BACKGROUND Splenectomy is an effective yet invasive intervention for alleviating portal pressure in patients with hepatitis cirrhosis.However,the current prognostic indicators for predicting long-term overall survival...BACKGROUND Splenectomy is an effective yet invasive intervention for alleviating portal pressure in patients with hepatitis cirrhosis.However,the current prognostic indicators for predicting long-term overall survival of these patients have several limitations.AIM To assess the potential of preoperative total bilirubin-albumin(B/A)ratio as a prognostic indicator for patients with hepatitis cirrhosis undergoing splenectomy.METHODS A total of 257 patients diagnosed with hepatitis cirrhosis were retrospectively enrolled in the study.Normality test,t-test,Wilcoxon test,χ2 test,or Fisher’s exact test was employed to analyze the intraoperative and postoperative conditions of the patients.Receiver operating characteristic(ROC)curve analysis was utilized to depict the 10-year overall survival rate.RESULTS During the follow-up period,85.99%of the patients survived,with a median survival time of 64.6 months.Multivariate analysis revealed that total serum B/A ratio was an independent risk factor for overall survival(P=0.037).ROC curve analysis demonstrated that a B/A ratio of 0.87 was the optimal cut-off value.Consequently,the patients were categorized into two groups:High B/A group(n=64)and low B/A group(n=193).The median follow-up time for the high B/A group and low B/A group was 56.8 months and 67.2 months,respectively(P=0.045).Notably,the high B/A group exhibited a significantly lower 10-year overall survival compared to the low B/A group(P<0.001).Patients with hepatocellular carcinoma(HCC)had lower overall survival rates.Patients with a high B/A ratio exhibited a lower overall survival than those with a low B/A rate in the overall cohort and the subgroups of patients with HCC or not,early Child-Pugh grade,low albumin-bilirubin grade,and model for end-stage liver disease score≥10(log-rank test,P<0.001 for all).CONCLUSION The B/A ratio can serve as an effective prognostic indicator for overall survival in patients with hepatitis B virusrelated cirrhosis following splenectomy,and a higher B/A ratio may suggest a poorer prognosis.展开更多
BACKGROUND Gastric cancer(GC)is a prevalent malignancy with a substantial health burden and high mortality rate,despite advances in prevention,early detection,and treatment.Compared with the global average,Asia,notabl...BACKGROUND Gastric cancer(GC)is a prevalent malignancy with a substantial health burden and high mortality rate,despite advances in prevention,early detection,and treatment.Compared with the global average,Asia,notably China,reports disproportionately high GC incidences.The disease often progresses asymptoma-tically in the early stages,leading to delayed diagnosis and compromised out-comes.Thus,it is crucial to identify early diagnostic biomarkers and enhance treatment strategies to improve patient outcomes and reduce mortality.METHODS Retrospectively analyzed the clinical data of 148 patients with GC treated at the Civil Aviation Shanghai Hospital between December 2022 and December 2023.The associations of coagulation indices-partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen,fibrinogen degradation products(FDP),fasting blood glucose,and D-dimer(D-D)with TNM stage and distant metastasis were examined.RESULTS Prolongation of APTT,PT,and TT was significantly correlated with the GC TNM stage.Hence,abnormal coagulation system activation was closely related to disease progression.Elevated FDP and D-D were significantly associated with distant metastasis in GC(P<0.05),suggesting that increased fibrinolytic activity contributes to increased metastatic risk.CONCLUSION Our Results reveal coagulation indices,FDPs as GC biomarkers,reflecting abnormal coagulation/fibrinolysis,aiding disease progression,metastasis prediction,and helping clinicians assess thrombotic risk for early intervention and personalized treatment plans.展开更多
The aim of this study was to investigate whether the sperm chromatin structure assay (SCSA) results after swim-up are related to fertilization rates, embryo quality and pregnancy rates following in vitrofertilizati...The aim of this study was to investigate whether the sperm chromatin structure assay (SCSA) results after swim-up are related to fertilization rates, embryo quality and pregnancy rates following in vitrofertilization (IVF). A total of 223 couples undergoing IVF in our hospital from October 2008 to September 2009 were included in this study. Data on the IVF process and sperm chromatin structure assay results were collected. Fertilization rate, embryo quality and IVF success rates of different DNA fragmentation index (DFI) subgroups and high DNA stainability (HDS) subgroups were compared. There were no significant differences in fertilization rate, clinical pregnancy or delivery rates between the DFI and HDS subgroups. However, the group with abnormal DFI had a lower good embryo rate. So, we concluded that the SCSA variables, either DFI or HDS after swim-up preparation, were not valuable in predicting fertilization failure or pregnancy rate, but an abnormal DFI meant a lower good embryo rate following IVF.展开更多
Traditional Chinese Medicine (TCM) has been widely and successfully used in treating illnesses ranging from inflammation to cancer, and compounds from medicinal herbs and minerals are playing more and more important...Traditional Chinese Medicine (TCM) has been widely and successfully used in treating illnesses ranging from inflammation to cancer, and compounds from medicinal herbs and minerals are playing more and more important roles in taming various kinds of diseases [1 ], exemplified by artemisinin and arsenic trioxide (ATO). Artemisinin (or Qinghaosu in Chinese) is isolated from a plant called sweet wormwood (Artemisia annua; or Qinghao in Chi- nese) which has been used as an antipyretic remedy for more than 1500 years in China. Artemisinin has impressive parasiticidal properties in vitro and in vivo, and is now one of the most important class of antimalarial agents [2, 3]. ATO is a common, naturally occurring substance which had been used in China for a long time as a therapeutic agent for some severe diseases with the ancient philosophy of 'treating an evil with a toxic' [4]. In 1990s, ATO was shown to be able to cause partial differentiation at low dose and apoptosis at high concentration of acute promyelocytic leukemia (APL) cells [5], and induce complete remission in 90% of patients with relapsed or refractory APL [6-8]. These paradigms suggest that TCM is the treasure house not only for the Chinese people, but also for the whole human beings. It is our responsibility to develop evidence-based therapeutic approaches from TCM for diseases with poor prognosis.展开更多
