Distribution and correlation of refractive parameters in children with different corneal curvatures in southeast China

AIM:To analyze the distribution of refractive status in school-age children with different corneal curvatures(CC)and the correlation between CC and refractive status.METHODS:A total of 2214 school-aged children of grade 4 in Hangzhou who were screened for school myopia were included.Uncorrected distance visual acuity(UCDVA),non-cycloplegic refraction,axial length(AL),horizontal and vertical corneal curvature(K1,K2)were measured and spherical equivalent(SE),corneal curvature radius(CCR)and axial length/corneal radius of curvature ratio(AL/CR)were calculated.UCDVA<5.0 and SE≤-0.50 D were classified as school-screening myopia.According to the different CCRs,the patients were divided into the lower corneal curvature(LCC)group(CCR≥7.92)and the higher corneal curvature(HCC)group(CCR<7.92).Each group was further divided into the normal AL subgroup and the long AL subgroup.The refractive parameters were compared to identify any differences between the two groups.RESULTS:Both SE and AL were greater in the LCC group(P=0.013,P<0.001).The prevalence of myopia was 38% in the LCC group and 44% in the HCC group(P<0.001).The proportion of children without screening myopia was higher in the LCC group(62%)than in the HCC group(56%).Among these children without screening myopia,the proportion of long AL in the LCC group(24%)was significantly higher than that in the HCC group(0.012%;P<0.001).The change of SE in the LCC group was less affected by the increase of AL than that in the HCC group.CONCLUSION:School-aged children in the LCC group have a lower incidence of screening myopia and longer AL.Low CC can mask SE reduction and AL growth to some extent,and the change of AL growth change more in children with low CC than high CC.Before the onset of myopia,its growth rate is even faster than that after the onset of myopia.

Exploring the potential mechanism of WuFuYin against hypertrophic scar using network pharmacology and molecular docking

BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be elucidated.AIM To explore the potential mechanism of WFY in treating HTS.METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.HTSrelated genes were obtained from the GeneCards,DisGeNET,and National Center for Biotechnology Information.The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome(KEGG)enrichment analysis.A protein+IBM-protein interaction(PPI)network was developed using STRING database and Cytoscape.To confirm the high affinity between compounds and targets,molecular docking was performed.RESULTS A total of 65 core genes,which were both related to compounds and HTS,were selected from multiple databases.PPI analysis showed that CKD2,ABCC1,MMP2,MMP9,glycogen synthase kinase 3 beta(GSK3B),PRARG,MMP3,and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)were the hub targets and MOL004941,MOL004935,MOL004866,MOL004993,and MOL004989 were the key compounds of WFY against HTS.The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway.Moreover,by performing molecular docking,we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity.CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941,MOL004989,and MOL004993 were the main compounds of WFY in HTS treatment.

New insights into the biological roles of immune cells in neural stem cells in post-traumatic injury of the central nervous system

Traumatic injuries in the central nervous system,such as traumatic brain injury and spinal cord injury,are associated with tissue inflammation and the infiltration of immune cells,which simultaneously affect the self-renewal and differentiation of neural stem cells.Howeve r,the tissue repair process instigated by endogenous neural stem cells is incapable of restoring central nervous system injuries without external intervention.Recently,resident/peripheral immune cells have been demonstrated to exert significant effects on neural stem cells.Thus,the resto ration of traumatic injuries in the central nervous system by the immune intervention in neural stem cells represents a potential therapeutic method.In this review,we discuss the roles and possible mechanisms of immune cells on the selfrenewal and differentiation of neural stem cells along with the prognosis of central nervous system injuries based on immune intervention.Finally,we discuss remaining research challenges that need to be considered in the future.Further elucidation of these challenges will fa cilitate the successful application of neural stem cells in central nervous system injuries.

Prevalence of dementia and the attributable contributions of modifiable risk factors in China

With the largest ageing population in the world,China is faced with the huge chal-lenge of dementia.-However,previously reported estimates on the prevalence of dementia among Chinese older adults were inconsistent,varying from 2%to 13%.5°It is crucial for dementia prevention to determine the number of cases that could be delayed or prevented,but how to do this remains unclear.To address these research gaps,we aimed to provide population estimates of the prevalence of dementia in China and estimate the population attributable fractions(PAFs)of potentially modifiable risk factors.

