New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individua...New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical Centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical Centers over a two-year period. Compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.展开更多
The tumor objective response rate(ORR)is an important parameter to demonstrate the efficacy of a treatment in oncology.The ORR is valuable for clinical decision making in routine practice and a significant end-point f...The tumor objective response rate(ORR)is an important parameter to demonstrate the efficacy of a treatment in oncology.The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials.World Health Organization and Response Evaluation Criteria in Solid Tumors(RECIST)are anatomic response criteria developed mainly for cytotoxic chemotherapy.These criteria are based on the visual assessment of tumor size in morphological images provided by computed tomography(CT)or magnetic resonance imaging.Anatomic response criteria may not be optimal for biologic agents,some disease sites,and some regional therapies.Consequently,modifications of RECIST,Choi criteria and Morphologic response criteria were developed based on the concept of the evaluation of viable tumors.Despite its limitations,RECIST v1.1 is validated in prospective studies,is widely accepted by regulatory agencies and has recently shown good performance for targeted cancer agents.Finally,some alternatives of RECIST were developed as immune-specific response criteria for checkpoint inhibitors.Immune RECIST criteria are based essentially on defining true progressive disease after a confirmatory imaging.Some graphical methods may be useful to show longitudinal change in the tumor burden over time.Tumor tissue is a tridimensional heterogenous mass,and tumor shrinkage is not always symmetrical;thus,metabolic response assessments using positron emission tomography(PET)or PET/CT may reflect the viability of cancer cells or functional changes evolving after anticancer treatments.The metabolic response can show the benefit of a treatment earlier than anatomic shrinkage,possibly preventing delays in drug approval.Computer-assisted automated volumetric assessments,quantitative multimodality imaging in radiology,new tracers in nuclear medicine and finally artificial intelligence have great potential in future evaluations.展开更多
BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,i...BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.展开更多
High-pressure solenoid valve with high flow rate and high speed is a key component in an underwater driving system.However,traditional single spool pilot operated valve cannot meet the demands of both high flow rate a...High-pressure solenoid valve with high flow rate and high speed is a key component in an underwater driving system.However,traditional single spool pilot operated valve cannot meet the demands of both high flow rate and high speed simultaneously.A new structure for a high pressure solenoid valve is needed to meet the demand of the underwater driving system.A novel parallel-spool pilot operated high-pressure solenoid valve is proposed to overcome the drawback of the current single spool design.Mathematical models of the opening process and flow rate of the valve are established.Opening response time of the valve is subdivided into 4 parts to analyze the properties of the opening response.Corresponding formulas to solve 4 parts of the response time are derived.Key factors that influence the opening response time are analyzed.According to the mathematical model of the valve,a simulation of the opening process is carried out by MATLAB.Parameters are chosen based on theoretical analysis to design the test prototype of the new type of valve.Opening response time of the designed valve is tested by verifying response of the current in the coil and displacement of the main valve spool.The experimental results are in agreement with the simulated results,therefore the validity of the theoretical analysis is verified.Experimental opening response time of the valve is 48.3 ms at working pressure of 10 MPa.The flow capacity test shows that the largest effective area is 126 mm2 and the largest air flow rate is 2320 L/s.According to the result of the load driving test,the valve can meet the demands of the driving system.The proposed valve with parallel spools provides a new method for the design of a high-pressure valve with fast response and large flow rate.展开更多
The aim of this study was to investigate the feasibility of stimulating ovarian fol icle development in order to improve fertility in water buffalo cows by immunization against inhibin. The experiment was carried out ...The aim of this study was to investigate the feasibility of stimulating ovarian fol icle development in order to improve fertility in water buffalo cows by immunization against inhibin. The experiment was carried out in early summer (May) and included 24 multi-parity crossbred Murrah-Swamp buffaloes that were divided into immunized (n=11) and control (n=13) groups. Each immunized cow was administered with a 2-mL immunogen of mineral oil adjuvant containing 2 mg of recombinant inhibinα-subunit fusion protein. The controls were treated with the adjuvant only. Al animals received Ovsynch protocol treatment, starting on the day of the antigen administration, and they were artiifcial y inseminated upon behavioral estrus. As a result, al of the immunized buffaloes generated antibodies against inhibin during the experimental period and had higher plasma concentrations of fol icle-stimulating hormone (FSH), activin, and estradiol (E2) related to estrous expression. A higher proportion of immunized animals expressed estrus behavior than did the controls (72%vs. 30%, P<0.05). On aver-age, inhibin-immunized buffaloes had signiifcantly more large fol icles (≥9 mm in diameter) than the controls (mean±SEM;1.2±0.1 vs. 0.84±0.1, respectively;P<0.05) and a slightly higher mean total number of fol icles (≥2 mm;11.4±0.7 vs. 9.0±1.1, respectively;P=0.09) and smal (2–4 mm) fol icles (8.81±0.6 vs. 6.84±1.0, respectively;P=0.12). A higher percentage of cows ovulated in the immunized group than in the control group (91%(10/11) vs. 54%(7/13), respectively;P<0.05). Moreover, inhibin-immunized cows had slightly larger corpus luteum (CL) than the controls 9 days after ovulation and signiifcantly higher (P<0.01) post-ovulation peak plasma progesterone (P4) concentrations. Immunization against inhibin also mar-ginal y increased the conception rate 42 days after insemination (45.8%vs. 15.4%;P>0.05). These results demonstrate that immunization against inhibin, coupled with the treatment with the Ovsynch protocol, can constitute a new technique to increase fertility in water buffalo cows.展开更多