Following a spinal cord injury,there are usually a number of neural pathways that remain intact in the spinal cord.These residual nerve fibers are important,as they could be used to reconstruct the neural circuits tha...Following a spinal cord injury,there are usually a number of neural pathways that remain intact in the spinal cord.These residual nerve fibers are important,as they could be used to reconstruct the neural circuits that enable motor function.Our group previously designed a novel magnetic stimulation protocol,targeting the motor cortex and the spinal nerve roots,that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury.Here,we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury.Rats underwent surgery to clamp the spinal cord at T10;three days later,the rats were treated with repetitive magnetic stimulation(5 Hz,25 pulses/train,20 pulse trains)targeting the nerve roots at the L5-L6 vertebrae.The treatment was repeated five times a week over a period of three weeks.We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord.In addition,the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex.Overall,the results suggest that nerve root magnetic stimulation may be an effective,noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.展开更多
AIM:To evaluate the changes in fundus parameters in patients with Alzheimer’s type dementia(ATD)using optical coherence tomography angiography(OCTA),to record flash electroretinograms(ERG)using the RETeval system and...AIM:To evaluate the changes in fundus parameters in patients with Alzheimer’s type dementia(ATD)using optical coherence tomography angiography(OCTA),to record flash electroretinograms(ERG)using the RETeval system and to explore changes in retinal function.METHODS:Twenty-nine patients with ATD and 26 age-matched normal subjects were enrolled.All subjects underwent OCTA scans to analyse the superficial retinal vessel parameters in the macular area,including the vessel length density,the vessel perfusion density and the area of foveal avascular zone(FAZ),as well as the choroidal thickness.The differences between the patients with ATD and the normal control group were compared and explored the relevant factors affecting vessel parameters.We also recorded the flash ERGs using the RETeval system and intended to explore changes in retinal function by analysing the ERG image amplitude in patients with ATD.RESULTS:The vessel parameters[Pvessel length density=0.005 and Pvessel perfusion density=0.006]and average choroid thickness(P<0.001)in the macular area of the ATD group was less than the control group.The FAZ area was statistically significantly enlarged in the ATD group(P<0.001).These parameters were correlated with the Mini-Mental State Examination(MMSE)score and the Montreal Cognitive Assessment(MoCA).CONCLUSION:Patients with ATD exhibit decreases in the parameters associated with fundus.In addition,these indicators significantly correlate with the MMSE score and the MoCA score.OCTA may be an adjunct tool with strong potential to track changes in the diagnosis and monitoring the progression of the disease.展开更多
Objective To investigate the possible involvement of erythropoietin (EPO)/erythropoietin receptor (EPOR) system in neovascularization and vascular regeneration in diabetic retinopathy (DR). Methods EPOR positive...Objective To investigate the possible involvement of erythropoietin (EPO)/erythropoietin receptor (EPOR) system in neovascularization and vascular regeneration in diabetic retinopathy (DR). Methods EPOR positive circulating progenitor cells (CPCs: CD34^+) and endothelial progenitor cells (EPCs: CD34^+KDR^+) were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes (n=7), non-prolif- erative DR (NPDR, n=7), proliferative DR (PDR, n=8), and PDR complicated with diabetic nephropathy (PDR-DN, n=7). Results The numbers of EPOR^+ CPCs and EPOR^+ EPCs were reduced remarkably in NPDR corn pared with the control group (both P(0.01), whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR^+ CPCs in CPCs (NPDR vs. control, P(0.01) and that of EPOR^+ EPCs in EPCs (NPDR vs. control, P〈0.05). Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the impaired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR^+ EPCs associated with ischemia.展开更多
BACKGROUND Interleukin 10 receptor alpha subunit(IL10RA)dysfunction is the main cause of very early-onset inflammatory bowel disease(VEO-IBD)in East Asians.AIM To identify disease-causing gene mutations in four patien...BACKGROUND Interleukin 10 receptor alpha subunit(IL10RA)dysfunction is the main cause of very early-onset inflammatory bowel disease(VEO-IBD)in East Asians.AIM To identify disease-causing gene mutations in four patients with VEO-IBD and verify functional changes related to the disease-causing mutations.METHODS From May 2016 to September 2020,four young patients with clinically diagnosed VEO-IBD were recruited.Before hospitalization,using targeted gene panel sequencing and trio-whole-exome sequencing(WES),three patients were found to harbor a IL10RA mutation(c.301C>T,p.R101W in one patient;c.537G>A,p.T179T in two patients),but WES results of the fourth patient were not conclusive.We performed whole-genome sequencing(WGS)on patients A and B and reanalyzed the data from patients C and D.Peripheral blood mononuclear cells(PBMCs)from patient D were isolated and stimulated with lipopolysaccharide(LPS),interleukin 10(IL-10),and LPS+IL-10.Serum IL-10 levels in four patients and tumor necrosis factor-α(TNF-α)in the cell supernatant were determined by enzyme-linked immunosorbent assay.Phosphorylation of signal transducer and activator of transcription 3(STAT3)at Tyr705 and Ser727 in PBMCs was determined by western blot analysis.RESULTS The four children in our study consisted of two males and two females.The age at disease onset ranged from 18 d to 9 mo.After hospitalization,a novel 333-bp deletion encompassing exon 1 of IL10RA was found in patients A and B using WGS and was found in patients C and D after reanalysis of their WES data.Patient D was homozygous for the 333 bp deletion.All four patients had elevated serum IL-10 levels.In vitro,IL-10-stimulated PBMCs from patient D failed to induce STAT3 phosphorylation at Tyr705 and only minimally suppressed TNF-αproduction induced by LPS.Phosphorylation at Ser727 in PBMCs was not affected by LPS or LPS+IL-10 in both healthy subjects and in patient D.CONCLUSION WGS revealed a novel 333-bp deletion of IL10RA in four patients with VEO-IBD,whereas the WES results were inconclusive.展开更多
China’s population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated,especially Alzheimer’s disease(AD)and related dementias(ADRD).AD’s inc...China’s population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated,especially Alzheimer’s disease(AD)and related dementias(ADRD).AD’s incidence rate,morbidity,and mortality have steadily increased to make it presently the fifth leading cause of death among urban and rural residents in China and magnify the resulting financial burdens on individuals,families and society.The‘Healthy China Action’plan of 2019-2030 promotes the transition from disease treatment to health maintenance for this expanding population with ADRD.This report describes related epidemiological trends,evaluates the economic burden of the disease,outlines current clinical diagnosis and treatment status and delineates existing available public health resources.More specifically,it examines the public health impact of ADRD,including prevalence,mortality,costs,usage of care,and the overall effect on caregivers and society.In addition,this special report presents technical guidance and supports for the prevention and treatment of AD,provides expertise to guide relevant governmental healthcare policy development and suggests an information platform for international exchange and cooperation.展开更多
