Objective： To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods： Seventy two female BALB/c mice were randomly assigned into six groups. The mice w...Objective： To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods： Seventy two female BALB/c mice were randomly assigned into six groups. The mice were vaccinated with soluble Leishmania antigens （SLA） alone, artemisinin co-administered with SLA, SLA and Bacille Calmette Gu fin （BCG） vaccine, and artemisinin and BCG alone. Unvaccinated mice formed the control group. The induction of cell-mediated immunity following vaccination was determined by measuring in vitro lymphocyte proliferation and the production of interleukin （IL）-4, IL-5 and gamma interferon （IFN-γ） determined by flow cytometry. Protection against L. major was determined by quantifying parasite burdens in L. major infected footpads using a limiting dilution assay and by measuring lesion sizes of the infected footpad compared to the contralateral uninfected footpad. Results： Mice receiving SLA plus artemisinin produced significantly high levels of IL-4 and IL-5 （P 〈 0.05） and low levels of IFN-γ, resulting in exacerbated disease. In addition, subcutaneous administration of SLA ＋ artemisinin, artemisinin alone or SLA alone resulted in the development of large footpad swellings and high parasite loads that were comparable to those of the control unvaccinated mice （P 〉 0.05）, resulting in exacerbated disease. Conclusion： These data suggest that artemisinin is not a suitable adjuvant for Leishmania vaccines. However, since artemisinin has been shown to be effective against Leishmania parasites in vitro and in vivo, further studies ought to be conducted to determine its immunochemotherapeutic potential when co-administered with Leishmania antigens.展开更多
Toll-like receptor 5 （TLR5） signaling in response to flagellin is dispensable for inducing humoral immunity, but alterations of aa 89-96, the TLR5 binding site, significantly reduced the adjuvanticity of flagellin. ...Toll-like receptor 5 （TLR5） signaling in response to flagellin is dispensable for inducing humoral immunity, but alterations of aa 89-96, the TLR5 binding site, significantly reduced the adjuvanticity of flagellin. These observations indicate that the underlying mechanism remains incompletely understood. Here, we found that the native form of Salmonella typhimurium aa 89-96-mutant flagellin extracted from flagella retains some TLR5 recognition activity, indicating that aa 89-96 is the primary, but not the only site that imparts TLR5 activity. Additionally, this mutation impaired the production of IL-lp and IL-18. Using TLR5KO mice, we found that aa 89-96 is critical for the humoral adjuvant effect, but this effect was independent of TLR5 activation triggered by this region of flageUin. In summary, our findings suggest that aa 89-96 of flagellin is not only the crucial site responsible for TLR5 recognition, but is also important for humoral immune adjuvanticity through a TLR5-independent pathway.展开更多
Background Cholera toxin B subunit （CTB） was shown to be a potent adjuvant for protein immunogen, especially when inoculated through mucosal route. We aimed to optimize the expression approach for CTB and thereafter...Background Cholera toxin B subunit （CTB） was shown to be a potent adjuvant for protein immunogen, especially when inoculated through mucosal route. We aimed to optimize the expression approach for CTB and thereafter to determine the adjuvant effect on DNA vaccine. Methods Wild type CTB coding gene was amplified and cloned into prokaryotic expression vector pET-30a, and the recombinant CTB was expressed in the presence of different concentration of chloramphenicol and isopropyl β-D-thiogalactoside. Purified recombinant CTB was mixed with HIV-1 AE2f tat-rev-integrase-vif-nef fusion gene DNA vaccine and female BALB/c mice were vaccinated with a DNA priming-recombinant vaccinia vectored vaccine boosting regimen through intramuscular injection. Interferon γ （IFN-γ） enzyme-linked immunospot （Elispot） assay was used to read out the specific T-cell immunity. Results Chloramphenicol was essential for the efficient expression of recombinant CTB （rCTB） in pET-30a/BL21 （DE3） system and could be optimized at the concentration of 0.625 μg/ml in the presence of chloramphenicol. The purified rCTB could bind with GM1 efficiently. INF-γ Elispot data showed the T-cell response induced in CTB adjuvanted group （（734±240） spot forming cells/106 splenocytes） was higher than that induced by non-adjuvanted （（520±150） spot forming cells/10e splenocytes）, all responses against different antigens were enhanced in parallel. Conclusion CTB could be efficiently expressed in the presence of chloramphenicol and purified CTB is functional and capable of enhancincl the specific T cell responses elicited by DNA vaccine, the mechanism needs to be explored in the future.展开更多
