Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers

Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.

Unveiling the role of hypoxia-inducible factor 2alpha in osteoporosis:Implications for bone health

BACKGROUND Osteoporosis(OP)has become a major public health problem worldwide.Most OP treatments are based on the inhibition of bone resorption,and it is necessary to identify additional treatments aimed at enhancing osteogenesis.In the bone marrow(BM)niche,bone mesenchymal stem cells(BMSCs)are exposed to a hypoxic environment.Recently,a few studies have demonstrated that hypoxiainducible factor 2alpha(HIF-2α)is involved in BMSC osteogenic differentiation,but the molecular mechanism involved has not been determined.AIM To investigate the effect of HIF-2αon the osteogenic and adipogenic differentiation of BMSCs and the hematopoietic function of hematopoietic stem cells(HSCs)in the BM niche on the progression of OP.METHODS Mice with BMSC-specific HIF-2αknockout(Prx1-Cre;Hif-2αfl/fl mice)were used for in vivo experiments.Bone quantification was performed on mice of two genotypes with three interventions:Bilateral ovariectomy,semilethal irradiation,and dexamethasone treatment.Moreover,the hematopoietic function of HSCs in the BM niche was compared between the two mouse genotypes.In vitro,the HIF-2αagonist roxadustat and the HIF-2αinhibitor PT2399 were used to investigate the function of HIF-2αin BMSC osteogenic and adipogenic differentiation.Finally,we investigated the effect of HIF-2αon BMSCs via treatment with the mechanistic target of rapamycin(mTOR)agonist MHY1485 and the mTOR inhibitor rapamycin.RESULTS The quantitative index determined by microcomputed tomography indicated that the femoral bone density of Prx1-Cre;Hif-2αfl/fl mice was lower than that of Hif-2αfl/fl mice under the three intervention conditions.In vitro,Hif-2αfl/fl mouse BMSCs were cultured and treated with the HIF-2αagonist roxadustat,and after 7 d of BMSC adipogenic differentiation,the oil red O staining intensity and mRNA expression levels of adipogenesis-related genes in BMSCs treated with roxadustat were decreased;in addition,after 14 d of osteogenic differentiation,BMSCs treated with roxadustat exhibited increased expression of osteogenesis-related genes.The opposite effects were shown for mouse BMSCs treated with the HIF-2αinhibitor PT2399.The mTOR inhibitor rapamycin was used to confirm that HIF-2αregulated BMSC osteogenic and adipogenic differentiation by inhibiting the mTOR pathway.Consequently,there was no significant difference in the hematopoietic function of HSCs between Prx1-Cre;Hif-2αfl/fl and Hif-2αfl/fl mice.CONCLUSION Our study showed that inhibition of HIF-2αdecreases bone mass by inhibiting the osteogenic differentiation and increasing the adipogenic differentiation of BMSCs through inhibition of mTOR signaling in the BM niche.

Self-assembly of differentiated dental pulp stem cells facilitates spheroid human dental organoid formation and prevascularization

BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine.Stem cells can self-organise into microsized organ units,partially modelling tissue function and regeneration.Dental pulp organoids have been used to recapitulate the processes of tooth development and related diseases.However,the lack of vasculature limits the utility of dental pulp organoids.AIM To improve survival and aid in recovery after stem cell transplantation,we demonstrated the three-dimensional(3D)self-assembly of adult stem cell-human dental pulp stem cells(hDPSCs)and endothelial cells(ECs)into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium(CM).METHODS During culture,primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and CM.The hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp organoids.The biological characteristics of the organoids were analysed,and the regulatory pathways associated with angiogenesis were studied.RESULTS The combination of these two agents resulted in prevascularized human dental pulp organoids(Vorganoids)that more closely resembled dental pulp tissue in terms of morphology and function.Single-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with angiogenesis.The biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of Vorganoids.CONCLUSION In this innovative study,we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration,facilitating the development of clinical treatment strategies.

