Global, regional and national availability of essential medicines for children, 2009-2020: a systematic review and meta-analysis.

BACKGROUND: Access to essential medicines is a vital component of universal health coverage. The low availability of essential medicines for children (EMC) has led the World Health Organization (WHO) to issue a number of resolutions calling on member states on its improvement. But its global progress has been unclear. We aimed to systematically evaluate the progress of availability of EMC over the past decade across economic regions and countries. METHODS: We searched eight databases from inception to December 2021 and reference lists to identify included studies. Two reviewers independently conducted literature screening, data extraction and quality evaluation. This study was registered with PROSPERO, CRD42022314003. RESULTS: Overall, 22 cross-sectional studies covering 17 countries, 4 income groups were included. Globally, the average availability rates of EMC were 39.0% (95%CI: 35.5-42.5%) in 2009-2015 and 43.1% (95%CI: 40.1-46.2%) in 2016-2020. Based on the World Bank classification of economic regions, income was not proportional to availability. Nationally, the availability rate of EMC was reasonable and high (> 50%) in only 4 countries, and low or very low for the rest 13 countries. The availability rates of EMC in primary healthcare centers had increased, while that for other levels of hospitals slightly declined. The availability of original medicines decreased while that of generic medicines was stable. All drug categories had not achieved the high availability rate. CONCLUSION: The availability rate of EMC was low globally, with slight increase in the last decade. Continuous monitoring and timely reporting of the availability of EMC are also needed to facilitate targets setting and inform relevant policy making.

Gender differences in health insurance coverage in China.

BACKGROUND: China initiated a reform of the health insurance system in the late 1990s. The new insurance, Urban Employee Basic Medical Insurance (UEBMI), is employment-based, which makes it more difficult than it used to be for those unemployed or informal employed (most of whom are women) to be covered by health insurance. METHODS: Based on three large sample of micro datasets, we first use statistical methods to identify gender differences in health insurance. Next, we construct a logistic regression model to capture the differences in insurance coverage across age groups using the parameter of interaction terms for gender and age groups. RESULTS: Based on data from a demographic survey that covers a large sample, we find that in the below 50 (in 2005) or 60 (in 2015) years age group, the coverage gap of UEBMI between men and women was relatively smaller, while a larger disparity existed in the above 50 (in 2005) or 60 (in 2015) group. Moreover, gender differences in health insurance were more significant in the low-education group, while no gender differences were found in the high-education group. CONCLUSIONS: This paper explains the gender gap in health insurance and the reason for the wider gap among older people. Our study indicates that because the UEBMI in China mainly covers people with formal jobs, a lower labor participation rate (even much lower in formal jobs) of women has led to their greater difficulty in obtaining health insurance. Since the older women's greater difficulty in obtaining jobs or susceptibility to lay-offs during the period of the UEBMI's implementation, the possibility of being covered was even much lower. In fact, it was because of the combined effects of the UEBMI system and the labor market condition at that time that older women had a lower proportion of being covered under the UEBMI.

Deregulation and pricing of medical services: a policy experiment based in China.

BACKGROUND: Price regulation is a common constraint in Chinese hospitals. Based on a policy experiment conducted in China on the price deregulation of private nonprofit hospitals, this study empirically examines the impact of medical service price regulation on the pricing of medical services by hospitals. METHODS: Using the claim data of insured inpatients residing in a major Chinese city for the period 2010-2015, this study constructs a DID (difference-in-differences) model to compare the impact of price deregulation on medical expenditure and expenditure structure between public and private nonprofit hospitals. RESULTS: The empirical results based on micro data reveal that, price deregulated significantly increased the total expenditure per inpatient visit by 10.5%. In the itemized expenditure, the diagnostic test and drug expenditure per inpatient visit of private nonprofit hospitals decreased significantly, whereas the physician service expenditure per inpatient visit increased significantly. For expenditure structure, the proportions of drug expenditure and diagnostic test expenditure per inpatient visit significantly decreased by 5.7 and 3.1%, respectively. Furthermore, this paper also found that hospitals had larger price changes for dominant diseases than for non-dominant diseases. CONCLUSIONS: Under price regulation, medical service prices generally become lower than their costs. Therefore, after price deregulation, private nonprofit hospitals increase medical service prices above their cost and achieve the service premium increasing physician medical services. Further, although price deregulation causes patient expenditure to increase to a certain level, it optimizes the expenditure structure, as well.