Quasi-static and high strain rate compressive experiments on vinyl ester casting were carried out by means of MTS (Material Test System) and Hopkinson bar. The behaviors of the compressed unstable and fracture of the ...Quasi-static and high strain rate compressive experiments on vinyl ester casting were carried out by means of MTS (Material Test System) and Hopkinson bar. The behaviors of the compressed unstable and fracture of the resin casting at different strain rates were investigated.The results indicate that the response behavior of the resin casting is controlled by different mechanisms at different strain rate, and some mechanical properties of vinyl ester casting are rate-dependent: the casting are destroyed in toughness model under strain rate 3.3×10 -4~6.6×10 -3/s, while the casting are destroyed in brittleness model under strain rate 950~5800/s. The yield stress, yield strain energy density are all increased with the increasing strain rates at quasi-static as well as at high strain rates. What is interesting is that the yield strain decreased with the strain rates increasing at quasi-static while increased at high strain rates. It is considered that the casting occurred forcing high elastic deformation at high strain rates. The damage of the specimens is mainly controlled by axial stress before unstable deformation, while mainly controlled by shear stress after unstable deformation, and then developed to fracture finally. This progress is rate-dependent: the development of the cracks inside the castings increased with the strain rate increasing.展开更多
Intrahepatic cholangiocarcinoma(iCCA)is recognized as the second most frequently diagnosed liver malignancy,following closely after hepatocellular carcinoma.Its incidence has seen a global upsurge in the past several ...Intrahepatic cholangiocarcinoma(iCCA)is recognized as the second most frequently diagnosed liver malignancy,following closely after hepatocellular carcinoma.Its incidence has seen a global upsurge in the past several years.Unfortunately,due to the lack of well-defined risk factors and limited diagnostic tools,iCCA is often diagnosed at an advanced stage,resulting in a poor prognosis.While surgery is the only potentially curative option,it is rarely feasible.Currently,there are ongoing investigations into various treatment approaches for unresectable iCCA,including conventional chemotherapies,targeted therapies,immunotherapies,and locoregional treatments.This study aims to explore the role of transarterial radioembolization(TARE)in the treatment of unresectable iCCA and provide a comprehensive review.The findings suggest that TARE is a safe and effective treatment option for unresectable iCCA,with a median overall survival(OS)of 14.9 months in the study cohort.Studies on TARE for unresectable iCCA,both as a first-line treatment(as a neo-adjuvant down-staging strategy)and as adjuvant therapy,have reported varying median response rates(ranging from 34%to 86%)and median OS(12-16 mo).These differences can be attributed to the heterogeneity of the patient population and the limited number of participants in the studies.Most studies have identified tumor burden,portal vein involvement,and the patient’s performance status as key prognostic factors.Furthermore,a phase 2 trial evaluated the combination of TARE and chemotherapy(cisplatin-gemcitabine)as a first-line therapy for locally advanced unresectable iCCA.The results showed promising outcomes,including a median OS of 22 mo and a 22%achievement in down-staging the tumor.In conclusion,TARE represents a viable treatment option for unresectable iCCA,and its combination with systemic chemotherapy has shown promising results.However,it is important to consider treatment-independent factors that can influence prognosis.Further research is necessary to identify optimal treatment combinations and predictive factors for a favorable response in iCCA patients.展开更多
In this study,we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m 2 with dexamethasone(BD) and compared it to the standard 1.3 mg/m 2 twice-weekly BD regimen in Chinese patients with newly...In this study,we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m 2 with dexamethasone(BD) and compared it to the standard 1.3 mg/m 2 twice-weekly BD regimen in Chinese patients with newly diagnosed multiple myeloma(MM).We assessed the difference in efficacy,safety profile and survival between the once-weekly and twice-weekly cohorts(13 vs.24 patients).The over response rate was similar with both arms of the study,being 77% in the once-weekly schedule and 74.9% in the twice-weekly schedule(P=0.690).The median overall survival was not reached in either schedule.Also,the median progression-free survival and duration of response of the once-weekly schedule did not significantly differ from those of the twice-weekly schedule(8 months vs.10 months,P=0.545 and 6 months vs.7 months,P=0.467 respectively).Peripheral sensory neuropathy and grade 3/4 hematologic toxic effects were more frequently reported in the twice-weekly schedule than the once-weekly schedule,but there was no statistically significant difference.This preliminary experience in Chinese patients with newly diagnosed MM indicated that once-weekly infusion of Bortezomib plus dexamethasone may improve safety without affecting outcome.展开更多
Objectives To analyze the six-minute walk test (6MWT) and gas exchange of 5 heart transplantation patients and to approach the variation tendency of exercise tolerance, oxygen uptake ( VO2 ) and heart rate chronot...Objectives To analyze the six-minute walk test (6MWT) and gas exchange of 5 heart transplantation patients and to approach the variation tendency of exercise tolerance, oxygen uptake ( VO2 ) and heart rate chronotropic response. Methods 5 cases of heart transplantation patients ( age 25 - 52 years) were undertaken 6MWT 6 - 30 months after operation, synchronizing gas exchanging parameters were measured by wireless portable remote sensing K4B^2 gas analyzer, 51 normal controls were compared. Results The six-minute walk distance (6MWD) of 5 patients were (592.6 ± 26.7 ) m (558 - 625 ) m, the ascending tendency during exercise was slower, the maximum heart rates were 80% ± 6% of age-predicting maximal heart rate, lower than normal control (86%) ; the end point VO2/kg were (21.8 ± 1.4 ) mL/min · kg ( 19. 94 - 23.60) mL/min · kg. Conclusions The 6WMD and VO2 of 5 patients reached normal range, but the heart rate chronotropic response and VO2 ascending tendency were slower than those of normal controls.展开更多