OBJECTIVE:To investigate the clinical efficacy of using a Jiedu formula(解毒方) as an adjunctive therapy in patients with hepatocellular carcinoma(HCC) after hepatectomy.METHODS:In total,354 patients were included in ...OBJECTIVE:To investigate the clinical efficacy of using a Jiedu formula(解毒方) as an adjunctive therapy in patients with hepatocellular carcinoma(HCC) after hepatectomy.METHODS:In total,354 patients were included in this study.All patients were categorized into the traditional herbal medicine(THM) group(n = 115) or the non-THM treatment(nTHM) group(n = 239),with the Jiedu formula administered twice a day to the patients in the THM group.The primary outcome was recurrence-free survival(RFS).Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors associated with RFS.Then,the high risk of recurrence among patients was identified,and propensity score matching(PSM) and RFS analysis were performed to analyze the prognostic factors for the outcomes of patients at a high risk of recurrence in different groups.RESULTS:The one,two,three,and five-year RFS rates of the THM and nTHM groups were 76.4% vs 66.1%,65.5% vs 48.8%,57.9% vs 39.9%,and 43.9% vs 29.2%,respectively.The results of the Multivariate Cox analysis showed that giant tumors [hazard ratio(HR),1.54,P = 0.04],poor degree of differentiation,microsatellite,or microvascular invasion(HR,1.29,P = 0.09) increased the risk of recurrence.In the population with a high risk of recurrence,after PSM,the one,two,three,and five-year survival rates were 70.6% vs 68.0%,63.0% vs 43.1%,59.6% vs 33.3%,and 41.9% vs 26.4%,respectively.CONCLUSION:In this study,THM was found to be an effective agent for adjuvant therapy for HCC to prevent early recurrence of HCC after hepatic resection.展开更多
Objective:To investigate the therapeutic adjuvant potential of fucoidan in cervical cancer and to evaluate its efficacy in combination with immunotherapy.Methods:Fucoidan extracted from Fucus vesiculosus was dissolved...Objective:To investigate the therapeutic adjuvant potential of fucoidan in cervical cancer and to evaluate its efficacy in combination with immunotherapy.Methods:Fucoidan extracted from Fucus vesiculosus was dissolved in phosphate buffered saline and used to treat TC-1 cervical cancer cells in vitro as well as tumor-bearing C57BL/6 mice in vivo.Mice were divided into four groups:the vehicle control group,the mRNA therapy-alone group,the fucoidan-only group,and the combination group.MAPK signaling proteins(p-ERK,T-ERK,p-p38)were analyzed by Western blotting assays.T cell surface markers and intracellular cytokines in splenocytes were assessed by flow cytometry,and plasma cytokine levels were measured by ELISA.Results:Fucoidan decreased the p-ERK/T-ERK ratio and p-p38.Fucoidan combined with mRNA therapy did not significantly affect CD4^(+)T-cell activation but reduced CD8^(+)T-cell activation compared with mRNA therapy alone.MCP-1 and IFN-γwere significantly reduced in the combination therapy group compared with mRNA therapy alone,while IL-6,TNF-α,perforin,and granzyme B did not show significant changes between the two groups.Conclusions:These findings suggest that fucoidan could inhibit excessive T cell activation and cytokine production by suppressing MAPK p-p38 protein expression.展开更多
Background:Hepatocellular carcinoma(HCC)recurrence following liver transplantation(LT)remains a major challenge.This study aimed to investigate the effect of adjuvant chemotherapy(ACT)with the modified FOLFOX-6(mFOLFO...Background:Hepatocellular carcinoma(HCC)recurrence following liver transplantation(LT)remains a major challenge.This study aimed to investigate the effect of adjuvant chemotherapy(ACT)with the modified FOLFOX-6(mFOLFOX-6)regimen on the post-transplant prognosis of HCC patients.Methods:HCC patients who underwent LT at our institution from June 2017 to December 2019 were enrolled.The cohort was divided into the ACT group(n=57)and the non-ACT group(n=93).The median post-transplant follow-up period was 54.0 months.The study endpoints were HCC recurrence and patient mortality following LT.The association between ACT and recurrence/mortality were evaluated through univariate and multivariate analyses utilizing a Cox proportional hazards model,propensity score adjustment,propensity score matching,and inverse probability of treatment weighting(IPTW)analyses.A stratification analysis was performed to determine the interaction effects.Results:The ACT group was younger and had worse tumor characteristics including tumor number,tu-mor size,portal vein tumor thrombosis,pathological differentiation and microvascular invasion(MVI).The ACT group also demonstrated a lower risk of mortality than the non-ACT group(hazard ratio=0.36,P=0.017).It was consistent across sensitivity analyses utilizing propensity score adjustment and match-ing.There was a significant stronger association between ACT and recurrence-free benefit in patients with grade M2 of MVI compared to patients with grade M0/1(P for interaction=0.002).Conclusions:ACT with mFOLFOX-6 regimen decreased the recurrence and mortality risks following LT for HCC patients.ACT may be considered in HCC patients with high risk of recurrence and mortality after LT.展开更多
While exerting their metabolic activities in the gastrointestinal milieu,probiotics impact the host well-being by boosting immunity,treating metabolic disorders,and modulating microbiota and metabolome.Due to the high...While exerting their metabolic activities in the gastrointestinal milieu,probiotics impact the host well-being by boosting immunity,treating metabolic disorders,and modulating microbiota and metabolome.Due to the high incidence of gluten-based disorders,the present work aims to deeply explore the metabolism of two selected microbial consortia(MCs)during gluten digestion under simulated gastrointestinal conditions.Featured by high protease and peptidase activity,both MCs accounted for different lactic acid bacteria and Bacillus strains that were combined with two commercial protease enzymes.Gluten substrates were used as purified extracts,white and whole wheat breads.Control samples,instead,relied onto the microbial enzyme lack.Twenty-four hours of simulated digestion were sufficient to completely hydrolyze gluten in one of the two MC-containing experimental sets,and the relative 48 h-digested extract did not alter the cytokine expression in duodenal biopsies from celiac disease(CeD)patients.When digested samples were assayed for antioxidant and phytase activities,microbial enzymes demonstrated to significantly improve both 