Efficacy of continuous gastric artery infusion chemotherapy in relieving digestive obstruction in advanced gastric cancer

BACKGROUND Obstruction or fullness after feeding is common in gastric cancer(GC)patients,affecting their nutritional status and quality of life.Patients with digestive obstruction are generally in a more advanced stage.Existing methods,including palliative gastrectomy,gastrojejunostomy,endoluminal stent,jejunal nutrition tube and intravenous chemotherapy,have limitations in treating these symptoms.AIM To analyze the efficacy of continuous gastric artery infusion chemotherapy(cGAIC)in relieving digestive obstruction in patients with advanced GC.METHODS This study was a retrospective study.Twenty-nine patients with digestive obstruction of advanced GC who underwent at least one cycle of treatment were reviewed at The Second Affiliated Hospital of Zhejiang University School of Medicine.The oxaliplatin-based intra-arterial infusion regimen was applied in all patients.Mild systemic chemotherapy was used in combination with local treatment.The clinical response was evaluated by contrast-enhanced computed tomography using Response Evaluation Criteria In Solid Tumors(RECIST)criteria.Digestive tract symptoms and toxic effects were analyzed regularly.A comparison of the Karnofsky Performance Status(KPS)score and Stooler’s Dysphagia Score before and after therapy was made.Univariate survival analysis and multivariate survival analysis were also performed to explore the key factors affecting patient survival.RESULTS All patients finished cGAIC successfully without microcatheter displacement,as confirmed by arteriography.The median follow-up time was 24 mo(95%CI:20.24-27.76 mo).The overall response rate was 89.7%after cGAIC according to the RECIST criteria.The postoperative Stooler’s Dysphagia Score was significantly improved.Twentytwo(75.9%)of the 29 patients experienced relief of digestive obstruction after the first two cycles,and 13(44.8%)initially unresectable patients were then considered radically resectable.The median overall survival time(mOS)was 16 mo(95%CI:9.32-22.68 mo).Patients who received radical surgery had a significantly longer mOS than other patients(P value<0.001).Multivariate Cox regression analysis indicated that radical resection after cGAIC,intravenous chemotherapy after cGAIC,and immunotherapy after cGAIC were independent predictors of mOS.None of the patients stopped treatment because of adverse events.CONCLUSION cGAIC was effective and safe in relieving digestive obstruction in advanced GC,and it could improve surgical conversion possibility and survival time.

Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature

BACKGROUND Perihilar cholangiocarcinoma(pCCA)is a highly malignant tumor arising from the biliary tree.Radical surgery is the only treatment offering a chance of long-term survival.However,limited by the tumor’s anatomic location and peri-vascular invasion,most patients lose the chance for curative treatment.Therefore,more methods to increase the resectability of tumors as well as to improve outcomes are needed.CASE SUMMARY A 68-year-old female patient had a hepatic hilar mass without obvious symptoms.Laboratory results showed hepatitis B positivity.Magnetic resonance imaging indicated that the mass(maximum diameter:41 mm)invaded the left and right branches of the main portal vein,as well as the middle,left and right hepatic veins;enlarged lymph nodes were also detected in the hilum.The patient was diagnosed with pCCA,and the clinical stage was determined to be T4N1M0(stage IIIC).Considering the tumor’s anatomic location and vascular invasion,systematic conversion therapy followed by ex vivo liver resection and autotrans-plantation(ELRA)was determined as personalized treatment for this patient.Our original systemic sequential therapeutic strategy(lenvatinib and tislelizumab in combination with gemcitabine and cisplatin)was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment,without severe toxicity.ELRA,anastomotic reconstruction of the middle hepatic vein,right hepatic vein,root of portal vein,inferior vena cava and right hepatic artery,and lymph node dissection were performed at one month after systemic therapy.Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis.Although the middle hepatic vein was partially obstructed four months later,hepatic vein stent implantation successfully addressed this problem.The patient has survived for 22 mo after the diagnosis,with no evidence of recurrence or metastasis.CONCLUSION An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.

Management of regional citrate anticoagulation for continuous renal replacement therapy:guideline recommendations from Chinese emergency medical doctor consensus

Continuous renal replacement therapy(CRRT)is widely used for treating critically-ill patients in the emergency department in China.Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT.Regional citrate anticoagulation(RCA)has been shown to potentially be safer and more effective,and is now recommended as the preferred anticoagulant method for CRRT.However,there is still a lack of unified standards for RCA management in the world,and there are many problems in using this method in clinical practice.The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association(CMDA)organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues,including the advantages and disadvantages of RCA in CRRT anticoagulation,the principle of RCA,parameter settings for RCA,monitoring of RCA(mainly metabolic acid-base disorders),and special issues during RCA.Based on the latest available research evidence as well as the paneled experts'clinical experience,considering the generalizability,suitability,and potential resource utilization,while also balancing clinical advantages and disadvantages,a total of 16 guideline recommendations were formed from the experts'consensus.

