Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.

Cytokine release syndrome triggered by programmed death 1 blockade(sintilimab)therapy in a psoriasis patient:A case report

BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity.At embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction.The LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three dosages.Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS group.Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS group.Quercetin significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS induction.Quercetin significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of AMPKα1,LC3-I,and LC3-II.Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.Conclusion Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy,programmed cell death,and myocardiocytes permeability.

Unresectable hepatocellular carcinoma:Transarterial chemoembolization combined with lenvatinib in combination with programmed death-1 inhibition is a possible approach

In this editorial,we review the article“Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma”.We specifically focused on whether transarterial chemoembolization combined with lenvatinib in combination with a programmed death 1 inhibitor could be used in patients with unresectable hepatocellular carcinoma.Since both transarterial chemoembolization as well as lenvatinib in combination with programmed death 1 inhibitors play an important role in the treatment of advanced liver cancer,but the combination of all three therapeutic approaches needs more research.

Pretreatment can alleviate programmed cell death in mesenchymal stem cells

In this editorial,we delved into the article titled“Cellular preconditioning and mesenchymal stem cell ferroptosis.”This groundbreaking study underscores a pivotal discovery:Ferroptosis,a type of programmed cell death,drastically reduces the viability of donor mesenchymal stem cells(MSCs)after engraftment,thereby undermining the therapeutic value of cell-based therapies.Furthermore,the article proposes that by manipulating ferroptosis mechanisms through preconditioning,we can potentially enhance the survival rate and functionality of MSCs,ultimately amplifying their therapeutic potential.Given the crucial role ferroptosis plays in shaping the therapeutic outcomes of MSCs,we deem it im-perative to further investigate the intricate interplay between programmed cell death and the therapeutic effectiveness of MSCs.

Efficacy comparison of fruquintinib,regorafenib monotherapy or plus programmed death-1 inhibitors for microsatellite stable metastatic colorectal cancer

BACKGROUND Regorafenib(R)and fruquintinib(F)are the standard third-line regimens for colorectal cancer(CRC)according to the National Comprehensive Cancer Network guidelines,but both have limited efficacy.Several phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair(MSS/pMMR)CRC.Due to the lack of studies comparing the efficacy between F,R,F plus programmed death-1(PD-1)inhibitor,and R plus PD-1 inhibitors(RP),it is still unclear whether the combination therapy is more effective than monotherapy.AIM To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC(mCRC)patients in clinical practice.METHODS A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital,and 313 MSS/pMMR mCRC patients were finally included.RESULTS A total of 313 eligible patients were divided into F(n=70),R(n=67),F plus PD-1 inhibitor(FP)(n=95)and RP(n=81)groups.The key clinical characteristics were well balanced among the groups.The median progression-free survival(PFS)of the F,R,FP,and RP groups was 3.5 months,3.6 months,4.9 months,and 3.0 months,respectively.The median overall survival(OS)was 14.6 months,15.7 months,16.7 months,and 14.1 months.The FP regimen had an improved disease control rate(DCR)(P=0.044)and 6-month PFS(P=0.014)and exhibited a better trend in PFS(P=0.057)compared with F,and it was also significantly better in PFS than RP(P=0.030).RP did not confer a significant survival benefit;instead,the R group had a trend toward greater benefit with OS(P=0.080)compared with RP.No significant differences were observed between the R and F groups in PFS or OS(P>0.05).CONCLUSION FP is superior to F in achieving 6-month PFS and DCR,while RP is not better than R.FP has an improved PFS and 6-month PFS compared with RP,but F and R had similar clinical efficacy.Therefore,FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics.METHODS We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy.PD-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive score.All PD-L1+PT staged as pN+were also tested for PD-L1 expression in their LNM.PD-L1(-)GC with pN+served as the comparison group.RESULTS Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the LNM.Regarding PD-L1(-)PT,9.1%(4/44)had PD-L1+in the LNM.The agreement between PT and LNM had a kappa value of 0.483.Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites.There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM.This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

Roles of the tumor microenvironment in the resistance to programmed cell death protein 1 inhibitors in patients with gastric cancer

Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advanced GC.In recent years,with the progress in tumor immunology research,attention has shifted toward immunotherapy as a therapeutic approach for GC.Programmed cell death protein 1(PD-1)inhibitors,as novel immunosuppressive medications,have been widely utilized in the treatment of GC.However,many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy.To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy,to maximize the clinical activity of immunosuppressive drugs,and to elicit a lasting immune response,it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients.This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment,aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.

