A Study on Integrated Construction of Luzhou Comprehensive Transportation Hub

The target of integrated construction of comprehensive transportation hub is to integrate the traffic resources,achieve butt joint of pan-regional transportation mode,and finally realize the"seamless connection"of the goods and"zero transfer"of the passenger traffic.Relying on the particularity of the geographical location and the convenience of the Yangtze River channel,Luzhou puts forth effort to build a comprehensive transport hub in Southern Sichuan and has made great efforts in traffic infrastructure construction.However,there are still some problems.Combining practice of Luzhou,using the advanced experience of foreign and domestic cities for reference,the paper pointed out that for the sake of constructing a comprehensive transportation hub,we need to build the traffic integration on the basis of the efficiency.Besides,the paper proposed the strategies for construction.

Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease

Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease.Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains unelucidated.In the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated.Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy.In addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo model.Moreover,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent.Most importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease mice.As revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.

Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

Prognostic value of circulating tumor cells combined with neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma

BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining these two indicators in HCC.METHODS Clinical data were collected from patients with advanced HCC who received im-mune therapy combined with targeted therapy at the Department of Oncology,the Affiliated Hospital of Southwest Medical University,Sichuan,China,from 2021 to 2023.The optimal cutoff values for CTC programmed death-ligand 1(PD-L1)(+)>1 or CTC PD-L1(+)≤1 and NLR>3.89 or NLR≤3.89 were evaluated using X-Tile software.Patients were categorized into three groups based on CTC PD-L1(+)counts and NLR:CTC-NLR(0),CTC-NLR(1),and CTC-NLR(2).The relationship between CTC-NLR and clinical variables as well as survival rates was assessed.RESULTS Patients with high CTC PD-L1(+)expression or NLR at baseline had shorter median progression-free survival(m-PFS)and median overall survival(mOS)than those with low levels of CTC PD-L1(+)or NLR(P<0.001).Mean-while,patients in the CTC-NLR(2)group showed a significant decrease in mPFS and mOS.Cox regression analysis revealed that alpha-fetoprotein(AFP),CTC PD-L1(+),and CTC-NLR were independent predictors of OS.The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months(0.821)and 18 months(0.821)was superior to that of AFP and CTC PD-L1(+).CONCLUSION HCC patients with high CTC PD-L1(+)or NLR expression tend to exhibit poor prognosis,and a high baseline CTC-NLR score may indicate low survival.CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.

The optimal atropine concentration for myopia control in Chinese children: a systematic review and network Metaanalysis

AIM:To figure out whether various atropine dosages may slow the progression of myopia in Chinese kids and teenagers and to determine the optimal atropine concentration for effectively slowing the progression of myopia.METHODS:A systematic search was conducted across the Cochrane Library,PubMed,Web of Science,EMBASE,CNKI,CBM,VIP,and Wanfang database,encompassing literature on slowing progression of myopia with varying atropine concentrations from database inception to January 17,2024.Data extraction and quality assessment were performed,and a network Meta-analysis was executed using Stata version 14.0 Software.Results were visually represented through graphs.RESULTS:Fourteen papers comprising 2475 cases were included;five different concentrations of atropine solution were used.The network Meta-analysis,along with the surface under the cumulative ranking curve(SUCRA),showed that 1%atropine(100%)>0.05%atropine(74.9%)>0.025%atropine(51.6%)>0.02%atropine(47.9%)>0.01%atropine(25.6%)>control in refraction change and 1%atropine(98.7%)>0.05%atropine(70.4%)>0.02%atropine(61.4%)>0.025%atropine(42%)>0.01%atropine(27.4%)>control in axial length(AL)change.CONCLUSION:In Chinese children and teenagers,the five various concentrations of atropine can reduce the progression of myopia.Although the network Meta-analysis showed that 1%atropine is the best one for controlling refraction and AL change,there is a high incidence of adverse effects with the use of 1%atropine.Therefore,we suggest that 0.05%atropine is optimal for Chinese children to slow myopia progression.

