BACKGROUND Colorectal cancer(CRC)during pregnancy poses significant risks to both maternal and fetal health;however,this topic remains under researched globally.AIM To investigate the impacts of clinical features,path...BACKGROUND Colorectal cancer(CRC)during pregnancy poses significant risks to both maternal and fetal health;however,this topic remains under researched globally.AIM To investigate the impacts of clinical features,pathology type,treatment strategies,and tumor stage on maternal and fetal outcomes in pregnant patients with pregnancy-associated CRC(pCRC).METHODS To address this research gap,we analyzed the clinical and pathological characteristics of pCRC by collecting and evaluating clinicopathological data from 43 patients treated at the National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences,between 1999 and 2023 using descriptive statistical methods.RESULTS Treatment for pCRC was initiated with surgery and/or chemotherapy.Among 43 patients,37 underwent surgery,including 21 radical resections(5 prenatal and 16 postpartum resections)and 16 palliative surgeries.Chemotherapy(with regimens such as CapeOx or FOLFOX4)was administered to 37 patients.Six advanced-stage patients received chemotherapy alone.The gestational outcomes among the patients varied.Specifically,5 patients who were diagnosed in early pregnancy chose abortion.Additionally,in mid-pregnancy,3 patients underwent abortion,1 required induced labor,and 2 underwent cesarean delivery with healthy neonates.Among the 3 late-pregnancy diagnoses,1 patient underwent induced abortion,1 delivered via cesarean section with a healthy fetus,and 1 underwent stillbirth management.The 5-year survival rate was 59.8%,with a rate of 100%for stage I/II patients,75%for stage III patients,and 21.1%for stage IV patients.CONCLUSION Patients with poorly differentiated tumors exhibited worse outcomes than those with moderately and highly differentiated tumors.Early-stage diagnosis and timely treatment significantly improved maternal survival and fetal outcomes in pregnant patients with CRC.Advanced tumor stages and delayed diagnosis were observed to be associated with poorer maternal prognoses and may require interventions that compromise fetal survival.Fetal outcomes depend on the pathological stage of the mother’s cancer,the gestational age at diagnosis,and treatment strategies.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
BACKGROUND RNA binding motif 5(RBM5)has emerged as crucial regulators in many cancers.AIM To explore more functional and mechanistic exploration of RBM5 since the lack of research on RBM5 in colorectal cancer(CRC)dict...BACKGROUND RNA binding motif 5(RBM5)has emerged as crucial regulators in many cancers.AIM To explore more functional and mechanistic exploration of RBM5 since the lack of research on RBM5 in colorectal cancer(CRC)dictates that is essential.METHODS Through Gene Expression Profiling Interactive Analysis,we analyzed RBM5 expression in colon adenocarcinoma and rectum adenocarcinoma tissues.For detecting the mRNA expression of RBM5,quantitative real time-polymerase chain reaction was performed.Protein expression levels of RBM5,hexokinase 2,lactate dehydrogenase A,phosphatase and tensin homolog(PTEN),phosphoinositide 3-kinase(PI3K),phosphorylated-protein kinase B(p-AKT),and AKT were determined via Western blot.Functionally,cell counting kit-8 and 5-ethynyl-2’-deoxyuridine(EDU)assay were performed to evaluate proliferation of CRC cells.Invasiveness and migration of CRC cells were evaluated through conducting transwell assays.Glucose consumption,lactate production and adenosinetriphosphate(ATP)production were measured through a glucose assay kit,a lactate assay kit and an ATP production assay kit,respectively.Besides,RNA immunoprecipitation assay,half-life RT-PCR and dual-luciferase reporter assay were applied to detect interaction between RBM5 and PTEN.To establish a xenotypic tumor mice,CRC cells were subcutaneously injected into the right flank of each mouse.Protein expression of RBM5,Ki67,and PTEN in tumor tissues was examined using immunohistochemistry staining.Haematoxylin and eosin staining was used to evaluate tumor liver metastasis in mice.RESULTS We discovered down-regulation of RBM5 expression in CRC tissues and cells.RBM5 overexpression repressed proliferation,migration and invasion of CRC cells.Meantime,RBM5 impaired glycolysis in CRC cells,presenting as decreased glucose consumption,decreased lactate production and decreased ATP production.Besides,RBM5 bound to PTEN mRNA to stabilize its expression.PTEN expression was positively regulated by RBM5 in CRC cells.The protein levels of PI3K and p-AKT were significantly decreased after RBM5 overexpression.The suppressive influences of RBM5 on glycolysis,proliferation and metastasis of CRC cells were partially counteracted by PTEN knockdown.RBM5 suppressed tumor growth and liver metastasis in vivo.CONCLUSION This investigation provided new evidence that RBM5 was involved in CRC by binding to PTEN,expanding the importance of RBM5 in the treatment of CRC.展开更多
BACKGROUND:Circulating biomarkers for sepsis are lacking,and research on circular RNAs(circR NAs)as potential biomarkers of pneumonia-induced sepsis is limited.This study aims to investigate the diagnostic and prognos...BACKGROUND:Circulating biomarkers for sepsis are lacking,and research on circular RNAs(circR NAs)as potential biomarkers of pneumonia-induced sepsis is limited.This study aims to investigate the diagnostic and prognostic potential of circRNAs in patients with pneumonia-induced sepsis.METHODS:This prospective cohort study included 40 healthy individuals,60 patients with pneumonia,and 80 patients with pneumonia-induced sepsis.CircRNAs identified through RNA-sequencing were validated using quantitative real-time polymerase chain reaction(qRT-PCR).Spearman correlation analysis was used to evaluate the associations between circRNAs,inflammatory markers,Sequential Organ Failure Assessment(SOFA)scores,and Acute Physiology and Chronic Health EvaluationⅡ(APACHEⅡ)scores.Receiver operating characteristic(ROC)curves analysis were used to assess the diagnostic performance of circRNAs,while ROC curves and Kaplan-Meier survival analysis were used to evaluate their prognostic value of 28-day mortality.RESULTS:qRT-PCR confirmed the significant upregulation of Circ-CTD-2281E23.2 and downregulation of Circ-0075723 and Circ-0008679 in sepsis patients.Spearman correlation analysis showed that Circ-CTD-2281E23.2 was positively correlated with inflammatory markers and severity scores,whereas Circ-0075723 and Circ-0008679 were negatively correlated with these parameters.The area under the curve(AUC)values for Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 in diagnosing pneumonia-induced sepsis were 0.728,0.706,and 0.793,respectively.The combination of these circRNAs(AUC=0.846)and the combination with other clinical indicators(AUC=0.990)demostrated enhanced AUC values.The AUC values for Circ-CTD-2281E23.2 and Circ-0075723 in predicting 28-day mortality were 0.664 and 0.765,respectively.CONCLUSION:This study suggest the additional diagnostic and prognostic value of circRNAs in pneumonia-induced sepsis.Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 exhibit diagnostic potential,with Circ-CTD-2281E23.2 and Circ-0075723 showing positive prognostic value for 28-day mortality in sepsis patients.展开更多
Objective:Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis.This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer.Methods:Patients with HE...Objective:Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis.This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer.Methods:Patients with HER2-negative breast cancer,who were pre-treated with anthracycline or taxanes in a neoadjuvant,adjuvant,or metastatic setting,and had treatment failure after at least one prior chemotherapy regimen in the metastatic setting were enrolled.Anlotinib was administered at 12 mg daily for 14 days in a 21-day cycle until disease progression or unacceptable toxicity occurred.Simultaneously,5–10 m L of venous blood was collected to perform circulating tumor DNA(ct DNA)testing every 2 treatment cycles.The primary endpoint was the objective response rate(ORR).Secondary endpoints included the disease control rate(DCR),progression-free survival(PFS),overall survival,safety,and biomarkers.Results:Twenty-six eligible patients were enrolled,with a median age of 56(30–75)years.The median follow-up time was 10.5 months.The ORR was 15.4%,the DCR was 80.8%,and the median PFS was 5.22 months(95%confidence interval 2.86–6.24).Fourteen(53.8%)patients survived for more than 10 months.The changes in the detectable ct DNA variant allele frequency were consistent with the tumor response.The most common treatment-related adverse events were hypertension(57.7%),thyroidstimulating hormone elevation(34.6%),and hand-foot syndrome(23.1%).Conclusion:Anlotinib showed objective efficacy with tolerable toxicity in heavily pre-treated,metastatic HER2-negative breast cancer.The dynamic changes in the ct DNA variant allele fraction may be predictive of the tumor response.展开更多