Effect of programmed comprehensive nursing on delirium incidence in intensive care unit children following severe cardiac surgery

BACKGROUND Programmed comprehensive nursing was adopted for intensive care unit(ICU)children following severe cardiac surgery to improve respiratory function and delirium incidence.AIM To explore how programmed comprehensive nursing impacts respiratory func-tion and delirium incidence in ICU children post cardiac surgery.METHODS Between January 2022 and January 2024,180 pediatric patients from the Chil-dren’s Hospital of Nanjing were admitted to the ICU after cardiac surgery and randomly grouped.The control group comprised 90 patients and received routine nursing care.The observation group comprised 90 patients and received program-med comprehensive nursing.Both groups received continuous nursing care until discharge.Their respiratory function,incidence of delirium,and clinical outcomes were compared.The memory state and sleep quality of both groups were com-pared.RESULTS The incidence of delirium was 5.56%in the observation group when admitted to ICU,which was lower than that in the control group(20.00%;P<0.05).The observation group demonstrated higher peak expiratory flow rate,respiratory frequency,deep breathing volume,and tidal volume in the ICU compared with the control group.Additionally,the observation group showed higher sleep depth,sleep latency,night awakening,return to sleep,and sleep quality com-pared with the control group(P<0.05).CONCLUSION Programmed comprehensive nursing in ICU patients following severe cardiac surgery can reduce the impact on respiratory function,improve sleep quality,and alleviate postoperative delirium,showing significant promise for clinical application.

C-reactive protein to albumin ratio predict responses to programmed cell death-1 inhibitors in hepatocellular carcinoma patients

BACKGROUND Over the years,programmed cell death-1(PD-1)inhibitors have been routinely used for hepatocellular carcinoma(HCC)treatment and yielded improved survival outcomes.Nonetheless,significant heterogeneity surrounds the outcomes of most studies.Therefore,it is critical to search for biomarkers that predict the efficacy of PD-1 inhibitors in patients with HCC.AIM To investigate the role of the C-reactive protein to albumin ratio(CAR)in evaluating the efficacy of PD-1 inhibitors for HCC.METHODS The clinical data of 160 patients with HCC treated with PD-1 inhibitors from January 2018 to November 2022 at the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed.RESULTS The optimal cut-off value for CAR based on progression-free survival(PFS)was determined to be 1.20 using x-tile software.Cox proportional risk model was used to determine the factors affecting prognosis.Eastern Cooperative Oncology Group performance status[hazard ratio(HR)=1.754,95%confidence interval(95%CI)=1.045-2.944,P=0.033],CAR(HR=2.118,95%CI=1.057-4.243,P=0.034)and tumor number(HR=2.932,95%CI=1.246-6.897,P=0.014)were independent prognostic factors for overall survival.CAR(HR=2.730,95%CI=1.502-4.961,P=0.001),tumor number(HR=1.584,95%CI=1.003-2.500,P=0.048)and neutrophil to lymphocyte ratio(HR=1.120,95%CI=1.022-1.228,P=0.015)were independent prognostic factors for PFS.Two nomograms were constructed based on independent prognostic factors.The C-index index and calibration plots confirmed that the nomogram is a reliable risk prediction tool.The ROC curve and decision curve analysis confirmed that the nomogram has a good predictive effect as well as a net clinical benefit.CONCLUSION Overall,we reveal that the CAR is a potential predictor of short-and long-term prognosis in patients with HCC treated with PD-1 inhibitors.If further verified,CAR-based nomogram may increase the number of markers that predict individualized prognosis.

