Introduction With the continuous advancement of surgical technique,combined vascular resection has become increasingly common during complex surgical procedures.In such cases,ensuring the safe and effective reconstruc...Introduction With the continuous advancement of surgical technique,combined vascular resection has become increasingly common during complex surgical procedures.In such cases,ensuring the safe and effective reconstruction of blood vessels after resection is of paramount importance.When direct vascular reconstruction is not feasible,the application of vascular grafts becomes necessary to restore vascular continuity and function.Commonly employed vascular grafts in clinical practice include allogeneic graft vessels(AGVs),autologous vessels,and artificial vessels.Among these,AGVs offer distinct advantages particularly in its complex structures and satisfying histocompatibility,making it a valuable option for vascular reconstruction.展开更多
The soot emitted during the operation of diesel engine exhaust seriously threatens the human health and environment,so treating diesel engine exhaust is critical.At present,the most effective method for eliminating so...The soot emitted during the operation of diesel engine exhaust seriously threatens the human health and environment,so treating diesel engine exhaust is critical.At present,the most effective method for eliminating soot particles is post-treatment technology.Preparation of economically viable and highly active soot combustion catalysts is a pivotal element of post-treatment technology.In this study,different single-metal oxide catalysts with fibrous structures and alkali metal-modified hollow nanotubular Mn-based oxide catalysts were synthesized using centrifugal spinning method.Activity evaluation results showed that the manganese oxide catalyst has the best catalytic activity among the prepared single-metal oxide catalysts.Further research on alkali metal modification showed that doping alkali metals is beneficial for improving the oxidation state of manganese and generating a large number of reactive oxygen species.Combined with the structural effect brought by the hollow nanotube structure,the alkali metal-modified Mn-based oxide catalysts exhibit superior catalytic performance.Among them,the Cs-modified Mn-based oxide catalyst exhibits the best catalytic performance because of its rich active oxygen species,excellent NO oxidation ability,abundant Mn^(4+)ions(M^(n4)+/Mn^(n+)=64.78%),and good redox ability.The T_(10),T_(50),T_(90),and CO_(2)selectivity of the Cs-modified Mn-based oxide catalyst were 267°C,324°C,360°C,and 97.8%,respectively.展开更多
To the Editor:Immune checkpoint inhibitors(ICIs)interact with critical factors involved in immunoregulation.Following the FDA approval of nivolumab as a second line therapy for unresectable hepatocellular carcinoma(HC...To the Editor:Immune checkpoint inhibitors(ICIs)interact with critical factors involved in immunoregulation.Following the FDA approval of nivolumab as a second line therapy for unresectable hepatocellular carcinoma(HCC)in 2017,numerous HCC patients have experienced benefits from ICIs[1].In 2020,the FDA approved the combination of atezolizumab and bevacizumab as first line treatment for unresectable HCCs that have not undergone prior systemic treatments[2].ICIs are driving a transformative change in the field of cancer therapy.展开更多
Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and...Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and c-MET;therefore,it exhibits both antitumor and anti-angiogenetic activities.A phase III trial has shown that anlotinib improved progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small cell lung cancer(NSCLC),who presented with progressive disease or intolerance after standard chemotherapy.This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods:Data were collected from March 2015 to January 2017 from a randomized,double-blind,placebo-controlled,multicenter,phase III trial of anlotinib(ALTER0303).A total of 437 patients were enrolled and randomly allocated(2:1)to the anlotinib and placebo groups.Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS.Cox proportional hazards model was adopted for multivariate prognostic analysis.Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS.Meanwhile,elevated thyroid-stimulating hormone,blood glucose,and triglyceride levels;hypertension;and hand–foot syndrome were independent protective factors of PFS.High posttherapeutic peripheral blood granulocyte/lymphocyte ratio,an Eastern Cooperative Oncology Group(ECOG)score≥2,and the sum of the maximal target lesion length at baseline were independent risk factors of OS,and hypertriglyceridemia was an independent protective factor of OS.Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC,and the baseline characteristics of the therapeutically dominant populations were then identified.展开更多
