Rapid acquisition of the kinematic deformation field and seismic intensity distribution of large earthquakes is crucial for postseismic emergency rescue,disaster assessment,and future seismic risk research.The advance...Rapid acquisition of the kinematic deformation field and seismic intensity distribution of large earthquakes is crucial for postseismic emergency rescue,disaster assessment,and future seismic risk research.The advancement of GNSS observation and data processing makes it play an important role in this field,especially the high-frequency GNSS.We used the differential positioning method to calculate the 1 HZ GNSS data from 98 sites within 1000 km of the M_(S)7.4 Maduo earthquake epicenter.The kinematic deformation field and the distribution of the seismic intensity by using the peak ground velocity derived from displacement waveforms were obtained.The results show that:1)Horizontal coseismic response deformation levels ranging from 25 mm to 301 mm can be observed within a 1000 km radius from the epicenter.Coseismic response deformation on the east and west sides shows bilateral asymmetry,which markedly differs from the symmetry presented by surface rupture.2)The seismic intensity obtained through high-frequency GNSS and field investigations exhibits good consistency of the scope and orientation in the high seismic intensity area,although the former is generally slightly smaller than the latter.3)There may exist obstacles on the eastern side of the seismogenic fault.The Maduo earthquake induced a certain tectonic stress loading effect on the western Kunlun Pass-Jiangcuo fault(KPJF)and Maqin-Maqu segment,resulting in higher seismic risk in the future.展开更多
Nitrogen doping has been widely used to improve the performance of carbon electrodes in supercapacitors,particularly in terms of their high-frequency response.However,the charge storage and electrolyte ion response me...Nitrogen doping has been widely used to improve the performance of carbon electrodes in supercapacitors,particularly in terms of their high-frequency response.However,the charge storage and electrolyte ion response mechanisms of different nitrogen dopants at high frequencies are still unclear.In this study,melamine foam carbons with different configurations of surfacedoped N were formed by gradient carbonization,and the effects of the configurations on the high-frequency response behavior of the supercapacitors were analyzed.Using a combination of experiments and first-principle calculations,we found that pyrrolic N,characterized by a higher adsorption energy,increases the charge storage capacity of the electrode at high frequencies.On the other hand,graphitic N,with a lower adsorption energy,increases the speed of ion response.We propose the use of adsorption energy as a practical descriptor for electrode/electrolyte design in high-frequency applications,offering a more universal approach for improving the performance of N-doped carbon materials in supercapacitors.展开更多
The specialized equipment utilized in long-line tunnel engineering is evolving towards large-scale,multifunctional,and complex orientations.The vibration caused by the high-frequency units during regular operation is ...The specialized equipment utilized in long-line tunnel engineering is evolving towards large-scale,multifunctional,and complex orientations.The vibration caused by the high-frequency units during regular operation is supported by the foundation of the units,and the magnitude of vibration and the operating frequency fluctuate in different engineering contexts,leading to variations in the dynamic response of the foundation.The high-frequency units yield significantly diverse outcomes under different startup conditions and times,resulting in failure to meet operational requirements,influencing the normal function of the tunnel,and causing harm to the foundation structure,personnel,and property in severe cases.This article formulates a finite element numerical computation model for solid elements using three-dimensional elastic body theory and integrates field measurements to substantiate and ascertain the crucial parameter configurations of the finite element model.By proposing a comprehensive startup timing function for high-frequency dynamic machines under different startup conditions,simulating the frequency andmagnitude variations during the startup process,and suggesting functions for changes in frequency and magnitude,a simulated startup schedule function for high-frequency machines is created through coupling.Taking into account the selection of the transient dynamic analysis step length,the dynamic response results for the lower dynamic foundation during its fundamental frequency crossing process are obtained.The validation checks if the structural magnitude surpasses the safety threshold during the critical phase of unit startup traversing the structural resonance region.The design recommendations for high-frequency units’dynamic foundations are provided,taking into account the startup process of the machine and ensuring the safe operation of the tunnel.展开更多
