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.

Efficacy and safety analysis of continued nursing of complications in discharged patients after percutaneous transhepatic biliary drainage

BACKGROUND Percutaneous hepatobiliary drainage(PTCD)is an effective method for the treatment of biliary obstruction and other diseases,but postoperative complications are still one of the important problems faced by patients.Continuous nursing is a comprehensive nursing model that plays an important role in postoperative recovery.The purpose of this study was to investigate the effect of continuous nursing on the incidence of complications in patients after PTCD surgery through meta-analysis and to evaluate its efficacy and safety.AIM To evaluate the effect of extended nursing on the incidence of complications in discharged patients after percutaneous transhepatic biliary drainage(PTBD).METHODS Randomized controlled studies on PTBD postdischarge extended care were identified in the CNKI,Wanfang,VIP,CBM,PubMed,Cochrane Library,Embase,Web of Science,and other databases.The quality of the included studies was evaluated using the Joanna Briggs Institute of Australia literature quality evaluation tool,and a meta-analysis of the included studies was performed with RevMan 5.4 software.RESULTS Finally,9 studies were included,with a total sample size of 854 patients(425 patients in the control group and 429 patients in the intervention group).Meta-analysis revealed that extended care effectively reduced biliary tract infection(RR:0.42,95%CI:0.30-0.57),puncture wound infection(RR:0.19,95%CI:0.06-0.65),catheter protrusion or displacement in discharged patients after PTBD(RR:0.31,95%CI:0.18-0.54),catheter blockage(RR:0.23,95%CI:0.13-0.42),skin infection around the drainage tube(RR:0.30,95%CI:0.12-0.77),and catheter-related readmissions(RR:0.34,95%CI:0.18-0.65)(P<0.05).CONCLUSION Compared with conventional discharge care,extended care can effectively reduce the occurrence of complications such as biliary tract infection,puncture wound infection,catheter prolapse or displacement,catheter blockage,skin infection around the drainage tube,and catheter-related readmission in discharged patients after PTBD.

Application progresses of ultrasound for snakebites and relative complications

Snakebite has become a serious public health problem with high mortality and disability rates.Ultrasound can provide imaging basis for diagnosis and treatment of snakebites and relative complications.The application progresses of ultrasound in snakebites and complications were reviewed in this article.

Differential expression of plasma cytokines in sepsis patients and their clinical implications

BACKGROUND Sepsis,which is characterized by acute systemic inflammation and is associated with high rates of morbidity and mortality,presents a significant challenge in health care.Some scholars have found that the sequential organ failure assessment(SOFA)and quick SOFA scores are not ideal for predicting severe sepsis and mortality.Microbial culture takes a long time(2-3 d)and provides no information for early diagnosis and treatment.Therefore,new diagnostic methods for sepsis need to be explored.AIM To assess cytokine levels in the plasma of sepsis patients and identify potential biomarkers for diagnosing sepsis.METHODS Ten sepsis patients admitted to the emergency department within 24 h of onset were enrolled as the observation group,whereas ten noninfected patients served as the control group.Of the 10 noninfected patients,9 hypertension combined with cerebral infarction,1 patients with vertiginous syndrome.Plasma Cytokines were measured using the Bio-Plex Pro^(TM)Human Chemokine Panel 40-plex.Differentially expressed cytokines in plasma of sepsis and nonsepsis patients were analyzed using Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses.RESULTS Interleukin(IL)-16,granulocyte-macrophage granulocyte-macrophage colony-stimulating factor(GM-CSF),CX3CL1,CXCL9,CXCL16,CCL25,and CCL23 plasma levels were significantly increased in sepsis patients.GO analysis revealed that these cytokines were mainly associated with cellular structures such as intermediates,nuclear plaques,adhesion plaques,lateral plasma membranes,and cell matrix junctions.These genes were involved in various molecular functions,such as cytokine activity,receptor ligand activity,and signal receptor activator activity,contributing to various biological functions,such as leukocyte chemotaxis,migration,and chemotaxis.KEGG analysis indicated involvement in cytokine cytokine receptor interactions,chemokine signaling pathways,virus–protein interactions with cytokines and cytokine receptors,and the tumor necrosis factor signaling pathway.CONCLUSION Elevated serum levels of IL-16,GM-CSF,CX3CL1,CXCL9,CXCL16,CCL25,and CCL23 in sepsis patients suggest their potential as diagnostic biomarkers for sepsis.