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS)and 1,1-diphenyl-2-picrylhydrazyl(DPPH)scavenging activity and to decrease the phytic acid concentration.The inspection of the free amino acid profiles allowed for distinguishing the two MCs,whereas the detection of a heterogeneous panel of volatile organic compounds supported the presence/activity of microbial enzymes without statistically significant differences between MCs.As functional contribution,digested extracts with MCs also proved to reduce the inflammatory cytokine concentrations in cell lines exposed to lipopolysaccharide trigger.Therefore,in line with studies exploring novel adjuvant therapies,the present innovative probiotic consortium featured by high gluten-hydrolyzing metabolism also showed the capability to improve various parameters usually found to be altered in patients affected by gluten-based disorders or CeD.展开更多
Hepatocellular carcinoma(HCC)is a lethalmalignancy.Formany years,chemotherapeutic regimens have served as the foundation of sys-temic therapies for advanced HCCdespite their limited efficacy and significant adverse ef...Hepatocellular carcinoma(HCC)is a lethalmalignancy.Formany years,chemotherapeutic regimens have served as the foundation of sys-temic therapies for advanced HCCdespite their limited efficacy and significant adverse effects.In recent decades,novel systemic therapies such as immunotherapy and targeted therapy have profoundly transformed HCC management.Although some patients with advanced HCC exhibit dramatically improved outcomes,the efficacy of immunotherapy and targeted therapy,either asmonotherapy or in combina-tion,remains limited.Numerous trials have indicated that locoregional therapies,including transarterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),and transarterial radioembolization(TARE),may synergize with systemic therapies to enhance ad-vanced HCC treatment.However,further studies are required to optimize these combination regimens.In contrast,curative treatments,such as surgical resection,liver transplantation,or local ablation,are typically recommended for patients with early-stage HCC.Although these treatments have achieved an impressivemedian overall survival(OS)exceeding 60months,more than half of the patients experience recurrence within 5 years.Consequently,the development of effective perioperative neoadjuvant or adjuvant therapies is urgently needed to reduce the incidence of recurrence and metastasis.It provides a comprehensive overview of recent advances in systemic therapies for advanced HCC,as well as adjuvant or neoadjuvant immunotherapies for early HCC.Additionally,emerging clinical trials and trial designs for future investigations into systemic therapies for HCC management are critically analyzed.展开更多
In a recent study by He et al,the nomogram integrates postoperative serum tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen,thereby improving the accuracy of identifying high-risk patients c...In a recent study by He et al,the nomogram integrates postoperative serum tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen,thereby improving the accuracy of identifying high-risk patients compared to relying solely on preoperative markers,which has significant implications for customizing adjuvant therapy and potentially improving outcomes for this aggressive form of cancer.However,the study’s single-center design and short follow-up period may limit the generalizability of its findings and potentially introduce reporting bias.Future studies could consider additional confounding factors,such as adjuvant chemotherapy and variations in surgical techniques,to improve the model’s accuracy.Furthermore,it would be valuable to validate the nomogram in broader,prospective cohorts and explore the inclusion of additional markers like circulating tumor DNA to refine further its predictive power and applicability across diverse patient populations.展开更多
This study reviews the findings of a recent study by Li et al,which demonstrated that perioperative chemotherapy benefits patients with diffuse-type gastric cancer compared to surgery alone.Despite potential biases,th...This study reviews the findings of a recent study by Li et al,which demonstrated that perioperative chemotherapy benefits patients with diffuse-type gastric cancer compared to surgery alone.Despite potential biases,the study supports the inclusion of perioperative chemotherapy in treatment guidelines.Neoadjuvant and adjuvant chemotherapy may also provide similar survival outcomes,allowing for flexible treatment planning.展开更多
BACKGROUND Gastric cancer(GC)is an aggressive malignancy of the gastrointestinal tract characterized by high recurrence rates following radical gastrectomy.To enhance treatment efficacy,reduce recurrence,and improve p...BACKGROUND Gastric cancer(GC)is an aggressive malignancy of the gastrointestinal tract characterized by high recurrence rates following radical gastrectomy.To enhance treatment efficacy,reduce recurrence,and improve patient survival,adjuvant chemotherapy is commonly administered based on established postoperative guidelines.Despite advancements in chemotherapy delivery,the overall response rate remains below 50%,primarily due to the lack of targeted therapies tailored to specific patient populations.AIM To explore sensitive biomarkers to assess the efficacy of postoperative adjuvant chemotherapy in appropriate patient subgroups.METHODS This study retrospectively analyzed 1628 patients who underwent radical gastrectomy for GC at our hospital in 2017 and 2018,with a subsequent five-year follow-up.Patients were divided based on whether they received postoperative adjuvant chemotherapy.The study aimed to determine optimal