Objective： To assess the clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma （DLBCL）. Methods： A retrospective study of 37 patients with primary testicular DLBCL ...Objective： To assess the clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma （DLBCL）. Methods： A retrospective study of 37 patients with primary testicular DLBCL was carried out from November 2003 to May 2012. Their clinical features, survival and prognostic factors were analyzed. Results： During a median follow-up period of 39.8 months （5.4-93.0 months）, the median progression-free survival （PFS） was 26.2 months （95% CI：0-65 months） and the 3-year overall survival （OS） rate was 78.4%. Within the whole cohort, the factors significantly associated with a superior PFS were limited stage （stage Ⅰ/Ⅱ）, lactate dehydrogenase （LDH） ≤245 U/L, international prognostic index （IPI） ≤1, primary tumor diameter 〈7.5 cm, and patients who had complete response （CR） and received doxoruhicin-contained chemotherapy （P〈0.05）. There was a trend toward superior outcome for patients who received combined therapy （surgery/ chemotherapy/radiotherapy） （P=0.055）. Patients who had CR, primary tumor diameter 〈7.5 cm and IPI score ≤1 were significantly associated with longer PFS at multivariate analysis. Conclusions： Primary testicular DLBCL had poorer survival. CR, primary tumor diameter and IPI were independent prognostic factors. The combined therapy of orchectomy, doxorubicin-contained chemotherapy and contralateral testicular radiotherapy （RT） seemed to improve survival.展开更多
Background In patients with acute ST-segment elevation myocardial infarction(STEMI)who undergo primary percutaneous coronary intervention(PCI),approximately 10%are concomitant with a chronic total occlusion(CTO)in a n...Background In patients with acute ST-segment elevation myocardial infarction(STEMI)who undergo primary percutaneous coronary intervention(PCI),approximately 10%are concomitant with a chronic total occlusion(CTO)in a non-culprit vessel.However,the impact of staged CTO recanalization on prognosis in this cohort remains disputable.This study aimed to compare the long-term outcomes of staged CTO recanalization versus medical therapy in patients with STEMI after primary PCI.Methods Between January 2005 and December 2016,a total of 287 patients were treated with staged CTO-PCI(n=91)or medical therapy(n=196)after primary PCI in our center.The primary endpoint was major adverse cardiovascular and cerebrovascular event(MACCE),defined as a composite of all-cause death,nonfatal myocardial infarction(MI),stroke or unplanned revascularization.After propensity-score matching,77 pairs of well-balanced patients were identified.Results The mean follow-up period was 6.06 years.Overall,the incidence of the primary endpoint of MACCE was significantly lower in staged CTO-PCI group than that in medical therapy group in both overall population(22.0%vs.46.9%;hazard ratio(HR)=0.48,95%CI:0.29-0.77)and propensity-matched cohorts(22.1%vs.42.9%;HR:0.48,95%CI:0.27-0.86).In addition,staged CTO-PCI was also associated with reduced risk of the composite of cardiac death,nonfatal MI or stroke compared with medical therapy in both overall population(9.9%vs.26.5%;hazard ratio(HR)=0.39,95%CI:0.19-0.79)and propensity-matched cohorts(9.1%vs.22.1%;HR:0.40,95%CI:0.16-0.96).After correction of the possible confounders,staged CTO-PCI was independently associated with reduced risks of MACCE(adjusted HR:0.46,95%CI:0.28-0.75),the composite of cardiac death,nonfatal MI or stroke(adjusted HR:0.45,95%CI:0.22-0.94)and all-cause mortality(adjusted HR:0.32,95%CI:0.13-0.83).Moreover,the results of sensitivity analysis were almost concordant with the overall analysis.Conclusions In patients with STEMI and a concurrent CTO who undergo primary PCI,successful staged recanalization of CTO in the non-culprit vessels is associated with better clinical outcomes during long-term follow-up.展开更多
BACKGROUND： It has been previously demonstrated that the neural cell microenvironment has the ability to induce differentiation of bone marrow mesenchymal stem cells （BMSCs） into the neural cells. OBJECTIVE： To es...BACKGROUND： It has been previously demonstrated that the neural cell microenvironment has the ability to induce differentiation of bone marrow mesenchymal stem cells （BMSCs） into the neural cells. OBJECTIVE： To establish a co-culture system of human BMSCs and neural cells, and to observe effects of this co-culture system on differentiation of human BMSCs into neural cells. DESIGN, TIME AND SETTING： A comparative observation experiment, performed at the Center Labora-tory of the Affiliated Hospital of Medical College Qingdao University from October 2006 to December 2007. MATERIALS： Neural cells were obtained from human fetal brain tissue. BMSCs were harvested from fe-male patients that underwent autonomous stem cell transplantation. METHODS： BMSCs in the co-culture group consisted of BMSCs and third passage neural cells. BMSCs in the control group were solely cultured in vitro. MAIN OUTCOME MEASURES： Morphological changes of BMSCs were observed, and expression of the neuronal specific marker, neuron-specific enolase （NSE）, was analyzed by immunofluorescence staining after 4-5-day co-culture. RESULTS： The number of neural cells in the co-culture group increased and the cells spread on the culture bottle surface. Radial dendrite formed and connected with each other. NSE-immunoreactive cells were also detected. The positive ratio of NSE-positive cells reached （32.7±11.5）%, with morphological characteristics similar to neuronal cells. Human BMSCs did not express NSE in the control group. CONCLUSION： The microenvironment provided by neurons induced differentiation of BMSCs into neu-ronal-like cells.展开更多
Tetragonal ZrO2-3 mol% Y2O3 （3Y-TZP） coated with CePO4 was synthesized by a co-precipitation method and the effects of CePO4 content and sintering temperature on its mechanical properties were investigated. The micr...Tetragonal ZrO2-3 mol% Y2O3 （3Y-TZP） coated with CePO4 was synthesized by a co-precipitation method and the effects of CePO4 content and sintering temperature on its mechanical properties were investigated. The microstructure and phase composition of the products were characterized using scanning and transmission electron microscopy as well as X-ray diffraction, respectively. The machinability index of CePO4-coated zirconia was calculated to be 1.05 when the CePO4 content is 25 wt.%. The sample hardness, bending strength and fracture toughness are 7.08 GPa, 457.85 MPa and 9.75 MPa m1/2, respectively, when the sintering temperature is 1400°C. The results show that as-prepared CePO4-coated 3Y-TZP ceramics are highly suitable biomaterials for dental applications and are expected to be used in a com-puter-aided design and computer-aided manufacturing （CAD/CAM） system to make dental crowns or bridge prostheses in a one-step sinter-ing process.展开更多
Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment o...Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment of choice in patients with m BC.This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m BC.In addition,we detected gene variants in ct DNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/taxanes.Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was PFS.The secondary endpoints were ORR,CBR,OS,and safety.Patients eligible for ct DNA detection were evaluated before and during treatment.Results:Forty patients were enrolled.The median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and hypertension.In 20 patients,ct DNA was detected at baseline and during treatment.A significant difference was found in PFS for undetected vs.detected baseline ct DNA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity profiles.Patients with no gene variant detected and lower variant allele frequencies in ct DNA at baseline showed longer PFS.展开更多
