Study on the accessibility and affordability of 50 drugs in Wuhan based on the WHO/HAI standardization method

ObjectiveTo understand the availability and affordability of essential drugs in Wuhan since the implementation of the national essential medicine system, and to provide a basis for the subsequent formulation and improvement of related policies.MethodsUsing the standard survey method jointly developed by the WHO and Health Action International (HAI), a sample of 50 essential drugs was selected to investigate and evaluate their availability and affordability in public medical and health institutions and social retail pharmacies in Wuhan, using six diseases with high clinical morbidity as the targets.ResultsThe availability of the original drug and the lowest-priced generic drug in public hospitals is 26.4 and 42.47% respectively, and that in retail pharmacies is 26.8 and 54.4% respectively. The median price ratio of the original drug and the lowest-priced generic drug is 28.71 and 2.23 respectively in public hospitals, and 29.24 and 3.59 respectively in retail pharmacies; In addition to individual drugs, such as omeprazole, others are affordable. The availability of essential drugs in public hospitals in Wuhan is lower than that in social retail pharmacies, and the availability of the lowest-priced generic drugs is much higher than that of original drugs.ConclusionThe availability of essential drugs in public hospitals in Wuhan is lower than that in social retail pharmacies, and the availability of the lowest-priced generic drugs is much higher than that of original drugs. The price of the original drug is much higher than the international reference price; The price of medicines in public hospitals is lower than that in retail pharmacies;the overall condition of affordability is good, but there is a big gap between the affordability levels of original drugs and generic drugs, and the affordability of original drugs is relatively poor. It is recommended to adjust the relevant policies according to the actual situation of Wuhan city itself, moderately ensure the supply of original drugs, improve the price transparency of retail pharmacies, and ensure that the basic drug needs of the public are met

Availability, prices and affordability of essential medicines in Zhejiang Province, China.

ObjectiveTo evaluate the availability, prices, and affordability of essential medicines in Zhejiang Province, China.MethodsThe survey was carried out in Zhejiang Province in 2018 following the methodology of the World Health Organization (WHO) and Health Action International (HAI). This method is an international standard method.Data on 50 medicines were collected from public health facilities and private pharmacies. Medication prices were compared with international reference prices to obtain a median price ratio. The affordability of medicines was measured based on the daily wage of the lowest-paid unskilled government worker. In private pharmacies, the mean availability of Originator Brands (OBs) and Lowest-priced Generics (LPGs) was 36.7% and 40.3%, respectively.FindingsThe effects of the mean availability of OBs and LPGs were seen in private pharmacies. Correspondingly, the average availability of OBs and LPGs was 41.8% and 35.1% in the public sector, respectively. In the public sector, the median price ratios (MPRs) were 5.21 for generics and 13.49 for OBs. In the private sector, the MPRs were 4.94 for generics and 14.75 for OBs. Treating common diseases with LPGs was generally affordable, while treatment with OBs was less affordable.ConclusionsIn Zhejiang Province, low availability was observed for medicines surveyed in the public and private sectors. Price differences between originator brands and generics in both sectors are apparent. OBs were more expensive than LPGs in both the public and private sectors. Low availability affects access to essential medicines. Policy measures should be taken to improve the availability of essential medicines

An Alternating Magnetic Field-Controlled Drug Delivery System Based on 4,4′-Azobis (4-cyanovaleric Acid)-Functioned Fe₃O₄@Chitosan Nanoparticles

Herein, we designed chitosan–coated Fe3O4 nanocomposites for the control release of drugs by an alternating magnetic field (AMF). The chitosan-coated Fe3O4 nanoparticles (Fe3O4@CS) were prepared by a alkaline co-precipitation method, and then, the model drug toluidine blue (TB) was covalently grafted onto the surface of the nanocomposite by a two-step amide reaction with the thermosensitive molecule 4,4′-azobis (4-cyanovaleric acid) (ACVA) as the linker group. The prepared nanocomposites were superparamagnetic and showed high magnetization saturation (about 54.0 emu g−1). In vitro hydrothermal release studies showed that most parts of the TB would be effectively enclosed within the nanocarriers at lower ambient temperatures (23 or 37 °C) due to the molecular bonding of ACVA. The results of kinetic fitting of hydrothermal release data showed that TB released from nanoparticles followed first-order kinetics (R2 > 0.99) and the Korsemeyer–Peppas model (R2 > 0.99, n 2 = 0.9712). Moreover, the increase in the cumulative release of the drug can be controlled by controlling the switch of the AMF generation device. Therefore, the ACVA-modified Fe3O4@CS nanocarrier designed in this study is a promising model for drug delivery that enables the control of drug release dose by AMF

Prognostic Analysis of Pneumocystis Jirovecii Pneumonia in Interstitial Lung Disease Patients: A Retrospective Clinical Study

(1) Background: The clinical characteristics and the prognostic factors of HIV-negative Pneumocystis jirovecii pneumonia (PJP) patients (non-HIV-PJP) with interstitial lung disease (ILD) remain unclear. Our objectives were to describe the clinical characteristics and to explore the prognostic factors of non-HIV-ILD-PJP patients. (2) Methods: The enrolled patients in this retrospective study were stratified based on the presence or absence of ILD and fibrotic ILD (FILD). The log-rank test and Cox regression models were used to analyze the prognostic factors. (3) Results: Among 378 non-HIV-PJP patients, there were 133 patients with ILD-PJP, and 70 patients were classified as having FILD-PJP. The all-cause mortality rate for the ILD-PJP group is higher than that of the ILD-PJP group (57.9% vs. 38.4%, p p = 0.003) and honeycomb appearance on the chest HRCT (HR = 16.3, p p p < 0.001). (4) Conclusions: Pre-existing ILD and honeycomb appearance on the chest HRCT are independent survival risk factors for PJP patients. Non-invasive ventilation is associated with poor survival for both ILD-PJP and FILD-PJP patients