High-frequency oscillation(HFO)of gridconnected wind power generation systems(WPGS)is one of the most critical issues in recent years that threaten the safe access of WPGS to the grid.Ensuring the WPGS can damp HFO is...High-frequency oscillation(HFO)of gridconnected wind power generation systems(WPGS)is one of the most critical issues in recent years that threaten the safe access of WPGS to the grid.Ensuring the WPGS can damp HFO is becoming more and more vital for the development of wind power.The HFO phenomenon of wind turbines under different scenarios usually has different mechanisms.Hence,engineers need to acquire the working mechanisms of the different HFO damping technologies and select the appropriate one to ensure the effective implementation of oscillation damping in practical engineering.This paper introduces the general assumptions of WPGS when analyzing HFO,systematically summarizes the reasons for the occurrence of HFO in different scenarios,deeply analyses the key points and difficulties of HFO damping under different scenarios,and then compares the technical performances of various types of HFO suppression methods to provide adequate references for engineers in the application of technology.Finally,this paper discusses possible future research difficulties in the problem of HFO,as well as the possible future trends in the demand for HFO damping.展开更多
Dielectric barrier discharge(DBD)plasma excited by a high-frequency alternating-current(AC)power supply is widely employed for the degradation of volatile organic compounds(VOCs).However,the thermal effect generated d...Dielectric barrier discharge(DBD)plasma excited by a high-frequency alternating-current(AC)power supply is widely employed for the degradation of volatile organic compounds(VOCs).However,the thermal effect generated during the discharge process leads to energy waste and low energy utilization efficiency.In this work,an innovative DBD thermally-conducted catalysis(DBD-TCC)system,integrating high-frequency AC-DBD plasma and its generated thermal effects to activate the Co/SBA-15 catalyst,was employed for toluene removal.Specifically,Co/SBA-15 catalysts are closely positioned to the ground electrode of the plasma zone and can be heated and activated by the thermal effect when the voltage exceeds 10 k V.At12.4 k V,the temperature in the catalyst zone reached 261℃ in the DBD-TCC system,resulting in an increase in toluene degradation efficiency of 17%,CO_(2)selectivity of 21.2%,and energy efficiency of 27%,respectively,compared to the DBD system alone.In contrast,the DBD thermally-unconducted catalysis(DBD-TUC)system fails to enhance toluene degradation due to insufficient heat absorption and catalytic activation,highlighting the crucial role of AC-DBD generated heat in the activation of the catalyst.Furthermore,the degradation pathway and mechanism of toluene in the DBD-TCC system were hypothesized.This work is expected to provide an energy-efficient approach for high-frequency AC-DBD plasma removal of VOCs.展开更多
BACKGROUND Superimposed high-frequency jet ventilation(SHFJV)is suitable for respiratory motion reduction and essential for effective lung tumor ablation.Fluid filling of the target lung wing one-lung flooding(OLF)is ...BACKGROUND Superimposed high-frequency jet ventilation(SHFJV)is suitable for respiratory motion reduction and essential for effective lung tumor ablation.Fluid filling of the target lung wing one-lung flooding(OLF)is necessary for therapeutic ultrasound applications.However,whether unilateral SHFJV allows adequate hemodynamics and gas exchange is unclear.AIM To compared SHFJV with pressure-controlled ventilation(PCV)during OLF by assessing hemodynamics and gas exchange in different animal positions.METHODS SHFJV or PCV was used alternatingly to ventilate the non-flooded lungs of the 12 anesthetized pigs during OLF.The animal positions were changed from left lateral position to supine position(SP)to right lateral position(RLP)every 30 min.In each position,ventilation was maintained for 15 min in both modalities.Hemodynamic variables and arterial blood gas levels were repeatedly measured.RESULTS Unilateral SHFJV led to lower carbon dioxide removal than PCV without abnormally elevated carbon dioxide levels.SHFJV slightly decreased oxygenation in SP and RLP compared with PCV;the lowest values of PaO_(2) and PaO_(2)/FiO_(2) ratio were found in SP[13.0;interquartile range(IQR):12.6-5.6 and 32.5(IQR:31.5-38.9)kPa].Conversely,during SHFJV,the shunt fraction was higher in all animal positions(highest in the RLP:0.30).CONCLUSION In porcine model,unilateral SHFJV may provide adequate ventilation in different animal positions during OLF.Lower oxygenation and CO_(2) removal rates compared to PCV did not lead to hypoxia or hypercapnia.SHFJV can be safely used for lung tumor ablation to minimize ventilation-induced lung motion.展开更多