Stimulation of the trigeminal nerve can elicit various cardiovascular and autonomic responses;however,the effects of anesthesia with pentobarbital sodium on these responses are unclear.Pentobarbital sodium was infused...Stimulation of the trigeminal nerve can elicit various cardiovascular and autonomic responses;however,the effects of anesthesia with pentobarbital sodium on these responses are unclear.Pentobarbital sodium was infused intravenously at a nominal rate and the lingual nerve was electrically stimulated at each infusion rate.Increases in systolic blood pressure(SBP) and heart rate(HR) were evoked by lingual nerve stimulation at an infusion rate between 5 and 7 mg?kg 21 ?h 21.This response was associated with an increase in the low-frequency band of SBP variability(SBP-LF).As the infusion rate increased to 10 mg?kg 21 ?h 21 or more,decreases in SBP and HR were observed.This response was associated with the reduction of SBP-LF.In conclusion,lingual nerve stimulation has both sympathomimetic and sympathoinhibitory effects,depending on the depth of pentobarbital anesthesia.The reaction pattern seems to be closely related to the autonomic balance produced by pentobarbital anesthesia.展开更多
Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy amo...Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy among patients presenting with intracranial lesions are limited.This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.Methods:Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable,asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1,2019 and September 30,2021.The patients were stratified into two groups according to the first-line treatment regimen received:ICI combined with chemotherapy(n=102)or chemotherapy(n=109).Systemic and intracranial objective response rates(ORRs)and progression-free survival(PFS)were analyzed.Adverse events were also compared between the groups.Results:Compared with the chemotherapy-based regimen,the ICI-containing regimen was associated with a significantly higher intracranial(44.1%[45/102]vs.28.4%[31/109],χ^(2)=5.620,P=0.013)and systemic(49.0%[50/102]vs.33.9%[37/109],χ^(2)=4.942,P=0.019)ORRs and longer intracranial(11.0 months vs.7.0 months,P<0.001)and systemic(9.0 months vs.5.0 months,P<0.001)PFS.Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS(hazard ratio[HR]=0.52,95%confidence interval[CI]:0.37-0.73,P<0.001)and systemic PFS(HR=0.48,95%CI:0.35-0.66,P<0.001).No unexpected serious adverse effects were observed.Conclusion:Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.Clinical trial registration:https://www.clinicaltrials.gov/,OMESIA,NCT05129202.展开更多
Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into t...Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects.Therefore,we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.Methods:In this single-arm prospective phase II trial,patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg,liposomal paclitaxel 150 mg/m2,and nedaplatin 50 mg/m2 on day 1,and apatinib 250 mg on days 1-14.The treatments were repeated every 14 days for up to 9 cycles,followed by maintenance therapy with camrelizumab and apatinib.The primary endpoint was objective response rate(ORR)according to the Response Evaluation Criteria in Solid Tumors(version 1.1).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and safety.Results:We enrolled 30 patients between August 7,2018 and February 23,2019.The median follow-up was 24.98 months(95%confidence interval[CI]:23.05-26.16 months).The centrally assessed ORR was 80.0%(95%CI:61.4%-92.3%),with a median duration of response of 9.77 months(range:1.54 to 24.82+months).The DCR reached 96.7%(95%CI:82.8%-99.9%).The median PFS was 6.85 months(95%CI:4.46-14.20 months),and the median OS was 19.43 months(95%CI:9.93 months–not reached).The most common grade 3-4 treatmentrelated adverse events(AEs)were leukopenia(83.3%),neutropenia(60.0%),and increased aspartate aminotransferase level(26.7%).Treatment-related serious AEs included febrile neutropenia,leukopenia,and anorexia in one patient(3.3%),and single cases of increased blood bilirubin level(3.3%)and toxic epidermal necrolysis(3.3%).No treatment-related deaths occurred.Conclusions:Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feasible anti-tumor activity and manageable safety in patients with advanced ESCC.Randomized trials to evaluate this new combination strategy are warranted.Trial registration:This trial was registered on July 27,2018,at ClinicalTrials.gov(identifier:NCT03603756).展开更多
Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been es...Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC.展开更多
Background: Oxaliplatin, irinotecan, 5-fluorouracil, and l-leucovorin (FOLFIRINOX) has become one of the first-line treatment options for advanced pancreatic cancer (PC). However, the relatively high rate of grade 3 o...Background: Oxaliplatin, irinotecan, 5-fluorouracil, and l-leucovorin (FOLFIRINOX) has become one of the first-line treatment options for advanced pancreatic cancer (PC). However, the relatively high rate of grade 3 or 4 adverse events associated with the standard dosage of FOLFIRINOX limits its widespread use in clinical practice. In this study, we were to evaluate the efficacy and safety of a modified FOLFIRINOX regimen as a first-line chemotherapy for Chinese patients with metastatic PC. Methods: Patients with histologically confirmed primary metastatic pancreatic adenocarcinoma with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 were recruited to receive the modified FOLFIRINOX regimen (intravenous infusion of oxaliplatin, 65 mg/m2;irinotecan, 150 mg/m2;l-leucovorin, 200 mg/ m2;and 5-fluorouracil, 2400 mg/m2, repeated every 2 weeks). The treatment was continued for 12 cycles unless the patient had progressive disease (PD), stable disease (SD) with symptom deterioration, unacceptable adverse events, or requested to terminate the treatment prematurely. The primary endpoint was objective response rate (ORR). Results: Sixty-five patients were enrolled from July 2012 to April 2017 in three institutions, and they all received at least one cycle of chemotherapy, with a median of 8 cycles (range 1-12 cycles). No complete response was observed. Twenty-one (32.3%) patients had partial responses, and 27 (41.5%) had SD. The ORR and disease control rate of the study cohort was 32.3% and 73.8%. The estimated median overall survival and progression-free survival were 11.60 (95% confidence interval [CI] 8.76-14.44) and 5.77 (95% CI 5.00-6.54) months. Major grade 3 or 4 adverse events included neutropenia (12.3%) and diarrhea (6.2%). No treatment-related death was observed. Conclusions: Modified FOLFIRINOX was well-tolerated and might be a promising option as first-line therapy for Chinese patients with metastatic PC.展开更多