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Cytokine release syndrome induced by anti-programmed death-1 treatment in a psoriasis patient:A dark side of immune checkpoint inhibitors

In recent years,cancer immunotherapy has introduced novel treatments,such as monoclonal antibodies,which have facilitated targeted therapies against tumor cells.Programmed death-1(PD-1)is an immune checkpoint expressed in T cells that regulates the immune system’s activity to prevent over-activation and tissue damage caused by inflammation.However,PD-1 is also expressed in tumor cells and functions as an immune evasion mechanism,making it a therapeutic target to enhance the immune response and eliminate tumor cells.Consequently,immune checkpoint inhibitors(ICIs)have emerged as an option for certain tumor types.Nevertheless,blocking immune checkpoints can lead to immune-related adverse events(irAEs),such as psoriasis and cytokine release syndrome(CRS),as exemp-lified in the clinical case presented by Zhou et al involving a patient with adva-nced gastric cancer who received sintilimab,a monoclonal antibody targeting PD-1.Subsequently,the patient experienced exacerbation of psoriasis and CRS.The objective of this editorial article is to elucidate potential immunologic mechanisms that may contribute to the development of CRS and psoriasis in patients receiving ICIs.It is crucial to acknowledge that while ICIs offer superior safety and efficacy compared to conventional therapies,they can also manifest irAEs affecting the skin,gastrointestinal tract,or respiratory system.In severe cases,these irAEs can lead to life-threatening complications such as circulatory shock or multiorgan failure.Consequently,it is recommended that patients receiving ICIs undergo regular monitoring to identify and manage these adverse events effectively.

Drug-eluting beads chemoembolization combined with programmed cell death 1 inhibitor and lenvatinib for large hepatocellular carcinoma

BACKGROUND The combination of transarterial chemoembolization(TACE),lenvatinib,and programmed cell death 1(PD-1)inhibitor has been widely used in the treatment of advanced hepatocellular carcinoma(HCC)and has achieved promising results.However,there are few studies comparing whether drug-eluting beads TACE(DTACE)can bring more survival benefits to patients with large HCC compared to conventional TACE(C-TACE)in this triplet therapy.AIM To compare the efficacy and adverse events(AEs)of triple therapy comprising DTACE,PD-1 inhibitors,and lenvatinib(D-TACE-P-L)and C-TACE,PD-1 inhibitors,and lenvatinib(C-TACE-P-L)in patients with large HCC(maximum diameter≥5 cm),and analyze the prognostic factors.METHODS Following a comprehensive review of our hospital’s medical records,this retrospective study included 104 patients:50 received D-TACE-P-L,and 54 received CTACE-P-L.We employed Kaplan-Meier estimation to assess the median progression-free survival(PFS)between the two groups,utilized Cox multivariate regression analysis to identify prognostic factors,and applied theχ2 test to evaluate AEs.RESULTS The objective response rate(ORR)and median PFS were significantly higher in the D-TACE-P-L group compared to the C-TACE-P-L group(ORR:66.0%vs 44.4%,P=0.027;median PFS:6.8 months vs 5.0 months,P=0.041).Cox regression analysis identified treatment option,portal vein tumor thrombus,and hepatic vein invasion as protective factors for PFS.AEs were comparable between the two CONCLUSION D-TACE-P-L may have significantly better PFS and ORR for large HCC,while exhibiting similar AEs to C-TACE-PL.