BACKGROUND Sudden sensorineural hearing loss(SSNHL),characterized by a rapid and unexplained loss of hearing,particularly at moderate to high frequencies,presents a significant clinical challenge.The therapeutic use o...BACKGROUND Sudden sensorineural hearing loss(SSNHL),characterized by a rapid and unexplained loss of hearing,particularly at moderate to high frequencies,presents a significant clinical challenge.The therapeutic use of methylprednisolone sodium succinate(MPSS)via different administration routes,in combination with conventional medications,remains a topic of interest.AIM To compare the therapeutic efficacy of MPSS administered via different routes in combination with conventional drugs for the treatment of mid-to high-frequency SSNHL.METHODS The medical records of 109 patients with mid-to high-frequency SSNHL were analyzed.The patients were divided into three groups based on the route of administration:Group A[intratympanic(IT)injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection],Group B(intravenous injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection),and Group C(single IT injection of MPSS).The intervention effects were compared and analyzed.RESULTS The posttreatment auditory thresholds in Group A(21.23±3.34)were significantly lower than those in Groups B(28.52±3.36)and C(30.23±4.21;P<0.05).Group A also exhibited a significantly greater speech recognition rate(92.23±5.34)than Groups B and C.The disappearance time of tinnitus,time to hearing recovery,and disappearance time of vertigo in Group A were significantly shorter than those in Groups B and C(P<0.05).The total effective rate in Group A(97.56%)was significantly greater than that in Groups B and C(77.14%and 78.79%,χ^(2)=7.898,P=0.019).Moreover,the incidence of adverse reactions in Groups A and C was significantly lower than that in Group B(4.88%,3.03%vs 2.57%,χ^(2)=11.443,P=0.003),and the recurrence rate in Group A was significantly lower than that in Groups B and C(2.44%vs 20.00%vs 21.21%,χ^(2)=7.120,P=0.028).CONCLUSION IT injection of MPSS combined with conventional treatment demonstrates superior efficacy and safety compared to systemic administration via intravenous infusion and a single IT injection of MPSS.This approach effectively improves patients'hearing and reduces the risk of disease recurrence.展开更多
A high-frequency magnetic probe is designed and developed on the XuanL ong-50(EXL-50)spherical torus to measure high-frequency magnetic field fluctuation.The magnetic loop,radio filters,radio-frequency limiter,and dat...A high-frequency magnetic probe is designed and developed on the XuanL ong-50(EXL-50)spherical torus to measure high-frequency magnetic field fluctuation.The magnetic loop,radio filters,radio-frequency limiter,and data acquisition system of the probe are comprehensively examined.The fluctuation data from the EXL-50 plasma are analyzed in the time–frequency domain using fast Fourier transforms.Moreover,distinct high-frequency instabilities are detected using this diagnostic system.In particular,significant frequency chirping is observed,which is consistent with the bumpon-tail drive instability predicted using the Berk–Breizman model.展开更多
Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been...Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.展开更多
Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of im...Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.展开更多
Drug addiction refers to a state of dependence that arises from habitual drug intake and can result in specific withdrawal symptoms upon cessation.The most commonly abused substances include psychostimulants,cannabino...Drug addiction refers to a state of dependence that arises from habitual drug intake and can result in specific withdrawal symptoms upon cessation.The most commonly abused substances include psychostimulants,cannabinoids,and opioids.When drugs are consumed,they stimulate the release of dopamine,a neurotransmitter crucial for the pleasure and reward centers of the brain.With repeated drug use,the brain undergoes various changes,leading to tolerance,dependence,and addiction(Lüscher et al.,2020).The mechanisms involved in drug addiction are highly complex and involve diverse cell types within the brain.展开更多
Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and resten...Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons(DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary vessels.As more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation.展开更多
One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon o...One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.展开更多
Magneto-dielectric properties of Co_(2)Z ferrite materials are tuned via Gd doping for applications in high-frequency antennas and filters in the present work.Ba_(3)Co_(2)Fe_(24-x)Gd_(x)O_(41)(x=0.00,0.05,0.10,0.15,an...Magneto-dielectric properties of Co_(2)Z ferrite materials are tuned via Gd doping for applications in high-frequency antennas and filters in the present work.Ba_(3)Co_(2)Fe_(24-x)Gd_(x)O_(41)(x=0.00,0.05,0.10,0.15,and 0.20)materials are successfully prepared by using solid-state method at 925℃for 4 h with 2.5-wt%Bi_(2)O_(3)sintering aids.The content of Gd^(3+)ion can affect micromorphology,grain size,bulk density,and magneto-dielectric properties of the ferrite.With Gd^(3+)ion content increasing,saturation magnetization(Ms)first increases and then decreases.The maximum value of Ms is 44.86 emu/g at x=0.15.Additionally,sites occupied by Gd^(3+)ions can change magnetic anisotropy constant of the ferrite.Magnetocrystalline anisotropy constant(K_1)is derived from initial magnetization curve,and found to be related to spin-orbit coupling and intersublattice interactions between metal ions.The real part of magnetic permeability(μ′)and real part of dielectric permittivity(ε′)are measured in a frequency range of 10 MHz-1 GHz.When x=0.15,material has excellent magneto-dielectric properties(μ′≈12.2 andε′≈17.61),low magnetic loss(tanδμ≈0.03 at 500 MHz),and dielectric loss(tanδε≈0.04 at 500 MHz).The results show that Gd-doped Co_(2)Z ferrite has broad application prospects in multilayer filters and high-frequency antennas.展开更多