AIM: To analyze the clinical characteristics of small bowel tumors detected by double-balloon enteroscopy (DBE) and to evaluate the diagnostic value of DBE in tumors. METHODS: Four hundred and forty consecutive DBE ex...AIM: To analyze the clinical characteristics of small bowel tumors detected by double-balloon enteroscopy (DBE) and to evaluate the diagnostic value of DBE in tumors. METHODS: Four hundred and forty consecutive DBE examinations were performed in 400 patients (250 males and 150 females, mean age 46.9 ± 16.3 years, range 14-86 years) between January 2007 and April 2012. Of these, 252 patients underwent the antegrade approach, and 188 patients underwent the retrograde approach. All the patients enrolled in our study were suspected of having small bowel diseases with a negative etiological diagnosis following other routine examinations, such as upper and lower gastrointestinal endoscopy and radiography tests. Data on tumors, such as clinical information, endoscopic findings and opera-tion results, were retrospectively collected. RESULTS: Small bowel tumors were diagnosed in 78 patients, of whom 67 were diagnosed using DBE, resulting in a diagnostic yield of 16.8% (67/400); the other 11 patients had negative DBE findings and were diagnosed through surgery or capsule endoscopy. Adenocarcinoma (29.5%, 23/78), gastrointestinal stromal tumor (24.4%, 19/78) and lymphoma (15.4%, 12/78) were the most common tumors. Among the 78 tumors, 60.3% (47/78) were located in the jejunum, and the overall number of malignant tumors was 74.4% (58/78). DBE examinations were frequently performed in patients with obscure gastrointestinal bleeding (47.4%) and abdominal pain (24.4%). The positive detection rate for DBE in the 78 patients with small bowel tumors was 85.9% (67/78), which was higher than that of a computed tomography scan (72.9%, 51/70). Based on the operation results, the accuracy rates of DBE for locating small bowel neoplasms, such as adenocarcinoma, gastrointestinal stromal tumor and lymphoma, were 94.4%, 100% and 100%, respectively. The positive biopsy rates for adenocarcinoma and lymphoma were 71.4% and 60%, respectively. CONCLUSION: DBE is a useful diagnostic tool with high clinical practice value and should be considered the gold standard for the investigation of small bowel tumors.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
Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associ...Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.展开更多
BACKGROUND Sarcomatoid hepatocellular carcinoma(SHC)is a rare subtype of hepatocellular carcinoma(HCC),with a high recurrence rate after surgery.In addition to limited effective treatment for the advanced stage of SHC...BACKGROUND Sarcomatoid hepatocellular carcinoma(SHC)is a rare subtype of hepatocellular carcinoma(HCC),with a high recurrence rate after surgery.In addition to limited effective treatment for the advanced stage of SHC,the prognosis of patients with this malignancy is worse than that of patients with conventional HCC.CASE SUMMARY We present the case of a 54-year-old man with SHC who underwent radical segmental hepatectomy,which relapsed 4 mo after surgery due to lymphatic metastasis in the porta hepatis.Although a second surgery was performed,new metastasis developed in the mediastinal lymph nodes.Therefore,sorafenib and lenvatinib were sequentially administered as first-and second-line systemic therapies,respectively.However,progressive disease was confirmed based on a recurrent hepatic lesion and new metastatic lesion in the abdominal cavity.Percutaneous transhepatic cholangial drainage was performed to alleviate the biliary obstruction.Because the tumor was strongly positive for programmed death-ligand 1,the patient was started on nivolumab.Imaging studies revealed that after two cycles of immunotherapy,the metastatic lesions decreased to undetectable levels.CONCLUSION The patient experienced continuous complete remission for 8 mo.Immune checkpoint inhibitors are useful for the treatment of advanced SHC.展开更多