Vitamin C-dependent lysine demethylase 6 (KDM6)-mediated demethylation promotes a chromatin state that supports the endothelial-to-hematopoietic transition.

Hematopoietic stem cells (HSCs)/progenitor cells (HPCs) are generated from hemogenic endothelial cells (HECs) during the endothelial-to-hematopoietic transition (EHT); however, the underlying mechanism remains poorly understood. Here, using an array of approaches, including CRSPR/Cas9 gene knockouts, RNA-Seq, ChIP-Seq, ATAC-Seq etc., we report that vitamin C (Vc) is essential in HPC generation during human pluripotent stem cell (hPSC) differentiation in defined culture conditions. Mechanistically, we found that the endothelial cells generated in the absence of Vc fail to undergo the EHT because of an apparent failure in opening up genomic loci essential for hematopoiesis. Under Vc deficiency, these loci exhibited abnormal accumulation of histone H3 trimethylation at Lys-27 (H3K27me3), a repressive histone modification that arose because of lower activities of demethylases that target H3K27me3. Consistently, deletion of the two H3K27me3 demethylases, Jumonji domain-containing 3 (JMJD3 or KDM6B) and histone demethylase UTX (UTX or KDM6A), impaired HPC generation even in the presence of Vc. Furthermore, we noted that Vc and jmjd3 are also important for HSC generation during zebrafish development. Together, our findings reveal an essential role for Vc in the EHT for hematopoiesis, and identify KDM6-mediated chromatin demethylation as an important regulatory mechanism in hematopoietic cell differentiation.

Effect of long-term care insurance in a pilot city of China: Health benefits among 12,930 disabled older adults.

BACKGROUND: The surge of disabled older people have brought enormous burdens to society. The aim of this study was to examine the impact of long-term care insurance (LTCI) implementation on mortality and changes in physical ability among disabled older adults. METHODS: This was a prospective observational study based on data from the government-led LTCI program in a pilot city of China from 2017 to 2021. Administrative data included the application survey of activities of daily living (ADL), the baseline characteristics and all-cause mortality. Return visit surveys of ADL were conducted between August 2021 and December 2021. A regression discontinuity model was used to analyze the impact of LTCI on mortality. RESULTS: A total of 12,930 individuals older than 65 years were included in this study, and 10,572 individuals were identified with severe disability and participated in the LTCI program. LTCI implementation significantly reduced mortality by 5.10 % (95 % CI, -9.30 % to -0.90 %) and extended the survival time by 33.74 days (95 % CI, 13.501 to 53.970). The ADL scores of the LTCI group dropped by 2.5 points on average, while the ADL scores of those did not participated in LTCI dropped by 25.0 points. The heterogeneity analysis revealed that the impact of LTCI on mortality reduction was more significant among females, individuals of lower age, those who were married, cared for by family members, and who lived in districts with rich care resources. CONCLUSIONS: LTCI implementation had a favorable impact on the mortality and physical ability of participants.

Air pollution and timing of childbirth: a retrospective survey analysis based on birth registration data of Chinese newborns.

Objectives: Currently, there is a lack of research on whether people will take action to avoid the harm of air pollution and the heterogeneous behavior of different groups. The goal of this paper is to examine the effects of air pollution on the resulting differential effects on newborns and the timing of pregnancy. Methods: Based on a survey of newborns in a total of 32 hospitals in 12 cities across China in 2011, and after matching with city-level air pollution data, a multiple regression statistical method is then used to examine how the pollution level in a certain period is related to the number of conceptions in that certain period, after controlling for region and season fixed effects. Results: We first demonstrate that exposure to air pollution during pregnancy is associated with a significant increase in adverse birth outcomes. Most importantly, the empirical results show that the number of conceptions decreased significantly during periods of severe air pollution. Conclusion: Evidence suggests that air pollution may be causing some families to delay conception to reduce the possible adverse impact on neonatal outcomes. This helps us to understand the social cost of air pollution more, and then make more accurate environmental policies.

Rhein alleviates advanced glycation end products (AGEs)-induced inflammatory injury of diabetic cardiomyopathy in vitro and in vivo models.

