ObjectivesEndovascular mechanical thrombectomy is an effective but expensive therapy for acute ischaemic stroke with proximal anterior circulation occlusion. This study aimed to determine the ...cost-effectiveness of mechanical thrombectomy in China, which is the largest developing country.DesignA combination of decision tree and Markov model was developed. Outcome and cost data were derived from the published literature and claims database. The efficacy data were derived from the meta-analyses of nine trials. One-way and probabilistic sensitivity analyses were performed in order to assess the uncertainty of the results.SettingHospitals in China.ParticipantsThe patients with acute ischaemic stroke caused by proximal anterior circulation occlusion within 6 hours.InterventionsMechanical thrombectomy within 6 hours with intravenous tissue plasminogen activator (tPA) treatment within 4.5 hours versus intravenous tPA treatment alone.Outcome measuresThe benefit conferred by the treatment was assessed by estimating the cost per quality-adjusted life-year (QALY) gained in the long term (30 years).ResultsThe addition of mechanical thrombectomy to intravenous tPA treatment compared with standard treatment alone yielded a lifetime gain of 0.794 QALYs at an additional cost of CNY 50 000 (US$7700), resulting in a cost of CNY 63 010 (US$9690) per QALY gained. The probabilistic sensitivity analysis indicated that mechanical thrombectomy was cost-effective in 99.9% of the simulation runs at a willingness-to-pay threshold of CNY 125 700 (US$19 300) per QALY.ConclusionsMechanical thrombectomy for acute ischaemic stroke caused by proximal anterior circulation occlusion within 6 hours was cost-effective in China. The data may be used as a reference with regard to medical resources allocation for stroke treatment in low-income and middle-income countries as well as in the remote areas in the developed countries.
Cr-doped γ-Fe2O3/reduced graphene oxide (rGO) nanocomposites are successfully synthesized through a rapid and environmentally friendly microwave method in just 10 min. Under the microwave heating, ...graphene oxide (GO) is reduced to rGO with ferrous ion (Fe2+) served as the reductant, and Cr-doped γ-Fe2O3 nanoparticles are synthesized in the meantime. It is found that Cr doping can not only affect the phase of Fe2O3, but also has an effect on the morphology, the electrical conductivity and the electrochemical properties. As anode material for lithium ion batteries, the 4.0 at% Cr-doped γ-Fe2O3/rGO nanocomposites exhibit the highest reversible capacity of 1060 mAh g−1 after 100 cycles (66.9% of the initial capacity) at a current density of 100 mA g−1. Furthermore, when assembled as a full cell against commercial cathode including LiCoO2 and LiNi1/3Mn1/3Co1/3O2, the battery shows promising cycling performance. The superior electrochemical performance could be attributed to the uniform nanostructure and the synergistic effect between Fe2O3 and rGO as well as the doping of chromium, which can reduce the size of Fe2O3 particles and improve the electrical conductivity.
•Cr-doped γ-Fe2O3/rGO is prepared through ultrafast microwave heating method.•Cr doping can reduce the size of Fe2O3 and improve the electrochemical properties.•Promising full cell performance when combined with LiCoO2 cathode.
Metabolic reprogramming contributes to patient prognosis. Here, we aimed to reveal the comprehensive landscape in metabolism of head and neck squamous carcinoma (HNSCC), and establish a novel ...metabolism-related prognostic model to explore the clinical potential and predictive value on therapeutic response. We screened 4752 metabolism-related genes (MRGs) and then identified differentially expressed MRGs in HNSCC. A novel 10-MRGs risk model for prognosis was established by the univariate Cox regression analysis and the least absolute shrinkage and selection operator (Lasso) regression analysis, and then verified in both internal and external validation cohort. Kaplan-Meier analysis was employed to explore its prognostic power on the response of conventional therapy. The immune cell infiltration was also evaluated and we used tumor immune dysfunction and exclusion (TIDE) algorithm to estimate potential response of immunotherapy in different risk groups. Nomogram model was constructed to further predict patients’ prognoses. We found the MRGs-related prognostic model showed good prediction performance. Survival analysis indicated that patients suffered obviously poorer survival outcomes in high-risk group (
p
< 0.001). The metabolism-related signature was further confirmed to be the independent prognostic value of HNSCC (HR = 6.387, 95% CI = 3.281-12.432,
p
< 0.001), the efficacy of predictive model was also verified by internal and external validation cohorts. We observed that HNSCC patients would benefit from the application of chemotherapy in the low-risk group (
p
= 0.029). Immunotherapy may be effective for HNSCC patients with high risk score (
p
< 0.01). Furthermore, we established a predictive nomogram model for clinical application with high performance. Our study constructed and validated a promising 10-MRGs signature for monitoring outcome, which may provide potential indicators for metabolic therapy and therapeutic response prediction in HNSCC.
In this paper, we design a dielectric-to-plasmonic slot waveguide mode converter based on the hybrid silicon-gold taper. The effects of mode matching, the effective index matching, and the metallic ...absorption loss on the conversion efficiency are studied. Consequently, a metallic taper-funnel coupler with an overall length of 1.7 μm is designed to achieve a very high conversion efficiency of 93.3% at 1550 nm. The configuration limitations for not allowing this mode converter to achieve a 100% conversion efficiency are also investigated. Such a high-efficiency converter can provide practical routes to realize ultracompact integrated circuits.
•Octahedral NiFe2O4 enclosed by high index (111) facets was synthesized successfully by a facile hydrothermal method.•The nanocomposites exhibit high reversible capacities as an anode material for ...lithium-ion batteries.•The octahedral NiFe2O4@graphene electrode shows excellent rate performance.