Ventricular system-unrelated cerebellar ependymoma:A case report

BACKGROUND An ependymoma is a glial tumor that usually occurs in or near the ventricle,close to the ependyma.It rarely occurs exclusively in the brain parenchyma without being associated with the ventricle.CASE SUMMARY Here,we report a rare case of a cerebellar ependymoma completely located in the brain parenchyma.A previously healthy 32-year-old female with a 1-month history of dizziness was admitted to our hospital.During hospitalization,magnetic resonance imaging of the brain revealed a space-occupying lesion measuring 57 mm×41 mm×51 mm in the right cerebellar hemisphere and inferior cerebellar vermis.The patient underwent surgical resection for the right cerebellar mass.Postoperative pathological examination revealed an ependymoma.At 1 year follow-up,the patient was doing well and showed no recurrence.CONCLUSION We conducted a literature review and summarized three theories regarding ependymomas located exclusively in the brain parenchyma,which are key to the diagnosis of intraparenchymal cerebellar ependymomas.Surgery and postoperative radiotherapy are the primary treatment options for ependymomas.

Effects of Helicobacter pylori and Moluodan on the Wnt/β-catenin signaling pathway in mice with precancerous gastric cancer lesions

BACKGROUND Helicobacter pylori(H.pylori)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis.GC has a high mortality rate and treatment cost,and there are no drugs to prevent the progression of gastric precancerous lesions to GC.Therefore,it is necessary to find a novel drug that is inexpensive and preventive to against GC.AIM To explore the effects of H.pylori and Moluodan on the Wnt/β-Catenin signaling pathway and precancerous lesions of GC(PLGC).METHODS Mice were divided into the control,N-methyl-N-nitrosourea(MNU),H.pylori+MNU,and Moluodan groups.We first created an H.pylori infection model in the H.pylori+MNU and Moluodan groups.A PLGC model was created in the remaining three groups except for the control group.Moluodan was fed to mice in the Moloudan group ad libitum.The general condition of mice were observed during the whole experiment period.Gastric tissues of mice were grossly and microscopically examined.Through quantitative real-time PCR(qRT-PCR)and Western blotting analysis,the expression of relevant genes were detected.RESULTS Mice in the H.pylori+MNU group showed the worst performance in general condition,gastric tissue visual and microscopic observation,followed by the MNU group,Moluodan group and the control group.QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes,the results showed that the H.pylori+MNU group had the highest expression,followed by the MNU group,Moluodan group and the control group.CONCLUSION H.pylori can activate the Wnt/β-catenin signaling pathway,thereby facilitating the development and progression of PLGC.Moluodan suppressed the activation of the Wnt/β-catenin signaling pathway,thereby decreasing the progression of PLGC.

Effects of high-quality neurosurgical nursing care on improving clinical nursing quality

BACKGROUND With continuous advancements in medical technology,neurosurgical nursing is constantly developing and improving to provide higher-quality nursing services.AIM To explore the effects of different types of high-quality nursing care on clinical nursing quality and patient satisfaction in neurosurgical nursing.METHODS Eighty patients who received neurosurgical treatment in the Affiliated Hospital of Southwest Medical University from June to December 2020 were selected as study participants and categorised into study and control groups.The study group comprised 40 patients who received 4 different types of high-quality nursing care,whereas the control group comprised 40 patients who received conventional nursing care.After a specific period,nursing satisfaction levels and adverse event and complication rates were compared between the two groups.RESULTS Satisfaction with high-quality care was higher than that with conventional care,and high-quality health services and regional services showed the highest satisfaction levels,with an average score of 12 on the Glasgow scale.The satisfaction levels of the study and control groups were 75%and 57%,respectively,with a statistically significant difference(t=7.314,P<0.05).During the nursing period,the adverse event and complication rates were the highest in patients with level III pathology grade and those who underwent neurosurgery(40.02%and 85.93%,respectively),and the difference was statistically significant.CONCLUSION In neurosurgical nursing,employing appropriate high-quality nursing methods can effectively reduce adverse event and complication rates in patients,thereby improving the quality of nursing care and increasing clinical nursing value.