Neoadjuvant chemotherapy(NAC)has shown promising results in patients with locally advanced penile cancer.However,no consensus exists on its applications for locally advanced penile cancer.Thus,it is unclear which kind...Neoadjuvant chemotherapy(NAC)has shown promising results in patients with locally advanced penile cancer.However,no consensus exists on its applications for locally advanced penile cancer.Thus,it is unclear which kind of chemotherapy regimen is the best choice.Consequently,a systematic search of PubMed,Web of Science,and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer.The Newcastle–Ottawa Scale was used to assess the risk of bias in each study.This study synthesized 14 published studies.The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response.In addition,the objective response rates(ORRs)and pathological complete response(pCR)rates were 0.57 and 0.11,respectively.The incidence of grade≥3 toxicity was 0.36.Subgroup analysis found that the ORR and pCR of the taxane–platinum(TP)regimen group performed better than those of the nontaxane–platinum(NTP)regimen group(0.57 vs 0.54 and 0.14 vs 0.07,respectively).Moreover,the TP regimen group had more frequent toxicity than the NTP regimen group(0.41 vs 0.26).However,further studies were warranted to confirm the findings.展开更多
In this study,issues concerning the design of scales for measuring teacher sense of efficacy(TSE)are first identified with particular attention to the Teacher Sense of Efficacy Scale(TSES).Psychometric issues concerni...In this study,issues concerning the design of scales for measuring teacher sense of efficacy(TSE)are first identified with particular attention to the Teacher Sense of Efficacy Scale(TSES).Psychometric issues concerning analysis and reporting of TSE data are subsequently identified.Recommendations are offered about all identified issues,and these recommendations are taken into account when obtaining and analyzing TSE data from Chinese mainland preservice and inservice teachers.Exploratory factor analyses yielded a single factor for both samples as well as for four subgroups within the inservice teacher sample.Results also provided insights about scale design as well as the TSES being limited for capturing the breadth of TSE.Suggestions are made for improvements in the assessment of TSE.展开更多
Objective:Several studies have found that epigallocatechin-3-gallate(EGCG)can alleviate acute radiation-induced esophagitis,inhibit pulmonary inflammation and fibrosis,and reduce the severity of cardiovascular disease...Objective:Several studies have found that epigallocatechin-3-gallate(EGCG)can alleviate acute radiation-induced esophagitis,inhibit pulmonary inflammation and fibrosis,and reduce the severity of cardiovascular disease.Therefore,this study was aimed at exploring the influence of EGCG on late radiation toxicity in the heart,esophagus,and lungs among patients with locally advanced lung cancer.Methods:The patients were divided into an EGCG group and a control group,the groups received EGCG and symptomatic treatment,respectively.The Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme was used to determine the late toxicity scores.Tumor responses were evaluated by chest computed tomography(CT),based on the Response Evaluation Criteria in Solid Tumors version 1.1.Results:We retrospectively analyzed 74 patients treated at our hospital from September 2012 to September 2016(37 patients received EGCG and 37 received supportive treatment).The late toxicity scores of the EGCG group decreased compared to those of the control group.An obvious clinical significance was observed for the oral EGCG solution in the treatment and prevention of late cardiac,esophageal,and pulmonary toxicity.However,no significant difference was found(P>0.05).The tumor response rates were similar in the two groups.Moreover,there was no difference in progression-free survival(PFS)between the groups(P>0.05).Conclusion:Oral EGCG solution might alleviate radiation-induced late cardiac,esophageal,and pulmonary toxicity but has no significant effect on the tumor response rate and PFS following radiotherapy.展开更多
This work evaluates the influence of energy consumption on the future air quality in Beijing,using 2000 as the base year and 2008 as the target year.It establishes the emission inventory of primary PM_(10),SO_(2) and ...This work evaluates the influence of energy consumption on the future air quality in Beijing,using 2000 as the base year and 2008 as the target year.It establishes the emission inventory of primary PM_(10),SO_(2) and NO_(x) related to energy utilization in eight areas of Beijing.The air quality model was adopted to simulate the temporal and spatial distribution of each pollutant concentration in the eight urban areas.Their emission,concentration distribution,and sectoral share responsibility rate were analyzed,and air quality in 2008 was predicted.The industrial sector contributed above 40% of primary PM_(10) and SO_(2) resulting from energy consumption,while vehicles accounted for about 65% of NO_(x).According to the current policy and development trend,air quality in the eight urban areas could become better in 2008 when the average concentrations of primary PM_(10),SO_(2) and NO_(2) related to energy utilization at each monitored site are predicted to be about 25,50 and 51μg/m^(3),respectively.展开更多
文摘New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical Centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical Centers over a two-year period. Compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.