Advances in the Mechanisms of Hemorrhagic Transformation and Therapeutic Agents after Intravenous Thrombolysis in Ischemic Stroke

Ischemic stroke is an important disease leading to death and disability for all human beings, and the key to its treatment lies in the early opening of obstructed vessels and restoration of perfusion to the local infarcted area. Intravenous thrombolysis with tissue plasminogen activator (tPA) is one of the effective therapies to achieve revascularization, but it faces strict indications with a narrow therapeutic time window, and significantly increases the incidence of hemorrhagic transformation, HT, after reperfusion of the infarcted foci, which greatly reduces the incidence of patients with ischemic stroke. which significantly increases the incidence of hemorrhagic transformation (HT) after reperfusion of the infarcted focus, greatly reducing patient utilization and clinical benefit. Since the mechanism of HT has not been fully elucidated, and the related molecular mechanisms are complex and interactive, there is no specific and effective therapy to avoid the occurrence of HT. In this article, we focus on the research progress on the mechanism of HT after tPA intravenous thrombolysis in ischemic stroke patients from the aspects of vascular integrity disruption, oxidative stress, and neuroinflammatory response and the corresponding therapeutic strategies, in order to improve the safety and prognosis of tPA intravenous thrombolysis in the clinic.

Low-temperature photothermal-induced alkyl radical release facilitates dihydroartemisinin-triggered“valve-off”starvation therapy

The high nutrient and energy demand of tumor cells compared to normal cells to sustain rapid proliferation offer a potentially auspicious avenue for implementing starvation therapy.However,conventional starvation therapy,such as glucose exhaustion and vascular thrombosis,can lead to systemic toxicity and exacerbate tumor hypoxia.Herein,we developed a new“valve-off”starvation tactic,which was accomplished by closing the valve of glucose transporter protein 1(GLUT1).Specifically,dihydroartemisinin(DHA),2,20-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride(AI),and Ink were co-encapsulated in a sodium alginate(ALG)hydrogel.Upon irradiation with the 1064 nm laser,AI rapidly disintegrated into alkyl radicals(R·),which exacerbated the DHA-induced mitochondrial damage through the generation of reactive oxygen species and further reduced the synthesis of adenosine triphosphate(ATP).Simultaneously,the production of R·facilitated DHA-induced starvation therapy by suppressing GLUT1,which in turn reduced glucose uptake.Systematic in vivo and in vitro results suggested that this radical-enhanced“valveoff”strategy for inducing tumor cell starvation was effective in reducing glucose uptake and ATP levels.This integrated strategy induces tumor starvation with efficient tumor suppression,creating a new avenue for controlled,precise,and concerted tumor therapy.

Exploring the pharmacological mechanism of Wuzhuyu decoction on hepatocellular carcinoma using network pharmacology

BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The active components of each Chinese herbal medicinal ingredient in Wuzhuyu decoction and their targets were obtained from the Traditional Chinese Medicine Database and Analysis Platform.HCC was used as a search query in GeneCards,Online Mendelian Inheritance in Man,Malacards,DisGeNET,Therapeutic Target Database,and Comparative Toxicogenomics Database.The overlapping targets of the Wuzhuyu decoction and HCC were defined,and then protein-protein interaction,Gene Ontology,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.CytoHubba was used to select hub genes,and their binding activities and key active components were verified using molecular docking.RESULTS A total of 764 compounds,77 active compounds,and 204 potential target genes were identified in Wuzhuyu decoction.For HCC,9468 potential therapeutic target genes were identified by combining the results from the six databases and removing duplicates.A total of 179 overlapping targets of Wuzhuyu decoction and HCC were defined,including 10 hub genes(tumor necrosis factor,interleukin-6,AKT1,TP53,caspase-3,mitogen-activated protein kinase 1,epidermal growth factor receptor,MYC,mitogen-activated protein kinase 8,and JUN).There were six main active components(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)that may act on hub genes to treat HCC in Wuzhuyu decoction.Kyoto Encyclopedia of Genes and Genomes enrichment analysis mainly involved the mitogen-activated protein kinase,p53,phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt,Janus kinase-signal transducer of activators of transcription,and Hippo signaling pathways.Further verification based on molecular docking results showed that the small molecule compounds(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)contained in Wuzhuyu decoction generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes.