Influence of Gut Microbiota and its Metabolites on Progression of Metabolic Associated Fatty Liver Disease

Metabolic associated fatty liver disease(MAFLD)has become a prevalent chronic liver disease worldwide because of lifestyle and dietary changes.Gut microbiota and its metabolites have been shown to play a critical role in the pathogenesis of MAFLD.Understanding of the function of gut microbiota and its metabolites in MAFLD may help to elucidate pathological mechanisms,identify diagnostic markers,and develop drugs or probiotics for the treatment of MAFLD.Here we review the pathogenesis of MAFLD by gut microbiota and its metabolites and discuss the feasibility of treating MAFLD from the perspective of gut microbes.

Long-chain acyl-CoA synthetase in fatty acid metabolism involved in liver and other diseases:An update

Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-Co As, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or lossof-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolismassociated effects of ACSLs in diseases.

Microglia-associated neuroinflammation is a potential therapeutic target for ischemic stroke

Microglia-associated neuroinflammation plays an important role in the pathophysiology of ischemic stroke.Microglial activation and polarization,and the inflammatory response mediated by these cells play important roles in the development,progression and outcome of brain injury after ischemic stroke.Currently,there is no effective strategy for treating ischemic stroke in clinical practice.Therefore,it is clinically important to study the role and regulation of microglia in stroke.In this review,we discuss the involvement of microglia in the neuroinflammatory process in ischemic stroke,with the aim of providing a better understanding of the relationship between ischemic stroke and microglia.

Progress of Targeting Transforming Growth Factor-β1 Small Interfering RNA in Liver Fibrosis

Liver fibrosis is a common pathological consequence of a variety of chronic stimuli, including viral, autoimmune, drug-induced, cholestatic and metabolic diseases. Fibrosis is driven by a dynamic process involving increased synthesis of matrix components and a failure of physiological mechanisms of matrix turnover. Activation of hepatic stellate cells(HSCs) remains a central event in fibrosis. HSCs are the main source of extracellular matrix(ECM). Transforming growth factor-beta(TGF-β), which is the fibrogenic master cytokine, can induce the activation of HSCs to produce a large amount of ECM, and is capable of inducing apoptosis of liver cells. RNA interference(RNAi) is a novel gene disruption technology. Studies have shown that small interfering RNA(si RNA) targeting TGF-β1 may inhibit the activation and proliferation of HSCs, suppress ECM synthesis and block liver fibrosis. TGF-β1 si RNA-mediated gene silencing therapy provides a new avenue for liver fibrosis. This review summarizes recent progresses in research on HSCs, TGF-β1 and TGF-β1 si RNA in liver fibrosis.

Epidemiological and clinical characteristics of COVID-19 patients in Hengyang,Hunan Province,China