Programmed cell death 1 inhibitor sintilimab plus concurrent chemoradiotherapy for locally advanced pancreatic adenocarcinoma

BACKGROUND Pancreatic adenocarcinoma,a malignancy that arises in the cells of the pancreas,is a devastating disease with unclear etiology and often poor prognosis.Locally advanced pancreatic cancer,a stage where the tumor has grown significantly but has not yet spread to distant organs,presents unique challenges in treatment.This article aims to discuss the current strategies,challenges,and future directions in the management of locally advanced pancreatic adenocarcinoma(LAPC).AIM To investigate the feasibility and efficacy of programmed cell death 1(PD-1)inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC.METHODS Eligible patients had LAPC,an Eastern cooperative oncology group performance status of 0 or 1,adequate organ and marrow functions,and no prior anticancer therapy.In the observation group,participants received intravenous sintilimab 200 mg once every 3 wk,and received concurrent chemoradiotherapy(concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-140 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression,death,or unacceptable toxicity).In the control group,participants only received concurrent chemoradiotherapy.From April 2020 to November 2021,64 participants were finally enrolled with 34 in the observation group and 30 in the control group.RESULTS Thirty-four patients completed the scheduled course of chemoradiotherapy,while 32(94.1%)received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group.Thirty patients completed the scheduled course of chemoradiotherapy in the control group.Based on the Response Evaluation Criteria in Solid Tumors guidelines,the analysis of the observation group revealed that a partial response was observed in 11 patients(32.4%),stable disease was evident in 19 patients(55.9%),and 4 patients(11.8%)experienced progressive disease;a partial response was observed in 6(20.0%)patients,stable disease in 18(60%),and progressive disease in 6(20%)in the control group.The major toxic effects were leukopenia and nausea.The incidence of severe adverse events(AEs)(grade 3 or 4)was 26.5%(9/34)in the observation group and 23.3%(7/30)in the control group.There were no treatment-related deaths.The observation group demonstrated a significantly longer median overall survival(22.1 mo compared to 15.8 mo)(P<0.05)and progression-free survival(12.2 mo vs 10.1 mo)(P<0.05)in comparison to the control group.The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group(P>0.05).CONCLUSION Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients,and warrants further investigation.

Effectiveness and tolerability of programmed cell death protein-1 inhibitor+chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers

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.

Mitochondrial dysfunction and programmed cell death in osteosarcoma

Osteosarcoma is the most prevalent primarymalignant bone tumor,primarily affecting adolescents aged 15–25 years.It is characterized by a high recurrence rate,poor prognosis,and lack of important biomarkers.Significant mitochondrial dysfunction in osteosarcoma cells has been widely reported by recent studies.Dysfunctional mitochondria occupy an important position in cellularmetabolic reprogramming,immune microenvironment regulation,and programmed cell death.Therefore,targeting mitochondrial dysfunction may represent a new mechanism to overcome therapeutic barriers in the treatment of osteosarcoma and provides crucial target molecules for further development of targeted therapies and immunotherapies.The present article summarizes the recent reports of mitochondrial dysfunction in osteosarcoma and links it to various programmed cell death mechanisms,aiming to provide the basis for further clinical practice.

基于GC-IMS和GC-MS技术结合化学计量法分析干燥方式对香椿挥发性成分的影响

为研究干燥方式对香椿挥发性风味物质的影响,利用气相色谱-离子迁移谱技术(gaschromatography-ion mobility spectrometry,GC-IMS)和气相色谱-质谱联用技术(gas chromatography-mass spectrometry,GC-MS)、相对香气活性值(relative odor activity value,ROAV)对真空冷冻干燥、热泵干燥、热风干燥、微波真空干燥的香椿样品进行挥发性成分分析,并进一步结合化学计量方法主成分分析(principal component analysis,PCA)和偏最小二乘判别分析(partial least squares-discriminant analysis,PLS-DA),探究样品间挥发性成分的差异性。结果表明,通过GC-IMS检测到78个峰,鉴定出59种化合物。通过GC-MS鉴定出94种挥发性化合物,主要挥发性成分是硫化物、烯烃类和醛类。经过干燥后总挥发性化合物的含量显著降低。通过ROAV法确定了(E,Z)-二-1-丙烯基二硫化物、2-巯基-3,4-二甲基-2,3-二氢噻吩、正己醛、2-己烯醛、丁香酚等为香椿样品中关键香气化合物。PCA和PLS-DA结果表明,不同干燥方式的样品与新鲜样品有明显的分离,彼此之间也有明显的区别。鲜样和真空冷冻干燥样品为一组,其他3个干燥香椿样品为一组。根据变量投影重要性(variable importance in projection,VIP)得分共筛选出10种(VIP>1)标志挥发性化合物。干燥方式对香椿风味特性影响显著,真空冷冻干燥组与鲜样最为接近,考虑实际应用热泵干燥为香椿最适宜的脱水方式。本研究为热加工过程中风味品质控制提供一定的理论参考。