The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combination...The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.展开更多
Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial i...Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.展开更多
BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis...BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.展开更多
Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune chec...Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints.Thousands of small molecule drugs or biological materials,especially antibody-based ICIs,are actively being studied and antibodies are currently widely used.Limitations,such as anti-tumor efficacy,poor membrane permeability,and unneglected tolerance issues of antibody-based ICIs,remain evident but are thought to be overcome by small molecule drugs.Recent structural studies have broadened the scope of candidate immune checkpoint molecules,as well as innovative chemical inhibitors.By way of comparison,small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features.Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions,including immune regulation,anti-angiogenesis,and cell cycle regulation.In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins,which will lay the foundation for further exploration.展开更多
Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between dr...Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes.In addition,DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease.Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems.This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.展开更多
BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review an...BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review and network meta-analysis to determine the optimal instructions.METHODS We searched for randomized controlled trials(RCTs)from PubMed,EMBASE,Google Scholar,CNKI,and Wanfang without restriction for publication date or language at August,2023.Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis.The surface under the cumulative ranking curve(SUCRA)analysis was used to rank the treatments.P value less than 0.05 was identified as statistically significant.RESULTS We included 8 RCTs(1127 patients)comparing 8 different instructions including meloxicam(0.125 qd and 0.250 qd),Celecoxib(3 mg/kg bid and 6 mg/kg bid),piroxicam,Naproxen(5.0 mg/kg/d,7.5 mg/kg/d and 12.5 mg/kg/d),inuprofen(30-40 mg/kg/d),Aspirin(60-80 mg/kg/d,75 mg/kg/d,and 55 mg/kg/d),Tolmetin(15 mg/kg/d),Rofecoxib,and placebo.There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response.The SUCRA shows that celecoxib(6 mg/kg bid)ranked first(SUCRA,88.9%),rofecoxib ranked second(SUCRA,68.1%),Celecoxib(3 mg/kg bid)ranked third(SUCRA,51.0%).There were no significant differences between any two NSAIDs regarding adverse events.The SUCRA shows that placebo ranked first(SUCRA,88.2%),piroxicam ranked second(SUCRA,60.5%),rofecoxib(0.6 mg/kg qd)ranked third(SUCRA,56.1%),meloxicam(0.125 mg/kg qd)ranked fourth(SUCRA,56.1%),and rofecoxib(0.3 mg/kg qd)ranked fifth(SUCRA,56.1%).CONCLUSION In summary,celecoxib(6 mg/kg bid)was found to be the most effective NSAID for treating JIA.Rofecoxib,piroxicam,and meloxicam may be safer options,but further research is needed to confirm these findings in larger trials with higher quality studies.展开更多
基金supported by Grants from the National Natural Science Foundation of China(42004010)the Beijing Natural Science Foundation(8204077)。
文摘Rapid acquisition of the kinematic deformation field and seismic intensity distribution of large earthquakes is crucial for postseismic emergency rescue,disaster assessment,and future seismic risk research.The advancement of GNSS observation and data processing makes it play an important role in this field,especially the high-frequency GNSS.We used the differential positioning method to calculate the 1 HZ GNSS data from 98 sites within 1000 km of the M_(S)7.4 Maduo earthquake epicenter.The kinematic deformation field and the distribution of the seismic intensity by using the peak ground velocity derived from displacement waveforms were obtained.The results show that:1)Horizontal coseismic response deformation levels ranging from 25 mm to 301 mm can be observed within a 1000 km radius from the epicenter.Coseismic response deformation on the east and west sides shows bilateral asymmetry,which markedly differs from the symmetry presented by surface rupture.2)The seismic intensity obtained through high-frequency GNSS and field investigations exhibits good consistency of the scope and orientation in the high seismic intensity area,although the former is generally slightly smaller than the latter.3)There may exist obstacles on the eastern side of the seismogenic fault.The Maduo earthquake induced a certain tectonic stress loading effect on the western Kunlun Pass-Jiangcuo fault(KPJF)and Maqin-Maqu segment,resulting in higher seismic risk in the future.