BACKGROUND In December 2019,an ongoing outbreak of coronavirus disease 2019(COVID-19)was first identified in Wuhan,China.The characteristics of COVID-19 patients treated in local hospitals in Wuhan are not fully representative of patients outside Wuhan.Therefore,it is highly essential to analyze the epidemiological and clinical characteristics of COVID-19 in areas outside Wuhan or Hubei Province.To date,a limited number of studies have concentrated on the epidemiological and clinical characteristics of COVID-19 patients with different genders,clinical classification,and with or without basic diseases.AIM To study the epidemiological and clinical characteristics of COVID-19 patients in Hengyang(China)and provide a reliable reference for the prevention and control of COVID-19.METHODS From January 16 to March 2,2020,a total of 48 confirmed cases of COVID-19 were reported in Hengyang,and those cases were included in this study.The diagnostic criteria,clinical classification,and discharge standard related to COVID-19 were in line with the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia(Trial Version 7)released by National Health Commission and National Administration of Traditional Chinese Medicine.The presence of SARS-CoV-2 in pharyngeal swab specimens was detected by quantitative reverse transcription polymerase chain reaction.All the data were imported into the excel worksheet and statistically analyzed by using SPSS 25.0 software.RESULTS A total of 48 cases of COVID-19 were collected,of which 1 was mild,38 were moderate,and 9 were severe.It was unveiled that there were 31(64.6%)male patients and 17(35.4%)female patients,with a female-to-male ratio of 1.82:1.The range of age of patients with COVID-19 was dominantly 30-49 years old[25(52.1%)of 48],followed by those aged over 60 years old[11(22.9%)].Besides,29.2%(14 of 48)of patients had basic diseases,and 57.2%(8 of 14)of patients with basic diseases were aged over 60 years old.The occupations of 48 COVID-19 patients were mainly farmers working in agricultural production[15(31.5%)of 48],rural migrant workers from Hengyang to Wuhan[15(31.5%)],and service workers operating in the service sector[8(16.7%)].The mean latent period was 6.86±3.57 d,and the median was 7[interquartile range(IQR):4-9]d.The mean time from onset of symptoms to the first physician visit was 3.38±2.98(95%CI:2.58-9.18)d,with a median of 2(IQR:1-5)d,and the mean time from hospital admission to confirmed diagnosis was 2.29±2.11(95%CI:1.18-6.42)d,with a median of 2(IQR:1-3)d.The main symptoms were fever[43(89.6%)of 48],cough and expectoration[41(85.4%)],fatigue[22(45.8%)],and chills[22(45.8%)].Other symptoms included poor appetite[13(27.1%)],sore throat[9(18.8%)],dyspnea[9(18.8%)],diarrhea[7(14.6%)],dizziness[5(10.4%)],headache[5(10.4%)],muscle pain[5(10.4%)],nausea and vomiting[4(8.3%)],hemoptysis[4(8.3%)],and runny nose[1(2.1%)].The numbers of peripheral blood leukocytes,lymphocytes,and eosinophils were significantly reduced in the majority of the patients.The levels of C-reactive protein,fibrinogen,blood glucose,lactate dehydrogenase,Ddimer,alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(γ-GT),myoglobin(MB),and creatine kinase(CK)were increased in 64.6%,44.7%,43.2%,37.0%,29.5%,22.9%,20.8%,21.6%,13.6%,and 12.8%of patients,respectively.The incidence of ALT elevation in male patients was remarkably higher than that in females(P<0.01),while the incidences of AST,CK,and blood glucose elevations in severe patients were remarkably higher than those in moderate patients(P<0.05,respectively).Except for the mild patients,chest computed tomography showed characteristic pulmonary lesions.All the patients received antiviral drugs,38(79.2%)accepted traditional Chinese medicine,and 2(4.2%)received treatment of human umbilical-cord mesenchymal stem cells.On March 2,2020,48 patients with COVID-19 were all cured and discharged.CONCLUSION Based on our results,patients with COVID-19 often have multiple organ dysfunction or damage.The incidences of ALT elevation in males,and AST,CK,and blood glucose elevations in severe patients are remarkably higher.

Research Progress in Targeted Therapy of Hepatocellular Carcinoma

Hepatocellular carcinoma(HCC)is one of the most common malignancies,and its treatment is limited.With the understanding of key genes and signaling pathways in the occurrence and development of HCC,targeted drugs with high selectivity and low toxicity have been developed continuously,bringing a variety of options for the treatment of advanced HCC.In this article,the research progress on representative drugs of targeted therapy and potential therapeutic targets for HCC are reviewed.

Roles of the Lipid Metabolism in Hepatic Stellate Cells Activation

Abstract The lipids present in hepatic stellate cells （HSCs） lipid droplets include retinyl ester, triglyceride, cholesteryl ester, cholesterol, phospholipids and free fatty acids. Activation of HSCs is crucial to the development of fibrosis in liver disease. During activation, HSCs transform into myofibroblasts with concomitant loss of their lipid droplets and production of excessive extracellular matrix. Release of lipid droplets containing retinyl esters and triglyceride is a defining feature of activated HSCs. Accumulating evidence supports the proposal that recovering the accumulation of lipids would inhibit the activation of HSCs. In healthy liver, quiescent HSCs store 80% of total liver retinols and release them depending on the extracellular retinol status. However, in injured liver activated HSCs lose their retinols and produce a considerable amount of extracelhilar matrix, subsequently leading to liver fibrosis. Further findings prove that lipid metabolism of HSCs is closely associated with its activation, yet relationship between activated HSCs and the lipid metabolism has remained mysterious.