BACKGROUND Kissing molars(KMs)are a scarcely reported form of molar impaction in which the occlusal surfaces contact each other within a single dental follicle and the roots point in opposite directions.The direction ...BACKGROUND Kissing molars(KMs)are a scarcely reported form of molar impaction in which the occlusal surfaces contact each other within a single dental follicle and the roots point in opposite directions.The direction of KMs impaction is generally tilted.KMs with vertical direction impaction have not been reported in the literature.CASE SUMMARY A 25-year-old female visited a dentist for right maxillary wisdom teeth extraction and was diagnosed with two vertically impacted KMs in the left mandible on panoramic radiography.After cone-beam computed tomography examination confirmed no secondary complication,the patient chose to undergo observation and regular follow-up.A literature review of KMs revealed that vertical impacted KMs are rare;high-quality evidence regarding their prevalence is still lacking.At present,the causality of KMs is controversial.In this study,we have tried to provide a detailed definition of KMs to allow an accurate evaluation of their prevalence and classification based on their impaction direction which may be related to their pathogenesis.The treatment plan of KMs depends on the condition and location of the affected teeth and associated complications;they may be either directly extracted or treated using a multidisciplinary approach including maxillofacial surgeons and orthodontists.CONCLUSION KMs are a rare clinical condition of impacted teeth with unclear pathogenesis.Vertically impacted KMs were seldom reported.Reasonable definition and classification of KMs can help in the understanding of their causes and prevalence.展开更多
AIM: To investigated whether sall3 transcription was regulated by promoter CpG island hypermethylation in hepatocellular carcinoma (HCC). METHODS: The cell lines Huh7, HepG2, SK-HEP1, SM-MC7721, Bel7402, QGY7703 and a...AIM: To investigated whether sall3 transcription was regulated by promoter CpG island hypermethylation in hepatocellular carcinoma (HCC). METHODS: The cell lines Huh7, HepG2, SK-HEP1, SM-MC7721, Bel7402, QGY7703 and a cohort of 38 HCC tissue specimens and corresponding nontumorous tissues were subjected to analysis for sall3 promoter CpG island methylation and mRNA transcription. sall3 promoter CpG island methylation levels were determined using the MassARRAY platform and mRNA transcription levels of the gene were detected by quantitative realtime polymerase chain reaction.RESULTS: The levels of sall3 mRNA were decreased by more than twofold in 33 of 38 tumor tissues compared to adjacent noncancerous tissues. Among these 33 tumor tissues with lower levels of sall3 mRNA, 24 showed higher levels of methylation. Based on these results, we hypothesized that the decrease in sall3 mRNA transcription level was likely due to promoter CpG island hypermethylation. Changes in sall3 mRNA transcription and promoter CpG island methylation were determined in the above six cell lines after treatment with 0, 0.1, 0.5 and 2.5 mmol 5-aza-2-deoxycytidine, a demethylating agent. Promoter CpG island methylation levels de- creased in a dose-dependent manner in all six cell lines, while the mRNA transcription level increased dose-dependently in Huh7, HepG2, SK-HEP1 and SMMC7721 cells and irregularly in Bel7402 and QGY7703 cells. CONCLUSION: These results indicated that promoter CpG island hypermethylation contributes to the downregulation of sall3 mRNA transcription in HCC.展开更多
Background: To investigate the effects of unsafe decompression on rat pulmonary endothelial function and its relevant mechanisms.Methods: Sixty male Sprague-Dawley(SD) rats were randomly divided into a control group(n...Background: To investigate the effects of unsafe decompression on rat pulmonary endothelial function and its relevant mechanisms.Methods: Sixty male Sprague-Dawley(SD) rats were randomly divided into a control group(n=30) and a decompression sickness(DCS) group(n=30). The DCS model was established by placing the rats in the DCS group in a pressurized cabin where they were exposed to a 600 k Pa compressed air environment for 60 min, and the pressure was then reduced by 100 k Pa/min until it reached atmospheric pressure. After the surviving rats in the DCS group and the rats in the control group were anesthetized, their pulmonary arteries were stripped to test the in vitro pulmonary artery endothelium-dependent vasodilation capacity. Western blotting was used to measure the expression and dissociation of endothelial nitric oxide synthase(e NOS) in pulmonary artery tissues and all protein nitration levels in pulmonary artery tissues; reactive oxygen species(ROS) formation was measured via in vitro pulmonary artery superoxide anion probe dihydroethidium(DHE) staining.Results: After experiencing unsafe decompression, 10 of the 30 rats in the DCS group died. The pulmonary artery endothelium-dependent vasodilation capacity in the surviving rats decreased significantly(P<0.05). The difference in e NOS expression between the DCS group and the control group was statistically insignificant(P>0.05), but the ratio of e NOS monomer/dimer in the DCS group was significantly higher than that in the control group(P<0.05). All protein tyrosine nitration levels in the pulmonary artery tissues of the DCS group were significantly higher than those of the control group(P<0.05). The results of DHE staining showed that the amount of ROS formation in the pulmonary arteries of the DCS group was significantly higher than that of the control group(P<0.05).Conclusion: Unsafe decompression during a simulated submarine escape process can lead to e NOS dimer uncoupling in the pulmonary artery endothelium. The dissociated e NOS monomer cannot synthesize nitric oxide(NO) and thus affect the endothelium-dependent vasodilation capacity. The e NOS monomer can promote peroxynitrite(ONOO–) synthesis, leading to an increase in protein tyrosine nitration levels in pulmonary artery tissues and causing disorder in cell cycle regulation. The e NOS monomer can also cause an increase in the formation of ROS and thus mediate peroxidation damage.展开更多
Objective:To investigate the therapeutic effects of dexamethasone,anisodamine and rhubarb(DAR) on endotoxin,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and pancreatic damage in rat models of acute pancreatiti...Objective:To investigate the therapeutic effects of dexamethasone,anisodamine and rhubarb(DAR) on endotoxin,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and pancreatic damage in rat models of acute pancreatitis(AP).Methods:The AP rat models were prepared and randomly assigned to AP group(n=10) and DAR group(n=10),while other healthy rats were assigned to the sham-operated group(n=10).The rats were euthanized at 6 h after operation,and then the serum levels of endotoxin,TNF-α,IL-6 and histology of pancreas were determined as the indexes of therapeutic effects.Results:At 6 h after operation,serum levels of endotoxin,TNF-α and IL-6,and pancreatic damage were significantly increased in AP group compared with those in sham-operated group(P<0.01).Compared with the AP group,DAR therapy remarkably attenuated the endotoxin,TNF-α,IL-6 levels and reduced pancreatic damage(P<0.05).Conclusion:The inhibition of pancreatic damage by DAR in rats with AP might contribute,in part at least,to the amelioration of pancreatic inflammation.The present study provides beneficial evidence that DAR may be useful in the treatment of AP model of rats.展开更多
Objective: To investigate the expression difference of protein kinase B/Akt (Akt-1) between hepatocellular carcinoma (HCC) and adjacent normal liver tissues through the use of semi-quantitative reverse transcription p...Objective: To investigate the expression difference of protein kinase B/Akt (Akt-1) between hepatocellular carcinoma (HCC) and adjacent normal liver tissues through the use of semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Northern blot. Methods: RT-PCR of 24 pairs of specimens and Northern blot of 4 pairs of specimens were performed to investigate the expression of Akt-1. Results: Akt-1 gene was overexpressed in 15 of 24 HCC (63.3%) by RT-PCR and in all HCC (4 paired tissues) by Northern blot. Conclusion: Akt-1 activation may play a role in the pathogenesis and progression of HCC. Akt-1 gene is reported to have changed in HCC for the first time. The precise relationship between Akt-1 and HCC is a matter of further investigation.展开更多