Objectives:Our study aimed to investigate the prevalence of cognitive impairment(CI)and the associated risk factors among elderly people in Shanghai urban area,China.Methods:A population-based survey was conducted amo...Objectives:Our study aimed to investigate the prevalence of cognitive impairment(CI)and the associated risk factors among elderly people in Shanghai urban area,China.Methods:A population-based survey was conducted among people aged 55 years or older in urban areas of Shanghai.Face-to-face interviews were carried out to collect information including demographic characteristics,medical history,and medication use,etc.The validated Chinese version of the Mini-Mental State Examination(MMSE)was used to screen subjects with CI,and the criteria of CI were adjusted for education levels.Results:A total of 3,176 home-living residents(≥55 years old)were included in the study.Among them,266 people(102 men and 164 women)were identified as cognition impaired,with a prevalence of 8.38%(266/3,176,95%CI:(8.26,8.49))for both genders,9.21%(102/1,107,95%CI:(9.18,9.33))for men and 7.93%(164/2,069,95%CI:(7.80,8.09))for women,respectively.Furthermore,we found that several significant risk factors,including social factors(education,number of children,marriage status,and family structure),physiological factors(age,blood glucose level,and obesity),factors on living styles(physical exercise,diet&chronic diseases),and genetic factor(ApoE),associated with CI onset.Conclusions:This study confirms the high prevalence of CI among the elderly population in the Shanghai urban in China,similar to previous epidemiologic studies in Western countries.The putative risk factors associated with CI merit further investigated.展开更多
BACKGROUND: As a cytokine highly expressed in internal organs, visfatin could be used as a biomarker of systemic inflammation response for chronic obstructive pulmonary diseases, but few studies have reported the use...BACKGROUND: As a cytokine highly expressed in internal organs, visfatin could be used as a biomarker of systemic inflammation response for chronic obstructive pulmonary diseases, but few studies have reported the use of visfatin in severe pneumonia. The present study was undertaken to determine the plasma levels of visfatin in patients with severe pneumonia. METHODS:A total of 70 patients, including 40 patients with severe pneumonia (group A) and 30 patients with non severe pneumonia (group B) who had been admitted to the ICU from June 2009 to June 2010, were enrolled in this prospective study. And another 30 healthy physical examinees served as healthy controls (group C). Patients were excluded if they suffered from severe diseases of the heart, brain and kidney, cancers, autoimmune diseases, or received special treatment in the latest month. The plasma levels of visfatin, IL-6, IL-8 and TNF-α were measured by ELISA, while the level of CRP was determined by immuneturbidimetry, and the routine blood test was performed. Blood gas analysis and Acute Physiology and Chronic Health Evaluation II (APACHE II) were performed in patients with pneumonia. Comparisons between the groups were conducted by Student's t test, ANOVA or nonparametric test. Correlation analysis was carried out by Pearson's correlation test or Spearman's rank-order correlation test. RESULTS:The plasma level of visfatin in group A was significantly higher than that in groups B and C (P〈0.001), and the level of visfatin in group B was significantly higher than that in group C (P〈0.001). The plasma level of visfatin was positively correlated with CRP, TNF-α, APACHE II and PMN% in patients with severe pneumonia (rho=0.653, r=0.554, r=0.558, r=0.484, respectively, P〈0.05 for all), while it was negatively correlated with PaO2 and PaO2/FiO2 (rho=-0.422, r=-0.543, respectively, P〈0.05 for all). CONCLUSION:Visfatin may be involved in the systematic inflammation response in patients with severe pneumonia as a pro-inflammatory cytokine, and it is valuable in assessing the severity of pneumonia..展开更多
This study is designed to serve as a reference for the establishment of health security systems for children's critical diseases. Through analysis of the operation of Shanghai Children Hospital Care Aid (SCHCA), th...This study is designed to serve as a reference for the establishment of health security systems for children's critical diseases. Through analysis of the operation of Shanghai Children Hospital Care Aid (SCHCA), this study explored the financing model and management of a children's critical disease healthcare system and analyzed the possibility of expanding this system to other areas. It is found that a premium as Iow as RMB 7 per capita per year under SCHCA can provide high-level security for children's critical diseases. With the good experience in Shanghai and based on the current basic medical insurance system for urban residents and the new rural cooperative medical scheme (NRCMS), it is necessary and feasible to build a health security system for children's critical diseases at the national level.展开更多
Purpose: The present study aimed to assess the accuracies of arterial stimulation with simultaneous venous sampling(ASVS) in preoperative localization of insulinomas. Materials and Methods: A cohort consisting of 6 ma...Purpose: The present study aimed to assess the accuracies of arterial stimulation with simultaneous venous sampling(ASVS) in preoperative localization of insulinomas. Materials and Methods: A cohort consisting of 6 males and 14 females(median age, 48.5y; range, 28–62y) with pathologically proven insulinomas were included in this study. Selective angiographies were performed with the superior mesenteric artery(SMA), gastroduodenal artery(GDA), proximal splenic artery, and midsplenic artery in all individuals. Then ASVS procedures were followed after angiographies for these arteries. Clinical characteristics of the patient and the tumor number, location, and size were recorded. The accuracy of preoperative localization of insulinomas was tested. Results: A total of 22 tumors were identified by histopathological diagnosis. The mean size of the tumor was 1.40±0.60 cm. Five tumors were in the head/neck region and 17 in the body/tail region. ASVS accurately localized 17/20(85%) cases with only biochemical data and 19/20(95%) cases with biochemical data and angiography images. Variant pancreatic arterial anatomy was revealed in 2 false cases with inferior pancreatic artery replaced by the superior mesenteric artery. Conclusion: ASVS was highly accurate in localizing insulinomas and should be performed in most of the patients with suspected insulinomas before the operation.展开更多
Introduction Omicron is more contagious and stealthier than the previous strains.The basic reproduction number of Omicron is around 8–12,whereas that of the previous mainstream strain Delta is only 5–8[1].Omicron’s...Introduction Omicron is more contagious and stealthier than the previous strains.The basic reproduction number of Omicron is around 8–12,whereas that of the previous mainstream strain Delta is only 5–8[1].Omicron’s symptoms are relatively mild[2]compared with Delta’s symptoms;however,Omicron’s transmission ability is very strong,and its risk to children and the elderly remains high[3].In addition,the vaccine’s preventive effect on Omicron has weakened.Therefore,Omicron can easily cause a rapid outbreak in a city.The population density of megacities and the limited public health resources further exacerbate the difficulty of Omicron prevention and control.展开更多