In diabetic patients, diabetic cardiomyopathy (DCM) is one of the most common causes of death. The inflammatory response is essential in the pathogenesis of DCM. Rhein, an anthraquinone compound, is extracted from the herb rhubarb, demonstrating various biological activities. However, it is unclear whether rhein has an anti-inflammatory effect in treating DCM. In our research, we investigated the anti-inflammatory properties as well as its possible mechanism. According to the findings in vitro, rhein could to exert an anti-inflammatory effect by reducing the production of NO, TNF-α, PGE2, iNOS, and COX-2 in RAW264.7 cells that had been stimulated with advanced glycosylation end products (AGEs). In addition, rhein alleviated H9C2 cells inflammation injury stimulated by AGEs/macrophage conditioned medium (CM). In vivo have depicted that continuous gavage of rhein could improve cardiac function and pathological changes. Moreover, it could inhibit the accumulation of AGEs and infiltration of inflammatory factors inside the heart of rats having DCM. Mechanism study showed rhein could suppress IKKß and IκB phosphorylation via down-regulating TRAF6 expression to inhibit NF-κB pathway in AGEs/CM-induced H9C2 cells. Moreover, the anti-inflammation effect of rhein was realized through down-regulation phosphorylation of JNK MAPK. Furthermore, we found JNK MAPK could crosstalk with NF-κB pathway by regulating IκB phosphorylation without affecting IKKß activity. And hence, the protective mechanism of rhein may involve the inhibiting of the TRAF6-NF/κB pathway, the JNK MAPK pathway, and the crosstalk between the two pathways. These results suggested that rhein may be a promising drug candidate in anti-inflammation and inflammation-related DCM therapy.

Availability of essential medicines, progress and regional distribution in China: a systematic review and meta-analysis.

Background: Essential medicines are the backbone of healthcare and meet the priority healthcare needs of the population. However, approximately one-third of the global population does not have access to essential medicines. Although China formulated essential medicine policies in 2009, the progress of availability of essential medicines and regional variations remains unknown. Therefore, this study was conducted to evaluate the availability of essential medicines, their progress, and regional distribution in China in the last decade. Methods: We searched eight databases from their inception to February 2022, relevant websites, and reference lists of included studies. Two reviewers selected studies, extracted data, and evaluated the risk of bias independently. Meta-analyses were performed to quantify the availability of essential medicines, their progress, and regional distribution. Results: Overall 36 cross-sectional studies conducted from 2009 to 2019 were included, with regional data for 14 provinces. The availability of essential medicines in 2015-2019 [28.1%, 95% confidence interval (CI): 26.4-29.9%] was similar to that in 2009-2014 (29.4%, 95% CI: 27.5-31.3%); lower in the Western region (19.8%, 95% CI: 18.1-21.5%) than Eastern (33.8%, 95% CI: 31.6-36.1%) and Central region (34.5%, 95% CI: 30.6-38.5%); very low for 8 Anatomical Therapeutic Chemical (ATC) categories (57.1%), and low for 5 categories (35.7%) among all ATC groups. Conclusion: The availability of essential medicines in China is low compared with the World Health Organization goal, has not changed much in the last decade, is unequal across regions, and lacks data for half of provinces. For policy-making, the monitoring system of the availability of essential medicines is to be strengthened to enable long-term surveillance, especially in provinces where the data has been missing. Meanwhile, Joint efforts from all stakeholders are warranted to improve the availability of essential medicines in China toward the universal health coverage target. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=315267, identifier: PROSPERO CRD42022315267.

The price and affordability of essential medicines, progress and regional distribution in China: a systematic review.