Uniform octahedral nickel ferrite nanocrystals wrapped by graphene (GNFO) have been synthesized and characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy analysis techniques, which reveal that the NiFe2O4 nanocrystals are enclosed by high index (111) facets and encapsulated by reduced graphene oxide sheets. When applied as anode electrodes for lithium ion batteries, GNFO nanocomposites present excellent electrochemical performances. The electrode maintains 1275mAhg−1 after 30 cycles at 0.1Ag−1 and a reversible capacity up to 937mAhg−1 after 250 cycles at 1Ag−1. A prominent rate capability is also obtained and the specific capacity remains 312mAhg−1 at 10.0Ag−1. The superior electrochemical properties could benefit from open surface structure of octahedral NiFe2O4 and synergistic effect between graphene and NiFe2O4, which shows promising applications in lithium-ion storage devices.
Aims
Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal ...women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis.
Methods
The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the
Bmal1
gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT.
Bmal1
lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene.
Results
Melatonin promoted apoptosis of RAW264.7 cells and increased the expression of BMAL1 to inhibit the activation of ROS and phosphorylation of mitogen-activated protein kinase (MAPK)-p38. Silencing the bmal1 gene weakened the above effects of melatonin. After that, we used dehydrocorydaline (DHC) to enhance the activation of MAPK-p38, and the effects of melatonin on reducing ROS levels and promoting apoptosis of RAW264.7 cells were also blocked. Then, we constructed a mouse model of postmenopausal osteoporosis and administered melatonin. The results showed that melatonin improves bone loss in ovariectomized mice. Finally, we established a model of overexpression of the bmal1 gene, and these results suggest that the bmal1 gene can regulate ROS activity and change the level of the MAPK-p38 signalling pathway.
Conclusion
Our study confirmed that melatonin promotes the apoptosis of RAW264.7 cells through BMAL1/ROS/MAPK-p38, and revealed the therapeutic effect and mechanism of melatonin in postmenopausal osteoporosis. This finding enriches BMAL1 as a potential target for the treatment of osteoporosis and the pathogenesis of postmenopausal osteoporosis.
Cite this article:
Bone Joint Res
2023;12(11):677–690.
•The therapeutic effect of Poria cocos decoction on functional dyspepsia was demonstrated by using modern pharmacological methods.•The function and potential mechanisms of three extracts including ...triterpenoid, water-soluble polysaccharide and acidic polysaccharide from Poria cocos on functional dyspepsia were evaluated for the first time.•The acidic polysaccharide of Poria cocos, which is often discarded in clinical, was proven to be effective on FD, this result provides a scientific basis for full use of medicinal materials.•The extracts of Poria cocos exerted improvement effect on functional dyspepsia through multiple pathways.
Poria cocos (Schw.) Wolf (PC), a fungus, has been used for more than 2000 years as a food and medicine in China. It has a very good therapeutic effect for functional dyspepsia (FD). However, the material basis and mechanism of PC on FD were not reported.
To investigate the function and potential mechanisms of PC including its three extracts (triterpenoid, PCT; water-soluble polysaccharide, PCWP; acidic polysaccharide, PCAP) on FD.
The study explored the therapeutic effect of PC and its three extracts on FD in rats for the first time and discussed its mechanisms based on brain-gut peptides, immunity and repair of the gastrointestinal mucosa.
The chemical components of PC extracts were analyzed and quantified using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) and gel permeation chromatography coupled with size exclusion chromatography (GPC/SEC). The FD rat models were established using weight-loaded forced swimming and alternate-day fasting for 42 days. After 14 days of treatment, the effect and mechanisms were investigated using ELISA, histopathology, immunohistochemistry as well as Western blot.
Seventy-seven triterpenoids in PCT were identified. PCWP was primarily composed of component A (Mw: 3.831 × 107 Da), component B (Mw: 5.650 × 106 Da) and component C (Mw: 113,117 Da). PCAP was a homogeneous composition with an average Mw of 74,320 Da. PCT, PCWP and PCAP alleviated the symptoms of FD. These extracts promoted the repair of gastrointestinal mucosa and regulated the balance between the T helper cell (Th)1/Th2 axis and the Th17/Treg axis. PCT and PCWP regulated brain-gut peptides more effectively, PCWP and PCAP enhanced immunity more effectively. Further study demonstrated that these extracts may have enhanced immunity via the Toll-like receptor (TLR) and c-Jun N-terminal kinase (JNK) signaling pathways.
PC extracts showed therapeutic effects on FD rats, and the mechanism of action involved multiple pathways. PCAP, which is often discarded in traditional applications, was effective. Our study provides new ideas for the application and development of PC extracts.
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Understanding the effects of fracture-related characteristic parameters on heat extraction performance is important to the development of geothermal reservoirs. A numerical model with parallel ...fractures was established to study the effects of fracture aperture, fracture dip angle, fracture interval, and fracture number on the heat extraction performance. The results showed that the heat of rock near the water inlet and the fractures are preferentially extracted. The evolution of outlet water temperature can be divided into stable and descending stages. It is also found that the fracture aperture is not the bigger the better, which needs to be set properly. Increasing fracture dip angle can slightly enhance heat extraction performance. Furthermore, the heat production effect is the best when the fracture interval is set as 1/
n
reservoir thickness. Increasing the fracture number can improve the heat extraction performance, but excessive fractures can be counterproductive and worsen the heat extraction performance of a single fracture. These results have guiding significance for the fracturing operation in the geothermal reservoir, such as fracture aperture design and multi-stage fracturing spacing setting.
Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the ...Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients.
Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
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