BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy ...BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.展开更多
Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic ...Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignancy,and transcatheter arterial embolization(TAE)has emerged as a pivotal therapeutic modality.How-ever,TAE may induce symptom distress and fatigue,adversel...BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignancy,and transcatheter arterial embolization(TAE)has emerged as a pivotal therapeutic modality.How-ever,TAE may induce symptom distress and fatigue,adversely affecting the quality of life of patients.AIM To investigate symptom distress,fatigue,and associated factors in HCC patients undergoing TAE.METHODS We used a cross-sectional design and purposive sampling to enroll HCC patients who underwent TAE at our institution from January to December 2022.Question-naires were utilized to collect data on symptom distress and fatigue scores from the first to the third day after TAE.RESULTS Our study revealed a significant reduction in fatigue and symptom distress among patients after TAE.Pain,fatigue,insomnia,fever and abdominal dis-tension were the most common symptoms troubling patients during the first 3 d post-TAE.Marital status,presence of family support,physical functional status,age,and symptom distress were identified as predictors of fatigue in patients.CONCLUSION Healthcare professionals should educate HCC patients on symptom distress and INTRODUCTION Hepatocellular carcinoma(HCC)ranks as the fifth most prevalent cancer and the third leading cause of cancer-related mortality globally.Surgical intervention remains the cornerstone of HCC treatment;however,due to the challenges associated with early diagnosis and the lack of specific diagnostic markers,a considerable proportion of patients are diagnosed at advanced stages,rendering them ineligible for surgical interventions.Transcatheter arterial embolization(TAE)is an interventional therapeutic approach involving the insertion of a fine catheter via the femoral artery to reach the vasculature near the tumor site.TAE aims to obstruct the arterial supply to the tumor by deploying embolic agents,thereby inducing necrosis in cancer cells.This procedure is suitable for patients with good liver function and overall health,particularly those with large HCCs that have not invaded the portal vein[1,2].Nonetheless,following TAE,hepatocytes incur variable degrees of damage,leading to the development of a constel-lation of symptoms reminiscent of acute hepatitis.These symptoms include fatigue and systemic discomfort,such as nausea,vomiting,fever,abdominal pain,as well as transient elevations in aspartate aminotransferase(AST)and alanine aminotransferase(ALT),collectively referred to as postembolization syndrome[3,4].These symptoms may arise due to ischemia of the liver and gallbladder,temporary liver enlargement,and peritoneal irritation.While many studies have explored fatigue and symptom distress in cancer patients both nationally and internationally,with some focusing on symptom distress following transcatheter arterial chemoembolization,there has been limited in-depth investigation into the fatigue and symptom distress resulting from TAE treatment[5-8].Fatigue and pain are both subjective experiences,typically arising from the gradual depletion of energy reserves during the course of illness[9].Fatigue is particularly prevalent among cancer patients,with rates soaring as high as 90%.Despite extensive research exploring cancer-related fatigue and its influencing factors,a unanimous consensus remains elusive.Hence,the primary objective of this study was to investigate the symptom distress and fatigue experienced by liver cancer patients following TAE treatment and to analyze potential contributing factors.展开更多
The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role o...The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.展开更多
Objectives:Human epidermal growth factor receptor 2(HER2)-targeted therapies have demonstrated potential benefits for metastatic colorectal cancer(mCRC)patients with HER2 amplification,but are not satisfactory in case...Objectives:Human epidermal growth factor receptor 2(HER2)-targeted therapies have demonstrated potential benefits for metastatic colorectal cancer(mCRC)patients with HER2 amplification,but are not satisfactory in cases of HER2 mutant CRCs.Methods:Consequently,further elucidation of amplifications and somatic mutations in erythroblastic oncogene B-2(ERBB2)is imperative.Comprehensive genomic profiling was conducted on 2454 Chinese CRC cases to evaluate genomic alterations in 733 cancer-related genes,tumor mutational burden,microsatellite instability,and programmed death ligand 1(PD-L1)expression.Results:Among 2454 CRC patients,85 cases(3.46%)exhibited ERBB2 amplification,and 55 cases(2.24%)carried ERBB2 mutation.p.R678Q(28%),p.V8421(24%),and p.S310F/Y(12%)were the most prevalent of the 16 detected mutation sites.In comparison to the ERBB2 altered(alt)group,KRAS/BRAF mutations were more prevalent in ERBB2 wild-type(wt)samples(ERBB2wt vs.ERBB2alt,KRAS:50.9%vs.25.6%,p<0.05;BRAF:8.5%vs.2.3%,p<0.05).32.7%(18/55)of CRCs with ERBB2 mutation exhibited microsatellite instability high(MSI-H),while no cases with HER2 amplification displayed MSI-H.Mutant genes varied between ERBB2 copy number variation(CNV)and ERBB2 single nucleotide variant(SNV);TP53 alterations tended to co-occur with ERBB2 amplification(92.3%)as opposed to ERBB2 mutation(58.3%).KRAS and PIK3CA alterations were more prevalent in ERBB2 SNV cases(KRAS/PIK3CA:45.8%/31.2%)compared to ERBB2 amplification cases(KRAS/PIK3CA:14.1%/7.7%).Conclusion:Our study delineates the landscape of HER2 alterations in a large-scale cohort of CRC patients from China.These findings enhance our understanding of the molecular features of Chinese CRC patients and offer valuable implications for further investigation.展开更多