The Wnt/β-catenin signaling pathway is the main target of tooth regeneration regulation.Treatment of cells with AZD2858 stimulates the Wnt/β-catenin signaling pathway,yet the function of this pathway in tooth regene...The Wnt/β-catenin signaling pathway is the main target of tooth regeneration regulation.Treatment of cells with AZD2858 stimulates the Wnt/β-catenin signaling pathway,yet the function of this pathway in tooth regeneration remains unclear.Here,we found that AZD2858 promotes the accumulation ofβ-catenin in the nuclei of stem cells from the apical papilla(SCAPs)and enhances cell proliferation.Single-cell sequencing was performed on SCAPs treated with AZD2858.Eight clusters were identified,namely SCAPs-CNTNAP2,SCAPs-DTL,SCAPs-MYH11,SCAPs-MKI67,SCAPs-CXCL8,SCAPs-TPM2,SCAPs-IFIT2 and SCAPs-NEK10.The pseudo-time trajectory analysis showed that AZD2858 enhanced the evolution of SCAPs from SCAPs-TMP2 clusters to SCAPs-MYH11,SCAPs-CNTNAPs and SCAPs-NEK10 clusters via up-regulation of PRKCA,SMURF2,MAGI2,RBMS3,EXT1,CAMK2D,PLCB4,and PLCB1.These results demonstrate that AZD2858 enhances the proliferation of SCAPs-TPM2 cluster by activating the non-canonical Wnt/β-catenin signaling pathway.展开更多
Background:The cell cycle is at the center of cellular activities and is orchestrated by complex regulatory mechanisms,among which transcriptional regulation is one of the most important components.Alternative splicin...Background:The cell cycle is at the center of cellular activities and is orchestrated by complex regulatory mechanisms,among which transcriptional regulation is one of the most important components.Alternative splicing dramatically expands the regulatory network by producing transcript isoforms of genes to exquisitely control the cell cycle.However,the patterns of transcript isoform expression in the cell cycle are unclear.Therapies targeting cell cycle checkpoints are commonly used as anticancer therapies,but none of them have been designed or evaluated at the alternative splicing transcript level.The utility of these transcripts as markers of cell cycle-related drug sensitivity is still unknown,and studies on the expression patterns of cell cycle-targeting drug-related transcripts are also rare.Methods:To explore alternative splicing patterns during cell cycle progression,we performed sequential transcriptomic assays following cell cycle synchronization in colon cancer HCT116 and breast cancer MDA-MB-231 cell lines,using flow cytometry and reference cell cycle transcripts to confirm the cell cycle phases of samples,and we developed a new algorithm to describe the periodic patterns of transcripts fluctuating during the cell cycle.Genomics of Drug Sensitivity in Cancer(GDSC)drug sensitivity datasets and Cancer Cell Line Encyclopedia(CCLE)transcript datasets were used to assess the correlation of genes and their transcript isoforms with drug sensitivity.We identified transcripts associated with typical drugs targeting cell cycle by determining correlation coefficients.Cytotoxicity assays were used to confirm the effect of ENST00000257904 against cyclin dependent kinase 4/6(CDK4/6)inhibitors.Finally,alternative splicing transcripts associated with mitotic(M)phase arrest were analyzed using an RNA synthesis inhibition assay and transcriptome analysis.Results:We established high-resolution transcriptome datasets of synchronized cell cycle samples from colon cancer HCT116 and breast cancer MDA-MB-231 cells.The results of the cell cycle assessment showed that 43,326,41,578 and 29,244 transcripts were found to be periodically expressed in HeLa,HCT116 and MDA-MB-231 cells,respectively,among which 1280 transcripts showed this expression pattern in all three cancer cell lines.Drug sensitivity assessments showed that a large number of these transcripts displayed a higher correlation with drug sensitivity than their corresponding genes.Cell cycle-related drug screening showed that the level of the CDK4 transcript ENST00000547281 was more significantly associated with the resistance of cells to CDK4/6 inhibitors than the level of the CDK4 reference transcript ENST00000257904.The transcriptional inhibition assay following M phase arrest further confirmed the M-phase-specific expression of the splicing transcripts.Combined with the cell cycle-related drug screening,the results also showed that a set of periodic transcripts,for example,ENST00000314392(a dolichylphosphate mannosyltransferase polypeptide 2 isoform transcript),was more associated with drug sensitivity than the levels of their corresponding gene transcripts.Conclusions:In summary,we identified a panel of cell cycle-related periodic transcripts and found that the levels of transcripts of drug target genes showed different values for predicting drug sensitivity,providing novel insights into alternative splicing-related drug development and evaluation.展开更多
Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with ...Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive(HR+)/human epidermal growth factor receptor-2-negative(HER2−)recurrent or metastatic breast cancer.Methods:Patients were intramuscularly administered fulvestrant 500 mg(day 1 per cycle for 28 days)and oral vinorelbine(60 mg/m2 on days 1,8,and 15 of each cycle).The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival,objective response rate,disease control rate,duration of response,and safety.Results:A total of 38 patients with HR+/HER2−advanced breast cancer included in the study were followed up for a median time of 25.1 months.The overall median PFS was 9.86 months[95%confidence interval(CI)7.2-23.13],and the median PFS of the first-line and the second-line treatment population was 20.73 months(95%CI 9.82 to NR)and 4.27 months(95%CI 3.68 to NR),respectively.Most adverse events reported were of grade 1/2,and none were of grade 4/5.Conclusions:This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2−recurrent and metastatic breast cancer.The combination chemo-endocrine therapy was efficacious,safe,and promising for patients with HR+/HER2−advanced breast cancer.展开更多
Objective ：To explore the effects of motilin in the hippocampus on the interdigestive migrating motor complex （MMC） in rats. Methods： Adult SD rats of either sex were used; 0.5 μl motilin （0. 74 retool/L） was i...Objective ：To explore the effects of motilin in the hippocampus on the interdigestive migrating motor complex （MMC） in rats. Methods： Adult SD rats of either sex were used; 0.5 μl motilin （0. 74 retool/L） was injected into the guide cannula which was stereotaxically implanted into the hippocampus previously. Then the MMC was recorded by a RM6240B multilead physiological recording system. Resuits： （1）MMC characteristics of normal rats＇ duodenum： the frequency of phase Ⅲ was （18. 1±0. 4） bursts/min; the amplitude of phase Ⅲ was （260.5±42.3）μV; the duration of phase Ⅲ was （354.1±21.6） s; MMC cycle duration was （690.2±58.7）s. （2） After motilin was injected into the hippocampus, the duodenal MMC cycle duration was decreased significantly. However, the amplitude of phase Ⅲ and the frequency of phase Ⅲ were increased. But there were no effects on the duration of phase Ⅲ . Frequency of phase Ⅲ percentage change was much more than amplitude of phase Ⅲ percentage change （57.2±2.8 vs 39.3±5. 2）. （3） Effects of motilin in the hippocampus on MMC were completely abolished by subdiaphragmal vagotomy. （4） Effects of motilin in the hippocampus on MMC were unaffected by intravenously injected atropine, phentolamine or propranolol. （5） The anti-motilin serum partly abolished the effects of motilin in the hippocampus on MMC. Conclusion： Motilin in the hippocampus has effects on the duodenal MMC cycle duration, the amplitude of phase Ⅲ and the frequency of phase Ⅲ. Motilin in the hippocampus plays an important role in duodenal MMC.展开更多
Objective:The aim of the study was to investigate the expression and significance of cyclin E in gastric carcinoma.Methods:We detected the expression of cyclin E in three different pathologic types gastric carcinoma s...Objective:The aim of the study was to investigate the expression and significance of cyclin E in gastric carcinoma.Methods:We detected the expression of cyclin E in three different pathologic types gastric carcinoma samples by immuno-histochemical staining technique (SP method).Results:In 59 gastric carcinoma samples the positive rate of cyclin E expression in gastric carcinoma was 55.93% (33/59), and it was significantly higher than that of normal gastric mucosa (10.53%, 2/19).The positive rates of cyclin E expression in poor differentiation group and mucoid carcinoma group were 68.75% (11/16) and 66.67% (16/24), respectively, and these were significantly higher than that in well-middle differentiation group (31.58%, 6/19), but there was no significant difference between the fronted two groups (P>0.05).Conclusion:The high expression of cyclin E is associated with the progression of gastric carcinoma and probably related to the behavior of cellular biology.展开更多
基金Supported by the National Natural Science Foundation of China,No.82372989.