Identified as the pathogenic genes of Alzheimer's disease(AD),APP,PSEN1,and PSEN2 mainly lead to early-onset AD,whose course is more aggressive,and atypical symptoms are more common than sporadic AD.Here,a novel m...Identified as the pathogenic genes of Alzheimer's disease(AD),APP,PSEN1,and PSEN2 mainly lead to early-onset AD,whose course is more aggressive,and atypical symptoms are more common than sporadic AD.Here,a novel missense mutation,APP E674Q(also named“Shanghai APP”),was detected in a Chinese index patient with typical late-onset AD(LOAD)who developed memory decline in his mid-70s.The results from neuroimaging were consistent with AD,where widespread amyloidβdeposition was demonstrated in 18 F-florbetapir Positron Emission Tomography(PET).APP E674Q is close to theβ-secretase cleavage site and the well-studied Swedish APP mutation(KM670/671NL),which was predicted to be pathogenic in silico.Molecular dynamics simulation indicated that the E674Q mutation resulted in a rearrangement of the interaction mode between APP and BACE1 and that the E674Q mutation was more prone to cleavage by BACE1.The in vitro results suggested that the E674Q mutation was pathogenic by facilitating the BACE1-mediated processing of APP and the production of Aβ.Furthermore,we applied an adeno-associated virus(AAV)-mediated transfer of the human E674Q mutant APP gene to the hippocampi of two-month-old C57Bl/6 J mice.AAV-E674Q-injected mice exhibited impaired learning behavior and increased pathological burden in the brain,implying that the E674Q mutation had a pathogenicity that bore a comparison with the classical Swedish mutation.Collectively,we report a strong amyloidogenic effect of the E674Q substitution in AD.To our knowledge,E674Q is the only pathogenic mutation within the amyloid processing sequence causing LOAD.展开更多
Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity,safeguarding receptor activation,and facilitating amplification of signal transduction across th...Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity,safeguarding receptor activation,and facilitating amplification of signal transduction across the cellular membrane.However,cell-surface antigeninduced multimerization(dubbed AIM herein)has not yet been consciously leveraged in chimeric antigen receptor(CAR)engineering for enriching T cell-based therapies.We co-developed ciltacabtagene autoleucel(cilta-cel),whose CAR incorporates two B-cell maturation antigen(BCMA)-targeted nanobodies in tandem,for treating multiple myeloma.Here we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated cytotoxicity.Crystallographic analysis of BCMA–nanobody complexes revealed atomic details of antigen–antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in solution.BCMA-induced nanobody CAR multimerization enhanced cytotoxicity,alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release,towards myeloma-derived cells.Our results provide a framework for contemplating the AIM approach in designing next-generation CARs.展开更多
In the era of personalized oncology,there have been accelerated efforts to develop clinically relevant platforms to test drug sensitivities of individual cancers.An ideal assay will serve as a diagnostic companion to ...In the era of personalized oncology,there have been accelerated efforts to develop clinically relevant platforms to test drug sensitivities of individual cancers.An ideal assay will serve as a diagnostic companion to inform the oncologist of the various treatments that are sensitive and insensitive,thus improving outcome while minimizing unnecessary toxicities and costs.To date,no such platform exists for clinical use,but promising approaches are on the horizon that take advantage of improved techniques in creating human cancer models that encompass the entire tumor microenvironment,alongside technologies for assessing and analyzing tumor response.This review summarizes a number of current strategies that make use of intact human cancer tissues as organotypic cultures in drug sensitivity testing.展开更多
Objective The aim of the study was to evaluate the clinical efficacy of decitabine(DEC)combined with ruxolitinib(RUX)in the treatment of chronic myelomonocytic leukemia(CMML).Methods The clinical characteristics of 12...Objective The aim of the study was to evaluate the clinical efficacy of decitabine(DEC)combined with ruxolitinib(RUX)in the treatment of chronic myelomonocytic leukemia(CMML).Methods The clinical characteristics of 12 patients with CMML were analyzed retrospectively and subsequent target sequencing was performed to investigate the efficacy of the combined treatment with DEC and RUX and the molecular signatures therein.Results Among the 12 cases,clinical improvement was observed in all patients(100%),spleen reduction was observed in six patients(67%),and hematologic improvement was observed in four patients(33%).In the CMML-1 group,the overall response was 50%(3/6),one case achieved complete response,one achieved bone marrow remission,and one achieved hematological improvement.In the CMML-2 group,the overall response was 17%(1/6),one case achieved complete response,four showed disease progression(PD),and one exhibited no response.As expected,ASXL1 mutation was predictive for the outcome of CMML(hazard ratio of 2.97,95%confidence interval of 1.21–7.06;P=0.02).Conclusion The use of DEC combined with RUX in the treatment of CMML effectively improved the clinical response and quality of life,especially for CMML-1 patients.Ongoing clinical trials will further evaluate the safety and efficacy of this novel therapeutic approach.展开更多
Corona virus disease 2019(COVID-19)due to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has affected the whole world.Acquired thrombotic thrombocytopenic purpura(TTP)has been reported after admi...Corona virus disease 2019(COVID-19)due to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has affected the whole world.Acquired thrombotic thrombocytopenic purpura(TTP)has been reported after administration of mRNA-or adenoviral vector-based COVID-19 vaccines,including Ad26.COV2-S,BNT162b2,mRNA-1273,and ChAdOx1 nCov-19.However,whether inactivated vaccines,such as CoronaVac,could cause TTP and whether the symptoms in TTPs caused by inactivated vaccines are different from previously reported cases are unknown.In this study,two cases were reported.Both cases developed TTP after the second CoronaVac vaccination shot,but not the first.They demonstrated symptoms of fever,neurological abnormalities,renal dysfunction,thrombocytopenia,and hemolysis.Both patients achieved complete remission through several sessions of plasma exchanges and immune suppression.The incidence of TTP in Nanjing area was analyzed.The number of patients with TTP was 12 in 2019,6 in 2020,16 in 2021,and 19 in 2022.To the authors’knowledge,this report is the first report of TTP associated with inactivated COVID-19 vaccine(CoronaVac).The rarity and delayed onset may be due to the relatively milder immune response caused by the inactivated vaccines than mRNA-based ones.Timely plasma exchange is a vital treatment for CoronaVac-related TTP,similar to activated vaccine-related TTP.展开更多
