Transcriptomic analysis provides an insight into the function of CmGH9B3, a key gene of ß-1, 4-glucanase, during the graft union healing of oriental melon scion grafted onto squash rootstock.

The melon (Cucumis melo L.) is a globally cherished and economically significant crop. The grafting technique has been widely used in the vegetative propagation of melon to promote environmental tolerance and disease resistance. However, mechanisms governing graft healing and potential incompatibilities in melons following the grafting process remain unknown. To uncover the molecular mechanism of healing of grafted melon seedlings, melon wild type (Control) and TRV-CmGH9B3 lines were obtained and grafted onto the squash rootstocks (C. moschata). Anatomical differences indicated that the healing process of the TRV-CmGH9B3 plants was slower than that of the control. A total of 335 significantly differentially expressed genes (DEGs) were detected between two transcriptomes. Most of these DEGs were down-regulated in TRV-CmGH9B3 grafted seedlings. GO and KEGG analysis showed that many metabolic, physiological, and hormonal responses were involved in graft healing, including metabolic processes, plant hormone signaling, plant MAPK pathway, and sucrose starch pathway. During the healing process of TRV-CmGH9B3 grafted seedlings, gene synthesis related to hormone signal transduction (auxin, cytokinin, gibberellin, brassinolide) was delayed. At the same time, it was found that most of the DEGs related to the sucrose pathway were down-regulated in TRV-CmGH9B3 grafted seedlings. The results showed that sugar was also involved in the healing process of melon grafted onto squash. These results deepened our understanding of the molecular mechanism of GH9B3, a key gene of ß-1, 4-glucanase. It also provided a reference for elucidating the gene mechanism and function analysis of CmGH9B3 in the process of graft union healing.

Exogenous Melatonin Application Accelerated the Healing Process of Oriental Melon Grafted onto Squash by Promoting Lignin Accumulation.

Melatonin (MT) is a vital hormone factor in plant growth and development, yet its potential to influence the graft union healing process has not been reported. In this study, we examined the effects of MT on the healing of oriental melon scion grafted onto squash rootstock. The studies indicate that the exogenous MT treatment promotes the lignin content of oriental melon and squash stems by increasing the enzyme activities of hydroxycinnamoyl CoA ligase (HCT), hydroxy cinnamaldehyde dehydrogenase (HCALDH), caffeic acid/5-hydroxy-conifer aldehyde O-methyltransferase (COMT), caffeoyl-CoA O-methyltransferase (CCoAOMT), phenylalanine ammonia-lyase (PAL), 4-hydroxycinnamate CoA ligase (4CL), and cinnamyl alcohol dehydrogenase (CAD). Using the oriental melon and squash treated with the exogenous MT to graft, the connection of oriental melon scion and squash rootstock was more efficient and faster due to higher expression of wound-induced dedifferentiation 1 (WIND1), cyclin-dependent kinase (CDKB1;2), target of monopteros 6 (TMO6), and vascular-related NAC-domain 7 (VND7). Further research found that the exogenous MT increased the lignin content of the oriental melon scion stem by regulating CmCAD1 expression, and then accelerated the graft healing process. In addition, the root growth of grafted seedlings treated with the exogenous MT was more vigorous.

New insight into the catalytic mechanism of ester hydrogenation over the Cu/ZnO catalyst: the contribution of hydrogen spillover.

The dimethyl maleate hydrogenation activity of Cu, ZnO-X and physically mixed Cu+ZnO-X samples was systematically investigated to probe the essential role of ZnO in ester hydrogenation processes. Cu samples exhibited high CC bond hydrogenation ability with dimethyl succinate as the main product. Comparatively, ZnO was inactive in hydrogenation due to its weak ability to dissociate hydrogen while the CO group could be activated and adsorbed on the ZnO surface. Interestingly, physical mixing with ZnO significantly improved the CO hydrogenation activity of Cu samples. The H2-TPD results reveal the origin of "Cu-ZnO synergy": hydrogen atoms formed on the copper surface can spill over to the ZnO surface and react with the adsorbed CO group.

Crop/Plant Modeling Supports Plant Breeding: I. Optimization of Environmental Factors in Accelerating Crop Growth and Development for Speed Breeding.