Effect of Autophagy Over Liver Diseases

In recent years, increasingly evidences show that autophagy plays an important role in the pathogenesis and development of liver diseases, and the relationship between them has increasingly become a focus of concern. Autophagy refers to the process through which the impaired organelles, misfolded protein, and intruding microorganisms is degraded by lysosomes to maintain stability inside cells. This article states the effect of autophagy on liver diseases （hepatic fibrosis, fatty liver, viral hepatitis, and liver cancer）, which aims to provide a new direction for the treatment of liver diseases.

The effect of lipid metabolism on biological characteristics of hepatic stellate cell

Hepatic stellate cells（HSCs） are a kind of fat-storing cells, the lipid droplets are rich in the Cytoplasm, in which retinyl ester accounts for 42%, triglyceride occupies 28%, cholesterol （total） occupies 13%, phospholipids occupies 4% respectively. Studies have continued that thetransforms of HSC phenotype follows the changing of the cell lipid. After the activation of HSC, with HSC phenotype changing from fat-storing cells into myofibroblast, the lipid droplets decreased or disappeared gradually, which means HSCs are under the differentiating process of removing adipose, meawhile triglyceride, and the main content of lipid droplets, also obviously reduced. It was ever declined that during the process of HSC re-fating, the activated HSC would turn into quiescent state. Therefore this shows HSCs fat metabolism is closely related to the biological activity.

Misidentification of hepatic tuberculosis as cholangiocarcinoma:A case report

BACKGROUND Hepatic tuberculosis(TB)is uncommon clinically.Because of a lack of specific signs,characteristic symptoms and clinical manifestations and because pathological samples are difficult to obtain,hepatic TB is easily missed or misdiagnosed.CASE SUMMARY A 62-year-old Chinese man presented with jaundice for 1 wk and no abnormal laboratory tests other than elevated bilirubin,aminotransferases and C-reactive protein.Computed tomography(CT)of the abdomen showed a mass in the left lobe of the liver and hepatic hilum with striped calcified foci.Mild enhancement was visible at the edges,along with extensive intrahepatic biliary ductal dilatation in the right lobe of the liver.In the arterial phase of both CT and magnetic resonance imaging,the main trunk and right branch of the portal artery were partially visualized.Magnetic resonance cholangiopancreatography(MRCP)indicated that the left lobe of the liver and most of the bile ducts in the hilum were not visible.Pathological examination revealed coagulative necrosis,and granulomatous nodules were seen around areas of necrosis;therefore,TB was considered.CONCLUSION Hepatic tuberculosis is easily misdiagnosed or missed on imaging.Percutaneous puncture biopsy is the most useful tool for definitive diagnosis.

Roles of Long-chain Acyl Coenzyme A Synthetase in Absorption and Transport of Fatty Acid

Long-chain acyl coenzyme A synthetase(ACSL) is a member of the synthetase family encoded by a multigene family;it plays an important role in the absorption and transport of fatty acid.Here we review the roles of ACSL in the regulating absorption and transport of fatty acid,as well as the connection between ACSL and some metabolic diseases.

Relation Between Cellular Senescence and Liver Diseases

Cellular senescence refers to a process that cellular proliferation and differentiation modulated by the multiple stimulating factors gradually decline. Aging cells present the irreversible stop of proliferation and differentiation and change in secretory function because the cell cycle of aging cells is steadily blocked at some point. It has have been shown that cellular senescence plays an important role in the occurrence and development of liver diseases. In this paper, we review the advances in relations between cellular senescence and liver diseases.

COVID-19 combined with liver injury:Current challenges and management

Coronavirus disease 2019(COVID-19)combined with liver injury has become a very prominent clinical problem.Due to the lack of a clear definition of liver injury in patients with COVID-19,the different selection of evaluation parameters and statistical time points,there are the conflicting conclusions about the incidence rate in different studies.The mechanism of COVID-19 combined with liver injury is complicated,including the direct injury of liver cells caused by severe acute respiratory syndrome coronavirus 2 replication and liver injury caused by cytokines,ischemia and hypoxia,and drugs.In addition,underlying diseases,especially chronic liver disease,can aggravate COVID-19 liver injury.In the treatment of COVID-19 combined with liver injury,the primary and basic treatment is to treat the etiology and pathogenesis,followed by support,liver protection,and symptomatic treatment according to the clinical classification and severity of liver injury.This article evaluates the incidence,pathogenesis and prevention and treatment of COVID-19 combined with liver injury,and aims to provide countermeasures for the prevention and treatment of COVID-19 combined with liver injury.

