIVE: Homocysteine (Hcy) is known as an independent risk factor for atherosclerosis. C-reactive protein (CRP) directly participates in initiation and progression of atherosclerosis. However, there is no direct evidence to demonstrate pro-inflammatory effect of Hcy on vascular smooth muscle cells (VSMCs) through CRP. In the present study, we examined the effect of Hcy on CRP expression and investigated the related mechanism in VSMCs. METHODS AND RESULTS: Protein expression and secretion were detected by Western blot and ELISA, respectively. mRNA expression was detected by RT-PCR. Superoxide anion was detected by lucigenin chemiluminometry and the immunofluorescence staining was observed by a fluorescence microscope. The results revealed that Hcy significantly induced mRNA and protein expressions of CRP in VSMCs both in vitro and in vivo, and anti-IL-1ß or anti-IL-6 neutralizing antibody alone or in combination partially reduced Hcy-induced CRP expression. Hcy increased the expression of NR1 subunit of N-methyl-d-aspartate receptor (NMDAr), and MK-801 alleviated Hcy-induced CRP expression in VSMCs. Further studies showed that Hcy-stimulated superoxide anion generation in VSMCs. Nevertheless, pretreatment of the cells with MK-801, TTFA and DPI significantly reduced Hcy-stimulated superoxide anion generation, and antioxidant NAC decreased Hcy-induced CRP expression in VSMCs. Additionally, PD98059, SB205380 or PDTC antagonized Hcy-induced CRP expression, and MK-801, NAC, PD98059 or SB205380 inhibited Hcy-activated phosphorylations of ERK1/2 and p38. CONCLUSION: The present study demonstrates that Hcy is able to initiate an inflammatory response in VSMCs by stimulating CRP production, which is mediated through NMDAr-ROS-ERK1/2/p38-NF-κB signal pathway. These findings provide new evidence for a role of Hcy in pathogenesis of atherosclerosis.

Sinapine as an active compound for inhibiting the proliferation of Caco-2 cells via downregulation of P-glycoprotein.

Sinapine, an alkaloid from seeds of the cruciferous species, shows favorable biological activities such as antioxidant and radio-protective activities. However, the inhibitory effect of sinapine on tumors, and the molecular mechanisms have not been completely understood thus far. In this study, we determined anti-proliferative effects of sinapine. We examined the anti-tumor effects of the combination of sinapine and doxorubicin. The results of the MTT assay and apoptosis showed that sinapine increased the sensitivity of Caco-2 cells to doxorubicin in a dose-dependent manner, whereas no or less effect was observed in the cells treated with doxorubicin alone. The combination of sinapine and doxorubicin had a synergistic effect and increased the cytotoxicity of doxorubicin against Caco-2 cells. Doxorubicin accumulation assay showed that sinapine increased the intracellular accumulation of doxorubicin in dose-dependent manner. Immunoblotting and QT-PCR analysis showed that sinapine suppressed P-glycoprotein (P-gp) expression via ubiquitination. A significant correlation was observed between the expression of p-ERK1/2 and P-gp. These results indicated that sinapine played an important role in the down-regulation of P-gp expression through suppression of FGFR4-FRS2α-ERK1/2 signaling pathway. To our knowledge, this is the first study to show that sinapine can be used as an effective natural compound for chemo-resistance.

Ellagic acid-induced thrombotic focal cerebral ischemic model in rats.

INTRODUCTION: Ischemic stroke is a common cause of human disability and death. Animal models of focal cerebral ischemia are widely utilized to mimic human ischemic stroke. Although models of focal cerebral ischemia have been well established, very few evidence is based on triggering the intrinsic coagulation system to induce focal cerebral ischemia. Ellagic acid (EA) has been identified to trigger the intrinsic coagulation system via activating coagulation factor XII. However, it remains unknown whether EA can serve as a novel pharmacological approach to induce a new model of focal cerebral ischemia in rats. METHODS: EA was used for inducing focal cerebral ischemia in adult rats. The dose- and time-dependent effects of EA were characterized. The cerebral infarction ratio was determined with triphenyltetrazolium chloride staining, and the histopathological analysis of the brain tissue was performed under light microscopy. The neurological deficit score was evaluated by a modified method of Bederson. Malondialdehyde (MDA) level and lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activities in serum were determined by spectrophotometry. RESULTS: Injection of EA into the middle cerebral artery of rats was able to generate focal cerebral infarction and increased the neurological deficit score and the brain weight to body weight ratio in dose- and time-dependent manners. Furthermore, EA raised serum LDH activity and MDA level and decreased serum SOD activity in a dose-related fashion. DISCUSSION: This is the first evidence to show that EA induces focal cerebral ischemia in rats, which is similar to human ischemia stroke in pathogenesis. This model holds promise for pathological, pharmacological and clinical studies of ischemic stroke.

Angiotensin II induces C-reactive protein expression via AT1-ROS-MAPK-NF-κB signal pathway in hepatocytes.

BACKGROUND: C-reactive protein (CRP) participates in development of inflammatory diseases. Hepatocytes are a major contributor of circulating CRP. Although angiotensin II (Ang II) is known to evoke inflammatory response, it remains unknown whether Ang II induces CRP expression in hepatocytes. The present study observed effect of Ang II on CRP expression and the related signal pathway in hepatocytes. METHODS: mRNA and protein expressions in human hepatocytes were determined with RT-PCR and Western blot respectively. Reactive oxygen species (ROS) was measured using a fluorescence probe. CRP in liver and serum of rats was determined by immunohistochemistry and ELISA respectively. RESULTS: Ang II induced mRNA and protein expression of CRP in hepatocytes and increased CRP production in liver and CRP level in serum. Losartan reduced Ang II- induced CRP expression in hepatocytes. Losartan and thenoyltrifluoroacetone decreased Ang II-stimulated ROS production. N-acetylcysteine antagonized Ang II-induced CRP expression. Losartan and N-acetylcysteine inhibited Ang II-activated ERK1/2. Unlike ERK1/2, only losartan inhibited Ang II-activated JNK. Furthermore, pyrrolidine dithiocarbamate abolished Ang II-induced CRP expression. CONCLUSION: Ang II has ability to induce CRP expression in hepatocytes in vitro and in vivo through AT1 receptor followed by ROS, MAPK and NF-κB signal pathway.

Screening of target compounds from Fructus Piperis using high α1A adrenoreceptor expression cell membrane chromatography online coupled with high performance liquid chromatography tandem mass spectrometry.

Benign prostatic hyperplasia (BPH) is a common disease in elderly men. The main treatment for BPH is α-adrenergic antagonists and 5α-reductase inhibitors. In this study, a two-dimensional (2D) α1A cell membrane chromatography (CMC) online liquid chromatography/mass spectrometry system was built. Fructus Piperis, a traditional Chinese medicine and food homolog, was assayed with this 2D system. Piperine was identified as the active compound acting on α1A receptors. A competitive binding assay and molecular docking assay were performed to investigate the binding sites and the affinity of piperine for the α1A receptor. The results of the competitive binding assay (dissociation equilibrium constant of tamsulosin was 1.43 × 10(-6)M and piperine was 2.13 × 10(-6)M) and molecular docking assay (total score for tamsulosin binding with the α1A receptor was 6.9719, and for piperine it was 4.4891) corresponded with the retention time of tamsulosin and piperine on the α1A/CMC column.