The environmental conditions in customered speed breeding practice are, to some extent, empirical and, thus, can be further optimized. Crop and plant models have been developed as powerful tools in predicting growth and development under various environments for extensive crop species. To improve speed breeding, crop models can be used to predict the phenotypes resulted from genotype by environment by management at the population level, while plant models can be used to examine 3-dimensional plant architectural development by microenvironments at the organ level. By justifying the simulations via numerous virtual trials using models in testing genotype × environment × management, an optimized combination of environmental factors in achieving desired plant phenotypes can be quickly determined. Artificial intelligence in assisting for optimization is also discussed. We admit that the appropriate modifications on modeling algorithms or adding new modules may be necessary in optimizing speed breeding for specific uses. Overall, this review demonstrates that crop and plant models are promising tools in providing the optimized combinations of environment factors in advancing crop growth and development for speed breeding.

Genome-Wide Characteristics of GH9B Family Members in Melon and Their Expression Profiles under Exogenous Hormone and Far-Red Light Treatment during the Grafting Healing Process.

ß-1,4-glucanase can not only promote the wound healing of grafted seedlings but can also have a positive effect on a plant's cell wall construction. As a critical gene of ß-1,4-glucanase, GH9B is involved in cell wall remodeling and intercellular adhesion and plays a vital role in grafting healing. However, the GH9B family members have not yet been characterized for melons. In this study, 18 CmGH9Bs were identified from the melon genome, and these CmGH9Bs were located on 15 chromosomes. Our phylogenetic analysis of these CmGH9B genes and GH9B genes from other species divided them into three clusters. The gene structure and conserved functional domains of CmGH9Bs in different populations differed significantly. However, CmGH9Bs responded to cis elements such as low temperature, exogenous hormones, drought, and injury induction. The expression profiles of CmGH9Bs were different. During the graft healing process of the melon scion grafted onto the squash rootstock, both exogenous naphthyl acetic acid (NAA) and far-red light treatment significantly induced the upregulated expression of CmGH9B14 related to the graft healing process. The results provided a technical possibility for managing the graft healing of melon grafted onto squash by regulating CmGH9B14 expression.

Nickel-Catalyzed Tunable Enantioconvergence and Kinetic Resolution in the Coupling of Tertiary Cyclobutenols with Arylboroxines.

We report that a nickel catalyst system with a modified 1,1'-spirobiindane-7,7'-diol-phosphoramidite (SPINOL) as the chiral ligand can enable the coupling of tertiary cyclobutenols and arylboroxines in an enantioconvergent manner, providing cyclobutenes with an all-carbon quaternary stereocenter in good yields (up to 84 % yield) with excellent enantioselectivities (up to >99 % ee). Moreover, the catalytic system can be applied in the kinetic resolution of cyclobutenols under slightly modified conditions, giving enantioenriched tertiary cyclobutenols with an s factor of up to >200. The reaction uses free hydroxyl groups as the leaving group without additional activation while the strained ring remains untouched. Preliminary mechanistic studies reveal that the inherent discrepant reactivity of the two enantiomers is the key to the controllable enantioconvergent and kinetic resolution process.

Physiology and Molecular Breeding in Sustaining Wheat Grain Setting and Quality under Spring Cold Stress.

Spring cold stress (SCS) compromises the reproductive growth of wheat, being a major constraint in achieving high grain yield and quality in winter wheat. To sustain wheat productivity in SCS conditions, breeding cultivars conferring cold tolerance is key. In this review, we examine how grain setting and quality traits are affected by SCS, which may occur at the pre-anthesis stage. We have investigated the physiological and molecular mechanisms involved in floret and spikelet SCS tolerance. It includes the protective enzymes scavenging reactive oxygen species (ROS), hormonal adjustment, and carbohydrate metabolism. Lastly, we explored quantitative trait loci (QTLs) that regulate SCS for identifying candidate genes for breeding. The existing cultivars for SCS tolerance were primarily bred on agronomic and morphophysiological traits and lacked in molecular investigations. Therefore, breeding novel wheat cultivars based on QTLs and associated genes underlying the fundamental resistance mechanism is urgently needed to sustain grain setting and quality under SCS.