BACKGROUND Nasolabial fold(NLF)depression can affect the facial appearance of patients to some extent and increase their psychological burdens.In recent years,autologous fat grafting(AFG)combined with botulinum toxin ...BACKGROUND Nasolabial fold(NLF)depression can affect the facial appearance of patients to some extent and increase their psychological burdens.In recent years,autologous fat grafting(AFG)combined with botulinum toxin A(BTX-A)injection(AFG+BTX-A injection)has been gradually applied in the treatment of patients with NLF depression.Although studies have been conducted on the efficacy and safety of AFG+BTX-A injection in treating NLF depression,the experimental design,observational indicators,and sample enrollment criteria vary remarkably,making it difficult to draw convincing and consistent conclusions.Thus,further relevant research is warranted.AIM To assess the esthetic improvement,efficacy,and safety of AFG+BTX-A injections in patients with NLF depression.METHODS This study included 60 patients with NLF depression who were treated in our hospital from February 2019 to April 2021.These patients were categorized into control(n=30)and observation(n=30)groups.The observation group received AFG+BTX-A injection,whereas the control group underwent AFG only.All patients were evaluated using the wrinkle severity rating scale(WSRS)and global aesthetic improvement scale.The compactness of facial contours,skin evaluation indexes,adverse reactions,and satisfaction of the two groups were evaluated 3 months postoperatively.RESULTS The WSRS scores of the observation group at 1,3,and 6 months postoperatively were lower than those of the control group(P<0.05).Three months postoperatively,facial fine lines and pores showed obvious improvement and the skin index score was higher in the observation group than in the control group(P<0.05).The compactness of facial contours was better in the observation group than in the control group(P<0.05).In addition,no remarkable differences were noted in the incidence of postoperative adverse reactions such as facial stiffness,facial asymmetry,facial bruising,and facial concavity inequality(P>0.05).CONCLUSION AFG+BTX-A injection is a highly safe,cost-effective,effective,and long-lasting treatment for NLF depression with high esthetic value,which should be promoted in the future.展开更多
Ossification of the Posterior Longitudinal Ligament(OPLL)is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone,resulting in limited spinal mobi...Ossification of the Posterior Longitudinal Ligament(OPLL)is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone,resulting in limited spinal mobility and nerve compression.Employing both bulk and single-cell RNA sequencing,we elucidate the molecular characteristics,cellular components,and their evolution during the OPLL process at a single-cell resolution,and validate these findings in clinical samples.This study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in vivo.Notably,our study identifies LOXL2 as a key regulator in this process.Through gain-and loss-of-function studies,we elucidate the role of LOXL2 in the endothelial-like differentiation of ligament cells.It acts via the HIF1A pathway,promoting the secretion of downstream VEGFA and PDGF-BB.This function is not related to the enzymatic activity of LOXL2.Furthermore,we identify sorafenib,a broad-spectrum tyrosine kinase inhibitor,as an effective suppressor of LOXL2-mediated vascular morphogenesis.By disrupting the coupling between vascularization and osteogenesis,sorafenib demonstrates significant inhibition of OPLL progression in both BMP-induced and enpp1 deficiency-induced animal models while having no discernible effect on normal bone mass.These findings underscore the potential of sorafenib as a therapeutic intervention for OPLL.展开更多
●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,...●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in vitro.Polymerase chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein expression.The transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux.Scanning electron microscopy was used to detect the existence of autolysosome.Short interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related pathway.Flow cytometry was employed to test the apoptosis and intracellular Ca^(2+)level.Mitochondrial membrane potential was measured by JC-1 staining.The cell counting kit-8 assay was used to calculate the cellular viability.The wound healing assay was used to evaluate the wound closure rate.GraphPad 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in LECs.Beclin 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression decreased.Transient Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early stage.Based on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress.Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased.Inhibition of autophagy by ATG7 knockdown had similar results.TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress.●CONCLUSION:A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.展开更多