Development and validation of a nomogram for predicting in-hospital mortality of intensive care unit patients with liver cirrhosis

BACKGROUND Liver cirrhosis patients admitted to intensive care unit(ICU)have a high mortality rate.AIM To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis.METHODS We extracted demographic,etiological,vital sign,laboratory test,comorbidity,complication,treatment,and severity score data of liver cirrhosis patients from the Medical Information Mart for Intensive Care IV(MIMIC-IV)and electronic ICU(eICU)collaborative research database(eICU-CRD).Predictor selection and model building were based on the MIMIC-IV dataset.The variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final predictors.The final predictors were included in the multivariate logistic regression model,which was used to construct a nomogram.Finally,we conducted external validation using the eICU-CRD.The area under the receiver operating characteristic curve(AUC),decision curve,and calibration curve were used to assess the efficacy of the models.RESULTS Risk factors,including the mean respiratory rate,mean systolic blood pressure,mean heart rate,white blood cells,international normalized ratio,total bilirubin,age,invasive ventilation,vasopressor use,maximum stage of acute kidney injury,and sequential organ failure assessment score,were included in the multivariate logistic regression.The model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases,respectively.The calibration curve also confirmed the predictive ability of the model,while the decision curve confirmed its clinical value.CONCLUSION The nomogram has high accuracy in predicting in-hospital mortality.Improving the included predictors may help improve the prognosis of patients.

Osteotomy combined with anterior cruciate ligament reconstruction for anterior cruciate ligament injury and biplanar deformity

BACKGROUND It has been confirmed that the increased posterior tibial slope over 12 degrees is a risk factor for anterior cruciate ligament injury,and varus deformity can aggravate the progression of medial osteoarthritis.AIM To evaluate the efficacy of modified high tibial osteotomy(HTO)and anterior cruciate ligament reconstruction(ACLR)in the treatment of anterior cruciate ligament(ACL)injuries with varus deformities and increased posterior tibial slope(PTS)based on clinical and imaging data.METHODS The patient data in this retrospective study were collected from 2019 to 2021.A total of 6 patients were diagnosed with ACL injury combined with varus deformities and increased PTS.All patients underwent modified open wedge HTO and ACLR.The degree of correction of varus deformity and the PTS was evaluated by radiography and magnetic resonance imaging.RESULTS All 6 patients(6 knee joints)were followed up for an average of 20.8±3.7 months.The average age at surgery was 29.5±3.8 years.At the last follow-up,all patients resumed competitive sports.The International Knee Documentation Committee score increased from 50.3±3.1 to 87.0±2.8,the Lysholm score increased from 43.8±4.9 to 86±3.1,and the Tegner activity level increased from 2.2±0.7 to 7.0±0.6.The average movement distance of the tibia anterior translation was 4.8±1.1 mm,medial proximal tibial angle(MPTA)was 88.9±1.3°at the last follow-up,and the PTS was 8.4±1.4°,both of which were significantly higher than those before surgery(P<0.05).CONCLUSION Modified open wedge HTO combined with ACLR can effectively treat patients with ACL ruptures with an associated increased PTS and varus deformity.The short-term effect is significant,but the long-term effect requires further follow-up.

A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis

Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.

Clinical efficacy and safety of double-channel anastomosis and tubular gastroesophageal anastomosis in gastrectomy