Lewis Acid-Catalyzed Ring-Opening Cross-Coupling Reaction of gem-Difluorinated Cyclopropanes Enabled by C-F Bond Activation.

gem-Difluorinated cyclopropanes have attracted wide research interest in organic synthesis due to their high reactivity. Herein, we report a Lewis acid-catalyzed cross-coupling reaction of mono- and disubstituted gem-difluorinated cyclopropanes with nucleophiles. The formation of a fluoroallyl cation species triggered via the Lewis acid-assisted activation of the C-F bond is proposed in this transformation. The cation species is then trapped by the nucleophiles, including electron-rich arenes and allylsilanes, to deliver a series of fluoroallylic products in good yields. The reaction provides an alternative mode for using gem-difluorinated cyclopropanes as fluoroallyl surrogates.

Overcoming Reproductive Compromise Under Heat Stress in Wheat: Physiological and Genetic Regulation, and Breeding Strategy.

The reproductive compromise under heat stress is a major obstacle to achieve high grain yield and quality in wheat worldwide. Securing reproductive success is the key solution to sustain wheat productivity by understanding the physiological mechanism and molecular basis in conferring heat tolerance and utilizing the candidate gene resources for breeding. In this study, we examined the performance on both carbon supply source (as leaf photosynthetic rate) and carbon sink intake (as grain yields and quality) in wheat under heat stress varying with timing, duration, and intensity, and we further surveyed physiological processes from source to sink and the associated genetic basis in regulating reproductive thermotolerance; in addition, we summarized the quantitative trait loci (QTLs) and genes identified for heat stress tolerance associated with reproductive stages. Discovery of novel genes for thermotolerance is made more efficient via the combination of transcriptomics, proteomics, metabolomics, and phenomics. Gene editing of specific genes for novel varieties governing heat tolerance is also discussed.

Catalytic Conversion of 5-Hydroxymethylfurfural to High-Value Derivatives by Selective Activation of C-O, C=O, and C=C Bonds.

With increasing concern for reducing CO2 emission and alleviating fossil resource dependence, catalytic transformation of 5-hydroxymethylfurfural (HMF), a vital platform compound derived from C6 sugars, holds great promise for producing value-added chemicals. Among several well-established catalytic systems, hydrogenation and oxidation processes have been efficiently adopted for upgrading HMF. This Review covers recent advances in the development of thermocatalytic conversion of HMF into value-added chemicals. The advances of metal-catalyzed hydrogenation, hydrogenolysis, ring-opening, decarbonylation, and oxidation involving selective activation of C-O, C=O, and C=C groups are described. The roles played by nature of metals, supports, additives, synergy of metal-acid sites, and metal-support interaction are also discussed at the molecular level. Finally, an outlook is provided to highlight major challenges associated with this huge research area.

Scion-to-Rootstock Mobile Transcription Factor CmHY5 Positively Modulates the Nitrate Uptake Capacity of Melon Scion Grafted on Squash Rootstock.

It is generally recognized that the root uptake capacity of grafted plants strongly depends on the rootstocks' well-developed root system. However, we found that grafted plants showed different nitrate uptake capacities when different varieties of oriental melon scion were grafted onto the same squash rootstock, suggesting that the scion regulated the nitrate uptake capacity of the rootstock root. In this study, we estimated the nitrate uptake capacity of grafted plants with the different oriental melon varieties' seedlings grafted onto the same squash rootstocks. The results indicated a significant difference in the nitrate uptake rate and activity of two heterologous grafting plants. We also showed a significant difference in CmoNRT2.1 expression in the roots of two grafting combinations and verified the positive regulation of nitrate uptake by CmoNRT2.1 expression. In addition, the two varieties of oriental melon scion had highly significant differences in CmHY5 expression, which was transported to the rootstock and positively induced CmoHY5-1 and CmoHY5-2 expression in the rootstock roots. Meanwhile, CmHY5 could positively regulate CmoNRT2.1 expression in the rootstock roots. Furthermore, CmoHY5-1 and CmoHY5-2 also positively regulated CmoNRT2.1 expression, respectively, and CmoHY5-1 dominated the positive regulation of CmoNRT2.1, while CmHY5 could interact with CmoHY5-1 and CmoHY5-2, respectively, to jointly regulate CmoNRT2.1 expression. The oriental melon scion regulated the nitrate uptake capacity of the melon/squash grafting plant roots, and the higher expression of CmHY5 in the oriental melon scion leaves, the more substantial the nitrate uptake capacity of squash rootstock roots.