文摘Nitrogen doping has been widely used to improve the performance of carbon electrodes in supercapacitors,particularly in terms of their high-frequency response.However,the charge storage and electrolyte ion response mechanisms of different nitrogen dopants at high frequencies are still unclear.In this study,melamine foam carbons with different configurations of surfacedoped N were formed by gradient carbonization,and the effects of the configurations on the high-frequency response behavior of the supercapacitors were analyzed.Using a combination of experiments and first-principle calculations,we found that pyrrolic N,characterized by a higher adsorption energy,increases the charge storage capacity of the electrode at high frequencies.On the other hand,graphitic N,with a lower adsorption energy,increases the speed of ion response.We propose the use of adsorption energy as a practical descriptor for electrode/electrolyte design in high-frequency applications,offering a more universal approach for improving the performance of N-doped carbon materials in supercapacitors.
基金Smart Integration Key Technologies and Application Demonstrations of Large Scale Underground Space Disaster Prevention and Reduction in Guangzhou International Financial City([2021]–KJ058).
文摘The specialized equipment utilized in long-line tunnel engineering is evolving towards large-scale,multifunctional,and complex orientations.The vibration caused by the high-frequency units during regular operation is supported by the foundation of the units,and the magnitude of vibration and the operating frequency fluctuate in different engineering contexts,leading to variations in the dynamic response of the foundation.The high-frequency units yield significantly diverse outcomes under different startup conditions and times,resulting in failure to meet operational requirements,influencing the normal function of the tunnel,and causing harm to the foundation structure,personnel,and property in severe cases.This article formulates a finite element numerical computation model for solid elements using three-dimensional elastic body theory and integrates field measurements to substantiate and ascertain the crucial parameter configurations of the finite element model.By proposing a comprehensive startup timing function for high-frequency dynamic machines under different startup conditions,simulating the frequency andmagnitude variations during the startup process,and suggesting functions for changes in frequency and magnitude,a simulated startup schedule function for high-frequency machines is created through coupling.Taking into account the selection of the transient dynamic analysis step length,the dynamic response results for the lower dynamic foundation during its fundamental frequency crossing process are obtained.The validation checks if the structural magnitude surpasses the safety threshold during the critical phase of unit startup traversing the structural resonance region.The design recommendations for high-frequency units’dynamic foundations are provided,taking into account the startup process of the machine and ensuring the safe operation of the tunnel.
基金supported in part by the Fundamental Research Funds for the Central Universities under Grant 2682023CX019National Natural Science Foundation of China under Grant U23B6007 and Grant 52307141Sichuan Science and Technology Program under Grant 2024NSFSC0115。
文摘High-frequency oscillation(HFO)of gridconnected wind power generation systems(WPGS)is one of the most critical issues in recent years that threaten the safe access of WPGS to the grid.Ensuring the WPGS can damp HFO is becoming more and more vital for the development of wind power.The HFO phenomenon of wind turbines under different scenarios usually has different mechanisms.Hence,engineers need to acquire the working mechanisms of the different HFO damping technologies and select the appropriate one to ensure the effective implementation of oscillation damping in practical engineering.This paper introduces the general assumptions of WPGS when analyzing HFO,systematically summarizes the reasons for the occurrence of HFO in different scenarios,deeply analyses the key points and difficulties of HFO damping under different scenarios,and then compares the technical performances of various types of HFO suppression methods to provide adequate references for engineers in the application of technology.Finally,this paper discusses possible future research difficulties in the problem of HFO,as well as the possible future trends in the demand for HFO damping.