Background: Essential medicine is a vital component to assure universal access to quality healthcare. However, the trend of affordability to essential medicines in China and its regional differences were not yet fully understood. This study aimed to systematically evaluate the price and affordability of essential medicines, their progress, and regional distribution in China in the last decades. Methods: We searched seven databases and three websites for potentially eligible studies from inception until March 2022. Studies on the price and affordability of essential medicines investigated in China were included. Median and interquartile range (IQR) was used to describe the price and affordability of essential medicines, and compared in three periods, before 2009, from 2009 to 2014, and from 2015 to 2019. Subgroup analysis was performed to examine the price and affordability by regions, health facilities, and ATC categories of medicines. The study was registered with PROSPERO (CRD42022310173). Results: A total of 65 studies including 11,639 health facilities investigated between 2006 and 2019 were included in this review. Median price ratios (MPR) and affordability of essential medicines were reported in 44 studies and 50 studies, respectively. The median MPRs of essential medicines in China was 1.59 (IQR: 5.39), with a tendency to rise first and then fall from 2006 to 2019. And the median affordability was equal to 0.88 (IQR: 2.58) days' wage of the lowest paid unskilled government worker, but steadily rose from 2006 to 2019. Subgroup analysis showed that the affordability in the western region (1.40, IQR: 2.88), urban area (0.95, IQR: 2.80), private sector (0.90, IQR: 2.30), of originator brands (OB) (2.90, IQR: 6.68), and antineoplastic and immunomodulating agents (5.68, IQR: 56.47) were worse than their counterparts. Conclusion: The prices of essential medicine were higher than international level, the overall affordability of essential medicines in China is acceptable but poor in the western region, for OB drugs and anti-cancer medicines. Further national essential medicine policies are needed to reduce regional disparities and improve the affordability of expensive drugs. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails.

The effect of subjective life expectancy on the participation in commercial pension insurance of Chinese elderly.

Objective: This paper studies the impact of the subjective life expectancy of the elderly on their commercial pension insurance participation at micro perspective, providing new evidence to explain the motivation of commercial pension insurance participation in China. Methods: Using 4 waves of data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018, a multiple linear regression model is constructed to investigate the effect of subjective life expectancy on commercial pension insurance participation among the Chinese elderly, and IV model estimation shows that the results are robust. Meanwhile, the heterogeneity of the effect of elderly life expectancy on commercial pension insurance participation behavior among different characteristic groups is also studied. Results: A one standard deviation improvement in our measure of subjective life expectancy predicts a 0.9% point higher participation rate in commercial pension insurance. We also find that there is significant heterogeneity in the effects of subjective life expectancy on the participation of elderly people in commercial pension insurance with respect to gender, education, hukou, and wealth. Conclusion: This paper provides a new perspective to explain the factors influencing commercial pension insurance participation in China. We suggest that improving residents' awareness of life expectancy is beneficial to their reasonable retirement planning, in the background of stepping into an aging society in China.

A Study of the Protective Effect of Bushen Huoxue Prescription on Cerebral Microvascular Endothelia Based on Proteomics and Bioinformatics.

Diabetic cognitive dysfunction is a serious complication of type 2 diabetes mellitus (T2DM), which can cause neurological and microvascular damage in the brain. At present, there is no effective treatment for this complication. Bushen Huoxue prescription (BSHX) is a newly formulated compound Chinese medicine containing 7 components. Previous research indicated that BSHX was neuroprotective against advanced glycosylation end product (AGE)-induced PC12 cell insult; however, the effect of BSHX on AGE-induced cerebral microvascular endothelia injury has not been studied. In the current research, we investigated the protective effects of BSHX on AGE-induced injury in bEnd.3 cells. Our findings revealed that BSHX could effectively protect bEnd.3 cells from apoptosis. Moreover, we analyzed the network regulation effect of BSHX on AGE-induced bEnd.3 cells injury at the proteomic level. The LC-MS/MS-based shotgun proteomics analysis showed BSHX negatively regulated multiple AGE-elicited proteins. Bioinformatics analysis revealed these differential proteins were involved in multiple processes, such as Foxo signaling pathway. Further molecular biology analysis confirmed that BSHX could downregulate the expression of FoxO1/3 protein and inhibit its nuclear transfer and inhibit the expression of downstream apoptotic protein Bim and the activation of caspase, so as to play a protective role in AGE-induced bEnd.3 injury. Taken together, these findings demonstrated the role of BSHX in the management of diabetic cerebral microangiopathy and provide some insights into the proteomics-guided pharmacological mechanism study of traditional Chinese Medicine.

Pro-Inflammatory diet accounts for higher prevalence of retinopathy in diabetes participants rather than normal glucose and prediabetes: Results from NHANES, 2005-2008.