The impact of policy on availability and price of low-price medicines in public healthcare institutions: A retrospective survey in Nanjing, China.

In an effort to promote rational drug pricing and relieve the pressure of drug shortages, the Chinese government implemented a low-price medicine (LPM) policy in July 2014, and abolished price regulations for most medications in June 2015. This study examines trends in the availability and pricing of LPMs since policy implementation. Data on price and availability of 752 LPMs during 2013-2017 were obtained from the Jiangsu Institute of Medicine Information. Availability was defined as the proportion of facilities in which a medicine was in inventory during each survey period. A price index was constructed based on purchasing prices in 40 public healthcare facilities, using a standard method developed by the International Labour Organization. Mean availability fluctuated slightly but held at low levels (<15%). Levels were conspicuously lower in primary hospitals than in secondary and tertiary hospitals. Our logistic regression model showed that the essential medicine designation was the main factor facilitating availability. The overall price index remained static before implementation of the policy, while there was a marked upward trend after implementation of the policy. Further efforts are needed to improve the pharmaceutical supply system, and simultaneously curb unreasonable inflation in medicine costs.

Microfluidic Chip with Two-Stage Isothermal Amplification Method for Highly Sensitive Parallel Detection of SARS-CoV-2 and Measles Virus.

A two-stage isothermal amplification method, which consists of a first-stage basic recombinase polymerase amplification (RPA) and a second-stage fluorescence loop-mediated isothermal amplification (LAMP), as well as a microfluidic-chip-based portable system, were developed in this study; these enabled parallel detection of multiplex targets in real time in around one hour, with high sensitivity and specificity, without cross-contamination. The consumption of the sample and the reagent was 2.1 µL and 10.6 µL per reaction for RPA and LAMP, respectively. The lowest detection limit (LOD) was about 10 copies. The clinical amplification of about 40 nasopharyngeal swab samples, containing 17 SARS-CoV-2 (severe acute respiratory syndrome coronavirus) and 23 measles viruses (MV), were parallel tested by using the microfluidic chip. Both clinical specificity and sensitivity were 100% for MV, and the clinical specificity and sensitivity were 94.12% and 95.83% for SARS-CoV-2, respectively. This two-stage isothermal amplification method based on the microfluidic chip format offers a convenient, clinically parallel molecular diagnostic method, which can identify different nucleic acid samples simultaneously and in a timely manner, and with a low cost of the reaction reagent. It is especially suitable for resource-limited areas and point-of-care testing (POCT).

Trends and Patterns of Antibiotics Use in China's Urban Tertiary Hospitals, 2016-19.

Objectives: This study aimed to identify the trends in antibiotics utilization and patients costs, evaluating the effect of the policy and exploring factors associated with the irrational use of antibiotics. Methods: Based on the Cooperation Project Database of Hospital Prescriptions, data were collected from 89 tertiary hospitals in nine cities in China during 2016-2019. The study sample consisted of prescription records with antibiotics for 3,422,710 outpatient and emergency visits and 26, 118, 436 inpatient hospitalizations. Results: For outpatients, the proportion of treated with antibiotics declined from 14.72 to 13.92% significantly (p < 0.01). The proportion of antibiotic costs for outpatients decreased from 5.79 to 4.45% significantly (p < 0.01). For emergency patients, the proportion of treated with antibiotics increased from 39.31 to 43.45% significantly (p < 0.01). The proportion of antibiotic costs for emergency patients decreased from 36.44 to 34.69%, with no significant change (p = 0.87). For inpatients, the proportion of treated with antibiotics increased from 23.82 to 27.25% significantly (p < 0.01). The proportion of antibiotic costs for outpatients decreased from 18.09 to 17.19% with no statistical significance (p = 0.89). Other ß-lactam antibacterials (1,663.03 ten thousand DDD) far exceeded other antibiotics categories. Stablely ranked first, followed by Macrolides, lincosamide and streptogramins (965.74 ten thousand DDD), Quinolone antibacterials (710.42 ten thousand DDD), and ß-lactam antibacterials, penicillins (497.01 ten thousand DDD). Conclusions: The proportion of treated with antibiotics for outpatients and inpatients meet the WHO standards. The antibiotics use varied by different survey areas, clinical departments, patient gender, patient age and antibiotics categories. More efforts should focus on improving the appropriateness of antibiotics use at the individual level.