Preclinical and clinical trials of oncolytic vaccinia virus in cancer immunotherapy:a comprehensive review

Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration.Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication;however,recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments.Specifically,oncolytic vaccinia virus(OVV)has gained popularity owing to its safety,potential for systemic delivery,and large gene insertion capacity.This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo,and provides an overview of ongoing clinical trials and combination therapies.In addition,we discuss the potential benefits and drawbacks of OVV as a cancer therapy,and explore different perspectives in this field.

Omadacycline for the treatment of Legionella pneumophila pneumonia caused by drowning:a case report

Drowning is a major cause of preventable death and pathology worldwide.Every year,more than 295,000people die from accidental drowning.Ninety percent of accidental drowning deaths occur in low-and middleincome countries,and nearly half occur in people under the age of 25.

Application of apical negative pressure irrigation in the nonsurgical treatment of radicular cysts:A case report

BACKGROUND Radicular cysts are one of the most common odontogenic cystic lesions found in the jaw.Nonsurgical treatment of large radicular cysts is a topic of ongoing debate,and there is still no clear consensus on the most effective therapies.The apical negative pressure irrigation system aspirates the cystic fluid and releases the static pressure in the radicular cyst,representing a minimally invasive approach for decompression.In this case,the radicular cyst was in close proximity to the mandibular nerve canal.We used nonsurgical endodontic treatment with a homemade apical negative pressure irrigation system and the prognosis was good.CASE SUMMARY A 27-year-old male presented to our Department of General Dentistry with complaints of pain in the mandibular right molar when chewing.The patient had no history of drug allergies or systemic disease.A multidisciplinary management approach was designed and included root canal retreatment with a homemade apical negative pressure irrigation system,deep margin elevation and prosthodontic treatment.According to a 1-year follow-up period,the patient showed a favorable outcome.CONCLUSION This report reveals that nonsurgical treatment with an apical negative pressure irrigation system may provide new insights into the treatment of radicular cysts.

The progress of combination therapy with immune checkpoint inhibitors in breast cancer

Immunotherapy targets the dysfunctional immune system to induce cancer cell killing by CD8-positive T cells.Immune checkpoint inhibitors(ICIs),specifically anti-PD-1 antibodies,anti-PD-L1 antibodies,and anti-CTLA4 antibodies,have revolutionized the management of many malignancies due to their significant role in generating a durable clinical response.However,clinical data suggest that response rates to ICI monotherapy are low due to the immunologically silent characteristics of breast cancer(BC).Chemotherapy,surgery,radiotherapy,and targeted therapy were recently reported to alter the tumor microenvironment and enhance the ICI response.Some clinical studies supported that ICIs,in combination with other treatment strategies,show superior efficacy in BC control,especially triple-negative breast cancer.Therefore,seeking a reasonable combination therapy is a promising way to improve ICI response.The present review highlights the clinical efficacy of ICIs treatment options in combination with standard-of-care therapies,such as chemotherapy and targeted therapy。

Application of refined management in prevention and control of the coronavirus disease 2019 epidemic in non-isolated areas of a general hospital

Objective:This article summarizes the experience in the prevention and control of coronavirus disease 2019(COVID-19)epidemic in non-isolated areas in a general hospital.Methods:Based on refined management theory,we professionally developed the standards for prevention and control of COVID-19 in non-isolated areas,systematically implemented various prevention and control measures,performed gridding audits,effectively communicated among teams and between medical staff and patients assisted by information techniques,and reported results for quality improvement.Results:There was no hospital-acquired COVID-19 infections among staff in the hospital.The rates of mask-wearing,epidemiological history screening,and the medical supplies disinfection were all 100%in the hospital.The accuracy rate of mask-wearing of patients and their families was 73.79%and the compliance rate of their hand hygiene was 40.78%.Conclusion:Refined management strategies for the prevention and control of COVID-19 infection in non-isolated areas of the general hospital are effective.The accuracy rate of mask-wearing and hand hygiene compliance of patients and their families need to be further improved.