cutoff values for various biomarkersneutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio,carcinoembryonic antigen(CEA),carbohydrate antigen(CA)199,CA724,and CA242-using receiver operating characteristic(ROC)curves.Based on the optimal ROC cut-off,a novel combined metric,NLR-CEA,was developed to assess the efficacy of adjuvant chemotherapy following GC surgery.RESULTS Cox subgroup analysis demonstrated that postoperative adjuvant chemotherapy significantly improved overall survival in the NLR-CEA_Low group with a rate of 0.41(0.26-0.63).In the NLR-CEA_Middle group,the protective effect was observed at 0.69(0.54-0.87),while in the NLR-CEA_High group,it was 0.73(0.53-0.99).Notably,a 32%difference in the efficacy of chemotherapy was observed between the NLR-CEA_Low and NLR-CEA_High groups.CONCLUSION NLR-CEA is an effective biomarker for evaluating the efficacy of postoperative adjuvant chemotherapy in GC.Patients with NLR-CEA_Low exhibit significantly better responses to chemotherapy compared to those with NLRCEA_High.展开更多
We read with great interest the article by Sun et al addressing the prognostic role of tumor deposits(TDs)and negative lymph nodes in N1c colorectal cancer.Their proposal of the NLNTD index is a valuable step toward r...We read with great interest the article by Sun et al addressing the prognostic role of tumor deposits(TDs)and negative lymph nodes in N1c colorectal cancer.Their proposal of the NLNTD index is a valuable step toward refining risk stratification in this subgroup.In our recently published population-based cohort of 111106 patients with early-stage colon cancer,TD positivity,classified as N1c according to AJCC definitions,was independently associated with significantly worse overall and disease-specific survival,even after propensity score matching.Taken together,these findings show that TDs are adverse prognostic factors across stages.They should inform treatment planning and follow-up,rather than be regarded as incidental.展开更多
Pterygium,a common ocular surface disorder characterized by the abnormal growth of conjunctival tissue onto the cornea,often necessitates surgical excision as its primary treatment.While effective,pterygium surgery is...Pterygium,a common ocular surface disorder characterized by the abnormal growth of conjunctival tissue onto the cornea,often necessitates surgical excision as its primary treatment.While effective,pterygium surgery is frequently associated with a spectrum of postoperative complications that significantly impact patient prognosis and quality of life.This comprehensive review systematically analyzes the classification,underlying pathophysiological mechanisms,and associated risk factors of these complications,with a particular focus on less commonly explored entities such as postoperative granuloma(PPG),corneal dellen,and scleral necrosis,alongside the more prevalent issue of recurrence.We delineate these complications based on their temporal presentation(early,intermediate,and late),and provide an in-depth analysis of general and specific contributing factors,including surgical trauma,individual patient characteristics,surgical technique,and perioperative management.Furthermore,this review synthesizes advancements in preventive strategies and therapeutic interventions,encompassing refined surgical techniques[e.g.,femtosecond laser-assisted pterygium surgery(FLAPS),pterygium extended removal followed by extended conjunctival transplant(P.E.R.F.E.C.T.)technique,Tissue Tuck technique],judicious application of adjuvant therapies[e.g.,mitomycin C(MMC),5-fluorouracil(5-FU),corticosteroids,anti-vascular endothelial growth factor(VEGF)agents],and optimized postoperative care protocols.By consolidating current evidence and identifying future research priorities,this review aims to provide ophthalmologists with a valuable theoretical foundation to guide individualized surgical planning,dynamic postoperative management,and ultimately minimize complications and improve patient satisfaction.展开更多
Objective:The aim of the current study was to identify independent prognostic factors,evaluate differential adjuvant chemotherapy efficacy across clinicopathologic subgroups,and define adjuvant chemotherapy-sensitive ...Objective:The aim of the current study was to identify independent prognostic factors,evaluate differential adjuvant chemotherapy efficacy across clinicopathologic subgroups,and define adjuvant chemotherapy-sensitive populations.Methods:A retrospective analysis of 168 AAC patients undergoing curative pancreaticoduodenectomy(2011-2020)was performed.Cases were classified into intestinal(28.0%),pancreatobiliary(30.4%),and mixed subtypes(18.5%)per NCCN(v2.2025)criteria.Independent prognostic factors for AAC patients were identified through uni-and multi-variable Cox proportional hazards modeling and subgroup analyses were stratified by age range,gender,differentiation,T stage,N stage,BVI,TDs,and PNI.Results:The pancreatobiliary signature(HR=2.884,P<0.001)and BVI(HR=2.330,P=0.001)were independent poor prognostic factors.Adjuvant chemotherapy improved overall survival(OS)in the following AAC patients:T3-T4 stage(HR=0.485,P=0.050);N1-N2 stage(HR=0.365,P=0.008);and TD-positive(HR=0.401,P=0.026).The median OS increased from 22.3-51.3 months with adjuvant chemotherapy in TD-positive patients(P=0.019).TD positivity conferred a worse prognosis in BVI-negative subgroups(OS:HR=3.840,95%CI:2.058-7.166,P<0.001;and progression-free survival(PFS):HR=2.950,95%CI:1.550-5.617,P=0.002).Conclusions:The pancreatobiliary signature and BVI constitute critical high-risk pathologic features in AAC.TD status identified high-risk cohorts,thus enabling postoperative risk-stratified treatment strategies.In patients negative for pancreatobiliary signature or BVI,TD positivity predicted significantly worse survival.展开更多