Retinopathy is a chronic inflammatory disease whose prognosis could be improved with dietary interventions. However, the association between a pro-inflammatory diet and the prevalence of retinopathy has not been fully elucidated. We assess the association between the dietary inflammatory index (DII), which is a comprehensive index determining inflammatory potential derived from food parameters according to literature, and the prevalence of retinopathy based on the data from the National Health and Nutritional Examination Survey (NHANES) 2005-2008 involving 2,403 participants. Energy-adjusted DII (E-DII) was not related to the occurrence of retinopathy in the general, non-diabetic, or middle-aged participants. In the diabetic and aged participants, one unit increment of E-DII accounted for 14 and 15% higher the prevalence of retinopathy respectively. The highest E-DII group had a 78 and 79% higher prevalence of retinopathy than the lowest group respectively. After adjusting for several covariables, the highest E-DII group was still associated with a 68% increase in retinopathy in diabetic patients. These results suggest that E-DII is positively associated with the prevalence of diabetic retinopathy among diabetic patients.

Schisandrol A protects AGEs-induced neuronal cells death by allosterically targeting ATP6V0d1 subunit of V-ATPase.

Diabetes have been shown to cause progressive neuronal injury with pain and numbness via advanced glycation end-products (AGEs)-induced neuronal cell apoptosis; however, the valuable drug targets for diabetic neuropathy have been poorly reported so far. In this study, we discovered a natural small-molecule schisandrol A (SolA) with significant protective effect against AGEs-induced neuronal cell apoptosis. ATP6V0D1, a major subunit of vacuolar-type ATPase (V-ATPase) in lysosome was identified as a crucial cellular target of SolA. Moreover, SolA allosterically mediated ATP6V0D1 conformation via targeting a unique cysteine 335 residue to activate V-ATPase-dependent lysosomal acidification. Interestingly, SolA-induced lysosome pH downregulation resulted in a mitochondrial-lysosomal crosstalk by selectively promoting mitochondrial BH3-only protein BIM degradation, thereby preserving mitochondrial homeostasis and neuronal cells survival. Collectively, our findings reveal ATP6V0D1 is a valuable pharmacological target for diabetes-associated neuronal injury via controlling lysosomal acidification, and also provide the first small-molecule template allosterically activating V-ATPase for preventing diabetic neuropathy.

Patient-Reported Outcomes Following the Use of Jiang Tang San Huang Tablets in Type 2 Diabetes Mellitus: A Retrospective Cohort Study in a Chinese Population.

Purpose: We aimed to assess the efficacy of the Jiang Tang San Huang (JTSH) tablet for the treatment of patients with type 2 diabetes mellitus (T2DM). Methods: All data for this retrospective cohort study were acquired from the outpatient clinic database of our institution, and all enrolled patients received JTSH tablet for at least two months. Overall, 147 patients were included in the analysis. The primary outcome was patient-reported outcomes on the efficacy of the JTSH tablets using a questionnaire survey. Correlation analysis evaluated the duration of JTSH tablet administration and glycemic control in patients with T2DM. The secondary outcome measures included: changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2-hour postprandial blood glucose, homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of ß-cell function (HOMA-ß) after 2 months of treatment with JTSH tablets. Results: Overall,120 patients (81.63%) reported a JTSH tablet treatment satisfaction score of ≥60 points, and believed that JTSH tablets had satisfactory hypoglycemic effects and could improve symptoms. The average duration of JTSH tablet treatment was 2.57±1.45 years. Overall, 111 patients achieved good blood glucose control, while 36 patients had poor glycemic control. Multivariate logistic regression model analysis showed that taking JTSH tablets for 1 year might reduce the risk of poor hypoglycemic effect by 17.00% (Risk ratio=0.830, 95% confidence interval:0.578, 1.021, P=0.066). Compared with the baseline data, the levels of HbA1c, FPG and HOMA-IR decreased significantly and HOMA-ß levels increased significantly (P<0.05). Conclusion: Good blood glucose control may be positively correlated with the duration of JTSH tablets administration. Patients with T2DM were satisfied with the anti-diabetic effects of JTSH tablets, which can significantly reduce blood glucose and insulin resistance, and improve the function of islet cells.

The impact of national centralized drug procurement on health expenditures for lung cancer inpatients: A difference-in-differences analysis in a large tertiary hospital in China.