Ischemic stroke can cause blood-brain barrier(BBB)injury,which worsens brain damage induced by stroke.Abnormal expression of tight junction proteins in endothelial cells(ECs)can increase intracellular space and BBB le...Ischemic stroke can cause blood-brain barrier(BBB)injury,which worsens brain damage induced by stroke.Abnormal expression of tight junction proteins in endothelial cells(ECs)can increase intracellular space and BBB leakage.Selective inhibition of mitogen-activated protein kinase,the negative regulatory substrate of mitogen-activated protein kinase phosphatase(MKP)-1,improves tight junction protein function in ECs,and genetic deletion of MKP-1 aggravates ischemic brain injury.However,whether the latter affects BBB integrity,and the cell type-specific mechanism underlying this process,remain unclear.In this study,we established an adult male mouse model of ischemic stroke by occluding the middle cerebral artery for 60 minutes and overexpressed MKP-1 in ECs on the injured side via lentiviral transfection before stroke.We found that overexpression of MKP-1 in ECs reduced infarct volume,reduced the level of inflammatory factors interleukin-1β,interleukin-6,and chemokine C-C motif ligand-2,inhibited vascular injury,and promoted the recovery of sensorimotor and memory/cognitive function.Overexpression of MKP-1 in ECs also inhibited the activation of cerebral ischemia-induced extracellular signal-regulated kinase(ERK)1/2 and the downregulation of occludin expression.Finally,to investigate the mechanism by which MKP-1 exerted these functions in ECs,we established an ischemic stroke model in vitro by depriving the primary endothelial cell of oxygen and glucose,and pharmacologically inhibited the activity of MKP-1 and ERK1/2.Our findings suggest that MKP-1 inhibition aggravates oxygen and glucose deprivation-induced cell death,cell monolayer leakage,and downregulation of occludin expression,and that inhibiting ERK1/2 can reverse these effects.In addition,co-inhibition of MKP-1 and ERK1/2 exhibited similar effects to inhibition of ERK1/2.These findings suggest that overexpression of MKP-1 in ECs can prevent ischemia-induced occludin downregulation and cell death via deactivating ERK1/2,thereby protecting the integrity of BBB,alleviating brain injury,and improving post-stroke prognosis.展开更多
Objective:Natural killer(NK)cells have gained considerable attention due to their potential in treating"cold tumors,"and are therefore considered as one of the new strategies for curing cancer,by using world...Objective:Natural killer(NK)cells have gained considerable attention due to their potential in treating"cold tumors,"and are therefore considered as one of the new strategies for curing cancer,by using worldwide development of their new possibilities and interventions with NK cell-related therapeutic products.Methods:We constructed a trispecific killer engager(TriKE)consisting of anti-CD16,IL-15,and anti-CD19.This TriKE was designed to attract CD19^(+)tumor cells to CD16^(+)NK cells,whereas IL-15 sustained the proliferation,development,and survival of NK cells.Results:Treatment with 161519 TriKE in the presence of CD19^(+)targets upregulated expression of CD69,CD107 a,TRAIL,IFN-γ,and TNF-α in NK cells,and significantly improved the proliferation and cytotoxicity of NK cells.NK cells"armed"with 161519 TriKE showed stronger cytolysis against CD19+targets compared with that of"unarmed"NK cells.A preclinical model of B-cell lymphoma in human peripheral blood mononuclear cell-reconstituted xenograft mice showed significant inhibition of tumor growth and prolonged overall survival after treatment with 161519 TriKE,when compared with that in control mice or mice treated with 1619 BiKE.Combined use of IL-2 was a more effective treatment with 1619 BiKE,when compared with that using 161519 TriKE.Conclusions:The newly generated 161519 TriKE enhanced the proliferation,activation,cytokine secretion,and cytotoxicity of NK cells in the presence of CD19+tumor cells.The 161519 TriKE aided inhibition of tumor growth and prolonged the overall survival of murine xenografts,and could be used to treat CD19-positive cancers.展开更多
Objectives: The aim of our study is to examine vestibular-evoked myogenic potentials(VEMPs) elicited by the galvanic vestibular stimulation in the sternocleidomastoid muscle(SCM) in healthy subjects for clinical appli...Objectives: The aim of our study is to examine vestibular-evoked myogenic potentials(VEMPs) elicited by the galvanic vestibular stimulation in the sternocleidomastoid muscle(SCM) in healthy subjects for clinical applications of auditory neuropathy or vestibular neuropathy in the future.Methods: We enrolled sixteen healthy subjects to record the average responses of SCM to galvanic vestibular stimulation(GVS) [current 3 mA;duration 1 ms] by electromyography(EMG). SPSS 18.0 software was used to analyze the obtained data for mean and standard deviation.Results: In all healthy subjects mastoid-forehead galvanic vestibular stimulation produced a positive-negative biphasic EMG responses on SCM ipsilateral to the cathodal electrode. The latency of p13 was 11.7 ± 3.0 ms. The latency of n23 was 17.8 ± 3.4 ms. The amplitude of p13-n23 was147.0 ± 69.0 μV. The interaural asymmetry ratio(AR) of p13, n23 latency and the amplitude was respectively 0.12 ± 0.09, 0.08 ± 0.08 and0.16 ± 0.10.Discussions: Galvanic vestibular stimulation could elicit biphasic EMG responses from SCM via the vestibular nerve but not from the otolith organs. Galvanic stimulation together with air conducted sound(ACS) or bone conducted vibration(BCV) can elicit VEMPs and may enable the differentiation of retrolabyrinthine lesions from labyrinthine lesions in vestibular system.展开更多
Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-de...Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.展开更多
Autism spectrum disorder(ASD)is typically characterized by common deficits in social skills and repetitive/stereotyped behaviors.It is widely accepted that genetic and environmental factors solely or in combination ca...Autism spectrum disorder(ASD)is typically characterized by common deficits in social skills and repetitive/stereotyped behaviors.It is widely accepted that genetic and environmental factors solely or in combination cause ASD.However,the underlying pathogenic mechanism is unclear due to its highly heterogeneous nature.To better understand the pathogenesis of ASD,various animal models have been generated,which can be generally divided into genetic,environment-induced,and idiopathic animal models.In this review,we summarize the common animals used for ASD study and then discuss the applications,clinical insights,as well as challenges and prospects of current ASD animal models.展开更多
Background Depression,anxiety and schizophrenia among older persons have become global public health challenges.However,the burden of these disorders in ageing and aged countries has not been analysed.Aims To investig...Background Depression,anxiety and schizophrenia among older persons have become global public health challenges.However,the burden of these disorders in ageing and aged countries has not been analysed.Aims To investigate the burden of depression,anxiety and schizophrenia among older adults in ageing and aged countries.Methods Using data from the Global Burden of Disease Study 2019,we calculated the estimated annual percentage change(EAPC)in the age-standardised incidence rates(ASiR)and age-standardised disability-adjusted life years(DALYs)rates(ASDR)for depression,anxiety and schizophrenia of older people in ageing countries(China,India,Indonesia)and aged countries(Japan,Italy,Portugal)between 1990 and 2019.Trends in incidence and DALYs were analysed by gender and age.Results In 2019,the highest incidence of depression,anxiety and schizophrenia in the older population in aged countries was in Japan(927271.3(752552.3-1125796.5),51498.2(37625.7-70487.3)and 126.0(61.0-223.2),respectively),while the highest incidence in ageing countries was in China(5797556.9(4599403.4-7133006.5),330256.1(246448.9-445987.4)and 1067.7(556.2-1775.9),respectively).DALYs for these disorders were similar,with the highest in Japan and China.From 1990 to 2019,the ASIR for depressive disorders decreased in aged countries but increased in ageing countries;the ASIR for anxiety disorders and schizophrenia declined in both ageing and aged countries.The ASDR for depressive disorders was consistent with the ASIR but not for anxiety disorders and schizophrenia.The ASIR for depressive disorders was higher in older women,while the opposite was observed in anxiety disorders and schizophrenia.Notably,the conditions of burden of depressive disorders,anxiety disorders and schizophrenia in the 65-70-year-old age group were the most burdensome.Conclusions The incidence and DALYs of these three mental disorders increased while exhibiting differences between ageing and aged countries.Raising awareness about formulating health policies for preventing and treating mental disorders in the older population is necessary to reduce the future burden posed by the ageing challenge.展开更多
基金supported by grants from the Research and Demonstration Application of Clinical Diagnostic and Treatment Techniques in the Capital(Z211100002921025)Capital’s Funds for Health Improvement and Research(CFH2020-2-2036)。
文摘Introduction With the continuous advancement of surgical technique,combined vascular resection has become increasingly common during complex surgical procedures.In such cases,ensuring the safe and effective reconstruction of blood vessels after resection is of paramount importance.When direct vascular reconstruction is not feasible,the application of vascular grafts becomes necessary to restore vascular continuity and function.Commonly employed vascular grafts in clinical practice include allogeneic graft vessels(AGVs),autologous vessels,and artificial vessels.Among these,AGVs offer distinct advantages particularly in its complex structures and satisfying histocompatibility,making it a valuable option for vascular reconstruction.