文摘BACKGROUND Splenectomy is an effective yet invasive intervention for alleviating portal pressure in patients with hepatitis cirrhosis.However,the current prognostic indicators for predicting long-term overall survival of these patients have several limitations.AIM To assess the potential of preoperative total bilirubin-albumin(B/A)ratio as a prognostic indicator for patients with hepatitis cirrhosis undergoing splenectomy.METHODS A total of 257 patients diagnosed with hepatitis cirrhosis were retrospectively enrolled in the study.Normality test,t-test,Wilcoxon test,χ2 test,or Fisher’s exact test was employed to analyze the intraoperative and postoperative conditions of the patients.Receiver operating characteristic(ROC)curve analysis was utilized to depict the 10-year overall survival rate.RESULTS During the follow-up period,85.99%of the patients survived,with a median survival time of 64.6 months.Multivariate analysis revealed that total serum B/A ratio was an independent risk factor for overall survival(P=0.037).ROC curve analysis demonstrated that a B/A ratio of 0.87 was the optimal cut-off value.Consequently,the patients were categorized into two groups:High B/A group(n=64)and low B/A group(n=193).The median follow-up time for the high B/A group and low B/A group was 56.8 months and 67.2 months,respectively(P=0.045).Notably,the high B/A group exhibited a significantly lower 10-year overall survival compared to the low B/A group(P<0.001).Patients with hepatocellular carcinoma(HCC)had lower overall survival rates.Patients with a high B/A ratio exhibited a lower overall survival than those with a low B/A rate in the overall cohort and the subgroups of patients with HCC or not,early Child-Pugh grade,low albumin-bilirubin grade,and model for end-stage liver disease score≥10(log-rank test,P<0.001 for all).CONCLUSION The B/A ratio can serve as an effective prognostic indicator for overall survival in patients with hepatitis B virusrelated cirrhosis following splenectomy,and a higher B/A ratio may suggest a poorer prognosis.
文摘BACKGROUND Gastric cancer(GC)is a prevalent malignancy with a substantial health burden and high mortality rate,despite advances in prevention,early detection,and treatment.Compared with the global average,Asia,notably China,reports disproportionately high GC incidences.The disease often progresses asymptoma-tically in the early stages,leading to delayed diagnosis and compromised out-comes.Thus,it is crucial to identify early diagnostic biomarkers and enhance treatment strategies to improve patient outcomes and reduce mortality.METHODS Retrospectively analyzed the clinical data of 148 patients with GC treated at the Civil Aviation Shanghai Hospital between December 2022 and December 2023.The associations of coagulation indices-partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen,fibrinogen degradation products(FDP),fasting blood glucose,and D-dimer(D-D)with TNM stage and distant metastasis were examined.RESULTS Prolongation of APTT,PT,and TT was significantly correlated with the GC TNM stage.Hence,abnormal coagulation system activation was closely related to disease progression.Elevated FDP and D-D were significantly associated with distant metastasis in GC(P<0.05),suggesting that increased fibrinolytic activity contributes to increased metastatic risk.CONCLUSION Our Results reveal coagulation indices,FDPs as GC biomarkers,reflecting abnormal coagulation/fibrinolysis,aiding disease progression,metastasis prediction,and helping clinicians assess thrombotic risk for early intervention and personalized treatment plans.
基金ACKNOWLEDGMENTS This study was supported by grants from the Natural Science Foundation of Shanghai (No. 10JC1410800). The support of Jian-Bin Liu in collecting the patient data is gratefully acknowledged.
文摘The aim of this study was to investigate whether the sperm chromatin structure assay (SCSA) results after swim-up are related to fertilization rates, embryo quality and pregnancy rates following in vitrofertilization (IVF). A total of 223 couples undergoing IVF in our hospital from October 2008 to September 2009 were included in this study. Data on the IVF process and sperm chromatin structure assay results were collected. Fertilization rate, embryo quality and IVF success rates of different DNA fragmentation index (DFI) subgroups and high DNA stainability (HDS) subgroups were compared. There were no significant differences in fertilization rate, clinical pregnancy or delivery rates between the DFI and HDS subgroups. However, the group with abnormal DFI had a lower good embryo rate. So, we concluded that the SCSA variables, either DFI or HDS after swim-up preparation, were not valuable in predicting fertilization failure or pregnancy rate, but an abnormal DFI meant a lower good embryo rate following IVF.
文摘Traditional Chinese Medicine (TCM) has been widely and successfully used in treating illnesses ranging from inflammation to cancer, and compounds from medicinal herbs and minerals are playing more and more important roles in taming various kinds of diseases [1 ], exemplified by artemisinin and arsenic trioxide (ATO). Artemisinin (or Qinghaosu in Chinese) is isolated from a plant called sweet wormwood (Artemisia annua; or Qinghao in Chi- nese) which has been used as an antipyretic remedy for more than 1500 years in China. Artemisinin has impressive parasiticidal properties in vitro and in vivo, and is now one of the most important class of antimalarial agents [2, 3]. ATO is a common, naturally occurring substance which had been used in China for a long time as a therapeutic agent for some severe diseases with the ancient philosophy of 'treating an evil with a toxic' [4]. In 1990s, ATO was shown to be able to cause partial differentiation at low dose and apoptosis at high concentration of acute promyelocytic leukemia (APL) cells [5], and induce complete remission in 90% of patients with relapsed or refractory APL [6-8]. These paradigms suggest that TCM is the treasure house not only for the Chinese people, but also for the whole human beings. It is our responsibility to develop evidence-based therapeutic approaches from TCM for diseases with poor prognosis.
基金supported by the National Natural Science Foundation of China(General Program),Nos.81772453,81974358(both to DSX).
文摘Following a spinal cord injury,there are usually a number of neural pathways that remain intact in the spinal cord.These residual nerve fibers are important,as they could be used to reconstruct the neural circuits that enable motor function.Our group previously designed a novel magnetic stimulation protocol,targeting the motor cortex and the spinal nerve roots,that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury.Here,we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury.Rats underwent surgery to clamp the spinal cord at T10;three days later,the rats were treated with repetitive magnetic stimulation(5 Hz,25 pulses/train,20 pulse trains)targeting the nerve roots at the L5-L6 vertebrae.The treatment was repeated five times a week over a period of three weeks.We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord.In addition,the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex.Overall,the results suggest that nerve root magnetic stimulation may be an effective,noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.