文摘The tumor objective response rate(ORR)is an important parameter to demonstrate the efficacy of a treatment in oncology.The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials.World Health Organization and Response Evaluation Criteria in Solid Tumors(RECIST)are anatomic response criteria developed mainly for cytotoxic chemotherapy.These criteria are based on the visual assessment of tumor size in morphological images provided by computed tomography(CT)or magnetic resonance imaging.Anatomic response criteria may not be optimal for biologic agents,some disease sites,and some regional therapies.Consequently,modifications of RECIST,Choi criteria and Morphologic response criteria were developed based on the concept of the evaluation of viable tumors.Despite its limitations,RECIST v1.1 is validated in prospective studies,is widely accepted by regulatory agencies and has recently shown good performance for targeted cancer agents.Finally,some alternatives of RECIST were developed as immune-specific response criteria for checkpoint inhibitors.Immune RECIST criteria are based essentially on defining true progressive disease after a confirmatory imaging.Some graphical methods may be useful to show longitudinal change in the tumor burden over time.Tumor tissue is a tridimensional heterogenous mass,and tumor shrinkage is not always symmetrical;thus,metabolic response assessments using positron emission tomography(PET)or PET/CT may reflect the viability of cancer cells or functional changes evolving after anticancer treatments.The metabolic response can show the benefit of a treatment earlier than anatomic shrinkage,possibly preventing delays in drug approval.Computer-assisted automated volumetric assessments,quantitative multimodality imaging in radiology,new tracers in nuclear medicine and finally artificial intelligence have great potential in future evaluations.
文摘BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.
文摘High-pressure solenoid valve with high flow rate and high speed is a key component in an underwater driving system.However,traditional single spool pilot operated valve cannot meet the demands of both high flow rate and high speed simultaneously.A new structure for a high pressure solenoid valve is needed to meet the demand of the underwater driving system.A novel parallel-spool pilot operated high-pressure solenoid valve is proposed to overcome the drawback of the current single spool design.Mathematical models of the opening process and flow rate of the valve are established.Opening response time of the valve is subdivided into 4 parts to analyze the properties of the opening response.Corresponding formulas to solve 4 parts of the response time are derived.Key factors that influence the opening response time are analyzed.According to the mathematical model of the valve,a simulation of the opening process is carried out by MATLAB.Parameters are chosen based on theoretical analysis to design the test prototype of the new type of valve.Opening response time of the designed valve is tested by verifying response of the current in the coil and displacement of the main valve spool.The experimental results are in agreement with the simulated results,therefore the validity of the theoretical analysis is verified.Experimental opening response time of the valve is 48.3 ms at working pressure of 10 MPa.The flow capacity test shows that the largest effective area is 126 mm2 and the largest air flow rate is 2320 L/s.According to the result of the load driving test,the valve can meet the demands of the driving system.The proposed valve with parallel spools provides a new method for the design of a high-pressure valve with fast response and large flow rate.
基金supported by the National Key Technology R&D Program of China (2011BAD19B02-6)the Open Grant of Guangxi Provincial Key Laboratory of Water Buffalo Genetics, Breeding and Reproduction, China (SNKF-2012-04)
文摘The aim of this study was to investigate the feasibility of stimulating ovarian fol icle development in order to improve fertility in water buffalo cows by immunization against inhibin. The experiment was carried out in early summer (May) and included 24 multi-parity crossbred Murrah-Swamp buffaloes that were divided into immunized (n=11) and control (n=13) groups. Each immunized cow was administered with a 2-mL immunogen of mineral oil adjuvant containing 2 mg of recombinant inhibinα-subunit fusion protein. The controls were treated with the adjuvant only. Al animals received Ovsynch protocol treatment, starting on the day of the antigen administration, and they were artiifcial y inseminated upon behavioral estrus. As a result, al of the immunized buffaloes generated antibodies against inhibin during the experimental period and had higher plasma concentrations of fol icle-stimulating hormone (FSH), activin, and estradiol (E2) related to estrous expression. A higher proportion of immunized animals expressed estrus behavior than did the controls (72%vs. 30%, P<0.05). On aver-age, inhibin-immunized buffaloes had signiifcantly more large fol icles (≥9 mm in diameter) than the controls (mean±SEM;1.2±0.1 vs. 0.84±0.1, respectively;P<0.05) and a slightly higher mean total number of fol icles (≥2 mm;11.4±0.7 vs. 9.0±1.1, respectively;P=0.09) and smal (2–4 mm) fol icles (8.81±0.6 vs. 6.84±1.0, respectively;P=0.12). A higher percentage of cows ovulated in the immunized group than in the control group (91%(10/11) vs. 54%(7/13), respectively;P<0.05). Moreover, inhibin-immunized cows had slightly larger corpus luteum (CL) than the controls 9 days after ovulation and signiifcantly higher (P<0.01) post-ovulation peak plasma progesterone (P4) concentrations. Immunization against inhibin also mar-ginal y increased the conception rate 42 days after insemination (45.8%vs. 15.4%;P>0.05). These results demonstrate that immunization against inhibin, coupled with the treatment with the Ovsynch protocol, can constitute a new technique to increase fertility in water buffalo cows.