BACKGROUND With the continuous progress of surgical technology and improvements in medical standards,the treatment of gastric cancer surgery is also evolving.Proximal gastrectomy is a common treatment,but double-channel anastomosis and tubular gastroesophageal anastomosis have attracted much attention in terms of surgical options.Each of these two surgical methods has advantages and disadvantages,so it is particularly important to compare and analyze their clinical efficacy and safety.AIM To compare the surgical safety,clinical efficacy,and safety of double-channel anastomosis and tubular gastroesophageal anastomosis in proximal gastrectomy.METHODS The clinical and follow-up data of 99 patients with proximal gastric cancer who underwent proximal gastrectomy and were admitted to our hospital between January 2018 and September 2023 were included in this retrospective cohort study.According to the different anastomosis methods used,the patients were divided into a double-channel anastomosis group(50 patients)and a tubular gastroesophageal anastomosis group(49 patients).In the double-channel anastomosis,Roux-en-Y anastomosis of the esophagus and jejunum was performed after proximal gastric dissection,and then side-to-side anastomosis was performed between the residual stomach and jejunum to establish an antireflux barrier and reduce postoperative gastroesophageal reflux.In the tubular gastroesophageal anastomosis group,after the proximal end of the stomach was cut,tubular gastroplasty was performed on the distal stump of the stomach and a linear stapler was used to anastomose the posterior wall of the esophagus and the anterior wall of the stomach tube.The main outcome measure was quality of life 1 year after surgery in both groups,and the evaluation criteria were based on the postgastrectomy syndrome assessment scale.The greater the changes in body mass,food intake per meal,meal quality subscale score,and total measures of physical and mental health score,the better the condition;the greater the other indicators,the worse the condition.The secondary outcome measures were intraoperative and postoperative conditions,the incidence of postoperative long-term complications,and changes in nutritional status at 1,3,6,and 12 months after surgery.RESULTS In the double-channel anastomosis cohort,there were 35 males(70%)and 15 females(30%),33(66.0%)were under 65 years of age,and 37(74.0%)had a body mass index ranging from 18 to 25 kg/m2.In the group undergoing tubular gastroesophageal anastomosis,there were eight females(16.3%),21(42.9%)individuals were under the age of 65 years,and 34(69.4%)had a body mass index ranging from 18 to 25 kg/m2.The baseline data did not significantly differ between the two groups(P>0.05 for all),with the exception of age(P=0.021).The duration of hospitalization,number of lymph nodes dissected,intraoperative blood loss,and perioperative complication rate did not differ significantly between the two groups(P>0.05 for all).Patients in the dual-channel anastomosis group scored better on quality of life measures than did those in the tubular gastroesophageal anastomosis group.Specifically,they had lower scores for esophageal reflux[2.8(2.3,4.0)vs 4.8(3.8,5.0),Z=3.489,P<0.001],eating discomfort[2.7(1.7,3.0)vs 3.3(2.7,4.0),Z=3.393,P=0.001],total symptoms[2.3(1.7,2.7)vs 2.5(2.2,2.9),Z=2.243,P=0.025],and other aspects of quality of life.The postoperative symptoms[2.0(1.0,3.0)vs 2.0(2.0,3.0),Z=2.127,P=0.033],meals[2.0(1.0,2.0)vs 2.0(2.0,3.0),Z=3.976,P<0.001],work[1.0(1.0,2.0)vs 2.0(1.0,2.0),Z=2.279,P=0.023],and daily life[1.7(1.3,2.0)vs 2.0(2.0,2.3),Z=3.950,P<0.001]were all better than those of the tubular gastroesophageal anastomosis group.The group that underwent tubular gastroesophageal anastomosis had a superior anal exhaust score[3.0(2.0,4.0)vs 3.5(2.0,5.0),Z=2.345,P=0.019]compared to the dual-channel anastomosis group.Hemoglobin,serum albumin,total serum protein,and the rate at which body mass decreased one year following surgery did not differ significantly between the two groups(P>0.05 for all).CONCLUSION The safety of double-channel anastomosis in proximal gastric cancer surgery is equivalent to that of tubular gastric surgery.Compared with tubular gastric surgery,double-channel anastomosis is a preferred surgical technique for proximal gastric cancer.It offers advantages such as less esophageal reflux and improved quality of life.

Cardiac remodeling in patients with atrial fibrillation reversing bradycardia-induced cardiomyopathy:A case report

BACKGROUND Bradycardia-induced cardiomyopathy(BIC),which is a disease resulting from bradycardia,is characterized by cardiac chamber enlargement and diminished cardiac function.The correction of bradycardia can allow for significant improvements in both cardiac function and structure;however,this disease has been infrequently documented.In this case,we conducted a longitudinal followup of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention.CASE SUMMARY A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7.Since she had no obvious symptoms,she did not receive any treatment to improve her bradycardia during the 42-year follow-up,except for the implantation of a temporary pacemaker during labor induction surgery.As time progressed,the patient's heart gradually expanded due to her low ventricular rate,and she was diagnosed with BIC.In 2014,the patient developed atrial fibrillation,her ventricular rate gradually increased,and her heart shape gradually returned to normal.This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years,introduces another possible outcome of BIC,and emphasizes the importance of early intervention in treating BIC.CONCLUSION BIC can induce atrial fibrillation,causing an increased ventricular rate and leading to positive cardiac remodeling.