文摘BACKGROUND Colorectal cancer(CRC)during pregnancy poses significant risks to both maternal and fetal health;however,this topic remains under researched globally.AIM To investigate the impacts of clinical features,pathology type,treatment strategies,and tumor stage on maternal and fetal outcomes in pregnant patients with pregnancy-associated CRC(pCRC).METHODS To address this research gap,we analyzed the clinical and pathological characteristics of pCRC by collecting and evaluating clinicopathological data from 43 patients treated at the National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences,between 1999 and 2023 using descriptive statistical methods.RESULTS Treatment for pCRC was initiated with surgery and/or chemotherapy.Among 43 patients,37 underwent surgery,including 21 radical resections(5 prenatal and 16 postpartum resections)and 16 palliative surgeries.Chemotherapy(with regimens such as CapeOx or FOLFOX4)was administered to 37 patients.Six advanced-stage patients received chemotherapy alone.The gestational outcomes among the patients varied.Specifically,5 patients who were diagnosed in early pregnancy chose abortion.Additionally,in mid-pregnancy,3 patients underwent abortion,1 required induced labor,and 2 underwent cesarean delivery with healthy neonates.Among the 3 late-pregnancy diagnoses,1 patient underwent induced abortion,1 delivered via cesarean section with a healthy fetus,and 1 underwent stillbirth management.The 5-year survival rate was 59.8%,with a rate of 100%for stage I/II patients,75%for stage III patients,and 21.1%for stage IV patients.CONCLUSION Patients with poorly differentiated tumors exhibited worse outcomes than those with moderately and highly differentiated tumors.Early-stage diagnosis and timely treatment significantly improved maternal survival and fetal outcomes in pregnant patients with CRC.Advanced tumor stages and delayed diagnosis were observed to be associated with poorer maternal prognoses and may require interventions that compromise fetal survival.Fetal outcomes depend on the pathological stage of the mother’s cancer,the gestational age at diagnosis,and treatment strategies.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
文摘BACKGROUND RNA binding motif 5(RBM5)has emerged as crucial regulators in many cancers.AIM To explore more functional and mechanistic exploration of RBM5 since the lack of research on RBM5 in colorectal cancer(CRC)dictates that is essential.METHODS Through Gene Expression Profiling Interactive Analysis,we analyzed RBM5 expression in colon adenocarcinoma and rectum adenocarcinoma tissues.For detecting the mRNA expression of RBM5,quantitative real time-polymerase chain reaction was performed.Protein expression levels of RBM5,hexokinase 2,lactate dehydrogenase A,phosphatase and tensin homolog(PTEN),phosphoinositide 3-kinase(PI3K),phosphorylated-protein kinase B(p-AKT),and AKT were determined via Western blot.Functionally,cell counting kit-8 and 5-ethynyl-2’-deoxyuridine(EDU)assay were performed to evaluate proliferation of CRC cells.Invasiveness and migration of CRC cells were evaluated through conducting transwell assays.Glucose consumption,lactate production and adenosinetriphosphate(ATP)production were measured through a glucose assay kit,a lactate assay kit and an ATP production assay kit,respectively.Besides,RNA immunoprecipitation assay,half-life RT-PCR and dual-luciferase reporter assay were applied to detect interaction between RBM5 and PTEN.To establish a xenotypic tumor mice,CRC cells were subcutaneously injected into the right flank of each mouse.Protein expression of RBM5,Ki67,and PTEN in tumor tissues was examined using immunohistochemistry staining.Haematoxylin and eosin staining was used to evaluate tumor liver metastasis in mice.RESULTS We discovered down-regulation of RBM5 expression in CRC tissues and cells.RBM5 overexpression repressed proliferation,migration and invasion of CRC cells.Meantime,RBM5 impaired glycolysis in CRC cells,presenting as decreased glucose consumption,decreased lactate production and decreased ATP production.Besides,RBM5 bound to PTEN mRNA to stabilize its expression.PTEN expression was positively regulated by RBM5 in CRC cells.The protein levels of PI3K and p-AKT were significantly decreased after RBM5 overexpression.The suppressive influences of RBM5 on glycolysis,proliferation and metastasis of CRC cells were partially counteracted by PTEN knockdown.RBM5 suppressed tumor growth and liver metastasis in vivo.CONCLUSION This investigation provided new evidence that RBM5 was involved in CRC by binding to PTEN,expanding the importance of RBM5 in the treatment of CRC.
基金supported by grants from the municipal Natural Science Foundation of Shanghai Scientific Committee of China(22ZR1451000 to TL)the peak supporting clinical discipline of Shanghai Health Bureau(2023ZDFC0104 to TL)+3 种基金the key clinical discipline of Shanghai Pudong Health Bureau(PWZxk2022-17 to TL)the clinical peak discipline of Shanghai Pudong Heath Bureau(PWYgf2021-03)the top-notch innovative medical talents of Shanghai Pudong Health Bureau(2025PDWSYCBJ-03 to TL)the leading medical talent project of Shanghai Pudong Heath Bureau(PWR12020-07 to LS)。
文摘BACKGROUND:Circulating biomarkers for sepsis are lacking,and research on circular RNAs(circR NAs)as potential biomarkers of pneumonia-induced sepsis is limited.This study aims to investigate the diagnostic and prognostic potential of circRNAs in patients with pneumonia-induced sepsis.METHODS:This prospective cohort study included 40 healthy individuals,60 patients with pneumonia,and 80 patients with pneumonia-induced sepsis.CircRNAs identified through RNA-sequencing were validated using quantitative real-time polymerase chain reaction(qRT-PCR).Spearman correlation analysis was used to evaluate the associations between circRNAs,inflammatory markers,Sequential Organ Failure Assessment(SOFA)scores,and Acute Physiology and Chronic Health EvaluationⅡ(APACHEⅡ)scores.Receiver operating characteristic(ROC)curves analysis were used to assess the diagnostic performance of circRNAs,while ROC curves and Kaplan-Meier survival analysis were used to evaluate their prognostic value of 28-day mortality.RESULTS:qRT-PCR confirmed the significant upregulation of Circ-CTD-2281E23.2 and downregulation of Circ-0075723 and Circ-0008679 in sepsis patients.Spearman correlation analysis showed that Circ-CTD-2281E23.2 was positively correlated with inflammatory markers and severity scores,whereas Circ-0075723 and Circ-0008679 were negatively correlated with these parameters.The area under the curve(AUC)values for Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 in diagnosing pneumonia-induced sepsis were 0.728,0.706,and 0.793,respectively.The combination of these circRNAs(AUC=0.846)and the combination with other clinical indicators(AUC=0.990)demostrated enhanced AUC values.The AUC values for Circ-CTD-2281E23.2 and Circ-0075723 in predicting 28-day mortality were 0.664 and 0.765,respectively.CONCLUSION:This study suggest the additional diagnostic and prognostic value of circRNAs in pneumonia-induced sepsis.Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 exhibit diagnostic potential,with Circ-CTD-2281E23.2 and Circ-0075723 showing positive prognostic value for 28-day mortality in sepsis patients.