Study of Immunotherapy and Intestinal Flora Changes in Patients with Liver Cancer

Hepatocellular carcinoma (HCC) is one of the common major malignancies worldwide and has the third highest mortality rate of any malignancy. The current field of treatment for hepatocellular carcinoma is multidisciplinary in involvement and a combination of therapeutic approaches, among which immunotherapy is the treatment modality for advanced hepatocellular carcinoma. This review provides new ideas for developing immunotherapy regimens and improving the efficacy of immunotherapy for patients with advanced liver cancer by summarising the progress of intestinal flora in the immunotherapy of patients with liver cancer.

Research Progress on the Prediction of TACE Efficacy by Lipiodol Deposition

Primary hepatocellular carcinoma is one of the most common and deadliest malignant tumors in the world, and most patients are diagnosed after missing the optimal treatment period. TACE (Transcatheter arterial chemoembolization) is currently the preferred treatment for advanced HCC (Hepatocellular Carcinoma), as it can induce local ischemic necrosis of the tumor while reducing the systemic side effects of drugs by embolizing the tumor-feeding arteries. Lipiodol, with its unique comprehensive properties of imaging, drug loading, and embolization, has become a key component in the process of TACE. Therefore, analyzing the deposition of lipiodol in hepatic tumor tissues after TACE can effectively evaluate the treatment efficacy. This article summarizes and analyzes the metabolism of lipiodol in tumors and the clinical application of lipiodol deposition status in predicting patient prognosis, aiming to provide clearer diagnostic and treatment strategies for clinical doctors.

Iodine-125 seed implantation in the treatment of malignant tumors

Malignant tumors are major causes of morbidity and mortality in China.Despite advances in surgical,radiological,chemotherapeutic,molecular targeting,and immunotherapeutic treatments,patients with malignant tumors still have poor prognoses.Low-dose-rate brachytherapy,specifically 125I seed implantation,is beneficial because of its high local delivery dose and minimal damage to surrounding tissues.Consequently,it has gained increasing acceptance as a treatment modality for various malignant tumors.In this study,we explored the fundamental principles,clinical applications,and new technologies associated with 125I radioactive seed implantation.

Research Progress in Intestinal Flora and Hepatocellular Carcinoma

Intestinal flora are involved in environmental homeostasis and the development of many diseases within the human body. The liver, as one of the most important digestive organs in human beings, communicates with the intestinal flora and their metabolites in the intestine through the biliary system, the hepatic portal system, and the corpuscular circulation, an interrelated system known as the intestinal-hepatic axis. Hepatocellular carcinoma is the most common malignant tumor of the liver and one of the leading causes of cancer-related deaths worldwide. There is increasing evidence that intestinal flora plays an important role in the evolution of hepatocellular carcinoma. Besides, intestinal flora has great potential in the treatment of liver cancer. On this basis, this paper summarizes the relevant studies on the role of intestinal flora in the development of hepatocellular carcinoma and discusses its potential value in the treatment of hepatocellular carcinoma.

Recent Progress in the Study of Respiratory Complications Correlated with TACE for HCC

Due to the insidious clinical symptoms of early hepatocellular carcinoma (HCC), most of the patients diagnosed at intermediate-to-advanced stage HCC, and they lost the opportunity for curative treatment. Comprehensive interventional therapy plays an important role in prolonging the median survival of patients with intermediate-to-advanced stage HCC, among which transcatheter hepatic artery chemoembolization (TACE) is the most commonly used minimally invasive treatment. However, TACE may cause many postoperative complications such as liver function damage, biliary tract injury, upper gastrointestinal bleeding. Among them, TACE-related respiratory complications have been reported in a few articles, which are extremely rare but serious, and there are still many uncertainties about their occurrence mechanisms and risk factors. This article is aim to focus on the research progress of the respiratory complications of TACE, thus making progress on TACE-treatment aftercare.