基金supported by National Natural Science Foundation of China(No.52177130)the Key Projects for Industrial Prospects and Core Technology Research in Suzhou City(No.SYC2022029)。
文摘Dielectric barrier discharge(DBD)plasma excited by a high-frequency alternating-current(AC)power supply is widely employed for the degradation of volatile organic compounds(VOCs).However,the thermal effect generated during the discharge process leads to energy waste and low energy utilization efficiency.In this work,an innovative DBD thermally-conducted catalysis(DBD-TCC)system,integrating high-frequency AC-DBD plasma and its generated thermal effects to activate the Co/SBA-15 catalyst,was employed for toluene removal.Specifically,Co/SBA-15 catalysts are closely positioned to the ground electrode of the plasma zone and can be heated and activated by the thermal effect when the voltage exceeds 10 k V.At12.4 k V,the temperature in the catalyst zone reached 261℃ in the DBD-TCC system,resulting in an increase in toluene degradation efficiency of 17%,CO_(2)selectivity of 21.2%,and energy efficiency of 27%,respectively,compared to the DBD system alone.In contrast,the DBD thermally-unconducted catalysis(DBD-TUC)system fails to enhance toluene degradation due to insufficient heat absorption and catalytic activation,highlighting the crucial role of AC-DBD generated heat in the activation of the catalyst.Furthermore,the degradation pathway and mechanism of toluene in the DBD-TCC system were hypothesized.This work is expected to provide an energy-efficient approach for high-frequency AC-DBD plasma removal of VOCs.
文摘BACKGROUND Superimposed high-frequency jet ventilation(SHFJV)is suitable for respiratory motion reduction and essential for effective lung tumor ablation.Fluid filling of the target lung wing one-lung flooding(OLF)is necessary for therapeutic ultrasound applications.However,whether unilateral SHFJV allows adequate hemodynamics and gas exchange is unclear.AIM To compared SHFJV with pressure-controlled ventilation(PCV)during OLF by assessing hemodynamics and gas exchange in different animal positions.METHODS SHFJV or PCV was used alternatingly to ventilate the non-flooded lungs of the 12 anesthetized pigs during OLF.The animal positions were changed from left lateral position to supine position(SP)to right lateral position(RLP)every 30 min.In each position,ventilation was maintained for 15 min in both modalities.Hemodynamic variables and arterial blood gas levels were repeatedly measured.RESULTS Unilateral SHFJV led to lower carbon dioxide removal than PCV without abnormally elevated carbon dioxide levels.SHFJV slightly decreased oxygenation in SP and RLP compared with PCV;the lowest values of PaO_(2) and PaO_(2)/FiO_(2) ratio were found in SP[13.0;interquartile range(IQR):12.6-5.6 and 32.5(IQR:31.5-38.9)kPa].Conversely,during SHFJV,the shunt fraction was higher in all animal positions(highest in the RLP:0.30).CONCLUSION In porcine model,unilateral SHFJV may provide adequate ventilation in different animal positions during OLF.Lower oxygenation and CO_(2) removal rates compared to PCV did not lead to hypoxia or hypercapnia.SHFJV can be safely used for lung tumor ablation to minimize ventilation-induced lung motion.