Malignant proliferative ependymoma of the neck with lymph node metastasis:A case report

BACKGROUND Malignant proliferating trichilemmal tumor(MPTT)is an infrequent malignant neoplasm originating from cutaneous appendages,with only a handful of documented cases.This report delineates a unique instance of MPTT situated in the neck,accompanied by lymph node metastasis.A comprehensive exposition of its clinical trajectory and imaging manifestation is presented,aiming to enhance comprehension and management of this atypical ailment.CASE SUMMARY Patient concerns:A 79-year-old male presented with a longstanding right neck mass persisting for over six decades,exhibiting recent enlargement over the past year.Diagnoses:Enhanced magnetic resonance imaging of the neck unveiled an elliptical mass on the right neck side,characterized by an ill-defined border and a heterogeneous signal pattern.The mass exhibited subdued signal intensity on T1-weighted imaging(T1WI)and a heterogeneous high signal on T2-weighted imaging(T2WI),interspersed with a lengthy T1 and T2 cystic signal motif.Close anatomical association with the submandibular gland joint was noted,and intravenous gadolinium diethylene triamine pentaacetic acid administration facilitated conspicuous enhancement.Substantial enhancement of the solid segment prompted an initial preoperative diagnosis of malignant nerve sheath tumor.However,post-surgery histopathological and immunohistochemical analysis conclusively confirmed the diagnosis as malignant hyperplastic external hair root sheath tumor.Intervention:Complete excision of the tumor was successfully executed.Outcomes:The patient experienced a favorable postoperative recovery.CONCLUSION Malignant proliferative trichilemmal tumor external hair root sheath tumor is a cystic-solid lesion,appearing as low signal on T1WI images or high signal on T2WI with enhancement of the solid component.Suspicions of malignancy are heightened when the tumor border is indistinct,tissue planes are breached,or when linear or patchy high signals are observed in the subcutaneous tissue on T1 liver acquisition with volume acceleration enhanced images along with intermediate signal on T2WI and restricted diffusion on diffusion-weighted imaging images.Strong consideration for malignancy should arise if there are signs of compromised adjacent tissue relationships or direct invasion evident on imaging.We have incorporated the above-mentioned content into the entire manuscript.

Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

Embryo Transfer Strategies for Women with Recurrent Implantation Failure During the Frozen-thawed Embryo Transfer Cycles:Sequential Embryo Transfer or Double-blastocyst Transfer?

Objective Both sequential embryo transfer(SeET)and double-blastocyst transfer(DBT)can serve as embryo transfer strategies for women with recurrent implantation failure(RIF).This study aims to compare the effects of SeET and DBT on pregnancy outcomes.Methods Totally,261 frozen-thawed embryo transfer cycles of 243 RIF women were included in this multicenter retrospective analysis.According to different embryo quality and transfer strategies,they were divided into four groups:group A,good-quality SeET(GQ-SeET,n=38 cycles);group B,poor-quality or mixed-quality SeET(PQ/MQ-SeET,n=31 cycles);group C,good-quality DBT(GQ-DBT,n=121 cycles);and group D,poor-quality or mixed-quality DBT(PQ/MQ-DBT,n=71 cycles).The main outcome,clinical pregnancy rate,was compared,and the generalized estimating equation(GEE)model was used to correct potential confounders that might impact pregnancy outcomes.Results GQ-DBT achieved a significantly higher clinical pregnancy rate(aOR 2.588,95%CI 1.267–5.284,P=0.009)and live birth rate(aOR 3.082,95%CI 1.482–6.412,P=0.003)than PQ/MQ-DBT.Similarly,the clinical pregnancy rate was significantly higher in GQ-SeET than in PQ/MQ-SeET(aOR 4.047,95%CI 1.218–13.450,P=0.023).The pregnancy outcomes of GQ-SeET were not significantly different from those of GQ-DBT,and the same results were found between PQ/MQ-SeET and PQ/MQ-DBT.Conclusion SeET relative to DBT did not seem to improve pregnancy outcomes for RIF patients if the embryo quality was comparable between the two groups.Better clinical pregnancy outcomes could be obtained by transferring good-quality embryos,no matter whether in SeET or DBT.Embryo quality plays a more important role in pregnancy outcomes for RIF patients.

Extracorporeal membrane oxygenation as a bridging therapy for patients with thiamine deficiency-induced pulmonary arterial hypertension

Thiamine deficiency is characterized by a deficiency of thiamine(vitamin B1),lactic acidosis,pulmonary arterial hypertension(PAH),right-sided heart failure,and peripheral nerve damage.Thiamine deficiency is easily misdiagnosed and missed during clinical practice and is associated with death in severe cases.[1,2]Here we reported a patient who was admitted to the hospital with severe metabolic acidosis and pulmonary hypertension and finally diagnosed with thiamine deficiency by detecting plasma vitamin B1 levels.Since clinically obvious thiamine deficiency is rare,and cases of thiamine deficiency requiring extracorporeal membrane oxygenation(ECMO)treatment are rarer,we believe that our case will be helpful for emergency clinicians.