Optimization of Extraction Process for Total Flavonoids from Penthorum chinense Pursh and Comparison of Their Contents from Different Parts

[Objectives]This study was conducted to optimize the extraction process of total flavonoids from Penthorum chinense Pursh and compare their contents from different parts.[Methods]Single factor and orthogonal experiments were designed to optimize the extraction process of total flavonoids from P.chinense Pursh with the volume fraction of ethanol,the ratio of material to liquid,heating reflux extraction time and extraction times as factors,and the content of total flavonoids as the index.A verification test was carried out.The optimized extraction process was adopted to compare the contents of total flavonoids from different parts of P.chinense Pursh.[Results]The best extraction process was extracting the powder of P.chinense Pursh for 2.0 h with 20 times of 55%ethanol by reflux twice.Under this condition,the contents of total flavonoids were 3.63%,8.90%,11.28%,and 4.36%from stems,leaves,flowers and whole grass of P.chinense Pursh,respectively.[Conclusions]The process is reasonable,feasible and stable,and can effectively extract total flavonoids from P.chinense Pursh.The contents of total flavonoids from different parts of P.chinense Pursh were quite different,and the value was higher in the leaves and flowers,so the proportions of leaves and flowers should be paid attention to in the industrial processing of P.chinense Pursh.

Analysis of the Exploration of Hematology Integration Education Model Guided by“Social Learning Theory”

Diseases of the blood system are highly complicated and involve many aspects.This article aimed to put forward the necessity of integrating quality and professional education,the necessity of learning logic,and the importance of establishing an integrated medical education model when teaching about blood system diseases.According to the requirements of the new medical science,this article puts forward the integration of an“online+offline+clinical”medical education mode based on the social learning theory and a learning evaluation mode based on medical literacy.The fundamental task of cultivating human beings into clinical medical talents with professional ethics,independent learning abilities,interpersonal communication abilities,complex problem-solving abilities,innovative consciousness,and critical thinking was implemented.This article aims to propose an improved construction plan to create a new and improved teaching system in medicine.

Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3

Extracellular matrix(ECM)stiffening is a typical characteristic of cartilage aging,which is a quintessential feature of knee osteoarthritis(KOA).However,little is known about how ECM stiffening affects chondrocytes and other molecules downstream.This study mimicked the physiological and pathological stiffness of human cartilage using polydimethylsiloxane(PDMS)substrates.It demonstrated that epigenetic Parkin regulation by histone deacetylase 3(HDAC3)represents a new mechanosensitive mechanism by which the stiffness matrix affected chondrocyte physiology.We found that ECM stiffening accelerated cultured chondrocyte senescence in vitro,while the stiffness ECM downregulated HDAC3,prompting Parkin acetylation to activate excessive mitophagy and accelerating chondrocyte senescence and osteoarthritis(OA)in mice.Contrarily,intra-articular injection with an HDAC3-expressing adeno-associated virus restored the young phenotype of the aged chondrocytes stimulated by ECM stiffening and alleviated OA in mice.The findings indicated that changes in the mechanical ECM properties initiated pathogenic mechanotransduction signals,promoted the Parkin acetylation and hyperactivated mitophagy,and damaged chondrocyte health.These results may provide new insights into chondrocyte regulation by the mechanical properties of ECM,suggesting that the modification of the physical ECM properties may be a potential OA treatment strategy.

Therapeutic potential of exosome-based personalized delivery platform in chronic inflammatory diseases

In the inflammatory microenvironment,there are numerous exosomes secreted by immune cells(Macrophages,neutrophils,dendritic cells),mesenchymal stem cells(MSCs)and platelets as intercellular communicators,which participate in the regulation of inflammation by modulating gene expression and releasing anti-inflammatory factors.Due to their good biocompatibility,accurate targeting,low toxicity and immunogenicity,these exosomes are able to selectively deliver therapeutic drugs to the site of inflammation through interactions between their surface-antibody or modified ligand with cell surface receptors.Therefore,the role of exosome-based biomimetic delivery strategies in inflammatory diseases has attracted increasing attention.Here we review current knowledge and techniques for exosome identification,isolation,modification and drug loading.More importantly,we highlight progress in using exosomes to treat chronic inflammatory diseases such as rheumatoid arthritis(RA),osteoarthritis(OA),atherosclerosis(AS),and inflammatory bowel disease(IBD).Finally,we also discuss their potential and challenges as anti-inflammatory drug carriers.

Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-^(89)(^(89)Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[^(89)Zr]Zr-desferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/mmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC_(50) values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[^(89)Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2().The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[^(89)Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.