AIM:To quantitatively assess the changes in mean vascular tortuosity(mVT)and mean vascular width(mVW)around the optic disc and their correlation with gestational age(GA)and birth weight(BW)in premature infants without...AIM:To quantitatively assess the changes in mean vascular tortuosity(mVT)and mean vascular width(mVW)around the optic disc and their correlation with gestational age(GA)and birth weight(BW)in premature infants without retinopathy of prematurity(ROP).METHODS:A single-center retrospective study included a total of 133(133 eyes)premature infants[mean corrected gestational age(CGA)43.6wk]without ROP as the premature group and 130(130 eyes)CGA-matched fullterm infants as the control group.The peripapillary mVT and mVW were quantitatively measured using computerassisted techniques.RESULTS:Premature infants had significantly higher mVT(P=0.0032)and lower mVW(P=0.0086)by 2.68(10^(4) cm^(-3))and 1.85μm,respectively.Subgroup analysis with GA showed significant differences(P=0.0244)in mVT between the early preterm and middle to late preterm groups,but the differences between mVW were not significant(P=0.6652).The results of the multiple linear regression model showed a significant negative correlation between GA and BW with mVT after adjusting sex and CGA(P=0.0211 and P=0.0006,respectively).For each day increase in GA at birth,mVT decreased by 0.1281(10^(4) cm^(-3))and for each 1 g increase in BW,mVT decreased by 0.006(10^(4) cm^(-3)).However,GA(P=0.9402)and BW(P=0.7275)were not significantly correlated with mVW.CONCLUSION:Preterm birth significantly affects the peripapillary vascular parameters that indicate higher mVT and narrower mVW in premature infants without ROP.Alterations in these parameters may provide new insights into the pathogenesis of ocular vascular disease.展开更多
To the editor:Two recent advisories from the US surgeon general have underscored the unprecedented public health crisis in youth mental health and emphasised the need for“timely data collection and research to identi...To the editor:Two recent advisories from the US surgeon general have underscored the unprecedented public health crisis in youth mental health and emphasised the need for“timely data collection and research to identify and respond to youth mental health needs more rapidly”.1 Increased rates of suicidal behaviour,depression and anxiety symptoms and substance use.展开更多
Objective:Traditional Chinese medicine(TCM)has been extensively used as one of popular alternative therapies for several cancers.However,it remains unclear whether TCM treatment is associated with longer survival in l...Objective:Traditional Chinese medicine(TCM)has been extensively used as one of popular alternative therapies for several cancers.However,it remains unclear whether TCM treatment is associated with longer survival in lung cancer patients.In this study,we explored the effect of long-term TCM treatment on patients with different stages of lung cancer.Methods:All information of lung cancer patients with stage I-III disease from January 2007 to September 2015 was collected for this retrospective cohort study.Those who were treated with TCM after surgery were divided into TCM group and the others were into the non-TCM group(control group).All patients were regularly followed up by clinic appointment or phone,and all survival data were collected from databases after the last follow-up in October 2017.Results:A total of 575 patients were included in this study,with 299 patients in the TCM group and 276 in the control group.For all patients,5-year disease-free survival(DFS)was 62.2% in TCM group and 42.1% in the control group,and 6-year DFSs were 51.8% and 35.4%,respectively(HR=0.51,95% CI:0.40 to 0.66,log-rank P≤0.001).For patients with stage I,5-year DFSs were 83.7%(TCM group)and 57.5%(control group)and 6-year DFSs were 73.7% and 51.9%,respectively(HR=0.30,95% CI:0.18 to 0.50,log-rank P≤0.001).For patients with stage II in the TCM group and the control group,5-year DFSs were 59.4% and 17.6% and 6-year DFSs were 44.7% and 17.6%,respectively(HR=0.31,95% CI:0.19 to 0.52,log-rank P≤0.001),and for patients with stage III,5-year and 6-year DFSs in the TCM group were 18.7% and 12.5% compared with 28.4% and 20.3% in the control group(HR=1.06,95% CI:0.72 to 1.56,log-rank P=0.76).Conclusions:This study demonstrated that long-term TCM treatment as an adjuvant therapy is able to improve the DFS of postoperative stage I-III lung cancer patients,especially in patients with stage I and II disease.However,these observational findings need being validated by large sample randomized controlled trials.展开更多
BACKGROUND Ciprofol is a novel agent for intravenous general anesthesia.In February 2022,it was approved by the National Medical Products Administration for general anesthesia induction and maintenance.It has the adva...BACKGROUND Ciprofol is a novel agent for intravenous general anesthesia.In February 2022,it was approved by the National Medical Products Administration for general anesthesia induction and maintenance.It has the advantages of fast onset,fast elimination,stable circulation,and few adverse reactions.However,the efficacy and safety of ciprofol in cardiac surgery with cardiopulmonary bypass have not been reported.Here we describe a case where ciprofol was successfully used for anesthesia in cardiac surgery with cardiopulmonary bypass.CASE SUMMARY A 72-year-old man(height 176 cm;weight 70 kg)was diagnosed with coronary atherosclerotic cardiomyopathy requiring coronary artery bypass grafting and left ventricular aneurysmectomy.Ciprofol was administered for induction(0.4 mg/kg)and maintenance(0.6-1.0 mg/kg/h)of general anesthesia.During the entire operation,the bispectral index,hemodynamics,and blood oxygen saturation were maintained at normal levels.The patient recovered well after surgery,with no serious adverse events related to ciprofol.CONCLUSION Ciprofol is safe and effective for anesthesia in cardiac surgery with cardiopulmonary bypass.展开更多