文摘AIM:To evaluate the changes in fundus parameters in patients with Alzheimer’s type dementia(ATD)using optical coherence tomography angiography(OCTA),to record flash electroretinograms(ERG)using the RETeval system and to explore changes in retinal function.METHODS:Twenty-nine patients with ATD and 26 age-matched normal subjects were enrolled.All subjects underwent OCTA scans to analyse the superficial retinal vessel parameters in the macular area,including the vessel length density,the vessel perfusion density and the area of foveal avascular zone(FAZ),as well as the choroidal thickness.The differences between the patients with ATD and the normal control group were compared and explored the relevant factors affecting vessel parameters.We also recorded the flash ERGs using the RETeval system and intended to explore changes in retinal function by analysing the ERG image amplitude in patients with ATD.RESULTS:The vessel parameters[Pvessel length density=0.005 and Pvessel perfusion density=0.006]and average choroid thickness(P<0.001)in the macular area of the ATD group was less than the control group.The FAZ area was statistically significantly enlarged in the ATD group(P<0.001).These parameters were correlated with the Mini-Mental State Examination(MMSE)score and the Montreal Cognitive Assessment(MoCA).CONCLUSION:Patients with ATD exhibit decreases in the parameters associated with fundus.In addition,these indicators significantly correlate with the MMSE score and the MoCA score.OCTA may be an adjunct tool with strong potential to track changes in the diagnosis and monitoring the progression of the disease.
基金Supported by Sciences and Technology Commission of Shanghai Municipality (08ZR1422100 and 08410701200)
文摘Objective To investigate the possible involvement of erythropoietin (EPO)/erythropoietin receptor (EPOR) system in neovascularization and vascular regeneration in diabetic retinopathy (DR). Methods EPOR positive circulating progenitor cells (CPCs: CD34^+) and endothelial progenitor cells (EPCs: CD34^+KDR^+) were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes (n=7), non-prolif- erative DR (NPDR, n=7), proliferative DR (PDR, n=8), and PDR complicated with diabetic nephropathy (PDR-DN, n=7). Results The numbers of EPOR^+ CPCs and EPOR^+ EPCs were reduced remarkably in NPDR corn pared with the control group (both P(0.01), whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR^+ CPCs in CPCs (NPDR vs. control, P(0.01) and that of EPOR^+ EPCs in EPCs (NPDR vs. control, P〈0.05). Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the impaired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR^+ EPCs associated with ischemia.
基金the National Natural Science Foundation of China,No.81741103.
文摘BACKGROUND Interleukin 10 receptor alpha subunit(IL10RA)dysfunction is the main cause of very early-onset inflammatory bowel disease(VEO-IBD)in East Asians.AIM To identify disease-causing gene mutations in four patients with VEO-IBD and verify functional changes related to the disease-causing mutations.METHODS From May 2016 to September 2020,four young patients with clinically diagnosed VEO-IBD were recruited.Before hospitalization,using targeted gene panel sequencing and trio-whole-exome sequencing(WES),three patients were found to harbor a IL10RA mutation(c.301C>T,p.R101W in one patient;c.537G>A,p.T179T in two patients),but WES results of the fourth patient were not conclusive.We performed whole-genome sequencing(WGS)on patients A and B and reanalyzed the data from patients C and D.Peripheral blood mononuclear cells(PBMCs)from patient D were isolated and stimulated with lipopolysaccharide(LPS),interleukin 10(IL-10),and LPS+IL-10.Serum IL-10 levels in four patients and tumor necrosis factor-α(TNF-α)in the cell supernatant were determined by enzyme-linked immunosorbent assay.Phosphorylation of signal transducer and activator of transcription 3(STAT3)at Tyr705 and Ser727 in PBMCs was determined by western blot analysis.RESULTS The four children in our study consisted of two males and two females.The age at disease onset ranged from 18 d to 9 mo.After hospitalization,a novel 333-bp deletion encompassing exon 1 of IL10RA was found in patients A and B using WGS and was found in patients C and D after reanalysis of their WES data.Patient D was homozygous for the 333 bp deletion.All four patients had elevated serum IL-10 levels.In vitro,IL-10-stimulated PBMCs from patient D failed to induce STAT3 phosphorylation at Tyr705 and only minimally suppressed TNF-αproduction induced by LPS.Phosphorylation at Ser727 in PBMCs was not affected by LPS or LPS+IL-10 in both healthy subjects and in patient D.CONCLUSION WGS revealed a novel 333-bp deletion of IL10RA in four patients with VEO-IBD,whereas the WES results were inconclusive.
基金This report was supported by a grant from Brain Science and Brain-Like Intelligence Technology of the Ministry of Science and Technology of China(2021ZD0201804).
文摘China’s population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated,especially Alzheimer’s disease(AD)and related dementias(ADRD).AD’s incidence rate,morbidity,and mortality have steadily increased to make it presently the fifth leading cause of death among urban and rural residents in China and magnify the resulting financial burdens on individuals,families and society.The‘Healthy China Action’plan of 2019-2030 promotes the transition from disease treatment to health maintenance for this expanding population with ADRD.This report describes related epidemiological trends,evaluates the economic burden of the disease,outlines current clinical diagnosis and treatment status and delineates existing available public health resources.More specifically,it examines the public health impact of ADRD,including prevalence,mortality,costs,usage of care,and the overall effect on caregivers and society.In addition,this special report presents technical guidance and supports for the prevention and treatment of AD,provides expertise to guide relevant governmental healthcare policy development and suggests an information platform for international exchange and cooperation.
基金This study was supported by the National Basic Research Development Program of China(No.2010CB945200)Shanghai Key Discipline Program(No.S30202)+4 种基金Shanghai Key Project of Basic Science Research(No.09DZ1950400)Shanghai Natural Scientific Fund(No.09JC1416402,09ZR1419100)Program for Outstanding Medical Academic Leader(No.LJ 06003)Shanghai Jiao Tong University Medical and Engineering Joint Key Project(No.YG2010ZD102)Sincere gratitude should also be extended to all of graduate students,doctors,nurses as well as those social workers in the communities who were involved in the study.Without their effort this paper would not come into being.