The availability and affordability of medicines remain major health challenges around the world. In March 2019, the Chinese government introduced a pilot National Centralized Drug Procurement (NCDP) program in order to reduce drug prices and improve the affordability of effective and safe medicines. This study aimed to assess the impact of NCDP policy on health expenditures of cancer patients. Using inpatient discharge records from a large hospital in the pilot city, we performed a difference-in-differences design to estimate the change in health expenditures before and after the policy. We found that the implementation of NCDP was associated with a significant decrease in total expenditures (14.13%) and drug expenditures (20.75%) per inpatient admission. There were also significant reductions in non-drug-related expenditures, including a 7.65% decrease in health service expenditures, a 38.28% decrease in diagnosis expenditures, and a 25.31% decrease in consumable material expenditures per inpatient admission. However, the NCDP implementation was associated with a 107.97% increase in the traditional Chinese medicine expenditures. Overall, the study provided evidence that the NCDP policy has achieved its goals of high-quality and affordable healthcare. The drug expenditures of lung cancer patients revealed a continuous decline, and the policy may have spillover effects on other healthcare expenditures. Further studies are needed to evaluate the long-term effects of NCDP on policy-related expenditures and health outcomes.

Access to medicines for children in China.

Access to essential medicines for children is a big challenge, particularly in low-income and middle-income countries. In China, the average availability of essential medicines for children is 1.6%-46.5%. The availability of generics was generally higher than original brands in public hospitals and the prices of generics were relatively lower and more reasonable (generics: availability, 27.3%-46.5%, prices, 0.52-4.28 times the international reference prices; original brands: 1.6%-33.0%, 2.59-11.38 times the international reference prices). In terms of affordability of medicines for children, generics were more affordable than original brands and tablets/capsules were more affordable than injections. Most commonly used anti-infective medicines (such as amoxicillin capsule, azithromycin tablet, cefuroxime tablet) and antipyretics (such as ibuprofen suspension) were relatively affordable. Six commonly used medicines in paediatrics, including amoxicillin/clavulanic acid, beclomethasone, cefazolin, ceftazidime, ceftriaxone, cyclosporine were unaffordable. Since August 2011, China has successively issued several policies to ensure the accessibility of medicines for children, covering research and development, production, procurement and prices of medicines. The accessibility of medicines for children has been partially improved, but still needs continuous improvement.

Institutional Design and Incentives for Migrant Workers to Participate in Social Insurance in China: Evidence From a Policy Experiment in Chengdu City.

Rural-to-urban migration has increased rapidly in China since the early 1980s, with the number of migrants has reached 376 million by 2020. Despite this sharp trend and the significant contributions that migrants have made to urban development, the migrant workers have had very limited access to the social insurance that the majority of urban workers enjoy. Against the background of the social insurance system adjustment in Chengdu in 2011, this study uses a difference-in-differences (DID) model to empirically test the impacts of changes in the social insurance policy contribution rates on the social insurance participation rates of migrant workers, using the China Migrants Dynamic Survey (CMDS) data for 2009-2016. We find that the social insurance participation rate of migrant workers was significantly reduced after they were incorporated into the urban worker insurance system. There was no significant change in the wages of migrant workers, but the working hours were increased and their consumption level decreased. In other words, simply changing the social insurance model of migrant workers from "comprehensive social insurance" to "urban employee insurance" reduces the incentives for migrant workers to participate in insurance and harms the overall welfare of migrant workers. Our study indicates that the design of the social security policy is an important reason for the lower participation rate of migrants. It is necessary to solve the problem of insufficient incentives through the targeted social security policies; primarily, the formulation of a social security policy contribution rate suitable for the migrants, and the establishment of a comprehensive social security policy and the gradual integration of the social security system.

Trading quality for quantity? Evidence from patient level data in China.

In China, overcrowding at hospitals increases the workload of medical staff, which may negatively impact the quality of medical services. This study empirically examined the impact of hospital admissions on the quality of healthcare services in Chinese hospitals. Specifically, we estimated the impact of the number of hospital admissions per day on a patient's length of stay (LOS) and hospital mortality rate using both ordinary least squares (OLS) and instrumental variable (IV) methods. To deal with potential endogeneity problems and accurately identify the impact of medical staff configuration on medical quality, the daily air quality index was selected as the IV. Furthermore, we examined the differential effects of hospital admissions on the quality of care across different hospital tiers. We used the data from a random sample of 10% of inpatients from a city in China, covering the period from January 2014 to June 2019. Our final regression analysis included a sample of 167 disease types (as per the ICD-10 classification list) and 862,722 patient cases from 517 hospitals. According to our results, the LOS decreased and hospital mortality rate increased with an increasing number of admissions. Using the IV method, for every additional hospital admission, there was a 6.22% (p < 0.01) decrease in LOS and a 1.86% (p < 0.01) increase in hospital mortality. The impact of healthcare staffing levels on the quality of care varied between different hospital tiers. The quality of care in secondary hospitals was most affected by the number of admissions, with the average decrease of 18.60% (p < 0.05) in LOS and the increase of 6.05% (p < 0.01) in hospital mortality for every additional hospital admission in our sample. The findings suggested that the supply of medical services in China should be increased and a hierarchical diagnosis and treatment system should be actively promoted.