Awareness and knowledge of human papillomavirus vaccination and their influential factors among Chinese women: a systematic review

Objectives: To systematically review the knowledge attitudes and the influential factors on human papillomavirus(HPV) vaccination among Chinese women.Methods: Published studies on knowledge and attitudes of HPV vaccination for preventing cervical cancer among Chinese female population were retrieved using the major Chinese and English databases. Meanwhile, handwork retrieval was also conducted and the references including in the literature were retrieved. The quality of the literature was rigorously evaluated and extracted independently by two researchers and the data were analyzed and described by review manager 5.3(RevMan5.3) software.Results: In all, 19 articles including 8 articles in Chinese and 11 in English were chosen. A total of 30,176 participants were included and the sample size ranged from 64 to 6,024. The overall awareness of HPV and HPV vaccine among Chinese women was at a low level. Chinese women generally showed poor knowledge about HPV and HPV vaccine. Acceptance of HPV vaccination among Chinese women was at a high level. Vaccination intentions were influenced by the theory of planned behavior(TPB) and measured by attitudes subjective norms and perceived behavioral control.Conclusions: The health authorities may evaluate and develop TPB-based interventions to increase HPV vaccination intentions of Chinese women. HPV vaccination programs should focus on carrying out multi-level and targeted health education and developing effective public health strategies after balancing the cost and benefit of HPV vaccine program. Medical staff should play the positive role in promoting the use of HPV vaccines in China. Integration of policy and community perspectives and multi-level interventions are essential to maximize the public health benefits of HPV vaccination.

Role of cyclooxygenase-2 in lipid metabolism in hepatic stellate cells

Hepatic stellate cells(HSCs) are a kind of adipocytes. In HSCs lipids mainly exist in the form of lipid droplets. They are abundantly found in the cytoplasm and their main constituents are triglycerides. Lipid metabolism in HSCs is closely related to its biological activity, however the mechanism of lipid droplets disappearance after HSC activation is not clearly established yet. Recent research shows that, cyclooxygenase-2 plays an important regulatory role in the lipid metabolism of HSCs. This paper seeks to review the subject based on studies that have been conducted so far to understand the role of cyclooxygenase-2 in the metabolism of lipids in HSCs.

A novel prognosis signature based on two cuprotosis-related genes for kidney renal clear cell carcinoma

Background:Cuprotosis is a newly discovered Copper-dependence form of cell death.Cuprotosis-related genes(CRGs)regulating mitochondrial metabolism and protein lipoylation suggest the critical roles cuprotosis for in cancer.However,the prognostic value of CRGs in the highly immunogenic cancer type,kidney renal clear cell carcinoma(KIRC)needs to be further studied.Herein,we aim to identify novel prognostic genes and construct a CRGs prognostic signature for KIRC.Methods:We downloaded the mRNA sequencing data from the Cancer Genome Atlas,differentially expressed CRGs were screened out and their bio-function was elucidated.Then we used Cox regression analysis to establish a prediction model of CRGs.Subsequently,a prognostic scoring model based on the regression coefficients of the screened out CRGs and their corresponding mRNA expressions were constructed and validated.Results:Seven differentially expressed CRGs were screened.A two-gene model was built to separate samples into high-risk and low-risk groups.Overall survival was lower in the high-risk group than in the low-risk group(p<0.05).The receiver operating characteristic curve showed a good diagnostic efficiency of the signature.We verified this prognostic model in the Cancer Genome Atlas test cohorts.The risk score was identified as an independent prognostic factor via multivariate Cox regression.Moreover,the nomogram was used to predict 1-/3-/5-year OS of KIRC patients.Furthermore,risk score has a very significant effect on the infiltration of immune cells and the expression of immune checkpoints.Conclusions:To conclude,we constructed a novel prognostic signature based on CRGs.Targeting cuprotosis may represent a promising approach for the treatment of KIRC.