Effects of hypoxia on bone metabolism and anemia in patients with chronic kidney disease

BACKGROUND Abnormal bone metabolism and renal anemia seriously affect the prognosis of patients with chronic kidney disease(CKD).Existing studies have mostly addressed the pathogenesis and treatment of bone metabolism abnormality and anemia in patients with CKD,but few have evaluated their mutual connection.Administration of exogenous erythropoietin to CKD patients with anemia used to be the mainstay of therapeutic approaches;however,with the availability of hypoxia-inducible factor(HIF)stabilizers such as roxadustat,more therapeutic choices for renal anemia are expected in the future.However,the effects posed by the hypoxic environment on both CKD complications remain incompletely understood.AIM To summarize the relationship between renal anemia and abnormal bone metabolism,and to discuss the influence of hypoxia on bone metabolism.METHODS CNKI and PubMed searches were performed using the key words“chronic kidney disease,”“abnormal bone metabolism,”“anemia,”“hypoxia,”and“HIF”to identify relevant articles published in multiple languages and fields.Reference lists from identified articles were reviewed to extract additional pertinent articles.Then we retrieved the Abstract and Introduction and searched the results from the literature,classified the extracted information,and summarized important information.Finally,we made our own conclusions.RESULTS There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Abnormal vitamin D metabolism and hyperparathyroidism can affect bone metabolism,blood cell production,and survival rates through multiple pathways.Anemia will further attenuate the normal bone growth.The hypoxic environment regulates bone morphogenetic protein,vascular endothelial growth factor,and neuropilin-1,and affects osteoblast/osteoclast maturation and differentiation through bone metabolic changes.Hypoxia preconditioning of mesenchymal stem cells(MSCs)can enhance their paracrine effects and promote fracture healing.Concurrently,hypoxia reduces the inhibitory effect on osteocyte differentiation by inhibiting the expression of fibroblast growth factor 23.Hypoxia potentially improves bone metabolism,but it still carries potential risks.The optimal concentration and duration of hypoxia remain unclear.CONCLUSION There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Hypoxia may improve bone metabolism but the concentration and duration of hypoxia remain unclear and need further study.

Malignant peripheral nerve sheath tumor in an elderly patient with superficial spreading melanoma:A case report

BACKGROUND Malignant peripheral nerve sheath tumor(MPNST)is a type of spindle cell sarcoma originating from the peripheral nerve,which usually results in the corresponding nerve sign on magnetic resonance imaging(MRI).Patients with MPNST may also have neurofibromatosis type 1.CASE SUMMARY A 78-year-old male was admitted to the hospital due to a tumor in his left knee.He had a previous history of superficial spreading melanoma on the left thigh.Color Doppler ultrasonography showed a hypoechoic mass in the subcutaneous soft tissues of the medial left knee with an abundant rich blood flow.Computed tomography scanning did not show obvious signs of bone destruction,but the skin adjacent to the tumor was slightly thickened.MRI examination revealed that the hypervascular lesion was well-circumscribed,lobulated,invaded the surrounding soft tissues and demonstrated heterogeneous enhancement but lacked an entering and exiting nerve sign.The MRI result indicated the invasiveness of the tumor.The patient underwent a left knee joint mass expanded resection and the first histopathological examination showed a MPNST with positive surgical margins.Therefore,the second extended resection was performed,and the patient had a good outcome in the short term.CONCLUSION MRI is a useful technique for revealing the biological characteristics of MPNST and provides clinical support for evaluation of the surgical area before operation.

Real role of growth factor receptor-binding protein 10:Linking lipid metabolism to diabetes cardiovascular complications

Cardiovascular complications of patients with type 2 diabetes mellitus(T2DM)threaten the health and life of numerous individuals.Recently,growth factor receptor-binding protein 10(GRB10)was found to play a pivotal role in vascular complications of T2DM,which participates in the regulation of lipid metabolism of T2DM patients.The genetic variation of GRB10 rs1800504 is closely related to the risk of coronary heart disease in patients with T2DM.The development of GRB10 as a key mediator in the association of lipid metabolism with cardiovascular complications in T2DM is detailed in and may provide new potential concerns for the study of cardiovascular complications in T2DM patients.