Objective This study aims to explore the correlation between traditional Chinese medicine(TCM)syndromes and the expression status of estrogen receptor(ER)and progesterone receptor(PR)in breast cancer patients before a...Objective This study aims to explore the correlation between traditional Chinese medicine(TCM)syndromes and the expression status of estrogen receptor(ER)and progesterone receptor(PR)in breast cancer patients before and after adjuvant chemotherapy.Methods A total of 222 breast cancer patients with consistent ER and PR expression scheduled to undergo adjuvant chemotherapy were classified according to TCM syndrome differentiation before and after chemotherapy.The data were analyzed using chi-square tests and binary logistic regression with SPSS 26.0 software,and compared with ER/PR expression results.Results(i)In the ER-positive/PR-positive group,compared with prechemotherapy,syndromes of spleen qi deficiency,spleen deficiency with dampness-phlegm,and spleen–kidney deficiency significantly increased during mid-chemotherapy and after chemotherapy.Compared with mid-chemotherapy,spleen yang deficiency syndrome significantly increased after chemotherapy,with statistical significance(p<0.05).(ii)In the ER-negative/PR-negative group,compared with prechemotherapy,syndromes of spleen qi deficiency and spleen deficiency with dampness-phlegm significantly increased during mid-chemotherapy,while spleen qi deficiency,spleen yang deficiency,and spleen–kidney deficiency significantly increased after chemotherapy.Compared with mid-chemotherapy,spleen–kidney deficiency and spleen yang deficiency syndromes significantly increased after chemotherapy,with statistical significance(p<0.05).(iii)The distribution of spleen qi deficiency syndrome during mid-chemotherapy and after chemotherapy was significantly higher in the ER-positive/PR-positive group than in the ER-negative/PR-negative group,with statistical significance(p<0.05).(iv)ER and PR were not independent influencing factors for the various syndrome types before and after adjuvant chemotherapy(p>0.05).Conclusion After chemotherapy initiation,syndromes of spleen qi deficiency,spleen yang deficiency,and spleen–kidney deficiency significantly increased in both ER-positive/PR-positive and ER-negative/PR-negative groups.The distribution of spleen qi deficiency during mid-chemotherapy and after chemotherapy was significantly higher in the ER-positive/PR-positive group than in the ER-negative/PR-negative group.ER and PR were not independent influencing factors for the syndrome types before and after adjuvant chemotherapy.展开更多
BACKGROUND Despite emerging evidence from studies on other malignancies that support early adjuvant chemotherapy(AC)initiation,the feasibility and oncologic benefits of this therapy remain underexplored in patients re...BACKGROUND Despite emerging evidence from studies on other malignancies that support early adjuvant chemotherapy(AC)initiation,the feasibility and oncologic benefits of this therapy remain underexplored in patients receiving gastric resection.AIM To evaluate the feasibility,safety,and oncologic outcomes of early postoperative AC in advanced gastric cancer patients.METHODS In this retrospective cohort study,219 stage Ⅱ/Ⅲ gastric adenocarcinoma patients who underwent laparoscopic gastrectomy between 2016 and 2021 were analyzed.Patients were stratified by AC initiation timing:Early(10-13 days,n=21)vs conventional(4-6 weeks,n=198).Propensity score matching(1:2)was performed,with balance assessed via standardized mean differences.Recurrence-free sur-vival,overall survival,and safety were compared between the two groups.Sensi-tivity analyses were conducted to assess the robustness of the findings.RESULTS After 1:2 matching(21 patients vs 42 patients),early AC demonstrated comparable 3-year recurrence-free survival(53.7%vs 61.6%,hazard ratio=0.89,P=0.562)and overall survival(69.1%vs 66.3%,P=0.874)rates to conventional timing.Peritoneal recurrence was significantly lower in the early group(4.8%vs 26.2%,P=0.048),although Cox regression did not confirm a significant difference(hazard ratio=0.418,P=0.257).Early initiation correlated with a 2.18-fold greater proportion of patients requiring dose reductions(57.1%vs 26.2%,P=0.026)but similar grade 3/4 toxicity(42.9%vs 57.1%,P=0.285).CONCLUSION Early AC initiation appears feasible in selected patients but necessitates individualized dose management.Our findings challenge traditional timing paradigms while highlighting the need for molecularly guided treatment sequencing strategies.展开更多
Gallbladder cancer is an aggressive malignancy notorious for its poor prognosis and treatment challenges,even at early stages.In their recent work,Kim et al utilized data from the National Cancer Database to explore w...Gallbladder cancer is an aggressive malignancy notorious for its poor prognosis and treatment challenges,even at early stages.In their recent work,Kim et al utilized data from the National Cancer Database to explore whether adding chemotherapy to surgical intervention could improve survival outcomes for patients diagnosed with stage II gallbladder cancer.The use of adjuvant chemotherapy following curative surgery in this patient population has been a longstanding source of debate.Historically,the lack of clear guidelines for managing stage II gallbladder cancer has resulted in inconsistent,sometimes contradictory findings from various studies regarding the effectiveness of postoperative chemotherapy.Consequently,many clinicians have relied on studies involving other biliary tract cancers to justify the routine use of prophylactic