High incidence(10.2%)and mortality(9.2%)rates led to the ranking of colorectal cancer(CRC)as the second most malignant tumor spectrum worldwide in 2020.Treatment strategies are becoming highly dependent on the molecul...High incidence(10.2%)and mortality(9.2%)rates led to the ranking of colorectal cancer(CRC)as the second most malignant tumor spectrum worldwide in 2020.Treatment strategies are becoming highly dependent on the molecular characteristics of CRC.The classical theories accept two models depicting the origin of CRC:The progression of adenoma to cancer and transformation from serrated polyps to cancer.However,the molecular mechanism of CRC development is very complex.For instance,CRCs originating from laterally spreading tumors(LST)do not adhere to any of these models and exhibit extremely serious progression and poor outcomes.In this article,we present another possible pathway involved in CRC development,particularly from LST,with important molecular characteristics,which would facilitate the design of a novel strategy for targeted therapy.展开更多
Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor a...Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.展开更多
Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In...Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.展开更多
Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial ...Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.展开更多
Gastric cancer(GC),the fifth-and fourth-leading causes of morbidity and mortality worldwide,still lacks effective diagnoses and treatment.Moreover,China accounts for nearly 50%of the newly diagnosed and death cases of...Gastric cancer(GC),the fifth-and fourth-leading causes of morbidity and mortality worldwide,still lacks effective diagnoses and treatment.Moreover,China accounts for nearly 50%of the newly diagnosed and death cases of GC globally1.Being directly exposed to external food intake,extremely acidic content,and microorganisms,such as Helicobacter pylori and Epstein-Barr virus(EBV),stomach homeostasis is easily perturbed and disrupted.Importantly,the gastric epithelium is composed of multiple cell types,including chief,parietal,pit,and stem cells.The lineages of these gastric epithelial cells are rather plastic,giving rise to a high degree of GC heterogeneity.展开更多
Pericytes are the main cellular components of tiny arteries and capillaries.Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines,thus affecting the contr...Pericytes are the main cellular components of tiny arteries and capillaries.Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines,thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation.Moreover,due to the characteristics of stem cells,pericytes can differentiate into a variety of inflammatory cell phenotypes,which then affect the immune function.Additionally,pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders.Here we review the origin,biological phenotype and function of pericytes,and discuss the potential mechanisms of pericytes in vascular microcirculation disorders,especially in pulmonary hypertension,so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.展开更多
Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-c...Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.展开更多
Obesity and type-2 diabetes mellitus(T2DM)are metabolic disorders.Obesity increases the risk of T2DM,and as obesity is becoming increasingly common,more individuals suffer from T2DM,which poses a considerable burden o...Obesity and type-2 diabetes mellitus(T2DM)are metabolic disorders.Obesity increases the risk of T2DM,and as obesity is becoming increasingly common,more individuals suffer from T2DM,which poses a considerable burden on health systems.Traditionally,pharmaceutical therapy together with lifestyle changes is used to treat obesity and T2DM to decrease the incidence of comorbidities and allcause mortality and to increase life expectancy.Bariatric surgery is increasingly replacing other forms of treatment of morbid obesity,especially in patients with refractory obesity,owing to its many benefits including good long-term outcomes and almost no weight regain.The bariatric surgery options have markedly changed recently,and laparoscopic sleeve gastrectomy(LSG)is gradually gaining popularity.LSG has become an effective and safe treatment for type-2 diabetes and morbid obesity,with a high cost-benefit ratio.Here,we review the mechanism associated with LSG treatment of T2DM,and we discuss clinical studies and animal experiments with regard to gastrointestinal hormones,gut microbiota,bile acids,and adipokines to clarify current treatment modalities for patients with obesity and T2DM.展开更多
基金Supported by Shanghai Hospital Development Center Foundation,No.SHDC2022CRS033.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.
基金supported by the National Key Research and Development Project,No.2019YFA0112100(to SF).
文摘Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.
基金The study was reviewed and approved by the Shanghai Fourth People’s Hospital Institutional Review Board(approval No.2022108-001).