Percutaneous Closure of Patent Foramen Ovale in a Patient with Mirror-Image Dextrocardia and Situs Inversus

A 26-year-old patient with mirror-image dextrocardia and situs inversus experienced a transient ischemic attack.We suspected that a patent foramen ovale was the reason.A Cardi-O-Fix occluder was used to close the patent foramen ovale with a mirror-reversed rotation of the radiologic views.During the 18-month follow-up,no symptoms of the transient ischemic attack appeared again.

CT-based radiomics to predict development of macrovascular invasion in hepatocellular carcinoma:A multicenter study

Background:Macrovascular invasion(MaVI)occurs in nearly half of hepatocellular carcinoma(HCC)patients at diagnosis or during follow-up,which causes severe disease deterioration,and limits the possibility of surgical approaches.This study aimed to investigate whether computed tomography(CT)-based radiomics analysis could help predict development of MaVI in HCC.Methods:A cohort of 226 patients diagnosed with HCC was enrolled from 5 hospitals with complete MaVI and prognosis follow-ups.CT-based radiomics signature was built via multi-strategy machine learning methods.Afterwards,MaVI-related clinical factors and radiomics signature were integrated to construct the final prediction model(CRIM,clinical-radiomics integrated model)via random forest modeling.Cox-regression analysis was used to select independent risk factors to predict the time of MaVI development.Kaplan-Meier analysis was conducted to stratify patients according to the time of MaVI development,progression-free survival(PFS),and overall survival(OS)based on the selected risk factors.Results:The radiomics signature showed significant improvement for MaVI prediction compared with conventional clinical/radiological predictors(P<0.001).CRIM could predict MaVI with satisfactory areas under the curve(AUC)of 0.986 and 0.979 in the training(n=154)and external validation(n=72)datasets,respectively.CRIM presented with excellent generalization with AUC of 0.956,1.000,and 1.000 in each external cohort that accepted disparate CT scanning protocol/manufactory.Peel9_fos_InterquartileRange[hazard ratio(HR)=1.98;P<0.001]was selected as the independent risk factor.The cox-regression model successfully stratified patients into the high-risk and low-risk groups regarding the time of MaVI development(P<0.001),PFS(P<0.001)and OS(P=0.002).Conclusions:The CT-based quantitative radiomics analysis could enable high accuracy prediction of subsequent MaVI development in HCC with prognostic implications.

Midkine ameliorates LPS-induced apoptosis of airway smooth muscle cells via the Notch2 pathway

Objective:To evaluate the effect of midkine on lipopolysaccharide(LPS)-induced airway smooth muscle cells(ASMCs).Methods:LPS-stimulated acute lung injury model was used to analyze the effect of midkine on ASMCs in vitro.Recombinant midkine and midkine siRNA were used to investigate the role of Notch2 signaling pathway.Cell proliferation was assessed using Cell Counting Kit-8 assay.Additionally,apoptosis was measured by flow cytometry and protein and mRNA expression of midkine and Notch2 was assessed by Western blotting and qPCR,respectively.Immunofluorescence analysis was also conducted.Results:LPS increased the mRNA and protein expression of midkine and Notch2.Midkine silencing reduced LPS-induced midkine and Notch2 expression.In addition,midkine silencing further reduced the viability and increased apoptosis of ASMCs induced by LPS,which was attenuated by recombinant midkine.Conclusions:The midkine/Notch2 signaling pathway plays a regulatory role in ASMC proliferation and apoptosis in airway inflammation.

Upper esophageal sphincter abnormalities on high-resolution esophageal manometry and treatment response of type Ⅱ achalasia