chemotherapy after surgery,aiming to minimize recurrence risk.Given the rarity,high mortality rate,and the small sample sizes typical in gallbladder cancer studies,Kim et al’s contribution represents a significant and commendable effort to address these challenges.Kim et al designed a retrospective cohort study with well-defined inclusion criteria and clear treatment classifications.Notably,their findings suggested that in stage II gallbladder cancer,adjuvant chemotherapy did not yield a meaningful survival benefit over surgery alone.These results therefore casted doubt on the routine practice of administering chemotherapy to all patients postoperatively,prompted clinicians to reconsider their approach.Furthermore,this controversy directly influences clinical decisionmaking and guideline recommendations,as uncertainty regarding the benefit of adjuvant chemotherapy may lead to heterogeneous practices across different institutions and regions.This article critically assessed the research design,methodology,and clinical implications of the study by Kim et al.It also provided an in-depth exploration of the broader question regarding the appropriateness of adjuvant chemotherapy following surgery for stage II gallbladder cancer,highlighting the necessity of rigorous study designs to produce reliable evidence.展开更多
This paper investigates the effects of graphene quantum dots and mesoporous silica as nanomaterial adjuvants on immune activity in mice both in vitro and in vivo.The two materials have distinct properties;graphene qua...This paper investigates the effects of graphene quantum dots and mesoporous silica as nanomaterial adjuvants on immune activity in mice both in vitro and in vivo.The two materials have distinct properties;graphene quantum dots possess unique optical and electrical characteristics,while mesoporous silica features a regular pore structure.In vitro experiments show differences in their effects on immune cell activation and cytokine secretion;in vivo experiments reveal varying performances in antibody production and immune cell function regulation.Their mechanisms of action and safety profiles also differ,offering distinct advantages in application prospects.These two nanomaterial adjuvants provide new directions for the development of immunology,warranting further exploration.展开更多
BACKGROUND Duodenal adenocarcinoma(DA),a rare gastrointestinal malignancy,lacks clear natural history and management strategies.This study aimed to investigate the long-term outcomes of patients with DA,focusing on lo...BACKGROUND Duodenal adenocarcinoma(DA),a rare gastrointestinal malignancy,lacks clear natural history and management strategies.This study aimed to investigate the long-term outcomes of patients with DA,focusing on long-term survival and the impact of tumor characteristics,surgery,and adjuvant therapy.AIM To bridge this knowledge gap,we conducted a hospital-based cohort study in our 15-year experience with DA aimed at investigating the long-term outcomes of the patients with DA,along with analyzing the impact of the tumor characteristics,operations and adjuvant therapy on survival outcomes.METHODS A retrospective analysis of 208 patients diagnosed with non-ampullary DA at a single institution between 2009 and 2023 was performed.This study used SPSS 26.0 software to make a comprehensive statistical analysis of demographic characteristics,clinical presentation,treatment modalities,and survival outcomes.The effectiveness of surgical resection and adjuvant therapy in 5-year oval survival(OS)and disease-free survival was evaluated using Kaplan-Meier survival curves,the Cox proportional hazards model,and statistical comparisons of survival distributions.RESULTS The median OS time for the cohort was 39 months,with 3-and 5-year OS rates of 51.2%and 43.6%,respectively.Radical resection was performed in 82.6%of cases,and was significantly associated with an improved 5-year OS,with a rate of 57.8%.Adjuvant therapy showed a survival benefit in the specific patient subsets,particularly in tumor stage Ⅱ or Ⅲ tumors,with an improved OS.Adjuvant therapy(hazard ratio=2.71,95%confidence interval:1.30-5.62,P=0.008),pancreatic invasion and advanced tumor stage were identified as significant predictors of OS in multivariate analyses.CONCLUSION Radical operation for DA is associated with a remarkable improvement in the 5-year OS.Importantly,postoperative adjuvant therapy can significantly prolong the OS time in patients with radical operation,especially in patients with stage III.It highlights the necessity for early diagnosis,tailored surgical approaches,and a nuanced understanding of the role of adjuvant therapy.展开更多
Objective:Radical nephroureterectomy(RNU)is considered the standard of care for patients with high-risk upper tract urothelial carcinoma.Current literature reveals a deficit in direct comparative studies evaluating th...Objective:Radical nephroureterectomy(RNU)is considered the standard of care for patients with high-risk upper tract urothelial carcinoma.Current literature reveals a deficit in direct comparative studies evaluating the efficacy of different chemotherapeutic agents administered in single postoperative instillation following RNU.The primary aim of this study was to compare the bladder recurrence(BR)rates between patients receiving a single instillation of mitomycin C(MMC)versus gemcitabine(Gem)after RNU.Methods:The ROBUUST(ROBotic surgery for Upper tract Urothelial cancer STudy)2.0 is an international,multicenter registry that aggregates data on patients who have undergone curative surgery for upper tract urothelial carcinoma across participating centers from January 2015 to December 2022.Data including primary baseline variables of