GC-MS结合电子鼻技术对不同茶区茉莉花茶香气的差异比较

为探究不同产区茉莉花茶香气差异,采用气相色谱-质谱(GasChromatography-Mass Spectrometry,GC-MS)结合电子鼻(Electronic Nose,E-nose)技术对西南、华南、江南三大茶区的8种茉莉花茶进行香气研究。结果表明,8个样品共鉴定出香气成分58种,其中西南、江南、华南茶区分别为45种、51种、47种。江南茶区香气化合物总量最高。共有香气成分主要包括邻氨基苯甲酸甲酯、顺式-3-己烯醇苯甲酸酯、乙酸苄酯、水杨酸甲酯、芳樟醇、吲哚等。其中水杨酸甲酯在江南茶区含量最高(22.32μg/g),分别较华南、西南茶区高33.96%、68.01%;邻氨基苯甲酸甲酯(67.39μg/g)和吲哚(43.84μg/g)含量在华南茶区最高。茉莉花茶香气评价指数(JasmineTea Flavor Index,JTF index)分析表明西南茶区样品等级最高。香气聚类分析将共有香气成分分为3类,分别呈花香、茉莉花香和草木香。通过电子鼻技术可知样品香气物质变化与硫化物、碳氢化合物、芳香化合物有关,并能有效区别样品香气。综上,三大茶区样品香气种类差异不明显,但各香气成分含量差异显著(P<0.05),江南和华南茶区的样品特征性香气成分含量较高,西南茶区样品综合指数高。

SPME-HS-GC-MS与电子鼻分析不同产地多花酒黄精气味特征

目的:分析不同产地多花酒黄精的气味特征,为产地判别、分析方法改进提供依据。方法:以11个产地的多花酒黄精细粉为研究样品,采用固相微萃取-顶空进样-气质联用法(SPME-HS-GC-MS)分析多花酒黄精挥发性成分,采用电子鼻智能感官评定技术分析多花酒黄精气味雷达图,采用主成分(PCA)、Loadings方法分析电子鼻信号响应结果,构建产地判别模型。结果:SPME-HS-GC-MS法结果共鉴别出32个挥发性成分,其中19个差异性挥发性成分可用于8个产地的区分。电子鼻结果表明,主成分判别分析能较好地区分不同产地多花酒黄精,多花酒黄精在气味上的差异主要体现在芳香成分,氮氧化合物、氨类、烷烃、甲烷等短链烷烃、无机硫化物、有机硫化物等。结论:不同产地多花酒黄精的气味特征存在差异,可作为产地判别依据。电子鼻技术可为多花酒黄精分析及质量标准提供简单、快速的新方法。

硅烷衍生化GC-MS检测香精中糖类物质成分

建立了基于硅烷衍生化气相色谱-质谱联用法快速检测香精中17种糖类物质的方法。结果表明:衍生化的最佳条件为以BSTFA为衍生化试剂、衍生化温度40℃、衍生化时间40 min,在此条件下共鉴定出17种糖类物质。17种糖类物质在一定质量浓度内具有良好的线性关系(R^(2)>0.99)。方法的检出限为0.027~0.077μg/mL,加标回收率为94.80%~110.03%,相对标准偏差为3.03%~8.06%。实际样品测定结果表明,建立的方法能够快速准确地检测香精中17种糖类物质成分,满足对香精中糖类物质的同时检测。