基金supported by National Key R&D Program of China(2022YFB3506200,2022YFB3504100)National Natural Science Foundation of China(22072095,22372107,22202058)+3 种基金Excellent Youth Science Foundation of Liaoning Province(2022-YQ-20)Shenyang Science and Technology Planning Project(22-322-3-28)Liaoning Xingliao talented youth Top talent program(XLYC2203007)University Joint Education Project for China-Central and Eastern European Countries(2021097).
文摘The soot emitted during the operation of diesel engine exhaust seriously threatens the human health and environment,so treating diesel engine exhaust is critical.At present,the most effective method for eliminating soot particles is post-treatment technology.Preparation of economically viable and highly active soot combustion catalysts is a pivotal element of post-treatment technology.In this study,different single-metal oxide catalysts with fibrous structures and alkali metal-modified hollow nanotubular Mn-based oxide catalysts were synthesized using centrifugal spinning method.Activity evaluation results showed that the manganese oxide catalyst has the best catalytic activity among the prepared single-metal oxide catalysts.Further research on alkali metal modification showed that doping alkali metals is beneficial for improving the oxidation state of manganese and generating a large number of reactive oxygen species.Combined with the structural effect brought by the hollow nanotube structure,the alkali metal-modified Mn-based oxide catalysts exhibit superior catalytic performance.Among them,the Cs-modified Mn-based oxide catalyst exhibits the best catalytic performance because of its rich active oxygen species,excellent NO oxidation ability,abundant Mn^(4+)ions(M^(n4)+/Mn^(n+)=64.78%),and good redox ability.The T_(10),T_(50),T_(90),and CO_(2)selectivity of the Cs-modified Mn-based oxide catalyst were 267°C,324°C,360°C,and 97.8%,respectively.
文摘To the Editor:Immune checkpoint inhibitors(ICIs)interact with critical factors involved in immunoregulation.Following the FDA approval of nivolumab as a second line therapy for unresectable hepatocellular carcinoma(HCC)in 2017,numerous HCC patients have experienced benefits from ICIs[1].In 2020,the FDA approved the combination of atezolizumab and bevacizumab as first line treatment for unresectable HCCs that have not undergone prior systemic treatments[2].ICIs are driving a transformative change in the field of cancer therapy.
文摘Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and c-MET;therefore,it exhibits both antitumor and anti-angiogenetic activities.A phase III trial has shown that anlotinib improved progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small cell lung cancer(NSCLC),who presented with progressive disease or intolerance after standard chemotherapy.This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods:Data were collected from March 2015 to January 2017 from a randomized,double-blind,placebo-controlled,multicenter,phase III trial of anlotinib(ALTER0303).A total of 437 patients were enrolled and randomly allocated(2:1)to the anlotinib and placebo groups.Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS.Cox proportional hazards model was adopted for multivariate prognostic analysis.Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS.Meanwhile,elevated thyroid-stimulating hormone,blood glucose,and triglyceride levels;hypertension;and hand–foot syndrome were independent protective factors of PFS.High posttherapeutic peripheral blood granulocyte/lymphocyte ratio,an Eastern Cooperative Oncology Group(ECOG)score≥2,and the sum of the maximal target lesion length at baseline were independent risk factors of OS,and hypertriglyceridemia was an independent protective factor of OS.Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC,and the baseline characteristics of the therapeutically dominant populations were then identified.