文摘Quasi-static and high strain rate compressive experiments on vinyl ester casting were carried out by means of MTS (Material Test System) and Hopkinson bar. The behaviors of the compressed unstable and fracture of the resin casting at different strain rates were investigated.The results indicate that the response behavior of the resin casting is controlled by different mechanisms at different strain rate, and some mechanical properties of vinyl ester casting are rate-dependent: the casting are destroyed in toughness model under strain rate 3.3×10 -4~6.6×10 -3/s, while the casting are destroyed in brittleness model under strain rate 950~5800/s. The yield stress, yield strain energy density are all increased with the increasing strain rates at quasi-static as well as at high strain rates. What is interesting is that the yield strain decreased with the strain rates increasing at quasi-static while increased at high strain rates. It is considered that the casting occurred forcing high elastic deformation at high strain rates. The damage of the specimens is mainly controlled by axial stress before unstable deformation, while mainly controlled by shear stress after unstable deformation, and then developed to fracture finally. This progress is rate-dependent: the development of the cracks inside the castings increased with the strain rate increasing.
文摘Intrahepatic cholangiocarcinoma(iCCA)is recognized as the second most frequently diagnosed liver malignancy,following closely after hepatocellular carcinoma.Its incidence has seen a global upsurge in the past several years.Unfortunately,due to the lack of well-defined risk factors and limited diagnostic tools,iCCA is often diagnosed at an advanced stage,resulting in a poor prognosis.While surgery is the only potentially curative option,it is rarely feasible.Currently,there are ongoing investigations into various treatment approaches for unresectable iCCA,including conventional chemotherapies,targeted therapies,immunotherapies,and locoregional treatments.This study aims to explore the role of transarterial radioembolization(TARE)in the treatment of unresectable iCCA and provide a comprehensive review.The findings suggest that TARE is a safe and effective treatment option for unresectable iCCA,with a median overall survival(OS)of 14.9 months in the study cohort.Studies on TARE for unresectable iCCA,both as a first-line treatment(as a neo-adjuvant down-staging strategy)and as adjuvant therapy,have reported varying median response rates(ranging from 34%to 86%)and median OS(12-16 mo).These differences can be attributed to the heterogeneity of the patient population and the limited number of participants in the studies.Most studies have identified tumor burden,portal vein involvement,and the patient’s performance status as key prognostic factors.Furthermore,a phase 2 trial evaluated the combination of TARE and chemotherapy(cisplatin-gemcitabine)as a first-line therapy for locally advanced unresectable iCCA.The results showed promising outcomes,including a median OS of 22 mo and a 22%achievement in down-staging the tumor.In conclusion,TARE represents a viable treatment option for unresectable iCCA,and its combination with systemic chemotherapy has shown promising results.However,it is important to consider treatment-independent factors that can influence prognosis.Further research is necessary to identify optimal treatment combinations and predictive factors for a favorable response in iCCA patients.
文摘In this study,we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m 2 with dexamethasone(BD) and compared it to the standard 1.3 mg/m 2 twice-weekly BD regimen in Chinese patients with newly diagnosed multiple myeloma(MM).We assessed the difference in efficacy,safety profile and survival between the once-weekly and twice-weekly cohorts(13 vs.24 patients).The over response rate was similar with both arms of the study,being 77% in the once-weekly schedule and 74.9% in the twice-weekly schedule(P=0.690).The median overall survival was not reached in either schedule.Also,the median progression-free survival and duration of response of the once-weekly schedule did not significantly differ from those of the twice-weekly schedule(8 months vs.10 months,P=0.545 and 6 months vs.7 months,P=0.467 respectively).Peripheral sensory neuropathy and grade 3/4 hematologic toxic effects were more frequently reported in the twice-weekly schedule than the once-weekly schedule,but there was no statistically significant difference.This preliminary experience in Chinese patients with newly diagnosed MM indicated that once-weekly infusion of Bortezomib plus dexamethasone may improve safety without affecting outcome.
文摘Objectives To analyze the six-minute walk test (6MWT) and gas exchange of 5 heart transplantation patients and to approach the variation tendency of exercise tolerance, oxygen uptake ( VO2 ) and heart rate chronotropic response. Methods 5 cases of heart transplantation patients ( age 25 - 52 years) were undertaken 6MWT 6 - 30 months after operation, synchronizing gas exchanging parameters were measured by wireless portable remote sensing K4B^2 gas analyzer, 51 normal controls were compared. Results The six-minute walk distance (6MWD) of 5 patients were (592.6 ± 26.7 ) m (558 - 625 ) m, the ascending tendency during exercise was slower, the maximum heart rates were 80% ± 6% of age-predicting maximal heart rate, lower than normal control (86%) ; the end point VO2/kg were (21.8 ± 1.4 ) mL/min · kg ( 19. 94 - 23.60) mL/min · kg. Conclusions The 6WMD and VO2 of 5 patients reached normal range, but the heart rate chronotropic response and VO2 ascending tendency were slower than those of normal controls.