Duplex Interpenetrating-Phase FeNiZn and FeNi_(3)Heterostructure with Low-Gibbs Free Energy Interface Coupling for Highly Efficient Overall Water Splitting

The sluggish kinetics of both hydrogen evolution reaction(HER)and oxygen evolution reaction(OER)generate the large overpotential in water electrolysis and thus high-cost hydrogen production.Here,multidimensional nanoporous interpenetrating-phase FeNiZn alloy and FeNi_(3)intermetallic heterostructure is in situ constructed on NiFe foam(FeNiZn/FeNi_(3)@NiFe)by dealloying protocol.Coupling with the eminent synergism among specific constituents and the highly efficient mass transport from integrated porous backbone,FeNiZn/FeNi_(3)@NiFe depicts exceptional bifunctional activities for water splitting with extremely low overpotentials toward OER and HER(η_(1000)=367/245 mV)as well as the robust durability during the 400 h testing in alkaline solution.The as-built water electrolyzer with FeNiZn/FeNi_(3)@NiFe as both anode and cathode exhibits record-high performances for sustainable hydrogen output in terms of much lower cell voltage of 1.759 and 1.919 V to deliver the current density of 500 and 1000 mA cm^(-2)as well long working lives.Density functional theory calculations disclose that the interface interaction between FeNiZn alloy and FeNi_(3)intermetallic generates the modulated electron structure state and optimized intermediate chemisorption,thus diminishing the energy barriers for hydrogen production in water splitting.With the merits of fine performances,scalable fabrication,and low cost,FeNiZn/FeNi_(3)@NiFe holds prospective application potential as the bifunctional electrocatalyst for water splitting.

Relationship between body mass index and short-term postoperative prognosis in patients undergoing colorectal cancer surgery

BACKGROUND Obesity is a state in which excess heat is converted into excess fat,which accumulates in the body and may cause damage to multiple organs of the circulatory,endocrine,and digestive systems.Studies have shown that the accumulation of abdominal fat and mesenteric fat hypertrophy in patients with obesity makes laparoscopic surgery highly difficult,which is not conducive to operation and affects patient prognosis.However,there is still controversy regarding these conclusions.AIM To explore the relationship between body mass index(BMI)and short-term prognosis after surgery for colorectal cancer.METHODS PubMed,Embase,Ovid,Web of Science,CNKI,and China Biology Medicine Disc databases were searched to obtain relevant articles on this topic.After the articles were screened according to the inclusion and exclusion criteria and the risk of literature bias was assessed using the Newcastle-Ottawa Scale,the prognostic indicators were combined and analyzed.RESULTS A total of 16 articles were included for quantitative analysis,and 15588 patients undergoing colorectal cancer surgery were included in the study,including 3775 patients with obesity and 11813 patients without obesity.Among them,12 articles used BMI≥30 kg/m^(2)and 4 articles used BMI≥25 kg/m^(2)for the definition of obesity.Four patients underwent robotic colorectal surgery,whereas 12 underwent conventional laparoscopic colorectal resection.The quality of the literature was good.Meta-combined analysis showed that the overall complication rate of patients with obesity after surgery was higher than that of patients without obesity[OR=1.35,95%CI:1.23-1.48,Z=6.25,P<0.0001].The incidence of anastomotic leak after surgery in patients with obesity was not significantly different from that in patients without obesity[OR=0.99,95%CI:0.70-1.41),Z=-0.06,P=0.956].The incidence of surgical site infection(SSI)after surgery in patients with obesity was higher than that in patients without obesity[OR=1.43,95%CI:1.16-1.78,Z=3.31,P<0.001].The incidence of reoperation in patients with obesity after surgery was higher than that in patients without obesity;however,the difference was not statistically significant[OR=1.15,95%CI:0.92-1.45,Z=1.23,P=0.23];Patients with obesity had lower mortality after surgery than patients without obesity;however,the difference was not statistically significant[OR=0.61,95%CI:0.35-1.06,Z=-1.75,P=0.08].Subgroup analysis revealed that the geographical location of the institute was one of the sources of heterogeneity.Robot-assisted surgery was not significantly different from traditional laparoscopic resection in terms of the incidence of complications.CONCLUSION Obesity increases the overall complication and SSI rates of patients undergoing colorectal cancer surgery but has no influence on the incidence of anastomotic leak,reoperation rate,and short-term mortality rate.