BACKGROUND Little is known about the clinical significance of upper esophageal sphincter(UES)motility disorders and their association with the treatment response of typeⅡachalasia.None of the three versions of the Chicago Classification of Esophageal Motility Disorders has defined UES abnormality metrics or their function.UES abnormalities exist in some patients and indicate a clinically significant problem in patients with achalasia.AIM To demonstrate the manometric differentiation on high-resolution esophageal manometry between subjects with abnormal UES and normal UES,and the association between UES type and the treatment response of typeⅡachalasia.METHODS In total,498 consecutive patients referred for high-resolution esophageal manometry were analyzed retrospectively.The patients were divided into two groups,those with normal and abnormal UES function.UES parameters were analyzed after determining lower esophageal sphincter(LES)function.Patients with typeⅡachalasia underwent pneumatic dilation for treatment.Using mixed model analyses,correlations between abnormal UES and treatment response were calculated among subjects with typeⅡachalasia.RESULTS Of the 498 consecutive patients,246(49.40%)were found to have UES abnormalities.Impaired relaxation alone was the most common UES abnormality(52.85%,n=130).The incidence rate of typeⅡachalasia was significantly higher in subjects with abnormal UES than those with normal UES(9.77%vs 2.58%,P=0.01).After pneumatic dilation,LES resting pressure,LES integrated relaxation pressure,and UES residual pressure were significantly decreased(41.91±9.20 vs 26.18±13.08,38.94±10.28 vs 16.71±5.65,and 11.18±7.93 vs 5.35±4.77,respectively,P<0.05).According to the Eckardt score,subjects with typeⅡachalasia and abnormal UES presented a significantly poorer treatment response than those with normal UES(83.33%vs 0.00%,P<0.05).CONCLUSION Impaired relaxation alone is the most common UES abnormality.The incidence of typeⅡachalasia is associated with abnormal UES.TypeⅡachalasia with abnormal UES has a poorer treatment response,which is a potentially prognostic indicator of treatment for this disease.

Clinical study about mild hypothermia + intravenous thrombolysis in promoting the neural functional recovery in patients with acute cerebral infarction

Objective: To explore the efficacy of mild hypothermia + intravenous thrombolysis in promoting the neural functional recovery in patients with acute cerebral infarction. Methods: A total of 176 patients with acute cerebral infarction who were treated in our hospital between September 2015 and February 2017 were reviewed and divided into the routine group (n=100 cases, receiving routine intravenous thrombolysis therapy) and the mild hypothermia group (n=76, receiving mild hypothermia + intravenous thrombolysis therapy), and the treatment lasted for 1 week. The differences in serum levels of nerve injury indexes, inflammatory mediators and neurotransmitters were compared between the two groups before treatment and after 1 week of treatment. Results: Before treatment, there was no statistically significant difference in serum levels of nerve injury indexes, inflammatory mediators and neurotransmitters between the two groups. After 1 week of treatment, serum nerve injury indexes H-FABP, NT-proBNP, NSE and S100B levels of mild hypothermia group were lower than those of routine group;inflammatory mediators sICAM-1, IL-8, IL-13 and IL-18 levels were lower than those of routine group;neurotransmitter Glu level was lower than that of routine group whereas GABA level was higher than that of routine group. Conclusion: mild hypothermia + intravenous thrombolysis therapy can effectively reduce the nerve injury and systemic inflammatory response, and optimize the neurotransmitter distribution in patients with acute cerebral infarction.

The Practice of Pharmacist-Driven Antimicrobial Stewardship Based on Value-Based Healthcare

Objective To evaluate the effect of pharmacist-driven antimicrobial stewardship based on value-based healthcare in a tertiary hospital in China.Methods The application of plan-do-check-action(PDCA)cycle and antimicrobial stewardship(AMS)were respectively used to improve the rational use of antimicrobial agents in prophylactic and therapeutic.Data were collected and the effect was assessed during the management period(2016-2019).Results and Conclusion From 2016(before implementation)to 2019(after implementation),the rational use of antibiotics were obviously enhanced in outpatients,inpatients,and emergency department.For instance,the utilization rate in type I incision operation was decreased from 26.42%to 14.60%(P=0.000),the daily doses of antibiotic per 100 patient-days decreased from 49.34±2.97 to 35.89±4.96(P=0.000),and the average antibiotic expenditures dropped from 948.53 yuan to 526.30 yuan(P=0.000).There was no significant change in infection rate,nosocomial mortality rate,and the length of hospital stay.After the implementation of clinical pharmacist-driven antimicrobial stewardship based on value-based healthcare,the consumption and cost of antibacterial have been greatly reduced.Therefore,the pharmacist-driven antimicrobial stewardship increases its value。