文摘Objectives:Our study aimed to investigate the prevalence of cognitive impairment(CI)and the associated risk factors among elderly people in Shanghai urban area,China.Methods:A population-based survey was conducted among people aged 55 years or older in urban areas of Shanghai.Face-to-face interviews were carried out to collect information including demographic characteristics,medical history,and medication use,etc.The validated Chinese version of the Mini-Mental State Examination(MMSE)was used to screen subjects with CI,and the criteria of CI were adjusted for education levels.Results:A total of 3,176 home-living residents(≥55 years old)were included in the study.Among them,266 people(102 men and 164 women)were identified as cognition impaired,with a prevalence of 8.38%(266/3,176,95%CI:(8.26,8.49))for both genders,9.21%(102/1,107,95%CI:(9.18,9.33))for men and 7.93%(164/2,069,95%CI:(7.80,8.09))for women,respectively.Furthermore,we found that several significant risk factors,including social factors(education,number of children,marriage status,and family structure),physiological factors(age,blood glucose level,and obesity),factors on living styles(physical exercise,diet&chronic diseases),and genetic factor(ApoE),associated with CI onset.Conclusions:This study confirms the high prevalence of CI among the elderly population in the Shanghai urban in China,similar to previous epidemiologic studies in Western countries.The putative risk factors associated with CI merit further investigated.
文摘BACKGROUND: As a cytokine highly expressed in internal organs, visfatin could be used as a biomarker of systemic inflammation response for chronic obstructive pulmonary diseases, but few studies have reported the use of visfatin in severe pneumonia. The present study was undertaken to determine the plasma levels of visfatin in patients with severe pneumonia. METHODS:A total of 70 patients, including 40 patients with severe pneumonia (group A) and 30 patients with non severe pneumonia (group B) who had been admitted to the ICU from June 2009 to June 2010, were enrolled in this prospective study. And another 30 healthy physical examinees served as healthy controls (group C). Patients were excluded if they suffered from severe diseases of the heart, brain and kidney, cancers, autoimmune diseases, or received special treatment in the latest month. The plasma levels of visfatin, IL-6, IL-8 and TNF-α were measured by ELISA, while the level of CRP was determined by immuneturbidimetry, and the routine blood test was performed. Blood gas analysis and Acute Physiology and Chronic Health Evaluation II (APACHE II) were performed in patients with pneumonia. Comparisons between the groups were conducted by Student's t test, ANOVA or nonparametric test. Correlation analysis was carried out by Pearson's correlation test or Spearman's rank-order correlation test. RESULTS:The plasma level of visfatin in group A was significantly higher than that in groups B and C (P〈0.001), and the level of visfatin in group B was significantly higher than that in group C (P〈0.001). The plasma level of visfatin was positively correlated with CRP, TNF-α, APACHE II and PMN% in patients with severe pneumonia (rho=0.653, r=0.554, r=0.558, r=0.484, respectively, P〈0.05 for all), while it was negatively correlated with PaO2 and PaO2/FiO2 (rho=-0.422, r=-0.543, respectively, P〈0.05 for all). CONCLUSION:Visfatin may be involved in the systematic inflammation response in patients with severe pneumonia as a pro-inflammatory cytokine, and it is valuable in assessing the severity of pneumonia..
文摘This study is designed to serve as a reference for the establishment of health security systems for children's critical diseases. Through analysis of the operation of Shanghai Children Hospital Care Aid (SCHCA), this study explored the financing model and management of a children's critical disease healthcare system and analyzed the possibility of expanding this system to other areas. It is found that a premium as Iow as RMB 7 per capita per year under SCHCA can provide high-level security for children's critical diseases. With the good experience in Shanghai and based on the current basic medical insurance system for urban residents and the new rural cooperative medical scheme (NRCMS), it is necessary and feasible to build a health security system for children's critical diseases at the national level.
基金This work was supported by the Shanghai Pujiang Program(16PJ1406200)the Scientific Research Innovation Projects of Shanghai Municipal Education Commission(15ZZ060)
文摘Purpose: The present study aimed to assess the accuracies of arterial stimulation with simultaneous venous sampling(ASVS) in preoperative localization of insulinomas. Materials and Methods: A cohort consisting of 6 males and 14 females(median age, 48.5y; range, 28–62y) with pathologically proven insulinomas were included in this study. Selective angiographies were performed with the superior mesenteric artery(SMA), gastroduodenal artery(GDA), proximal splenic artery, and midsplenic artery in all individuals. Then ASVS procedures were followed after angiographies for these arteries. Clinical characteristics of the patient and the tumor number, location, and size were recorded. The accuracy of preoperative localization of insulinomas was tested. Results: A total of 22 tumors were identified by histopathological diagnosis. The mean size of the tumor was 1.40±0.60 cm. Five tumors were in the head/neck region and 17 in the body/tail region. ASVS accurately localized 17/20(85%) cases with only biochemical data and 19/20(95%) cases with biochemical data and angiography images. Variant pancreatic arterial anatomy was revealed in 2 false cases with inferior pancreatic artery replaced by the superior mesenteric artery. Conclusion: ASVS was highly accurate in localizing insulinomas and should be performed in most of the patients with suspected insulinomas before the operation.
文摘Introduction Omicron is more contagious and stealthier than the previous strains.The basic reproduction number of Omicron is around 8–12,whereas that of the previous mainstream strain Delta is only 5–8[1].Omicron’s symptoms are relatively mild[2]compared with Delta’s symptoms;however,Omicron’s transmission ability is very strong,and its risk to children and the elderly remains high[3].In addition,the vaccine’s preventive effect on Omicron has weakened.Therefore,Omicron can easily cause a rapid outbreak in a city.The population density of megacities and the limited public health resources further exacerbate the difficulty of Omicron prevention and control.
基金supported by grants from the Ministry of Science and Technology of the People's Republic of China(No.2021ZD020180)the Natural Science Foundation of China(No.81971068,81922021,81773635,82073765).