Large-scale field phenotyping using backpack LiDAR and CropQuant-3D to measure structural variation in wheat.

Plant phenomics bridges the gap between traits of agricultural importance and genomic information. Limitations of current field-based phenotyping solutions include mobility, affordability, throughput, accuracy, scalability, and the ability to analyze big data collected. Here, we present a large-scale phenotyping solution that combines a commercial backpack Light Detection and Ranging (LiDAR) device and our analytic software, CropQuant-3D, which have been applied jointly to phenotype wheat (Triticum aestivum) and associated 3D trait analysis. The use of LiDAR can acquire millions of 3D points to represent spatial features of crops, and CropQuant-3D can extract meaningful traits from large, complex point clouds. In a case study examining the response of wheat varieties to three different levels of nitrogen fertilization in field experiments, the combined solution differentiated significant genotype and treatment effects on crop growth and structural variation in the canopy, with strong correlations with manual measurements. Hence, we demonstrate that this system could consistently perform 3D trait analysis at a larger scale and more quickly than heretofore possible and addresses challenges in mobility, throughput, and scalability. To ensure our work could reach non-expert users, we developed an open-source graphical user interface for CropQuant-3D. We, therefore, believe that the combined system is easy-to-use and could be used as a reliable research tool in multi-location phenotyping for both crop research and breeding. Furthermore, together with the fast maturity of LiDAR technologies, the system has the potential for further development in accuracy and affordability, contributing to the resolution of the phenotyping bottleneck and exploiting available genomic resources more effectively.

Impact of the National Health Insurance Coverage Policy on the Utilisation and Accessibility of Innovative Anti-cancer Medicines in China: An Interrupted Time-Series Study.

Objective: The study aimed to evaluate the impact of the National Health Insurance Coverage (NHIC) policy on the utilisation and accessibility of innovative anti-cancer medicines in Nanjing, China. Methods: We used the adjusted World Health Organisation and Health Action International methodology to calculate the price and availability of 15 innovative anti-cancer medicines included in the National Health Insurance drug list in 20 tertiary hospitals and six secondary hospitals in Nanjing before and after NHIC policy implementation. Interrupted time-series regression was used to analyse the changes in the utilisation of the study medicines. Results: The price reduction rates of innovative anti-cancer medicines ranged between 34 and 65%. The mean availability rate was 27.44% before policy implementation and increased to 47.33% after policy implementation. The utilisation of anti-cancer medicines suddenly increased with a slope of 33.19-2,628.39 when the policy was implemented. Moreover, the usage rate of bevacizumab, bortezomib, and apatinib significantly increased (p < 0.001, p = 0.009, and p < 0.001, respectively) after policy implementation. With regard to price reduction and medical insurance reimbursement, the medicines became more affordable after policy implementation (0.06-1.90 times the per capita annual disposable income for urban patients and 0.13-4.46 times the per capita annual disposable income for rural patients). Conclusion: The NHIC policy, which was released by the central government, effectively improved the utilisation and affordability of innovative anti-cancer medicines. However, the availability of innovative anti-cancer medicines in hospitals remained low and the utilisation of innovative anti-cancer medicines was affected by some factors, including the incidence of cancer, limitation of indications within the insurance program, and the rational use of innovative anti-cancer medicines. It is necessary to improve relevant supporting policies to promote the affordability of patients. The government should speed up the process of price negotiation to include more innovative anti-cancer medicines in the medical insurance coverage, consider including both medical examinations and adjuvant chemotherapy in the medical insurance, and increase investment in health care.

Availability, cost and affordability of selected antibiotics and antiviral medicines against infectious diseases from 2013 to 2019 in Nanjing, China.