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignancy,and transcatheter arterial embolization(TAE)has emerged as a pivotal therapeutic modality.How-ever,TAE may induce symptom distress and fatigue,adversely affecting the quality of life of patients.AIM To investigate symptom distress,fatigue,and associated factors in HCC patients undergoing TAE.METHODS We used a cross-sectional design and purposive sampling to enroll HCC patients who underwent TAE at our institution from January to December 2022.Question-naires were utilized to collect data on symptom distress and fatigue scores from the first to the third day after TAE.RESULTS Our study revealed a significant reduction in fatigue and symptom distress among patients after TAE.Pain,fatigue,insomnia,fever and abdominal dis-tension were the most common symptoms troubling patients during the first 3 d post-TAE.Marital status,presence of family support,physical functional status,age,and symptom distress were identified as predictors of fatigue in patients.CONCLUSION Healthcare professionals should educate HCC patients on symptom distress and INTRODUCTION Hepatocellular carcinoma(HCC)ranks as the fifth most prevalent cancer and the third leading cause of cancer-related mortality globally.Surgical intervention remains the cornerstone of HCC treatment;however,due to the challenges associated with early diagnosis and the lack of specific diagnostic markers,a considerable proportion of patients are diagnosed at advanced stages,rendering them ineligible for surgical interventions.Transcatheter arterial embolization(TAE)is an interventional therapeutic approach involving the insertion of a fine catheter via the femoral artery to reach the vasculature near the tumor site.TAE aims to obstruct the arterial supply to the tumor by deploying embolic agents,thereby inducing necrosis in cancer cells.This procedure is suitable for patients with good liver function and overall health,particularly those with large HCCs that have not invaded the portal vein[1,2].Nonetheless,following TAE,hepatocytes incur variable degrees of damage,leading to the development of a constel-lation of symptoms reminiscent of acute hepatitis.These symptoms include fatigue and systemic discomfort,such as nausea,vomiting,fever,abdominal pain,as well as transient elevations in aspartate aminotransferase(AST)and alanine aminotransferase(ALT),collectively referred to as postembolization syndrome[3,4].These symptoms may arise due to ischemia of the liver and gallbladder,temporary liver enlargement,and peritoneal irritation.While many studies have explored fatigue and symptom distress in cancer patients both nationally and internationally,with some focusing on symptom distress following transcatheter arterial chemoembolization,there has been limited in-depth investigation into the fatigue and symptom distress resulting from TAE treatment[5-8].Fatigue and pain are both subjective experiences,typically arising from the gradual depletion of energy reserves during the course of illness[9].Fatigue is particularly prevalent among cancer patients,with rates soaring as high as 90%.Despite extensive research exploring cancer-related fatigue and its influencing factors,a unanimous consensus remains elusive.Hence,the primary objective of this study was to investigate the symptom distress and fatigue experienced by liver cancer patients following TAE treatment and to analyze potential contributing factors.
文摘The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.
基金sponsored by National Natural Science Foundation of China(Grant Numbers 81972280,81972290)Natural Science Foundation of Shanghai(Grant Number 23ZR1452300)+2 种基金Research Grant for Health Science and Technology of Pudong Health Bureau of Shanghai(Grant Number PW2022E-02)Academic Leaders Training Program of Pudong Health Bureau of Shanghai(Grant Number PWRd2022-02)Foundation of Beijing CSCO Clinical Oncology Research(Grant Number Y-HR2019-0384).
文摘Objectives:Human epidermal growth factor receptor 2(HER2)-targeted therapies have demonstrated potential benefits for metastatic colorectal cancer(mCRC)patients with HER2 amplification,but are not satisfactory in cases of HER2 mutant CRCs.Methods:Consequently,further elucidation of amplifications and somatic mutations in erythroblastic oncogene B-2(ERBB2)is imperative.Comprehensive genomic profiling was conducted on 2454 Chinese CRC cases to evaluate genomic alterations in 733 cancer-related genes,tumor mutational burden,microsatellite instability,and programmed death ligand 1(PD-L1)expression.Results:Among 2454 CRC patients,85 cases(3.46%)exhibited ERBB2 amplification,and 55 cases(2.24%)carried ERBB2 mutation.p.R678Q(28%),p.V8421(24%),and p.S310F/Y(12%)were the most prevalent of the 16 detected mutation sites.In comparison to the ERBB2 altered(alt)group,KRAS/BRAF mutations were more prevalent in ERBB2 wild-type(wt)samples(ERBB2wt vs.ERBB2alt,KRAS:50.9%vs.25.6%,p<0.05;BRAF:8.5%vs.2.3%,p<0.05).32.7%(18/55)of CRCs with ERBB2 mutation exhibited microsatellite instability high(MSI-H),while no cases with HER2 amplification displayed MSI-H.Mutant genes varied between ERBB2 copy number variation(CNV)and ERBB2 single nucleotide variant(SNV);TP53 alterations tended to co-occur with ERBB2 amplification(92.3%)as opposed to ERBB2 mutation(58.3%).KRAS and PIK3CA alterations were more prevalent in ERBB2 SNV cases(KRAS/PIK3CA:45.8%/31.2%)compared to ERBB2 amplification cases(KRAS/PIK3CA:14.1%/7.7%).Conclusion:Our study delineates the landscape of HER2 alterations in a large-scale cohort of CRC patients from China.These findings enhance our understanding of the molecular features of Chinese CRC patients and offer valuable implications for further investigation.
基金Supported by Medical and Health Science and Technology Project of Hangzhou,No.B20230855Hangzhou Science and Technology Plan Development Project,No.20210133X01.