基金supported by the National Natural Science Foundation of China(Grant No.81672634)National Key Research and Development Program of China(Grant No.2018YFC0115204)+2 种基金Capital Health Development Scientific Research Project(Grant No.2018-2-4023)Clinical Translation and Medical Research Fund of Chinese Academy of Medical Sciences(Grant No.12019XK320071)Peking Union Medical College Graduate Innovation Fund(Grant No.2018-1002-02-25)。
文摘Objective:Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis.This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer.Methods:Patients with HER2-negative breast cancer,who were pre-treated with anthracycline or taxanes in a neoadjuvant,adjuvant,or metastatic setting,and had treatment failure after at least one prior chemotherapy regimen in the metastatic setting were enrolled.Anlotinib was administered at 12 mg daily for 14 days in a 21-day cycle until disease progression or unacceptable toxicity occurred.Simultaneously,5–10 m L of venous blood was collected to perform circulating tumor DNA(ct DNA)testing every 2 treatment cycles.The primary endpoint was the objective response rate(ORR).Secondary endpoints included the disease control rate(DCR),progression-free survival(PFS),overall survival,safety,and biomarkers.Results:Twenty-six eligible patients were enrolled,with a median age of 56(30–75)years.The median follow-up time was 10.5 months.The ORR was 15.4%,the DCR was 80.8%,and the median PFS was 5.22 months(95%confidence interval 2.86–6.24).Fourteen(53.8%)patients survived for more than 10 months.The changes in the detectable ct DNA variant allele frequency were consistent with the tumor response.The most common treatment-related adverse events were hypertension(57.7%),thyroidstimulating hormone elevation(34.6%),and hand-foot syndrome(23.1%).Conclusion:Anlotinib showed objective efficacy with tolerable toxicity in heavily pre-treated,metastatic HER2-negative breast cancer.The dynamic changes in the ct DNA variant allele fraction may be predictive of the tumor response.
文摘Objective： To assess the clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma （DLBCL）. Methods： A retrospective study of 37 patients with primary testicular DLBCL was carried out from November 2003 to May 2012. Their clinical features, survival and prognostic factors were analyzed. Results： During a median follow-up period of 39.8 months （5.4-93.0 months）, the median progression-free survival （PFS） was 26.2 months （95% CI：0-65 months） and the 3-year overall survival （OS） rate was 78.4%. Within the whole cohort, the factors significantly associated with a superior PFS were limited stage （stage Ⅰ/Ⅱ）, lactate dehydrogenase （LDH） ≤245 U/L, international prognostic index （IPI） ≤1, primary tumor diameter 〈7.5 cm, and patients who had complete response （CR） and received doxoruhicin-contained chemotherapy （P〈0.05）. There was a trend toward superior outcome for patients who received combined therapy （surgery/ chemotherapy/radiotherapy） （P=0.055）. Patients who had CR, primary tumor diameter 〈7.5 cm and IPI score ≤1 were significantly associated with longer PFS at multivariate analysis. Conclusions： Primary testicular DLBCL had poorer survival. CR, primary tumor diameter and IPI were independent prognostic factors. The combined therapy of orchectomy, doxorubicin-contained chemotherapy and contralateral testicular radiotherapy （RT） seemed to improve survival.
基金funded by the Ministry of Science and Technology of the People’s Republic of China,State Science and Technology Support Program (No.2011BAI11B05)Beijing Lab for Cardiovascular Precision Medicine, Beijing, China (PXM2019_014226_000023)
文摘Background In patients with acute ST-segment elevation myocardial infarction(STEMI)who undergo primary percutaneous coronary intervention(PCI),approximately 10%are concomitant with a chronic total occlusion(CTO)in a non-culprit vessel.However,the impact of staged CTO recanalization on prognosis in this cohort remains disputable.This study aimed to compare the long-term outcomes of staged CTO recanalization versus medical therapy in patients with STEMI after primary PCI.Methods Between January 2005 and December 2016,a total of 287 patients were treated with staged CTO-PCI(n=91)or medical therapy(n=196)after primary PCI in our center.The primary endpoint was major adverse cardiovascular and cerebrovascular event(MACCE),defined as a composite of all-cause death,nonfatal myocardial infarction(MI),stroke or unplanned revascularization.After propensity-score matching,77 pairs of well-balanced patients were identified.Results The mean follow-up period was 6.06 years.Overall,the incidence of the primary endpoint of MACCE was significantly lower in staged CTO-PCI group than that in medical therapy group in both overall population(22.0%vs.46.9%;hazard ratio(HR)=0.48,95%CI:0.29-0.77)and propensity-matched cohorts(22.1%vs.42.9%;HR:0.48,95%CI:0.27-0.86).In addition,staged CTO-PCI was also associated with reduced risk of the composite of cardiac death,nonfatal MI or stroke compared with medical therapy in both overall population(9.9%vs.26.5%;hazard ratio(HR)=0.39,95%CI:0.19-0.79)and propensity-matched cohorts(9.1%vs.22.1%;HR:0.40,95%CI:0.16-0.96).After correction of the possible confounders,staged CTO-PCI was independently associated with reduced risks of MACCE(adjusted HR:0.46,95%CI:0.28-0.75),the composite of cardiac death,nonfatal MI or stroke(adjusted HR:0.45,95%CI:0.22-0.94)and all-cause mortality(adjusted HR:0.32,95%CI:0.13-0.83).Moreover,the results of sensitivity analysis were almost concordant with the overall analysis.Conclusions In patients with STEMI and a concurrent CTO who undergo primary PCI,successful staged recanalization of CTO in the non-culprit vessels is associated with better clinical outcomes during long-term follow-up.
文摘BACKGROUND： It has been previously demonstrated that the neural cell microenvironment has the ability to induce differentiation of bone marrow mesenchymal stem cells （BMSCs） into the neural cells. OBJECTIVE： To establish a co-culture system of human BMSCs and neural cells, and to observe effects of this co-culture system on differentiation of human BMSCs into neural cells. DESIGN, TIME AND SETTING： A comparative observation experiment, performed at the Center Labora-tory of the Affiliated Hospital of Medical College Qingdao University from October 2006 to December 2007. MATERIALS： Neural cells were obtained from human fetal brain tissue. BMSCs were harvested from fe-male patients that underwent autonomous stem cell transplantation. METHODS： BMSCs in the co-culture group consisted of BMSCs and third passage neural cells. BMSCs in the control group were solely cultured in vitro. MAIN OUTCOME MEASURES： Morphological changes of BMSCs were observed, and expression of the neuronal specific marker, neuron-specific enolase （NSE）, was analyzed by immunofluorescence staining after 4-5-day co-culture. RESULTS： The number of neural cells in the co-culture group increased and the cells spread on the culture bottle surface. Radial dendrite formed and connected with each other. NSE-immunoreactive cells were also detected. The positive ratio of NSE-positive cells reached （32.7±11.5）%, with morphological characteristics similar to neuronal cells. Human BMSCs did not express NSE in the control group. CONCLUSION： The microenvironment provided by neurons induced differentiation of BMSCs into neu-ronal-like cells.
基金supported by the National High-Technology Research and Development Program of China (No.2009AA03Z422)
文摘Tetragonal ZrO2-3 mol% Y2O3 （3Y-TZP） coated with CePO4 was synthesized by a co-precipitation method and the effects of CePO4 content and sintering temperature on its mechanical properties were investigated. The microstructure and phase composition of the products were characterized using scanning and transmission electron microscopy as well as X-ray diffraction, respectively. The machinability index of CePO4-coated zirconia was calculated to be 1.05 when the CePO4 content is 25 wt.%. The sample hardness, bending strength and fracture toughness are 7.08 GPa, 457.85 MPa and 9.75 MPa m1/2, respectively, when the sintering temperature is 1400°C. The results show that as-prepared CePO4-coated 3Y-TZP ceramics are highly suitable biomaterials for dental applications and are expected to be used in a com-puter-aided design and computer-aided manufacturing （CAD/CAM） system to make dental crowns or bridge prostheses in a one-step sinter-ing process.
基金funded by the National Natural Science Foundation of China(Grant No.81472753 and 81672634)。
文摘Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment of choice in patients with m BC.This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m BC.In addition,we detected gene variants in ct DNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/taxanes.Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was PFS.The secondary endpoints were ORR,CBR,OS,and safety.Patients eligible for ct DNA detection were evaluated before and during treatment.Results:Forty patients were enrolled.The median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and hypertension.In 20 patients,ct DNA was detected at baseline and during treatment.A significant difference was found in PFS for undetected vs.detected baseline ct DNA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity profiles.Patients with no gene variant detected and lower variant allele frequencies in ct DNA at baseline showed longer PFS.
