Research Progress of Atomizers and Drugs Used in Atomization Therapy

At present,the commonly used treatment methods for chronic respiratory diseases are drug,oxygen,interventional and atomization therapy.Atomization therapy is the most widely used because of its characteristics of fast effect,high local drug concentration,less drug dosage,convenient application and few systemic adverse reactions.In this paper,the mechanism,characteristics,commonly used drugs and clinical application of atomization therapy are discussed.

Research Progress of Drug Therapy for Diabetes

Diabetes is mainly a series of symptoms of glucose metabolism disorder caused by relative or absolute insufficiencies of insulin.Most patients are accompanied by protein,fat,water and electrolyte disorders,including diabetes type 1 and diabetes type 2,of which diabetes type 2 accounts for more than 90%.The incidence rate of diabetes is high,the course of disease is long,and it is difficult to cure.Most patients need long-term medication.This study analyzed the clinical manifestations and predisposing factors of diabetes,and explored the progress of drug treatment of diabetes,which is summarized as follows.

Peptide drugs: a new direction in cancer immunotherapy

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.

Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma

Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.

Observation on the Clinical Effect of Applying Venetoclax Combined with Demethylation Drug Therapy in Patients with Acute Myeloid Leukemia

Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.

Is tumor necrosis factor-α monoclonal therapy with proactive therapeutic drug monitoring optimized for inflammatory bowel disease? Network meta-analysis

BACKGROUND The efficacy and safety of anti-tumor necrosis factor-α(TNF-α)monoclonal antibody therapy[adalimumab(ADA)and infliximab(IFX)]with therapeutic drug monitoring(TDM),which has been proposed for inflammatory bowel disease(IBD)patients,are still controversial.AIM To determine the efficacy and safety of anti-TNF-αmonoclonal antibody therapy with proactive TDM in patients with IBD and to determine which subtype of IBD patients is most suitable for proactive TDM interventions.METHODS As of July 2023,we searched for randomized controlled trials(RCTs)and observa-tional studies in PubMed,Embase,and the Cochrane Library to compare anti-TNF-αmonoclonal antibody therapy with proactive TDM with therapy with reactive TDM or empiric therapy.Pairwise and network meta-analyses were used to determine the IBD patient subtype that achieved clinical remission and to determine the need for surgery.RESULTS This systematic review and meta-analysis yielded 13 studies after exclusion,and the baseline indicators were balanced.We found a significant increase in the number of patients who achieved clinical remission in the ADA[odds ratio(OR)=1.416,95%confidence interval(CI):1.196-1.676]and RCT(OR=1.393,95%CI:1.182-1.641)subgroups and a significant decrease in the number of patients who needed surgery in the proactive vs reactive(OR=0.237,95%CI:0.101-0.558)and IFX+ADA(OR=0.137,95%CI:0.032-0.588)subgroups,and the overall risk of adverse events was reduced(OR=0.579,95%CI:0.391-0.858)according to the pairwise meta-analysis.Moreover,the network meta-analysis results suggested that patients with IBD treated with ADA(OR=1.39,95%CI:1.19-1.63)were more likely to undergo TDM,especially in comparison with patients with reactive TDM(OR=1.38,95%CI:1.07-1.77).CONCLUSION Proactive TDM is more suitable for IBD patients treated with ADA and has obvious advantages over reactive TDM.We recommend proactive TDM in IBD patients who are treated with ADA.

Vasculogenic mimicry:a pivotal mechanism contributing to drug resistance in antiangiogenic therapy

The growth of solid tumors relies on establishing a robust blood supply,with angiogenesis playing a key role in this intricate process.Based on this understanding,therapeutic strategies targeting tumor angiogenesis have been developed.However,the clinical effectiveness of antiangiogenic therapy(AAT)in treating tumors has not lived up to expectations.In recent years,vasculogenic mimicry(VM)has attracted increasing attention from the academic community as a longstanding but often overlooked mechanism of nonangiogenic tumor vascularization.Within the tumor microenvironment,neoplastic cells can autonomously form vessel-like structures,creating a blood supply that does not rely on endothelial cells.This phenomenon,known as VM,is a critical marker of aggressive tumors and may play a significant role in conferring resistance to AAT.In this review,we thoroughly examine the evidence,clinical characteristics,and mechanisms of VM across various tumor types and explore its potential role and importance in resistance to AAT and the development of new antitumor therapies.