文摘BACKGROUND Nasolabial fold(NLF)depression can affect the facial appearance of patients to some extent and increase their psychological burdens.In recent years,autologous fat grafting(AFG)combined with botulinum toxin A(BTX-A)injection(AFG+BTX-A injection)has been gradually applied in the treatment of patients with NLF depression.Although studies have been conducted on the efficacy and safety of AFG+BTX-A injection in treating NLF depression,the experimental design,observational indicators,and sample enrollment criteria vary remarkably,making it difficult to draw convincing and consistent conclusions.Thus,further relevant research is warranted.AIM To assess the esthetic improvement,efficacy,and safety of AFG+BTX-A injections in patients with NLF depression.METHODS This study included 60 patients with NLF depression who were treated in our hospital from February 2019 to April 2021.These patients were categorized into control(n=30)and observation(n=30)groups.The observation group received AFG+BTX-A injection,whereas the control group underwent AFG only.All patients were evaluated using the wrinkle severity rating scale(WSRS)and global aesthetic improvement scale.The compactness of facial contours,skin evaluation indexes,adverse reactions,and satisfaction of the two groups were evaluated 3 months postoperatively.RESULTS The WSRS scores of the observation group at 1,3,and 6 months postoperatively were lower than those of the control group(P<0.05).Three months postoperatively,facial fine lines and pores showed obvious improvement and the skin index score was higher in the observation group than in the control group(P<0.05).The compactness of facial contours was better in the observation group than in the control group(P<0.05).In addition,no remarkable differences were noted in the incidence of postoperative adverse reactions such as facial stiffness,facial asymmetry,facial bruising,and facial concavity inequality(P>0.05).CONCLUSION AFG+BTX-A injection is a highly safe,cost-effective,effective,and long-lasting treatment for NLF depression with high esthetic value,which should be promoted in the future.
基金supported by grants from the National Natural Science Foundation of China(82372431 to L.L.Y.,92168204 and 82225030 to J.L.)the Shanghai Municipal Health Commission(2022LJ007 to L.L.Y.)+3 种基金the Science and Technology Commission of Shanghai Municipality(22ZR1476700 to L.L.Y.)Shanghai Municipal Annual Innovative Medical Device Application Demonstration Project(23SHS05700-06 to L.L.Y.)the Fifth Round Innovation Team of Shanghai Changning District(to L.L.Y.)“Open bidding for selecting the best candidates”cultivation project of Shanghai Changzheng Hospital(2023YJBF-PY10 to L.L.Y.).
文摘Ossification of the Posterior Longitudinal Ligament(OPLL)is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone,resulting in limited spinal mobility and nerve compression.Employing both bulk and single-cell RNA sequencing,we elucidate the molecular characteristics,cellular components,and their evolution during the OPLL process at a single-cell resolution,and validate these findings in clinical samples.This study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in vivo.Notably,our study identifies LOXL2 as a key regulator in this process.Through gain-and loss-of-function studies,we elucidate the role of LOXL2 in the endothelial-like differentiation of ligament cells.It acts via the HIF1A pathway,promoting the secretion of downstream VEGFA and PDGF-BB.This function is not related to the enzymatic activity of LOXL2.Furthermore,we identify sorafenib,a broad-spectrum tyrosine kinase inhibitor,as an effective suppressor of LOXL2-mediated vascular morphogenesis.By disrupting the coupling between vascularization and osteogenesis,sorafenib demonstrates significant inhibition of OPLL progression in both BMP-induced and enpp1 deficiency-induced animal models while having no discernible effect on normal bone mass.These findings underscore the potential of sorafenib as a therapeutic intervention for OPLL.
文摘●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in vitro.Polymerase chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein expression.The transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux.Scanning electron microscopy was used to detect the existence of autolysosome.Short interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related pathway.Flow cytometry was employed to test the apoptosis and intracellular Ca^(2+)level.Mitochondrial membrane potential was measured by JC-1 staining.The cell counting kit-8 assay was used to calculate the cellular viability.The wound healing assay was used to evaluate the wound closure rate.GraphPad 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in LECs.Beclin 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression decreased.Transient Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early stage.Based on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress.Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased.Inhibition of autophagy by ATG7 knockdown had similar results.TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress.●CONCLUSION:A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.
基金Supported by the Fundamental Research Funds for the Central Universities (No.WK2100000045)the National Natural Science Foundation of China (No.U19B2044)+1 种基金Hefei Health Care Commission 2022 Applied Medical Research Project (No.Hwk2022yb028)Zhejiang Lab Open Research Project (No.K2022QA0AB04).
文摘AIM:To quantitatively assess the changes in mean vascular tortuosity(mVT)and mean vascular width(mVW)around the optic disc and their correlation with gestational age(GA)and birth weight(BW)in premature infants without retinopathy of prematurity(ROP).METHODS:A single-center retrospective study included a total of 133(133 eyes)premature infants[mean corrected gestational age(CGA)43.6wk]without ROP as the premature group and 130(130 eyes)CGA-matched fullterm infants as the control group.The peripapillary mVT and mVW were quantitatively measured using computerassisted techniques.RESULTS:Premature infants had significantly higher mVT(P=0.0032)and lower mVW(P=0.0086)by 2.68(10^(4) cm^(-3))and 1.85μm,respectively.Subgroup analysis with GA showed significant differences(P=0.0244)in mVT between the early preterm and middle to late preterm groups,but the differences between mVW were not significant(P=0.6652).The results of the multiple linear regression model showed a significant negative correlation between GA and BW with mVT after adjusting sex and CGA(P=0.0211 and P=0.0006,respectively).For each day increase in GA at birth,mVT decreased by 0.1281(10^(4) cm^(-3))and for each 1 g increase in BW,mVT decreased by 0.006(10^(4) cm^(-3)).However,GA(P=0.9402)and BW(P=0.7275)were not significantly correlated with mVW.CONCLUSION:Preterm birth significantly affects the peripapillary vascular parameters that indicate higher mVT and narrower mVW in premature infants without ROP.Alterations in these parameters may provide new insights into the pathogenesis of ocular vascular disease.