文摘AIM: To analyze the clinical characteristics of small bowel tumors detected by double-balloon enteroscopy (DBE) and to evaluate the diagnostic value of DBE in tumors. METHODS: Four hundred and forty consecutive DBE examinations were performed in 400 patients (250 males and 150 females, mean age 46.9 ± 16.3 years, range 14-86 years) between January 2007 and April 2012. Of these, 252 patients underwent the antegrade approach, and 188 patients underwent the retrograde approach. All the patients enrolled in our study were suspected of having small bowel diseases with a negative etiological diagnosis following other routine examinations, such as upper and lower gastrointestinal endoscopy and radiography tests. Data on tumors, such as clinical information, endoscopic findings and opera-tion results, were retrospectively collected. RESULTS: Small bowel tumors were diagnosed in 78 patients, of whom 67 were diagnosed using DBE, resulting in a diagnostic yield of 16.8% (67/400); the other 11 patients had negative DBE findings and were diagnosed through surgery or capsule endoscopy. Adenocarcinoma (29.5%, 23/78), gastrointestinal stromal tumor (24.4%, 19/78) and lymphoma (15.4%, 12/78) were the most common tumors. Among the 78 tumors, 60.3% (47/78) were located in the jejunum, and the overall number of malignant tumors was 74.4% (58/78). DBE examinations were frequently performed in patients with obscure gastrointestinal bleeding (47.4%) and abdominal pain (24.4%). The positive detection rate for DBE in the 78 patients with small bowel tumors was 85.9% (67/78), which was higher than that of a computed tomography scan (72.9%, 51/70). Based on the operation results, the accuracy rates of DBE for locating small bowel neoplasms, such as adenocarcinoma, gastrointestinal stromal tumor and lymphoma, were 94.4%, 100% and 100%, respectively. The positive biopsy rates for adenocarcinoma and lymphoma were 71.4% and 60%, respectively. CONCLUSION: DBE is a useful diagnostic tool with high clinical practice value and should be considered the gold standard for the investigation of small bowel tumors.
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 grants from the Demonstrative Research Platform of Clinical Evaluation Technology for New Anticancer Drugs(Grant Nos.18ZX09201-015 and 2017ZX09304015)the Innovation Fund for Medical Sciences of the Chinese Academy of Medical Sciences(Grant No.CIFMS,2016-I2M-1-001)。
文摘Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.
基金The National 13th Five-Year Science and Technology Plan Major Projects of China,No.2017ZX10203205-006-001.
文摘BACKGROUND Sarcomatoid hepatocellular carcinoma(SHC)is a rare subtype of hepatocellular carcinoma(HCC),with a high recurrence rate after surgery.In addition to limited effective treatment for the advanced stage of SHC,the prognosis of patients with this malignancy is worse than that of patients with conventional HCC.CASE SUMMARY We present the case of a 54-year-old man with SHC who underwent radical segmental hepatectomy,which relapsed 4 mo after surgery due to lymphatic metastasis in the porta hepatis.Although a second surgery was performed,new metastasis developed in the mediastinal lymph nodes.Therefore,sorafenib and lenvatinib were sequentially administered as first-and second-line systemic therapies,respectively.However,progressive disease was confirmed based on a recurrent hepatic lesion and new metastatic lesion in the abdominal cavity.Percutaneous transhepatic cholangial drainage was performed to alleviate the biliary obstruction.Because the tumor was strongly positive for programmed death-ligand 1,the patient was started on nivolumab.Imaging studies revealed that after two cycles of immunotherapy,the metastatic lesions decreased to undetectable levels.CONCLUSION The patient experienced continuous complete remission for 8 mo.Immune checkpoint inhibitors are useful for the treatment of advanced SHC.