基金financially supported by our department (Department of DentalAnesthesiology,Osaka University Graduate School of Dentistry)
文摘Stimulation of the trigeminal nerve can elicit various cardiovascular and autonomic responses;however,the effects of anesthesia with pentobarbital sodium on these responses are unclear.Pentobarbital sodium was infused intravenously at a nominal rate and the lingual nerve was electrically stimulated at each infusion rate.Increases in systolic blood pressure(SBP) and heart rate(HR) were evoked by lingual nerve stimulation at an infusion rate between 5 and 7 mg?kg 21 ?h 21.This response was associated with an increase in the low-frequency band of SBP variability(SBP-LF).As the infusion rate increased to 10 mg?kg 21 ?h 21 or more,decreases in SBP and HR were observed.This response was associated with the reduction of SBP-LF.In conclusion,lingual nerve stimulation has both sympathomimetic and sympathoinhibitory effects,depending on the depth of pentobarbital anesthesia.The reaction pattern seems to be closely related to the autonomic balance produced by pentobarbital anesthesia.
基金support from the National Natural Science Foundation of China(Nos.82003206 and 82173338)Natural Science Foundation of Hunan Province(Nos.2020SK2031,2020SK2030,2021RC4040,and 2020JJ3025).
文摘Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy among patients presenting with intracranial lesions are limited.This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.Methods:Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable,asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1,2019 and September 30,2021.The patients were stratified into two groups according to the first-line treatment regimen received:ICI combined with chemotherapy(n=102)or chemotherapy(n=109).Systemic and intracranial objective response rates(ORRs)and progression-free survival(PFS)were analyzed.Adverse events were also compared between the groups.Results:Compared with the chemotherapy-based regimen,the ICI-containing regimen was associated with a significantly higher intracranial(44.1%[45/102]vs.28.4%[31/109],χ^(2)=5.620,P=0.013)and systemic(49.0%[50/102]vs.33.9%[37/109],χ^(2)=4.942,P=0.019)ORRs and longer intracranial(11.0 months vs.7.0 months,P<0.001)and systemic(9.0 months vs.5.0 months,P<0.001)PFS.Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS(hazard ratio[HR]=0.52,95%confidence interval[CI]:0.37-0.73,P<0.001)and systemic PFS(HR=0.48,95%CI:0.35-0.66,P<0.001).No unexpected serious adverse effects were observed.Conclusion:Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.Clinical trial registration:https://www.clinicaltrials.gov/,OMESIA,NCT05129202.
基金This study was supported by the Chinese Society of Clinical Oncology(CSCO)-Hengrui Oncology Research Fund(No.Y-HR2018-364)。
文摘Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects.Therefore,we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.Methods:In this single-arm prospective phase II trial,patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg,liposomal paclitaxel 150 mg/m2,and nedaplatin 50 mg/m2 on day 1,and apatinib 250 mg on days 1-14.The treatments were repeated every 14 days for up to 9 cycles,followed by maintenance therapy with camrelizumab and apatinib.The primary endpoint was objective response rate(ORR)according to the Response Evaluation Criteria in Solid Tumors(version 1.1).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and safety.Results:We enrolled 30 patients between August 7,2018 and February 23,2019.The median follow-up was 24.98 months(95%confidence interval[CI]:23.05-26.16 months).The centrally assessed ORR was 80.0%(95%CI:61.4%-92.3%),with a median duration of response of 9.77 months(range:1.54 to 24.82+months).The DCR reached 96.7%(95%CI:82.8%-99.9%).The median PFS was 6.85 months(95%CI:4.46-14.20 months),and the median OS was 19.43 months(95%CI:9.93 months–not reached).The most common grade 3-4 treatmentrelated adverse events(AEs)were leukopenia(83.3%),neutropenia(60.0%),and increased aspartate aminotransferase level(26.7%).Treatment-related serious AEs included febrile neutropenia,leukopenia,and anorexia in one patient(3.3%),and single cases of increased blood bilirubin level(3.3%)and toxic epidermal necrolysis(3.3%).No treatment-related deaths occurred.Conclusions:Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feasible anti-tumor activity and manageable safety in patients with advanced ESCC.Randomized trials to evaluate this new combination strategy are warranted.Trial registration:This trial was registered on July 27,2018,at ClinicalTrials.gov(identifier:NCT03603756).
基金This study was supported by the National Key Basic Research Program of China(973 Program No.2015CB553902)
文摘Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC.