基金The funder or sponsor had no role in the study design,analysis,data interpretation or preparation of the manuscript.The effort was supported in part by NIDA(K12 DA041449,KYX)the APA Psychiatric Research Fellowship funded by NIDA(KYX).BYL was an APA/APA Foundation Public Psychiatry Fellow at the time of acceptance.The contents of this publication are solely the responsibility of the author and do not necessarily represent the official views of the Department of Health and Human Service,APA or APA Foundation.Mention of trade names,commercial practices or organisations does not imply endorsement by the US Government.ASK receives research funding from Alto Neuroscience,Liva Nova,Curemark and Beam Diagnostics.
文摘To the editor:Two recent advisories from the US surgeon general have underscored the unprecedented public health crisis in youth mental health and emphasised the need for“timely data collection and research to identify and respond to youth mental health needs more rapidly”.1 Increased rates of suicidal behaviour,depression and anxiety symptoms and substance use.
基金the Nation Natural Science Foundation of China (No.814737627, No.81673947)the Science and Technology Commission of Shanghai Municipality (No.17401933500)the Shanghai Municipal Population and Family Planning Commission (No.201740059).
文摘Objective:Traditional Chinese medicine(TCM)has been extensively used as one of popular alternative therapies for several cancers.However,it remains unclear whether TCM treatment is associated with longer survival in lung cancer patients.In this study,we explored the effect of long-term TCM treatment on patients with different stages of lung cancer.Methods:All information of lung cancer patients with stage I-III disease from January 2007 to September 2015 was collected for this retrospective cohort study.Those who were treated with TCM after surgery were divided into TCM group and the others were into the non-TCM group(control group).All patients were regularly followed up by clinic appointment or phone,and all survival data were collected from databases after the last follow-up in October 2017.Results:A total of 575 patients were included in this study,with 299 patients in the TCM group and 276 in the control group.For all patients,5-year disease-free survival(DFS)was 62.2% in TCM group and 42.1% in the control group,and 6-year DFSs were 51.8% and 35.4%,respectively(HR=0.51,95% CI:0.40 to 0.66,log-rank P≤0.001).For patients with stage I,5-year DFSs were 83.7%(TCM group)and 57.5%(control group)and 6-year DFSs were 73.7% and 51.9%,respectively(HR=0.30,95% CI:0.18 to 0.50,log-rank P≤0.001).For patients with stage II in the TCM group and the control group,5-year DFSs were 59.4% and 17.6% and 6-year DFSs were 44.7% and 17.6%,respectively(HR=0.31,95% CI:0.19 to 0.52,log-rank P≤0.001),and for patients with stage III,5-year and 6-year DFSs in the TCM group were 18.7% and 12.5% compared with 28.4% and 20.3% in the control group(HR=1.06,95% CI:0.72 to 1.56,log-rank P=0.76).Conclusions:This study demonstrated that long-term TCM treatment as an adjuvant therapy is able to improve the DFS of postoperative stage I-III lung cancer patients,especially in patients with stage I and II disease.However,these observational findings need being validated by large sample randomized controlled trials.
文摘BACKGROUND Ciprofol is a novel agent for intravenous general anesthesia.In February 2022,it was approved by the National Medical Products Administration for general anesthesia induction and maintenance.It has the advantages of fast onset,fast elimination,stable circulation,and few adverse reactions.However,the efficacy and safety of ciprofol in cardiac surgery with cardiopulmonary bypass have not been reported.Here we describe a case where ciprofol was successfully used for anesthesia in cardiac surgery with cardiopulmonary bypass.CASE SUMMARY A 72-year-old man(height 176 cm;weight 70 kg)was diagnosed with coronary atherosclerotic cardiomyopathy requiring coronary artery bypass grafting and left ventricular aneurysmectomy.Ciprofol was administered for induction(0.4 mg/kg)and maintenance(0.6-1.0 mg/kg/h)of general anesthesia.During the entire operation,the bispectral index,hemodynamics,and blood oxygen saturation were maintained at normal levels.The patient recovered well after surgery,with no serious adverse events related to ciprofol.CONCLUSION Ciprofol is safe and effective for anesthesia in cardiac surgery with cardiopulmonary bypass.