基金supported by Research Start-up Funding of Shenzhen Traditional Chinese Medicine Hospital,No.2021-07(to FB)Sanming Project of Medicine in Shenzhen,No.SZZYSM 202111011(to XDQ and FB)+1 种基金Key Discipline Established by Zhejiang Province,Jiaxing City Jointly-Pain Medicine,No.2019-ss-ttyx(to LSX)Jiaxing Key Laboratory of Neurology and Pain Medicine,No.[2014]81(to LSX)。
文摘Ischemic stroke can cause blood-brain barrier(BBB)injury,which worsens brain damage induced by stroke.Abnormal expression of tight junction proteins in endothelial cells(ECs)can increase intracellular space and BBB leakage.Selective inhibition of mitogen-activated protein kinase,the negative regulatory substrate of mitogen-activated protein kinase phosphatase(MKP)-1,improves tight junction protein function in ECs,and genetic deletion of MKP-1 aggravates ischemic brain injury.However,whether the latter affects BBB integrity,and the cell type-specific mechanism underlying this process,remain unclear.In this study,we established an adult male mouse model of ischemic stroke by occluding the middle cerebral artery for 60 minutes and overexpressed MKP-1 in ECs on the injured side via lentiviral transfection before stroke.We found that overexpression of MKP-1 in ECs reduced infarct volume,reduced the level of inflammatory factors interleukin-1β,interleukin-6,and chemokine C-C motif ligand-2,inhibited vascular injury,and promoted the recovery of sensorimotor and memory/cognitive function.Overexpression of MKP-1 in ECs also inhibited the activation of cerebral ischemia-induced extracellular signal-regulated kinase(ERK)1/2 and the downregulation of occludin expression.Finally,to investigate the mechanism by which MKP-1 exerted these functions in ECs,we established an ischemic stroke model in vitro by depriving the primary endothelial cell of oxygen and glucose,and pharmacologically inhibited the activity of MKP-1 and ERK1/2.Our findings suggest that MKP-1 inhibition aggravates oxygen and glucose deprivation-induced cell death,cell monolayer leakage,and downregulation of occludin expression,and that inhibiting ERK1/2 can reverse these effects.In addition,co-inhibition of MKP-1 and ERK1/2 exhibited similar effects to inhibition of ERK1/2.These findings suggest that overexpression of MKP-1 in ECs can prevent ischemia-induced occludin downregulation and cell death via deactivating ERK1/2,thereby protecting the integrity of BBB,alleviating brain injury,and improving post-stroke prognosis.
基金supported by grants from the National Key R&D Program of China(Grant No.2019YFA0508502)the CAMS Innovation Fund for Medical Sciences(Grant No.2019-I2M-5-073)the National Natural Science Foundation of China(Grant Nos.81788101,81972679,and 81821001)。
文摘Objective:Natural killer(NK)cells have gained considerable attention due to their potential in treating"cold tumors,"and are therefore considered as one of the new strategies for curing cancer,by using worldwide development of their new possibilities and interventions with NK cell-related therapeutic products.Methods:We constructed a trispecific killer engager(TriKE)consisting of anti-CD16,IL-15,and anti-CD19.This TriKE was designed to attract CD19^(+)tumor cells to CD16^(+)NK cells,whereas IL-15 sustained the proliferation,development,and survival of NK cells.Results:Treatment with 161519 TriKE in the presence of CD19^(+)targets upregulated expression of CD69,CD107 a,TRAIL,IFN-γ,and TNF-α in NK cells,and significantly improved the proliferation and cytotoxicity of NK cells.NK cells"armed"with 161519 TriKE showed stronger cytolysis against CD19+targets compared with that of"unarmed"NK cells.A preclinical model of B-cell lymphoma in human peripheral blood mononuclear cell-reconstituted xenograft mice showed significant inhibition of tumor growth and prolonged overall survival after treatment with 161519 TriKE,when compared with that in control mice or mice treated with 1619 BiKE.Combined use of IL-2 was a more effective treatment with 1619 BiKE,when compared with that using 161519 TriKE.Conclusions:The newly generated 161519 TriKE enhanced the proliferation,activation,cytokine secretion,and cytotoxicity of NK cells in the presence of CD19+tumor cells.The 161519 TriKE aided inhibition of tumor growth and prolonged the overall survival of murine xenografts,and could be used to treat CD19-positive cancers.