基金Supported by Strategic Cooperation Project between Sichuan University and Luzhou Municipal Government,No. 2018CDLZ-14Aba Tibetan and Qiang Autonomous Prefecture Science and Technology Bureau,No. 21YYJSYJ0052
文摘BACKGROUND Kissing molars(KMs)are a scarcely reported form of molar impaction in which the occlusal surfaces contact each other within a single dental follicle and the roots point in opposite directions.The direction of KMs impaction is generally tilted.KMs with vertical direction impaction have not been reported in the literature.CASE SUMMARY A 25-year-old female visited a dentist for right maxillary wisdom teeth extraction and was diagnosed with two vertically impacted KMs in the left mandible on panoramic radiography.After cone-beam computed tomography examination confirmed no secondary complication,the patient chose to undergo observation and regular follow-up.A literature review of KMs revealed that vertical impacted KMs are rare;high-quality evidence regarding their prevalence is still lacking.At present,the causality of KMs is controversial.In this study,we have tried to provide a detailed definition of KMs to allow an accurate evaluation of their prevalence and classification based on their impaction direction which may be related to their pathogenesis.The treatment plan of KMs depends on the condition and location of the affected teeth and associated complications;they may be either directly extracted or treated using a multidisciplinary approach including maxillofacial surgeons and orthodontists.CONCLUSION KMs are a rare clinical condition of impacted teeth with unclear pathogenesis.Vertically impacted KMs were seldom reported.Reasonable definition and classification of KMs can help in the understanding of their causes and prevalence.
基金Supported by Key Programs for Science and Technology Development of Guangzhou, No. 2008A1-E4151the National High Technology Research and Development Program of China,No. 2006AA02A311
文摘AIM: To investigated whether sall3 transcription was regulated by promoter CpG island hypermethylation in hepatocellular carcinoma (HCC). METHODS: The cell lines Huh7, HepG2, SK-HEP1, SM-MC7721, Bel7402, QGY7703 and a cohort of 38 HCC tissue specimens and corresponding nontumorous tissues were subjected to analysis for sall3 promoter CpG island methylation and mRNA transcription. sall3 promoter CpG island methylation levels were determined using the MassARRAY platform and mRNA transcription levels of the gene were detected by quantitative realtime polymerase chain reaction.RESULTS: The levels of sall3 mRNA were decreased by more than twofold in 33 of 38 tumor tissues compared to adjacent noncancerous tissues. Among these 33 tumor tissues with lower levels of sall3 mRNA, 24 showed higher levels of methylation. Based on these results, we hypothesized that the decrease in sall3 mRNA transcription level was likely due to promoter CpG island hypermethylation. Changes in sall3 mRNA transcription and promoter CpG island methylation were determined in the above six cell lines after treatment with 0, 0.1, 0.5 and 2.5 mmol 5-aza-2-deoxycytidine, a demethylating agent. Promoter CpG island methylation levels de- creased in a dose-dependent manner in all six cell lines, while the mRNA transcription level increased dose-dependently in Huh7, HepG2, SK-HEP1 and SMMC7721 cells and irregularly in Bel7402 and QGY7703 cells. CONCLUSION: These results indicated that promoter CpG island hypermethylation contributes to the downregulation of sall3 mRNA transcription in HCC.
基金supported by the Army on the Subject of China (10ZYZ219)
文摘Background: To investigate the effects of unsafe decompression on rat pulmonary endothelial function and its relevant mechanisms.Methods: Sixty male Sprague-Dawley(SD) rats were randomly divided into a control group(n=30) and a decompression sickness(DCS) group(n=30). The DCS model was established by placing the rats in the DCS group in a pressurized cabin where they were exposed to a 600 k Pa compressed air environment for 60 min, and the pressure was then reduced by 100 k Pa/min until it reached atmospheric pressure. After the surviving rats in the DCS group and the rats in the control group were anesthetized, their pulmonary arteries were stripped to test the in vitro pulmonary artery endothelium-dependent vasodilation capacity. Western blotting was used to measure the expression and dissociation of endothelial nitric oxide synthase(e NOS) in pulmonary artery tissues and all protein nitration levels in pulmonary artery tissues; reactive oxygen species(ROS) formation was measured via in vitro pulmonary artery superoxide anion probe dihydroethidium(DHE) staining.Results: After experiencing unsafe decompression, 10 of the 30 rats in the DCS group died. The pulmonary artery endothelium-dependent vasodilation capacity in the surviving rats decreased significantly(P<0.05). The difference in e NOS expression between the DCS group and the control group was statistically insignificant(P>0.05), but the ratio of e NOS monomer/dimer in the DCS group was significantly higher than that in the control group(P<0.05). All protein tyrosine nitration levels in the pulmonary artery tissues of the DCS group were significantly higher than those of the control group(P<0.05). The results of DHE staining showed that the amount of ROS formation in the pulmonary arteries of the DCS group was significantly higher than that of the control group(P<0.05).Conclusion: Unsafe decompression during a simulated submarine escape process can lead to e NOS dimer uncoupling in the pulmonary artery endothelium. The dissociated e NOS monomer cannot synthesize nitric oxide(NO) and thus affect the endothelium-dependent vasodilation capacity. The e NOS monomer can promote peroxynitrite(ONOO–) synthesis, leading to an increase in protein tyrosine nitration levels in pulmonary artery tissues and causing disorder in cell cycle regulation. The e NOS monomer can also cause an increase in the formation of ROS and thus mediate peroxidation damage.
基金Supported by the Science and Technology Foundation of Shaanxi [2006K14-G2 (1)]
文摘Objective:To investigate the therapeutic effects of dexamethasone,anisodamine and rhubarb(DAR) on endotoxin,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and pancreatic damage in rat models of acute pancreatitis(AP).Methods:The AP rat models were prepared and randomly assigned to AP group(n=10) and DAR group(n=10),while other healthy rats were assigned to the sham-operated group(n=10).The rats were euthanized at 6 h after operation,and then the serum levels of endotoxin,TNF-α,IL-6 and histology of pancreas were determined as the indexes of therapeutic effects.Results:At 6 h after operation,serum levels of endotoxin,TNF-α and IL-6,and pancreatic damage were significantly increased in AP group compared with those in sham-operated group(P<0.01).Compared with the AP group,DAR therapy remarkably attenuated the endotoxin,TNF-α,IL-6 levels and reduced pancreatic damage(P<0.05).Conclusion:The inhibition of pancreatic damage by DAR in rats with AP might contribute,in part at least,to the amelioration of pancreatic inflammation.The present study provides beneficial evidence that DAR may be useful in the treatment of AP model of rats.
基金support by the National“863”High-Tech Program of China(No.Z19-01-01-02)
文摘Objective: To investigate the expression difference of protein kinase B/Akt (Akt-1) between hepatocellular carcinoma (HCC) and adjacent normal liver tissues through the use of semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Northern blot. Methods: RT-PCR of 24 pairs of specimens and Northern blot of 4 pairs of specimens were performed to investigate the expression of Akt-1. Results: Akt-1 gene was overexpressed in 15 of 24 HCC (63.3%) by RT-PCR and in all HCC (4 paired tissues) by Northern blot. Conclusion: Akt-1 activation may play a role in the pathogenesis and progression of HCC. Akt-1 gene is reported to have changed in HCC for the first time. The precise relationship between Akt-1 and HCC is a matter of further investigation.
基金the fund of National Natural Science Foundation of China(82170951)Beijing Natural Science Foundation(7222079).