基金Supported by the National Natural Science Foundation of China,No.72171170 and 82071964.
文摘High incidence(10.2%)and mortality(9.2%)rates led to the ranking of colorectal cancer(CRC)as the second most malignant tumor spectrum worldwide in 2020.Treatment strategies are becoming highly dependent on the molecular characteristics of CRC.The classical theories accept two models depicting the origin of CRC:The progression of adenoma to cancer and transformation from serrated polyps to cancer.However,the molecular mechanism of CRC development is very complex.For instance,CRCs originating from laterally spreading tumors(LST)do not adhere to any of these models and exhibit extremely serious progression and poor outcomes.In this article,we present another possible pathway involved in CRC development,particularly from LST,with important molecular characteristics,which would facilitate the design of a novel strategy for targeted therapy.
基金National Key R&D Program of China(2022YFA1103200,2017YFA0106400,2021YFA1100900)Ministry of Science and Technology of China(2020YFC2002804)+3 种基金National Natural Science Foundation of China(91749124,81772389,82070108)Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone(ZJ2018-ZD-004)Fundamental Research Funds for the Central Universities(22120190149 and kx0200020173386)Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai。
文摘Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.
基金supported by the Notional Natural Science Foundation of China,Nos.81371213 and 8107098 7the Natural Science Foundation of Shanghai,No.21ZR1468400 (all to QLY)。
文摘Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.
基金supported by grants from Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120)General Research Project of Guangzhou Science and Technology Bureau (Grant No. 201607010391)+1 种基金National Key Research and Development Program of China (Grant No. 2016YFC1303800)Guangdong Provincial Applied S&T R&D Program (Grant No. 2016B020237006)
文摘Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.
基金supported by the National Key R&D Program of China(Grant Nos.2020YFA0803200 and 2017YFA0504504)the National Natural Science Foundation of China(Grant Nos.82222052 and 32070710)+1 种基金the Science and Technology Commission of Shanghai Municipality(Grant Nos.22QA1407300,23ZR1480400,and 23YF1432900)Talent Climbing Project from Shanghai Tenth People’s Hospital(Grant Nos.2021SYPDRC003)。
文摘Gastric cancer(GC),the fifth-and fourth-leading causes of morbidity and mortality worldwide,still lacks effective diagnoses and treatment.Moreover,China accounts for nearly 50%of the newly diagnosed and death cases of GC globally1.Being directly exposed to external food intake,extremely acidic content,and microorganisms,such as Helicobacter pylori and Epstein-Barr virus(EBV),stomach homeostasis is easily perturbed and disrupted.Importantly,the gastric epithelium is composed of multiple cell types,including chief,parietal,pit,and stem cells.The lineages of these gastric epithelial cells are rather plastic,giving rise to a high degree of GC heterogeneity.
基金Program of Fundamental Research Funds for the Central Universities,Grant/Award Number:22120220562Program of Natural Science Foundation of Shanghai,Grant/Award Number:201409004100 and 21ZR1453800+1 种基金Three Year Action Plan to Promote Clinical Skills and Clinical Innovation in Municipal Hospitals,Grant/Award Number:SHDC2020CR6016-002 and SHDC2020CR4021Program of Shanghai Pulmonary Hospital,Grant/Award Number:fkzr2320 and FKLY20005。
文摘Pericytes are the main cellular components of tiny arteries and capillaries.Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines,thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation.Moreover,due to the characteristics of stem cells,pericytes can differentiate into a variety of inflammatory cell phenotypes,which then affect the immune function.Additionally,pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders.Here we review the origin,biological phenotype and function of pericytes,and discuss the potential mechanisms of pericytes in vascular microcirculation disorders,especially in pulmonary hypertension,so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.
基金supported by funds from the National Natural Science Foundation of China(Grant Nos.81830002,81830004,82070168,and 32070951)the Translational Research grant of NCRCH(Grant No.2020ZKZC04)National Key R&D Program of China(Grant No.2021YFA1100800)。
文摘Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.
文摘Obesity and type-2 diabetes mellitus(T2DM)are metabolic disorders.Obesity increases the risk of T2DM,and as obesity is becoming increasingly common,more individuals suffer from T2DM,which poses a considerable burden on health systems.Traditionally,pharmaceutical therapy together with lifestyle changes is used to treat obesity and T2DM to decrease the incidence of comorbidities and allcause mortality and to increase life expectancy.Bariatric surgery is increasingly replacing other forms of treatment of morbid obesity,especially in patients with refractory obesity,owing to its many benefits including good long-term outcomes and almost no weight regain.The bariatric surgery options have markedly changed recently,and laparoscopic sleeve gastrectomy(LSG)is gradually gaining popularity.LSG has become an effective and safe treatment for type-2 diabetes and morbid obesity,with a high cost-benefit ratio.Here,we review the mechanism associated with LSG treatment of T2DM,and we discuss clinical studies and animal experiments with regard to gastrointestinal hormones,gut microbiota,bile acids,and adipokines to clarify current treatment modalities for patients with obesity and T2DM.