基金supported by Japan China Sasakawa Medical Fellowship 2016(YL)
文摘Objectives: The aim of our study is to examine vestibular-evoked myogenic potentials(VEMPs) elicited by the galvanic vestibular stimulation in the sternocleidomastoid muscle(SCM) in healthy subjects for clinical applications of auditory neuropathy or vestibular neuropathy in the future.Methods: We enrolled sixteen healthy subjects to record the average responses of SCM to galvanic vestibular stimulation(GVS) [current 3 mA;duration 1 ms] by electromyography(EMG). SPSS 18.0 software was used to analyze the obtained data for mean and standard deviation.Results: In all healthy subjects mastoid-forehead galvanic vestibular stimulation produced a positive-negative biphasic EMG responses on SCM ipsilateral to the cathodal electrode. The latency of p13 was 11.7 ± 3.0 ms. The latency of n23 was 17.8 ± 3.4 ms. The amplitude of p13-n23 was147.0 ± 69.0 μV. The interaural asymmetry ratio(AR) of p13, n23 latency and the amplitude was respectively 0.12 ± 0.09, 0.08 ± 0.08 and0.16 ± 0.10.Discussions: Galvanic vestibular stimulation could elicit biphasic EMG responses from SCM via the vestibular nerve but not from the otolith organs. Galvanic stimulation together with air conducted sound(ACS) or bone conducted vibration(BCV) can elicit VEMPs and may enable the differentiation of retrolabyrinthine lesions from labyrinthine lesions in vestibular system.
基金sponsored by BeiGene.Third-party medical writing assistance was provided by Ghina Yaacoub,MSc,of Ashfield MedComms,an Inizio Company,and funded by BeiGene.
文摘Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.
基金This work was supported by the National Natural Science Foundation of China(82071540)and Yunnan University(CZ21623201)。
文摘Autism spectrum disorder(ASD)is typically characterized by common deficits in social skills and repetitive/stereotyped behaviors.It is widely accepted that genetic and environmental factors solely or in combination cause ASD.However,the underlying pathogenic mechanism is unclear due to its highly heterogeneous nature.To better understand the pathogenesis of ASD,various animal models have been generated,which can be generally divided into genetic,environment-induced,and idiopathic animal models.In this review,we summarize the common animals used for ASD study and then discuss the applications,clinical insights,as well as challenges and prospects of current ASD animal models.
基金Shanghai'Science and Technology Innovation Action Plan'medical innovation research(21Y11905600)Shanghai'Science and Technology Innovation Action Plan'Natural Science Foundation of Shanghai(21ZR1455100)+1 种基金the National Natural Science Foundation of China(81701344)the Shanghai Mental Health Center General Projects(2021-YJ-02).
文摘Background Depression,anxiety and schizophrenia among older persons have become global public health challenges.However,the burden of these disorders in ageing and aged countries has not been analysed.Aims To investigate the burden of depression,anxiety and schizophrenia among older adults in ageing and aged countries.Methods Using data from the Global Burden of Disease Study 2019,we calculated the estimated annual percentage change(EAPC)in the age-standardised incidence rates(ASiR)and age-standardised disability-adjusted life years(DALYs)rates(ASDR)for depression,anxiety and schizophrenia of older people in ageing countries(China,India,Indonesia)and aged countries(Japan,Italy,Portugal)between 1990 and 2019.Trends in incidence and DALYs were analysed by gender and age.Results In 2019,the highest incidence of depression,anxiety and schizophrenia in the older population in aged countries was in Japan(927271.3(752552.3-1125796.5),51498.2(37625.7-70487.3)and 126.0(61.0-223.2),respectively),while the highest incidence in ageing countries was in China(5797556.9(4599403.4-7133006.5),330256.1(246448.9-445987.4)and 1067.7(556.2-1775.9),respectively).DALYs for these disorders were similar,with the highest in Japan and China.From 1990 to 2019,the ASIR for depressive disorders decreased in aged countries but increased in ageing countries;the ASIR for anxiety disorders and schizophrenia declined in both ageing and aged countries.The ASDR for depressive disorders was consistent with the ASIR but not for anxiety disorders and schizophrenia.The ASIR for depressive disorders was higher in older women,while the opposite was observed in anxiety disorders and schizophrenia.Notably,the conditions of burden of depressive disorders,anxiety disorders and schizophrenia in the 65-70-year-old age group were the most burdensome.Conclusions The incidence and DALYs of these three mental disorders increased while exhibiting differences between ageing and aged countries.Raising awareness about formulating health policies for preventing and treating mental disorders in the older population is necessary to reduce the future burden posed by the ageing challenge.