文摘BACKGROUND Sudden sensorineural hearing loss(SSNHL),characterized by a rapid and unexplained loss of hearing,particularly at moderate to high frequencies,presents a significant clinical challenge.The therapeutic use of methylprednisolone sodium succinate(MPSS)via different administration routes,in combination with conventional medications,remains a topic of interest.AIM To compare the therapeutic efficacy of MPSS administered via different routes in combination with conventional drugs for the treatment of mid-to high-frequency SSNHL.METHODS The medical records of 109 patients with mid-to high-frequency SSNHL were analyzed.The patients were divided into three groups based on the route of administration:Group A[intratympanic(IT)injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection],Group B(intravenous injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection),and Group C(single IT injection of MPSS).The intervention effects were compared and analyzed.RESULTS The posttreatment auditory thresholds in Group A(21.23±3.34)were significantly lower than those in Groups B(28.52±3.36)and C(30.23±4.21;P<0.05).Group A also exhibited a significantly greater speech recognition rate(92.23±5.34)than Groups B and C.The disappearance time of tinnitus,time to hearing recovery,and disappearance time of vertigo in Group A were significantly shorter than those in Groups B and C(P<0.05).The total effective rate in Group A(97.56%)was significantly greater than that in Groups B and C(77.14%and 78.79%,χ^(2)=7.898,P=0.019).Moreover,the incidence of adverse reactions in Groups A and C was significantly lower than that in Group B(4.88%,3.03%vs 2.57%,χ^(2)=11.443,P=0.003),and the recurrence rate in Group A was significantly lower than that in Groups B and C(2.44%vs 20.00%vs 21.21%,χ^(2)=7.120,P=0.028).CONCLUSION IT injection of MPSS combined with conventional treatment demonstrates superior efficacy and safety compared to systemic administration via intravenous infusion and a single IT injection of MPSS.This approach effectively improves patients'hearing and reduces the risk of disease recurrence.
基金supported by National Natural Science Foundation of China(No.11706151)。
文摘A high-frequency magnetic probe is designed and developed on the XuanL ong-50(EXL-50)spherical torus to measure high-frequency magnetic field fluctuation.The magnetic loop,radio filters,radio-frequency limiter,and data acquisition system of the probe are comprehensively examined.The fluctuation data from the EXL-50 plasma are analyzed in the time–frequency domain using fast Fourier transforms.Moreover,distinct high-frequency instabilities are detected using this diagnostic system.In particular,significant frequency chirping is observed,which is consistent with the bumpon-tail drive instability predicted using the Berk–Breizman model.
基金supported by funding from the Bluesand Foundation,Alzheimer's Association(AARG-21-852072 and Bias Frangione Early Career Achievement Award)to EDan Australian Government Research Training Program scholarship and the University of Sydney's Brain and Mind Centre fellowship to AH。
文摘Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.
基金supported by grants from the National Natural Science Foundation of China (Grant No. U20A20369)GuangDong Basic and Applied Basic Research Foundation (Grant No. 2022B1515120085)。
文摘Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.
基金supported by the STI2030-Major Projects(2021ZD0203000(2021ZD0203003))National Science Foundation of China(22207105)+1 种基金Beijing National Laboratory for Molecular Sciences(BNLMS202108)Chinese Academy of Sciences Pioneer Hundred Talents Program。
文摘Drug addiction refers to a state of dependence that arises from habitual drug intake and can result in specific withdrawal symptoms upon cessation.The most commonly abused substances include psychostimulants,cannabinoids,and opioids.When drugs are consumed,they stimulate the release of dopamine,a neurotransmitter crucial for the pleasure and reward centers of the brain.With repeated drug use,the brain undergoes various changes,leading to tolerance,dependence,and addiction(Lüscher et al.,2020).The mechanisms involved in drug addiction are highly complex and involve diverse cell types within the brain.
文摘Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons(DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary vessels.As more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation.
文摘One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.
基金the National Key Research and Development Program of China(Grant No.2022YFB3504800)the National Natural Science Foundation of China(Grant Nos.61901142,52003256,and 51902037)the Natural Science Foundation of Shanxi Province,China(Grant No.201901D211259)。
文摘Magneto-dielectric properties of Co_(2)Z ferrite materials are tuned via Gd doping for applications in high-frequency antennas and filters in the present work.Ba_(3)Co_(2)Fe_(24-x)Gd_(x)O_(41)(x=0.00,0.05,0.10,0.15,and 0.20)materials are successfully prepared by using solid-state method at 925℃for 4 h with 2.5-wt%Bi_(2)O_(3)sintering aids.The content of Gd^(3+)ion can affect micromorphology,grain size,bulk density,and magneto-dielectric properties of the ferrite.With Gd^(3+)ion content increasing,saturation magnetization(Ms)first increases and then decreases.The maximum value of Ms is 44.86 emu/g at x=0.15.Additionally,sites occupied by Gd^(3+)ions can change magnetic anisotropy constant of the ferrite.Magnetocrystalline anisotropy constant(K_1)is derived from initial magnetization curve,and found to be related to spin-orbit coupling and intersublattice interactions between metal ions.The real part of magnetic permeability(μ′)and real part of dielectric permittivity(ε′)are measured in a frequency range of 10 MHz-1 GHz.When x=0.15,material has excellent magneto-dielectric properties(μ′≈12.2 andε′≈17.61),low magnetic loss(tanδμ≈0.03 at 500 MHz),and dielectric loss(tanδε≈0.04 at 500 MHz).The results show that Gd-doped Co_(2)Z ferrite has broad application prospects in multilayer filters and high-frequency antennas.