OBJECTIVES: As economic globalisation develops in-depth, infectious diseases that occur in a country or region no longer remains a regional issue. Antibiotics and antiviral medicines are essential medicines for the therapy of infectious diseases. This study aims to evaluate their availability, cost and affordability of AaAMs against infectious diseases in 41 public hospitals from 2013 to 2019 in Nanjing, China. METHODS: Data on the availability and price of 17 antibiotics and 6 antiviral medicines in 41 public hospitals were obtained from the Jiangsu Institute of Medicine Information. We adopted the WHO/Health Action International method to measure the availability, cost and affordability of these medicines. RESULTS: The availability of selected medicines against infectious diseases was relatively low; the median availability of originator brands was near-zero and that of lowest-priced generics during the survey period less than 50%. The total availability of medicines was poor in primary hospitals as compared to secondary and tertiary hospitals. The median daily-defined dose cost of originator brands was expensive (range from 66.11 RMB to 107.83 RMB), whereas that of lowest price generics was fairly acceptable at < 8 RMB. The affordability of most surveyed medicines was reasonable, which showed significant improvement over time, but the daily cost of a few medicines for originator brands exceeded the average daily wage. CONCLUSIONS: In general, the affordability of medicines surveyed was acceptable, while the availability was too low. There should be a great concern for improving the reserve system of anti-infective medicines in healthcare institutions. Policy should focus on improving the availability of generic drugs in hospitals and encouraging preferentially prescribed.

The Effects of County Public Hospital Reform on the Consumption and Costs of Antibiotics: Evidence from a Quasinatural Experiment in Jiangsu, China.

BACKGROUND: Overuse of antibiotics is a major driver for rapid spread of antimicrobial resistance worldwide, particularly common in China. The close linkage between hospital revenue and sales of drugs has become the key incentive for overprescription of antibiotics. Since 2009, the Chinese government implemented a series of measures to cut off the link, including removing the markup of drugs, increasing financial subsidies, and adjusting charges for medical service. OBJECTIVE: To evaluate the impacts of county public hospital reform on the consumption and costs of procured antibiotics in Jiangsu province. METHODS: A quasiexperiment design was conducted in Jiangsu province where 99 county public hospitals implemented the reform successively in different periods. Of these, 37 county public hospitals implemented the reform since January 2013, which were regarded as the intervention group, and the remaining 62 hospitals were included in the control group. A difference-in-differences (DID) analysis with generalized linear regressions was used on the procurement records of antibiotics from January 2012 to December 2013. Modified Park test was used for family distribution and Box-Cox test for log link. Placebo tests were employed to test the common-trend hypothesis of two groups. RESULTS: For the intervention group, the average volume of procured restricted antibiotics and injectable antibiotics increased by 24.12% and 2.75% while the costs increased by 19.01% and 9.09%, respectively. The average costs per DDD of restricted and injectable antibiotics were much higher than unrestricted and oral antibiotics. The DID results showed that the reform had a positive impact on the average volume (p = 0.005) and costs (p = 0.001) of nonrestricted antibiotics. In addition, the implementation of the reform was associated with a reduction in volume (p = 0.031) and costs (p = 0.043) of procured oral antibiotics. The reform also contributed to an increase in average costs per DDD of total antibiotics (p = 0.049). CONCLUSIONS: The reform is effective in reducing the consumption and costs of unrestricted and oral antibiotics, but it has failed to reduce the consumption and costs of expensive restricted and injectable antibiotics, leading to increased burden of diseases. It is critical that the health policy initiatives can deincentivize overuse of antibiotics at both hospital and individual physician's levels. The reform should enforce government financial support, improve hospital governance, optimize performance evaluation, and establish specialized management approach for antibiotic use.

The Effect of the Full Coverage of Essential Medicines Policy on Utilization and Accessibility of Primary Healthcare Service for Rural Seniors: A Time Series Study in Qidong, China.