文摘Identified as the pathogenic genes of Alzheimer's disease(AD),APP,PSEN1,and PSEN2 mainly lead to early-onset AD,whose course is more aggressive,and atypical symptoms are more common than sporadic AD.Here,a novel missense mutation,APP E674Q(also named“Shanghai APP”),was detected in a Chinese index patient with typical late-onset AD(LOAD)who developed memory decline in his mid-70s.The results from neuroimaging were consistent with AD,where widespread amyloidβdeposition was demonstrated in 18 F-florbetapir Positron Emission Tomography(PET).APP E674Q is close to theβ-secretase cleavage site and the well-studied Swedish APP mutation(KM670/671NL),which was predicted to be pathogenic in silico.Molecular dynamics simulation indicated that the E674Q mutation resulted in a rearrangement of the interaction mode between APP and BACE1 and that the E674Q mutation was more prone to cleavage by BACE1.The in vitro results suggested that the E674Q mutation was pathogenic by facilitating the BACE1-mediated processing of APP and the production of Aβ.Furthermore,we applied an adeno-associated virus(AAV)-mediated transfer of the human E674Q mutant APP gene to the hippocampi of two-month-old C57Bl/6 J mice.AAV-E674Q-injected mice exhibited impaired learning behavior and increased pathological burden in the brain,implying that the E674Q mutation had a pathogenicity that bore a comparison with the classical Swedish mutation.Collectively,we report a strong amyloidogenic effect of the E674Q substitution in AD.To our knowledge,E674Q is the only pathogenic mutation within the amyloid processing sequence causing LOAD.
基金supported by grants from the Double First-Class Project from the Ministry of Education(grant code:WF510162602)Innovative Research Team of High-Level Local Universities in Shanghai,Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(grant code:2019CXJQ01)+4 种基金Overseas Expertise Introduction Project for Discipline Innovation(111 Projectgrant code:B17029)National Natural Science Foundation of China(grant numbers:82230006 and 81900206)Shanghai Shenkang Hospital Development Center(grant code:SHDC2020CR5002)Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine-ShanghaiTech University,Shanghai Pilot Program for Basic Research-Shanghai Jiao Tong University(grant code:21TQ1400226).
文摘Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity,safeguarding receptor activation,and facilitating amplification of signal transduction across the cellular membrane.However,cell-surface antigeninduced multimerization(dubbed AIM herein)has not yet been consciously leveraged in chimeric antigen receptor(CAR)engineering for enriching T cell-based therapies.We co-developed ciltacabtagene autoleucel(cilta-cel),whose CAR incorporates two B-cell maturation antigen(BCMA)-targeted nanobodies in tandem,for treating multiple myeloma.Here we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated cytotoxicity.Crystallographic analysis of BCMA–nanobody complexes revealed atomic details of antigen–antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in solution.BCMA-induced nanobody CAR multimerization enhanced cytotoxicity,alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release,towards myeloma-derived cells.Our results provide a framework for contemplating the AIM approach in designing next-generation CARs.
基金This research was funded by the Department of Defense(DOD-AMRAA/W81XWH-19-1-0546 to V.P.,T.S.G.,and R.S.Y.)National Institutes of Health(R01 CA181445 to V.P.and T.S.G.)+2 种基金the Fibrolamellar Cancer Foundation(T.S.G.)the American Cancer Society(RSG-19-197-01-CDD to T.S.G.)the Climb to Fight Cancer Fellowship(Y.L.H.).L.K.D.is the recipient of a Cancer Research Institute/Fibrolamellar Cancer Foundation Postdoctoral Fellowship(CRI Award#4093).
文摘In the era of personalized oncology,there have been accelerated efforts to develop clinically relevant platforms to test drug sensitivities of individual cancers.An ideal assay will serve as a diagnostic companion to inform the oncologist of the various treatments that are sensitive and insensitive,thus improving outcome while minimizing unnecessary toxicities and costs.To date,no such platform exists for clinical use,but promising approaches are on the horizon that take advantage of improved techniques in creating human cancer models that encompass the entire tumor microenvironment,alongside technologies for assessing and analyzing tumor response.This review summarizes a number of current strategies that make use of intact human cancer tissues as organotypic cultures in drug sensitivity testing.
基金Supported by a grant from the Fund of Ruijin Hospital North affiliated to Shanghai Jiao Tong University School of Medicine(No:2018ZY03)
文摘Objective The aim of the study was to evaluate the clinical efficacy of decitabine(DEC)combined with ruxolitinib(RUX)in the treatment of chronic myelomonocytic leukemia(CMML).Methods The clinical characteristics of 12 patients with CMML were analyzed retrospectively and subsequent target sequencing was performed to investigate the efficacy of the combined treatment with DEC and RUX and the molecular signatures therein.Results Among the 12 cases,clinical improvement was observed in all patients(100%),spleen reduction was observed in six patients(67%),and hematologic improvement was observed in four patients(33%).In the CMML-1 group,the overall response was 50%(3/6),one case achieved complete response,one achieved bone marrow remission,and one achieved hematological improvement.In the CMML-2 group,the overall response was 17%(1/6),one case achieved complete response,four showed disease progression(PD),and one exhibited no response.As expected,ASXL1 mutation was predictive for the outcome of CMML(hazard ratio of 2.97,95%confidence interval of 1.21–7.06;P=0.02).Conclusion The use of DEC combined with RUX in the treatment of CMML effectively improved the clinical response and quality of life,especially for CMML-1 patients.Ongoing clinical trials will further evaluate the safety and efficacy of this novel therapeutic approach.
基金supported by the National Natural Science Foundation of China(Nos.81700130,82370134,92169114,81802932)the Natural Science Fund for Distinguished Young Scholars of Hubei Province(No.2022CFA054)the National Key Research and Development Program of China(No.2018YFE0113600).
文摘Corona virus disease 2019(COVID-19)due to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has affected the whole world.Acquired thrombotic thrombocytopenic purpura(TTP)has been reported after administration of mRNA-or adenoviral vector-based COVID-19 vaccines,including Ad26.COV2-S,BNT162b2,mRNA-1273,and ChAdOx1 nCov-19.However,whether inactivated vaccines,such as CoronaVac,could cause TTP and whether the symptoms in TTPs caused by inactivated vaccines are different from previously reported cases are unknown.In this study,two cases were reported.Both cases developed TTP after the second CoronaVac vaccination shot,but not the first.They demonstrated symptoms of fever,neurological abnormalities,renal dysfunction,thrombocytopenia,and hemolysis.Both patients achieved complete remission through several sessions of plasma exchanges and immune suppression.The incidence of TTP in Nanjing area was analyzed.The number of patients with TTP was 12 in 2019,6 in 2020,16 in 2021,and 19 in 2022.To the authors’knowledge,this report is the first report of TTP associated with inactivated COVID-19 vaccine(CoronaVac).The rarity and delayed onset may be due to the relatively milder immune response caused by the inactivated vaccines than mRNA-based ones.Timely plasma exchange is a vital treatment for CoronaVac-related TTP,similar to activated vaccine-related TTP.