基金sponsored by the National Research Foundation of Korea(NRF)Grant funded by the Korean government(MSIT)(Grant No.:2018R1A5A2021242).
文摘The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.
基金support from the National Natural Science Foundation of China(Nos.52073230,62204204,and 62288102)the Shaanxi Provincial Science Fund for Distinguished Young Scholars(No.2023-JC-JQ-32)+2 种基金the Science and Technology Innovation 2030-Major Project(No.2022ZD0208601)the Shanghai Sailing Program(No.21YF1451000)the China National Postdoctoral Program for Innovative Talents(No.BX20230494).
文摘Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.
基金Supported by Science and Technology Plan Project of Shaoyang City,No.2022GX4139.
文摘BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.
基金supported by the National Natural Science Foundation of China(Grant Nos.82203539 and 92259102)Provincial Cooperation Project of Science and Technology Department of Sichuan Province(Grant No.2023YFSY0043)the National Key Research and Development Program of China(Grant No.2023YFC3402100).
文摘Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints.Thousands of small molecule drugs or biological materials,especially antibody-based ICIs,are actively being studied and antibodies are currently widely used.Limitations,such as anti-tumor efficacy,poor membrane permeability,and unneglected tolerance issues of antibody-based ICIs,remain evident but are thought to be overcome by small molecule drugs.Recent structural studies have broadened the scope of candidate immune checkpoint molecules,as well as innovative chemical inhibitors.By way of comparison,small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features.Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions,including immune regulation,anti-angiogenesis,and cell cycle regulation.In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins,which will lay the foundation for further exploration.
文摘Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes.In addition,DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease.Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems.This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.
基金Supported by the Science and Technology Plan Project of Jingmen Science and Technology Bureau,No.2018YFZD025。
文摘BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review and network meta-analysis to determine the optimal instructions.METHODS We searched for randomized controlled trials(RCTs)from PubMed,EMBASE,Google Scholar,CNKI,and Wanfang without restriction for publication date or language at August,2023.Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis.The surface under the cumulative ranking curve(SUCRA)analysis was used to rank the treatments.P value less than 0.05 was identified as statistically significant.RESULTS We included 8 RCTs(1127 patients)comparing 8 different instructions including meloxicam(0.125 qd and 0.250 qd),Celecoxib(3 mg/kg bid and 6 mg/kg bid),piroxicam,Naproxen(5.0 mg/kg/d,7.5 mg/kg/d and 12.5 mg/kg/d),inuprofen(30-40 mg/kg/d),Aspirin(60-80 mg/kg/d,75 mg/kg/d,and 55 mg/kg/d),Tolmetin(15 mg/kg/d),Rofecoxib,and placebo.There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response.The SUCRA shows that celecoxib(6 mg/kg bid)ranked first(SUCRA,88.9%),rofecoxib ranked second(SUCRA,68.1%),Celecoxib(3 mg/kg bid)ranked third(SUCRA,51.0%).There were no significant differences between any two NSAIDs regarding adverse events.The SUCRA shows that placebo ranked first(SUCRA,88.2%),piroxicam ranked second(SUCRA,60.5%),rofecoxib(0.6 mg/kg qd)ranked third(SUCRA,56.1%),meloxicam(0.125 mg/kg qd)ranked fourth(SUCRA,56.1%),and rofecoxib(0.3 mg/kg qd)ranked fifth(SUCRA,56.1%).CONCLUSION In summary,celecoxib(6 mg/kg bid)was found to be the most effective NSAID for treating JIA.Rofecoxib,piroxicam,and meloxicam may be safer options,but further research is needed to confirm these findings in larger trials with higher quality studies.