文摘Background: Oxaliplatin, irinotecan, 5-fluorouracil, and l-leucovorin (FOLFIRINOX) has become one of the first-line treatment options for advanced pancreatic cancer (PC). However, the relatively high rate of grade 3 or 4 adverse events associated with the standard dosage of FOLFIRINOX limits its widespread use in clinical practice. In this study, we were to evaluate the efficacy and safety of a modified FOLFIRINOX regimen as a first-line chemotherapy for Chinese patients with metastatic PC. Methods: Patients with histologically confirmed primary metastatic pancreatic adenocarcinoma with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 were recruited to receive the modified FOLFIRINOX regimen (intravenous infusion of oxaliplatin, 65 mg/m2;irinotecan, 150 mg/m2;l-leucovorin, 200 mg/ m2;and 5-fluorouracil, 2400 mg/m2, repeated every 2 weeks). The treatment was continued for 12 cycles unless the patient had progressive disease (PD), stable disease (SD) with symptom deterioration, unacceptable adverse events, or requested to terminate the treatment prematurely. The primary endpoint was objective response rate (ORR). Results: Sixty-five patients were enrolled from July 2012 to April 2017 in three institutions, and they all received at least one cycle of chemotherapy, with a median of 8 cycles (range 1-12 cycles). No complete response was observed. Twenty-one (32.3%) patients had partial responses, and 27 (41.5%) had SD. The ORR and disease control rate of the study cohort was 32.3% and 73.8%. The estimated median overall survival and progression-free survival were 11.60 (95% confidence interval [CI] 8.76-14.44) and 5.77 (95% CI 5.00-6.54) months. Major grade 3 or 4 adverse events included neutropenia (12.3%) and diarrhea (6.2%). No treatment-related death was observed. Conclusions: Modified FOLFIRINOX was well-tolerated and might be a promising option as first-line therapy for Chinese patients with metastatic PC.
基金This study was supported by grants from National Natural Science Foundation of China(No.82070784 and No.81974099)a grant from 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYGD18011)to HL.
文摘Neoadjuvant chemotherapy(NAC)has shown promising results in patients with locally advanced penile cancer.However,no consensus exists on its applications for locally advanced penile cancer.Thus,it is unclear which kind of chemotherapy regimen is the best choice.Consequently,a systematic search of PubMed,Web of Science,and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer.The Newcastle–Ottawa Scale was used to assess the risk of bias in each study.This study synthesized 14 published studies.The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response.In addition,the objective response rates(ORRs)and pathological complete response(pCR)rates were 0.57 and 0.11,respectively.The incidence of grade≥3 toxicity was 0.36.Subgroup analysis found that the ORR and pCR of the taxane–platinum(TP)regimen group performed better than those of the nontaxane–platinum(NTP)regimen group(0.57 vs 0.54 and 0.14 vs 0.07,respectively).Moreover,the TP regimen group had more frequent toxicity than the NTP regimen group(0.41 vs 0.26).However,further studies were warranted to confirm the findings.
文摘In this study,issues concerning the design of scales for measuring teacher sense of efficacy(TSE)are first identified with particular attention to the Teacher Sense of Efficacy Scale(TSES).Psychometric issues concerning analysis and reporting of TSE data are subsequently identified.Recommendations are offered about all identified issues,and these recommendations are taken into account when obtaining and analyzing TSE data from Chinese mainland preservice and inservice teachers.Exploratory factor analyses yielded a single factor for both samples as well as for four subgroups within the inservice teacher sample.Results also provided insights about scale design as well as the TSES being limited for capturing the breadth of TSE.Suggestions are made for improvements in the assessment of TSE.
基金The authors declare that they have no competing interests.We thank the patients and their families who participated in this studyThis work was supported by the National Natural Science Foundation of China(Grant No.81502667)the Shandong Provincial Natural Science Foundation(ZR2016HM35).
文摘Objective:Several studies have found that epigallocatechin-3-gallate(EGCG)can alleviate acute radiation-induced esophagitis,inhibit pulmonary inflammation and fibrosis,and reduce the severity of cardiovascular disease.Therefore,this study was aimed at exploring the influence of EGCG on late radiation toxicity in the heart,esophagus,and lungs among patients with locally advanced lung cancer.Methods:The patients were divided into an EGCG group and a control group,the groups received EGCG and symptomatic treatment,respectively.The Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme was used to determine the late toxicity scores.Tumor responses were evaluated by chest computed tomography(CT),based on the Response Evaluation Criteria in Solid Tumors version 1.1.Results:We retrospectively analyzed 74 patients treated at our hospital from September 2012 to September 2016(37 patients received EGCG and 37 received supportive treatment).The late toxicity scores of the EGCG group decreased compared to those of the control group.An obvious clinical significance was observed for the oral EGCG solution in the treatment and prevention of late cardiac,esophageal,and pulmonary toxicity.However,no significant difference was found(P>0.05).The tumor response rates were similar in the two groups.Moreover,there was no difference in progression-free survival(PFS)between the groups(P>0.05).Conclusion:Oral EGCG solution might alleviate radiation-induced late cardiac,esophageal,and pulmonary toxicity but has no significant effect on the tumor response rate and PFS following radiotherapy.
基金This work was supported by the Foundation of the World Bank and Global Environment Facility(Grant No.60K04772).
文摘This work evaluates the influence of energy consumption on the future air quality in Beijing,using 2000 as the base year and 2008 as the target year.It establishes the emission inventory of primary PM_(10),SO_(2) and NO_(x) related to energy utilization in eight areas of Beijing.The air quality model was adopted to simulate the temporal and spatial distribution of each pollutant concentration in the eight urban areas.Their emission,concentration distribution,and sectoral share responsibility rate were analyzed,and air quality in 2008 was predicted.The industrial sector contributed above 40% of primary PM_(10) and SO_(2) resulting from energy consumption,while vehicles accounted for about 65% of NO_(x).According to the current policy and development trend,air quality in the eight urban areas could become better in 2008 when the average concentrations of primary PM_(10),SO_(2) and NO_(2) related to energy utilization at each monitored site are predicted to be about 25,50 and 51μg/m^(3),respectively.