Stem cell-based ischemic stroke therapy:Novel modifications and clinical challenges

Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and paracrine abilities give hope for neuroprotection.Recent studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and pretreatment.Thesemethods improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic areas.However,many problems must be resolved before SC therapy can be clinically applied.These issues include production quality and quantity,stability during transportation and storage,as well as usage regulations.Herein,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy challenges.We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.

Metastatic stomach lymphoepithelioma-like carcinoma and immune checkpoint inhibitor therapy:A case report

BACKGROUND Pulmonary lymphoepithelioma-like carcinoma(PLELC)is a rare type of nonsmall-cell lung cancer.Stomach lymphoepithelioma-like carcinoma(LELC)metastasis secondary to PLELC has not been reported recently.CASE SUMMARY A 64-year-old female was admitted to our hospital for a regular gastroscopy examination with a 6-year history of surgical resection for left PLELC.Positron emission tomography/computed tomography suggested high accumulation of 18F-fludeoxyglucose in the gastric cardia region.Upper gastrointestinal endoscopy confirmed a large mass at the stomach fundus.Immunohistochemistry(IHC)of the biopsy suggested metastatic stomach LELC.Proximal gastrectomy showed that this 6.5 cm×5.0 cm mass was located in the stomach fundus near the cardia.Histopathological examination showed a poorly differentiated carcinoma with prominent lymphoplasmacytic infiltration.IHC demonstrated that the tumor was positive for CK(AE1/AE3),p63,p40,p53,Ki-67(70%),and EGFR(3+)and negative for CK7,CK20,Her2,and CD10.In situ hybridization analysis showed positive staining Epstein-Barr virus-encoded RNA.Tumor programmed cell death ligand 1(PD-L1)expression score was 98%,and the combined positive score was 100,with no evidence of microsatellite instability.Thus,the patient was unequivocally diagnosed with metastatic stomach LELC secondary to pulmonary LELC.After discharge,this patient underwent PD-1 inhibitor treatment(toripalimab,240 mg)every 3 wk for ten cycles,and she has had no tumor recurrence.CONCLUSION For gastric LELC metastasis,PD-1 inhibitor therapy could become a new therapeutic approach,though there is still no evidence from large data sets to support this.

Risk Factors of Enternal Nutrition Intolerance in Septic Patients:A Case-control Study

Objective:This study aimed to investigate the incidence of enteral nutrition intolerance(ENI)in patients with sepsis and explore potential risk factors.Methods:A case-control study was conducted in patients with sepsis who were receiving enteral nutrition(EN)at a tertiary hospital in China.The included patients were divided into the ENI group and the non-ENI group.Univariate and multivariate analyses were performed to identify the risk factors for ENI.Results:A total of 859 patients were included in the study.Among them,288(33.53%)patients experienced symptoms of ENI,including diarrhea,vomiting,bloating,and gastric retention.Logistic regression analysis revealed that the Acute Physiology and Chronic Health Evaluation H(APACHE H)score,thoracocentesis,and usage of cardiotonic drugs(namely,inotropes)were independent predictors of the ENI.Conclusion:The incidence of ENI is relatively high in patients with sepsis,especially in those who have higher APACHE H scores,have undergone thoracocentesis,and have received inotropes.

In Situ Deposition of Drug and Gene Nanoparticles on a Patterned Supramolecular Hydrogel to Construct a Directionally Osteochondral Plug

The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone.Constructing multifactorial,spatially oriented scaffolds to stimulate osteochondral regeneration,has immense significance.Herein,targeted drugs,namely kartogenin@polydopamine(KGN@PDA)nanoparticles for cartilage repair and miRNA@calcium phosphate(miRNA@CaP)NPs for bone regeneration,were in situ deposited on a patterned supramolecular-assembled 2-ureido-4[lH]-pyrimidinone(UPy)modified gelation hydrogel film,facilitated by the dynamic and responsive coordination and complexation of metal ions and their ligands.This hydrogel film can be rolled into a cylindrical plug,mimicking the Haversian canal structure of natural bone.The resultant hydrogel demonstrates stable mechanical properties,a self-healing ability,a high capability for reactive oxygen species capture,and controlled release of KGN and miR-26a.In vitro,KGN@PDA and miRNA@CaP promote chondrogenic and osteogenic differentiation of mesenchymal stem cells via the JNK/RUNX1 and GSK-3β/β-catenin pathways,respectively.In vivo,the osteochondral plug exhibits optimal subchondral bone and cartilage regeneration,evidenced by a significant increase in glycosaminoglycan and collagen accumulation in specific zones,along with the successful integration of neocartilage with subchondral bone.This biomaterial delivery approach represents a significant toward improved osteochondral repair.