SENP1 regulates the transformation of lung resident mesenchymal stem cells and is associated with idiopathic pulmonary fibrosis progression

Abstract Background Lung resident mesenchymal stem cells (LR-MSCs) play an important role in idiopathic pulmonary fibrosis (IPF) by transforming into myofibroblasts, thereby losing their repair ability. Evidence suggests that key proteins of multiple signaling pathways are involved in myofibroblast differentiation of LR-MSCs, such as β-Catenin and GLI family zinc finger 1 (GLI1). These proteins are regulated by SUMO (small ubiquitin-like modifier) modification, which is a post-translational modification that promotes protein degradation, while Sumo specific protein 1 (SENP1)-mediated deSUMOylation produces the opposite biological effects. Therefore, we speculated that SENP1 might be a potential target for treating pulmonary fibrosis by preventing the myofibroblast differentiation of LR-MSCs. Methods LR-MSCs were isolated from mice by using immunomagnetic beads. The extracted LR-MSCs were identified by flow cytometric analysis and multilineage differentiation assays. Lentivirus packaged shRNA silenced the expression of SENP1 in vitro and vivo. The silencing efficacy of SENP1 was verified by real-time quantitative PCR. The effect of down-regulated SENP1 on the myofibroblast differentiation of LR-MSCs was assessed by Immunofluorescence and Western blot. Immunoprecipitation was used to clarify that SENP1 was a key target for regulating the activity of multiple signaling pathways in the direction of LR-MSCs differentiation. LR-MSCs resident in the lung was analyzed with in vivo imaging system. HE and Masson staining was used to evaluate the therapeutic effect of LR-MSCs with SENP1 down-regulation on the lung of BLM mice. Results In this study, we found that the myofibroblast differentiation of LR-MSCs in IPF lung tissue was accompanied by enhanced SENP1-mediated deSUMOylation. The expression of SENP1 increased in LR-MSCs transition of bleomycin (BLM)-induced lung fibrosis. Interfering with expression of SENP1 inhibited the transformation of LR-MSCs into myofibroblasts in vitro and in vivo and restored their therapeutic effect in BLM lung fibrosis. In addition, activation of the WNT/β-Catenin and Hedgehog/GLI signaling pathways depends on SENP1-mediated deSUMOylation. Conclusions SENP1 might be a potential target to restore the repair function of LR-MSCs and treat pulmonary fibrosis. Video Abstrac

Scab-Inspired Cytophilic Membrane of Anisotropic Nanofibers for Rapid Wound Healing

This work investigates the influence of cytophilic and anisotropic nanomaterials on accelerated cell attachment and directional migration toward rapid wound healing. Inspired by the anisotropic protein nanofibers in scab, a polyurethane (PU) nanofibrous membrane with an aligned structure was fabricated. The membrane showed good affinity for wound-healing-related cells and could guide cell migration in the direction of PU nanofibers. Also, the morphology and distribution of F-actin and paxillin of attached cells were influenced by the underlying nanofibers. The randomly distributed PU nanofibers and planar PU membrane did not show a distinct impact on cell migration. This scab-inspired cytophilic membrane is promising in applications as functional interfacial biomaterials for rapid wound healing, bone repair, and construction of neural networks

The Combination of RAD001 and MK-2206 Exerts Synergistic Cytotoxic Effects against PTEN Mutant Gastric Cancer Cells: Involvement of MAPK-Dependent Autophagic, but Not Apoptotic Cell Death Pathway

<div><p>In the current study, we showed that the combination of mammalian target of rapamycin (mTOR) inhibitor RAD001 (everolimus) and Akt inhibitor MK-2206 exerted synergistic cytotoxic effects against low-phosphatase and tensin homolog (PTEN) gastric cancer cells (HGC-27 and SNU-601 lines). In HGC-27 cells, RAD001 and MK-2206 synergistically induced G1/S cell cycle arrest, growth inhibition, cell death but not apoptosis. RAD001 and MK-2206 synergistically induced light chain 3B (LC3B) and beclin-1 expression, two important autophagy indicators. Meanwhile, the autophagy inhibitor 3-methyladenine (3-MA) and chloroquine inhibited the cytotoxic effects by RAD001 and MK-2206, suggesting that autophagic, but not apoptotic cell death was important for the cytotoxic effects by the co-administration. We observed that the combination of RAD001 and MK-2206 exerted enhanced effects on Akt/mTOR inhibition, cyclin D1 down-regulation and ERK/MAPK(extracellular signal-regulated kinase/mitogen-activated protein kinases) activation. Intriguingly, MEK/ERK inhibitors PD98059 and U0126 suppressed RAD001 plus MK-2206-induced beclin-1 expression, autophagy induction and cytotoxicity in HGC-27 cells. In conclusion, these results suggested that the synergistic anti-gastric cancer cells ability by RAD001 and MK-2206 involves ERK-dependent autophagic cell death pathway.</p></div