Role of targeting ferroptosis as a component of combination therapy in combating drug resistance in colorectal cancer

Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.

Yinqiao Sanhuang Paste Combined with Traditional Chinese Medicine Plaster for the Intervention of Drug Rash Induced by Targeted Therapy in Lung Cancer

Objective:To observe the efficacy and safety of Yinqiao Sanhuang Paste combined with traditional Chinese medicine plaster in treating drug rash caused by targeted therapy in lung cancer.Methods:A total of 100 lung cancer patients treated at our hospital from January 2021 to December 2023 were selected and randomly divided into an observation group and a control group,with 50 patients in each group.The control group received conventional medication,while the observation group was treated with Yinqiao Sanhuang Paste combined with traditional Chinese medicine plaster.The clinical symptom improvement and adverse reactions in both groups were observed.Results:The effective rate in the control group was 80.00%,while in the observation group,it was 96.00%,with a statistically significant difference between the two groups(P<0.05).The onset time,duration,and significant effect time in the control group were(2.41±0.29)days,(4.42±1.21)days,and(5.45±0.29)days,respectively;in the observation group,they were(2.44±0.21)days,(4.28±1.11)days,and(5.57±1.01)days,respectively.There was no statistically significant difference in the total onset time and total duration between the two groups(P>0.05).The incidence of adverse reactions in the control group was 28.00%,higher than the observation group’s 10.00%(P<0.05).Conclusion:Yinqiao Sanhuang Paste combined with traditional Chinese medicine plaster can effectively reduce the symptoms of drug rash induced by targeted therapy in lung cancer and lower the incidence of adverse reactions,indicating good clinical application value.

Ionizable drug delivery systems for efficient and selective gene therapy

Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.

Smart drug delivery systems to overcome drug resistance in cancer immunotherapy

Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.

Combination therapy to overcome ferroptosis resistance by biomimetic self-assembly nano-prodrug

Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer.Herein,we have constructed a biomimetic self-assembly nano-prodrug system that enables the co-delivery of gefitinib(Gefi),ferrocene(Fc)and dihydroartemisinin(DHA)for the combined therapy of both ferroptosis and apoptosis.In the tumor microenvironment,this nano-prodrug is able to disassemble and trigger drug release under high levels of GSH.Interestingly,the released DHA can downregulate GPX4 level for the enhancement of intracellular ferroptosis from Fc,further executing tumor cell death with concomitant chemotherapy by Gefi.More importantly,this nano-prodrug provides highly homologous targeting ability by coating related cell membranes and exhibits outstanding inhibition of tumor growth and metastasis,as well as no noticeable side-effects during treatments.This simple small molecular self-assembled nano-prodrug provides a new reasonably designed modality for ferroptosis-combined chemotherapy.

Prolonged dual antiplatelet therapy after drug-eluting stent implantation improves long-term prognosis for acute coronary syndrome:five-year results from a large cohort study

BACKGROUND:To investigate the most appropriate dual antiplatelet therapy(DAPT)duration for patients with acute coronary syndrome(ACS)after drug-eluting stent(DES)implantation in the largest cardiovascular center of China.METHODS:We enrolled 5,187 consecutive patients with ACS who received DES from January to December 2013.Patients were divided into four groups based on DAPT duration:standard DAPT group(11-13 months,n=1,568)and prolonged DAPT groups(13-18 months[n=308],18-24 months[n=2,125],and>24 months[n=1,186]).Baseline characteristics and 5-year clinical outcomes were recorded.RESULTS:Baseline characteristics were similar across the four groups.Among the four groups,those with prolonged DAPT(18-24 months)had the lowest incidence of major adverse cardiovascular and cerebrovascular events(MACCEs)(14.1%vs.11.7%vs.9.6%vs.24.2%,P<0.001),all-cause death(4.8%vs.3.9%vs.2.1%vs.2.6%,P<0.001),cardiac death(3.1%vs.2.6%vs.1.4%vs.1.9%,P=0.004),and myocardial infarction(MI)(3.8%vs.4.2%vs.2.5%vs.5.8%,P<0.001).The incidence of bleeding was not different among the four groups(9.9%vs.9.4%vs.11.0%vs.9.4%,P=0.449).Cox multivariable analysis showed that prolonged DAPT(18-24 months)was an independent protective factor for MACCEs(hazard ratio[HR]0.802,95%confidence interval[CI]0.729-0.882,P<0.001),all-cause death(HR 0.660,95%CI 0.547-0.795,P<0.001),cardiac death(HR 0.663,95%CI 0.526-0.835,P<0.001),MI(HR 0.796,95%CI 0.662-0.957,P=0.015),and target vessel revascularization(HR 0.867,95%CI 0.755-0.996,P=0.044).Subgroup analysis for high bleeding risk showed that prolonged DAPT remained an independent protective factor for all-cause death and MACCEs.CONCLUSION:For patients with ACS after DES,appropriately prolonging the DAPT duration may be associated with a reduced risk of adverse ischemic events without increasing the bleeding risk.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province,China,2014–2020

Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Strategies for translating proteomics discoveries into drug discovery for dementia

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.

Microglia in drug addiction:A perspective from neuroimmunopharmacology

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.

Prognostic characterization of copper death-related immune checkpoint genes and analysis of immunologic and pharmacologic therapy in bladder cancer

Objective:Copper death-induced tumor cell death and immune checkpoint blockade therapy are highly selective.Combining their advantages and understanding their characteristics in bladder cancer is very important for the development of new targeted therapy.The identification of bladder cancer by screening the characteristic genes of copper death-related immune checkpoints provide a theoretical basis for the selection of adjuvant treatment options and the application of new targets.Methods:The expression samples of normal bladder tissue and bladder cancer were obtained from TCGA and GEO databases,and 13 cop-per death genes and 79 immune checkpoint genes were extracted from previous studies.The mRNA expression of prognostic genes was verified by qPCR.The copper death-related immune checkpoint genes were screened by correlation analysis to construct a prognostic model,and the differences in the efficacy of immunotherapy and chemotherapy between the high-risk group and the low-risk group were evaluated.Results:A prognostic model consisting of BTNL9,CD160,TNFRSF14 and TNFRSF18 was constructed.Its reliable predictive ability was proved in both databases,and qPCR showed that the expression levels of the four genes were significantly different between the normal group and the cancer cell group.The effect of immunotherapy in the lowrisk group was better than that in the high-risk group.Patients in the high-risk group had better chemotherapy efficacy.Conclusion:The copper death-related immune checkpoint gene model can accurately predict the prognosis of patients.Drug and immune analysis provide a basis for clinical treatment,and the discovery of potential targets provides a new solution for clinical decision-making.

High frequency strong current tACS:a new dawn of non-drug therapy for patients with major depressive disorder

A commentary on:Transcranial alternating current stimulation for treating depression:a randomized controlled trial.By Wang H,Wang K,Xue Q,et al.Brain.2022;1451:83-91.doi:10.1093/brain/awab252.Major depressive disorder(MDD)is a common severe mental illness with recurring episodes.The most commonly used treatment is drug therapy,which is associated with a series of side effects and has an efficacy rate below 50%.1 Non-invasive brain stimulation technique has been gradually applied in clinical practice.Transcranial alternating current stimulation(tACS),a form of non-invasive brain stimulation,is a light,wearable piece of equipment for cortical stimulation.It modulates cortical excitability and spontaneous brain activity by applying an electric current to the scalp.

Psychedelic Drug Therapy for Mental Disorders?

Objective: Psychedelic drug therapy is banned in all countries of the world except Australia, where the government regulatory watchdog, the Therapeutic Goods Administration, is planning to allow approved psychiatrists, as of July 1, 2023, to prescribe psilocybin to treat depression and MDMA to treat post-traumatic stress disorder, a move precipitated by the U.S. Food and Drug Administration’s designation of these two drugs as “breakthrough therapy”. The objective of the present article is to demonstrate that the evidence on which the FDA and then the TGA relied is irretrievably flawed and should be dismissed. Method: Expert review of psychedelic therapy clinical trials and specifically of the methodology and measures used. Results: The present review demonstrates that the studies the U.S. FDA and the Australian TGA relied on to approve these two psychedelic drugs for therapy are irretrievably flawed. All future trials will follow the same procedure and are therefore bound to be flawed as well. Conclusions: Psychedelic drug studies have so far provided no trustworthy evidence of their effectiveness for treating mental disorders and are not likely to produce this evidence in the future. Psychedelic drug therapy is in any event impractical because of its specialized training requirements and very high treatment costs. It is also dangerous because false publicity about its effectiveness will almost certainly lead to unsupervised self-dosing with drugs that not only are illegal but have an unacceptably high addiction rate.