Procyanidin B2 Alleviates Palmitic Acid-Induced Injury in HepG2 Cells via Endoplasmic Reticulum Stress Pathway.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome featuring ectopic lipid accumulation in hepatocytes. NAFLD has been a severe threat to humans with a global prevalence of over 25% yet no approved drugs for the treatment to date. Previous studies showed that procyanidin B2 (PCB2), an active ingredient from herbal cinnamon, has an excellent hepatoprotective effect; however, the mechanism remains inconclusive. The present study aimed to investigate the protective effect and underlying mechanism of PCB2 on PA-induced cellular injury in human hepatoma HepG2 cells. Our results showed that PA-induced oxidative stress, calcium disequilibrium, and subsequent endoplasmic reticulum stress (ERS) mediated cellular injury, with elevated protein levels of GRP78, GRP94, CHOP, and hyperphosphorylation of PERK and IRE1α as well as the increased ratio of Bax/Bcl-2, which was restored by PCB2 in a concentration-dependent manner, proving the excellent antiapoptosis effect. In addition, 4-phenylbutyric acid (4-PBA), the ER stress inhibitor, increased cell viability and decreased protein levels of GRP78 and CHOP, which is similar to PCB2, and thapsigargin (TG), the ER stress agonist, exhibited conversely meanwhile partly counteracted the hepatic protection of PCB2. What is more, upregulated protein expression of p-IKKα/ß, p-NF-κB p65, NLRP3, cleaved caspase 1, and mature IL-1ß occurred in HepG2 cells in response to PA stress while rescued with the PCB2 intervention. In conclusion, our study demonstrated that PA induces ERS in HepG2 cells and subsequently activates downstream NLRP3 inflammasome-mediated cellular injury, while PCB2 inhibits NLRP3/caspase 1/IL-1ß pathway, inflammation, and apoptosis with the presence of ERS, thereby promoting cell survival, which may provide pharmacological evidence for clinical approaches on NAFLD.

Effect of Bushen Huoxue Prescription on Cognitive Dysfunction of KK-Ay Type 2 Diabetic Mice.

Diabetic cognitive impairment is one of the common complications of type 2 diabetes, which can cause neurological and microvascular damage in the brain. Bushen Huoxue prescription (BSHX), a compound Chinese medicine, has been used clinically to treat diabetes-induced cognitive impairment. However, its underlying mechanisms remain unclear. In this study, KK-Ay diabetic model mouse was administered BSHX daily for 12 weeks. Bodyweight, random blood glucose (RBG), and fasting blood glucose (FBG) were measured every 4 weeks. Triglycerides (TG), cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting serum insulin (FINS), and Morris water maze were tested after 12 weeks of administration. On the day of sacrifice, the hippocampus was collected for pathological staining and advanced glycation end products (AGEs) analysis to evaluate the neuroprotective effect of BSHX. Our results showed that BSHX treatment significantly ameliorated the T2DM related insults, including the increased bodyweight, blood glucose, TG, insulin levels, AGEs, the reduced HDL-C, the impaired spatial memory, and the neurological impairment. Moreover, Western blot analysis showed that increased expression of receptors of AGEs (RAGEs), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and activation of nuclear factor-κB (NF-κB) in the hippocampus were significantly inhibited by BSHX treatment. These results indicate that BSHX can significantly ameliorate glucose and lipid metabolism dysfunction, reduce the morphological changes in hippocampus tissues, and improve the cognitive function of KK-Ay mice. These protective effects of BSHX may involve regulation of the AGEs/RAGE/NF-κB signaling pathway.