Background: Since 2015, in order to handle the increasing prevalence of age-related diseases and escalating health expenditures arising from the aging population, the full coverage of essential medicines (FCEMs) policy for rural seniors has been implemented in primary healthcare institutions of Qidong County of Jiangsu, China. The purpose of this study is to examine the long-term effects of the introduction of FCEMs' policy on the utilization and accessibility of primary healthcare service for elderly beneficiaries. Methods: The retrospective study was conducted in Qidong County in the Jiangsu province, China. A 47-month longitudinal dataset involving 91,444 health insurance claims records of inpatients aged 70 and older in primary healthcare institutions was analyzed. Changes in health service utilization (average length of stay), patient copayments (out-of-pocket expenses), New Rural Cooperative Medical System (NRCMS) reimbursement rate and daily hospitalization costs per patient were analyzed using interrupted time series analysis. Augment Dicky-Fuller unit root method was used to test the stationarity of the series alongside the Durbin Watson method to test autocorrelation. Results: Average length of stay increased at 0.372 bed-days per month before the implementation of FCEMs policy, whereas the increasing trend was slowed down at 0.003 bed-days per month after the implementation of FCEMs policy (p < 0.001). The average out-of-pocket expenses increased by 38.035 RMB monthly in pre-implementation of the policy period, but it decreased at the rate of 5.180 RMB per month after the implementation of the FCEMs policy (p = 0.006). The NRCMS reimbursement rate increased at 0.066% per month in pre-implementation of policy and the increasing trend was sharper at 0.349% in post-implementation of policy (p = 0.135). The daily hospitalization costs per patient decreased by 6.263 RMB (p = 0.030) per month, whereas it increased at the rate of 3.119 RMB (p = 0.002) per month afterwards. Conclusions: Based on interrupted time series analyses, we concluded that FCEMs policy was associated with positive changes of average LOS and average OOP expenses. The FCEMs policy has alleviated the financial burden of the rural seniors and slightly improved the efficiency of primary health service utilization. However, it had no positive effect on daily hospitalization costs. Therefore, in the general framework of FCEMs policy, the Chinese health policy-maker should take necessary supporting measures to curb climbing hospitalization expenditures and promote the rational drug use in primary healthcare institutions.

Availability, Price and Affordability of Anticancer Medicines: Evidence from Two Cross-Sectional Surveys in the Jiangsu Province, China.

OBJECTIVES: With the increasing incidence of cancer, poor access to affordable anticancer medicines has been a serious public health problem in China. To help address this issue, we assessed the availability, price and affordability of pharmacotherapy for cancer in public hospitals in the Jiangsu Province, China. METHODS: In 2012 and 2016, anticancer medicine availability and price information in the capital and five other cities was collected. A total of six cancer care hospitals, 26 tertiary general hospitals and 28 secondary general hospitals were sampled, using an adaptation of the World Health Organization/Health Action International methodology. Data was collected for the anticancer medicines in stock at the time of the surveys. Prices were expressed as inflation-adjusted median unit prices (MUPs). Medicine was affordable if the overall cost of all the prescribed anticancer medicines was less than 20% of the household's capacity to pay. We used generalized estimating equations to estimate the significance of differences in availability from 2012 to 2016 and the Wilcoxon rank test to estimate the significance of differences in MUPs. Multivariate logistic regression was computed to measure predictors of affordability. RESULTS: From 2012 to 2016 there was a significant decrease in the mean availability of originator brands (OBs) (from 7.79% to 5.71%, p = 0.012) and lowest-priced generics (LPGs) (36.29% to 32.67%, p = 0.009). The mean availability of anticancer medicines in secondary general hospitals was significantly lower than the cancer care, as well as in tertiary general hospitals. The MUPs of OBs (difference: -21.29%, p < 0.01) and their LPGs (-22.63%, p < 0.01) decreased significantly from 2012 to 2016. The OBs (16.67%) of all the anticancer medicines were found to be less affordable than LPGs (34.62% for urban residents and 30.77% for rural residents); their affordability varied among the different income regions. From 2012 to 2016, the proportion of LPGs with low availability and low affordability dropped from 30.77% to 19.23% in urban areas and 34.62% to 26.92% in rural areas, respectively. Generic substitution and medicine covered by basic medical insurance are factors facilitating affordability. CONCLUSION: There were concerning decreases in the availability of anticancer medicines in 2016 from already low availability in 2012. Anticancer medicines were more affordable for the patients in high-income regions than the patients in low-income regions. Governments should consider using their bargaining power to reduce procurement prices and abolish taxes on anticancer medicines. Policy should focus on the special health insurance plan for low-income patients with cancer. The goal of drug policy should ensure that first-line generic drugs are available for cancer patients and preferentially prescribed.