文摘The Wnt/β-catenin signaling pathway is the main target of tooth regeneration regulation.Treatment of cells with AZD2858 stimulates the Wnt/β-catenin signaling pathway,yet the function of this pathway in tooth regeneration remains unclear.Here,we found that AZD2858 promotes the accumulation ofβ-catenin in the nuclei of stem cells from the apical papilla(SCAPs)and enhances cell proliferation.Single-cell sequencing was performed on SCAPs treated with AZD2858.Eight clusters were identified,namely SCAPs-CNTNAP2,SCAPs-DTL,SCAPs-MYH11,SCAPs-MKI67,SCAPs-CXCL8,SCAPs-TPM2,SCAPs-IFIT2 and SCAPs-NEK10.The pseudo-time trajectory analysis showed that AZD2858 enhanced the evolution of SCAPs from SCAPs-TMP2 clusters to SCAPs-MYH11,SCAPs-CNTNAPs and SCAPs-NEK10 clusters via up-regulation of PRKCA,SMURF2,MAGI2,RBMS3,EXT1,CAMK2D,PLCB4,and PLCB1.These results demonstrate that AZD2858 enhances the proliferation of SCAPs-TPM2 cluster by activating the non-canonical Wnt/β-catenin signaling pathway.
基金supported by grants from the National Key Research and Development Program of China(2021YFF1201300)the National Natural Science Foundation of China(81872280,82073094)+2 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-014)the Open Issue of State Key Laboratory of Molecular Oncology(SKL-KF-2021-16)the Independent Issue of State Key Laboratory of Molecular Oncology(SKL-2021-16).
文摘Background:The cell cycle is at the center of cellular activities and is orchestrated by complex regulatory mechanisms,among which transcriptional regulation is one of the most important components.Alternative splicing dramatically expands the regulatory network by producing transcript isoforms of genes to exquisitely control the cell cycle.However,the patterns of transcript isoform expression in the cell cycle are unclear.Therapies targeting cell cycle checkpoints are commonly used as anticancer therapies,but none of them have been designed or evaluated at the alternative splicing transcript level.The utility of these transcripts as markers of cell cycle-related drug sensitivity is still unknown,and studies on the expression patterns of cell cycle-targeting drug-related transcripts are also rare.Methods:To explore alternative splicing patterns during cell cycle progression,we performed sequential transcriptomic assays following cell cycle synchronization in colon cancer HCT116 and breast cancer MDA-MB-231 cell lines,using flow cytometry and reference cell cycle transcripts to confirm the cell cycle phases of samples,and we developed a new algorithm to describe the periodic patterns of transcripts fluctuating during the cell cycle.Genomics of Drug Sensitivity in Cancer(GDSC)drug sensitivity datasets and Cancer Cell Line Encyclopedia(CCLE)transcript datasets were used to assess the correlation of genes and their transcript isoforms with drug sensitivity.We identified transcripts associated with typical drugs targeting cell cycle by determining correlation coefficients.Cytotoxicity assays were used to confirm the effect of ENST00000257904 against cyclin dependent kinase 4/6(CDK4/6)inhibitors.Finally,alternative splicing transcripts associated with mitotic(M)phase arrest were analyzed using an RNA synthesis inhibition assay and transcriptome analysis.Results:We established high-resolution transcriptome datasets of synchronized cell cycle samples from colon cancer HCT116 and breast cancer MDA-MB-231 cells.The results of the cell cycle assessment showed that 43,326,41,578 and 29,244 transcripts were found to be periodically expressed in HeLa,HCT116 and MDA-MB-231 cells,respectively,among which 1280 transcripts showed this expression pattern in all three cancer cell lines.Drug sensitivity assessments showed that a large number of these transcripts displayed a higher correlation with drug sensitivity than their corresponding genes.Cell cycle-related drug screening showed that the level of the CDK4 transcript ENST00000547281 was more significantly associated with the resistance of cells to CDK4/6 inhibitors than the level of the CDK4 reference transcript ENST00000257904.The transcriptional inhibition assay following M phase arrest further confirmed the M-phase-specific expression of the splicing transcripts.Combined with the cell cycle-related drug screening,the results also showed that a set of periodic transcripts,for example,ENST00000314392(a dolichylphosphate mannosyltransferase polypeptide 2 isoform transcript),was more associated with drug sensitivity than the levels of their corresponding gene transcripts.Conclusions:In summary,we identified a panel of cell cycle-related periodic transcripts and found that the levels of transcripts of drug target genes showed different values for predicting drug sensitivity,providing novel insights into alternative splicing-related drug development and evaluation.
基金supported by grants from the National Key R&D Program of China(Grant No.2018YFC0115204)the National Natural Science Foundation of China(Grant No.81672634)+3 种基金the Chinese Society of Clinical Oncology Foundation(Grant No.Y-2019AZMS-0377)the Beijing Medical Award Foundation(Grant No.YXJL-2020-0941-0763)Beijing Hope Run Special Fund of Cancer Foundation of China(Grant No.LC2019B16)Beijing Xisike Clinical Oncology Research Foundation(Grant No.Y-pirrefabre202101-0008).
文摘Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive(HR+)/human epidermal growth factor receptor-2-negative(HER2−)recurrent or metastatic breast cancer.Methods:Patients were intramuscularly administered fulvestrant 500 mg(day 1 per cycle for 28 days)and oral vinorelbine(60 mg/m2 on days 1,8,and 15 of each cycle).The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival,objective response rate,disease control rate,duration of response,and safety.Results:A total of 38 patients with HR+/HER2−advanced breast cancer included in the study were followed up for a median time of 25.1 months.The overall median PFS was 9.86 months[95%confidence interval(CI)7.2-23.13],and the median PFS of the first-line and the second-line treatment population was 20.73 months(95%CI 9.82 to NR)and 4.27 months(95%CI 3.68 to NR),respectively.Most adverse events reported were of grade 1/2,and none were of grade 4/5.Conclusions:This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2−recurrent and metastatic breast cancer.The combination chemo-endocrine therapy was efficacious,safe,and promising for patients with HR+/HER2−advanced breast cancer.
文摘Objective ：To explore the effects of motilin in the hippocampus on the interdigestive migrating motor complex （MMC） in rats. Methods： Adult SD rats of either sex were used; 0.5 μl motilin （0. 74 retool/L） was injected into the guide cannula which was stereotaxically implanted into the hippocampus previously. Then the MMC was recorded by a RM6240B multilead physiological recording system. Resuits： （1）MMC characteristics of normal rats＇ duodenum： the frequency of phase Ⅲ was （18. 1±0. 4） bursts/min; the amplitude of phase Ⅲ was （260.5±42.3）μV; the duration of phase Ⅲ was （354.1±21.6） s; MMC cycle duration was （690.2±58.7）s. （2） After motilin was injected into the hippocampus, the duodenal MMC cycle duration was decreased significantly. However, the amplitude of phase Ⅲ and the frequency of phase Ⅲ were increased. But there were no effects on the duration of phase Ⅲ . Frequency of phase Ⅲ percentage change was much more than amplitude of phase Ⅲ percentage change （57.2±2.8 vs 39.3±5. 2）. （3） Effects of motilin in the hippocampus on MMC were completely abolished by subdiaphragmal vagotomy. （4） Effects of motilin in the hippocampus on MMC were unaffected by intravenously injected atropine, phentolamine or propranolol. （5） The anti-motilin serum partly abolished the effects of motilin in the hippocampus on MMC. Conclusion： Motilin in the hippocampus has effects on the duodenal MMC cycle duration, the amplitude of phase Ⅲ and the frequency of phase Ⅲ. Motilin in the hippocampus plays an important role in duodenal MMC.
文摘Objective:The aim of the study was to investigate the expression and significance of cyclin E in gastric carcinoma.Methods:We detected the expression of cyclin E in three different pathologic types gastric carcinoma samples by immuno-histochemical staining technique (SP method).Results:In 59 gastric carcinoma samples the positive rate of cyclin E expression in gastric carcinoma was 55.93% (33/59), and it was significantly higher than that of normal gastric mucosa (10.53%, 2/19).The positive rates of cyclin E expression in poor differentiation group and mucoid carcinoma group were 68.75% (11/16) and 66.67% (16/24), respectively, and these were significantly higher than that in well-middle differentiation group (31.58%, 6/19), but there was no significant difference between the fronted two groups (P>0.05).Conclusion:The high expression of cyclin E is associated with the progression of gastric carcinoma and probably related to the behavior of cellular biology.