the patients,characteristics of the tumors,surgical management,and definitive histopathological characterizations were collected and stratified based on the type of postoperative bladder instillation:MMC(the MMC group)and Gem(the Gem group).We selected variables correlated with our primary outcome to conduct a propensity-score match analysis.Results:One hundred patients in the MMC group were matched 1:1 with 100 patients in the Gem group.At 36 months of follow-up,30 patients in the MMC group and 39 patients in the Gem group experienced BR,representing recurrence rates of 30%and 39%,respectively(p=0.2).The Cox proportional hazards model comparing BR between the groups revealed a hazard ratio of 1.58(95%confidence interval:0.98-2.55)with a non-statistically significant increased risk of BR in the Gem group compared with the MMC group(p=0.059).Conclusion:A single perioperative instillation of Gem or MMC seems to offer similar efficacy in reducing the risk of BR in patients undergoing RNU.Further research,ideally within the framework of prospective studies,is warranted to elucidate the optimal chemotherapeutic approach in this setting.展开更多
文摘Objective： To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods： Seventy two female BALB/c mice were randomly assigned into six groups. The mice were vaccinated with soluble Leishmania antigens （SLA） alone, artemisinin co-administered with SLA, SLA and Bacille Calmette Gu fin （BCG） vaccine, and artemisinin and BCG alone. Unvaccinated mice formed the control group. The induction of cell-mediated immunity following vaccination was determined by measuring in vitro lymphocyte proliferation and the production of interleukin （IL）-4, IL-5 and gamma interferon （IFN-γ） determined by flow cytometry. Protection against L. major was determined by quantifying parasite burdens in L. major infected footpads using a limiting dilution assay and by measuring lesion sizes of the infected footpad compared to the contralateral uninfected footpad. Results： Mice receiving SLA plus artemisinin produced significantly high levels of IL-4 and IL-5 （P 〈 0.05） and low levels of IFN-γ, resulting in exacerbated disease. In addition, subcutaneous administration of SLA ＋ artemisinin, artemisinin alone or SLA alone resulted in the development of large footpad swellings and high parasite loads that were comparable to those of the control unvaccinated mice （P 〉 0.05）, resulting in exacerbated disease. Conclusion： These data suggest that artemisinin is not a suitable adjuvant for Leishmania vaccines. However, since artemisinin has been shown to be effective against Leishmania parasites in vitro and in vivo, further studies ought to be conducted to determine its immunochemotherapeutic potential when co-administered with Leishmania antigens.
文摘Toll-like receptor 5 （TLR5） signaling in response to flagellin is dispensable for inducing humoral immunity, but alterations of aa 89-96, the TLR5 binding site, significantly reduced the adjuvanticity of flagellin. These observations indicate that the underlying mechanism remains incompletely understood. Here, we found that the native form of Salmonella typhimurium aa 89-96-mutant flagellin extracted from flagella retains some TLR5 recognition activity, indicating that aa 89-96 is the primary, but not the only site that imparts TLR5 activity. Additionally, this mutation impaired the production of IL-lp and IL-18. Using TLR5KO mice, we found that aa 89-96 is critical for the humoral adjuvant effect, but this effect was independent of TLR5 activation triggered by this region of flageUin. In summary, our findings suggest that aa 89-96 of flagellin is not only the crucial site responsible for TLR5 recognition, but is also important for humoral immune adjuvanticity through a TLR5-independent pathway.
基金This study was supported by the grants from the Chinese National Grand Program on Key Infectious Disease Control （No. 2008ZX10001-012 and -002）, the National Natural Science Foundation of China （No. 81072496H1014） and the Fund for Young Scientists from Fudan University （No. 07L03）.
文摘Background Cholera toxin B subunit （CTB） was shown to be a potent adjuvant for protein immunogen, especially when inoculated through mucosal route. We aimed to optimize the expression approach for CTB and thereafter to determine the adjuvant effect on DNA vaccine. Methods Wild type CTB coding gene was amplified and cloned into prokaryotic expression vector pET-30a, and the recombinant CTB was expressed in the presence of different concentration of chloramphenicol and isopropyl β-D-thiogalactoside. Purified recombinant CTB was mixed with HIV-1 AE2f tat-rev-integrase-vif-nef fusion gene DNA vaccine and female BALB/c mice were vaccinated with a DNA priming-recombinant vaccinia vectored vaccine boosting regimen through intramuscular injection. Interferon γ （IFN-γ） enzyme-linked immunospot （Elispot） assay was used to read out the specific T-cell immunity. Results Chloramphenicol was essential for the efficient expression of recombinant CTB （rCTB） in pET-30a/BL21 （DE3） system and could be optimized at the concentration of 0.625 μg/ml in the presence of chloramphenicol. The purified rCTB could bind with GM1 efficiently. INF-γ Elispot data showed the T-cell response induced in CTB adjuvanted group （（734±240） spot forming cells/106 splenocytes） was higher than that induced by non-adjuvanted （（520±150） spot forming cells/10e splenocytes）, all responses against different antigens were enhanced in parallel. Conclusion CTB could be efficiently expressed in the presence of chloramphenicol and purified CTB is functional and capable of enhancincl the specific T cell responses elicited by DNA vaccine, the mechanism needs to be explored in the future.
基金Natural Science Foundation-funded Project:Mechanism of Action of Detoxification Formula to Inhibit Hypoxia-Inducible Factor 1 Alpha-Exosomal MicroRNA-130b-3p-Sterile Alpha Motif Domain-Containing Protein 90-mediated Macrophage M2-type Polarisation to Improve the Immunosuppressive Microenvironment in Hepatocellular Carcinoma (No.82374540)Medical Innovation Research Project of Shanghai Science and Technology Commission:a Multicenter Prospective Randomized Controlled Study of “Arsenic Target” Combination Therapy for Unresectable Hepatocellular Carcinoma (No.22Y11921200)。
文摘OBJECTIVE:To investigate the clinical efficacy of using a Jiedu formula(解毒方) as an adjunctive therapy in patients with hepatocellular carcinoma(HCC) after hepatectomy.METHODS:In total,354 patients were included in this study.All patients were categorized into the traditional herbal medicine(THM) group(n = 115) or the non-THM treatment(nTHM) group(n = 239),with the Jiedu formula administered twice a day to the patients in the THM group.The primary outcome was recurrence-free survival(RFS).Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors associated with RFS.Then,the high risk of recurrence among patients was identified,and propensity score matching(PSM) and RFS analysis were performed to analyze the prognostic factors for the outcomes of patients at a high risk of recurrence in different groups.RESULTS:The one,two,three,and five-year RFS rates of the THM and nTHM groups were 76.4% vs 66.1%,65.5% vs 48.8%,57.9% vs 39.9%,and 43.9% vs 29.2%,respectively.The results of the Multivariate Cox analysis showed that giant tumors [hazard ratio(HR),1.54,P = 0.04],poor degree of differentiation,microsatellite,or microvascular invasion(HR,1.29,P = 0.09) increased the risk of recurrence.In the population with a high risk of recurrence,after PSM,the one,two,three,and five-year survival rates were 70.6% vs 68.0%,63.0% vs 43.1%,59.6% vs 33.3%,and 41.9% vs 26.4%,respectively.CONCLUSION:In this study,THM was found to be an effective agent for adjuvant therapy for HCC to prevent early recurrence of HCC after hepatic resection.
文摘Objective:To investigate the therapeutic adjuvant potential of fucoidan in cervical cancer and to evaluate its efficacy in combination with immunotherapy.Methods:Fucoidan extracted from Fucus vesiculosus was dissolved in phosphate buffered saline and used to treat TC-1 cervical cancer cells in vitro as well as tumor-bearing C57BL/6 mice in vivo.Mice were divided into four groups:the vehicle control group,the mRNA therapy-alone group,the fucoidan-only group,and the combination group.MAPK signaling proteins(p-ERK,T-ERK,p-p38)were analyzed by Western blotting assays.T cell surface markers and intracellular cytokines in splenocytes were assessed by flow cytometry,and plasma cytokine levels were measured by ELISA.Results:Fucoidan decreased the p-ERK/T-ERK ratio and p-p38.Fucoidan combined with mRNA therapy did not significantly affect CD4^(+)T-cell activation but reduced CD8^(+)T-cell activation compared with mRNA therapy alone.MCP-1 and IFN-γwere significantly reduced in the combination therapy group compared with mRNA therapy alone,while IL-6,TNF-α,perforin,and granzyme B did not show significant changes between the two groups.Conclusions:These findings suggest that fucoidan could inhibit excessive T cell activation and cytokine production by suppressing MAPK p-p38 protein expression.
基金supported by grants from Zhejiang Provincial Natural Science Foundation of China(LTGY24H030006)Re-search Project of Jinan Microecological Biomedicine Shandong Lab-oratory(JNL-2022015B).
文摘Background:Hepatocellular carcinoma(HCC)recurrence following liver transplantation(LT)remains a major challenge.This study aimed to investigate the effect of adjuvant chemotherapy(ACT)with the modified FOLFOX-6(mFOLFOX-6)regimen on the post-transplant prognosis of HCC patients.Methods:HCC patients who underwent LT at our institution from June 2017 to December 2019 were enrolled.The cohort was divided into the ACT group(n=57)and the non-ACT group(n=93).The median post-transplant follow-up period was 54.0 months.The study endpoints were HCC recurrence and patient mortality following LT.The association between ACT and recurrence/mortality were evaluated through univariate and multivariate analyses utilizing a Cox proportional hazards model,propensity score adjustment,propensity score matching,and inverse probability of treatment weighting(IPTW)analyses.A stratification analysis was performed to determine the interaction effects.Results:The ACT group was younger and had worse tumor characteristics including tumor number,tu-mor size,portal vein tumor thrombosis,pathological differentiation and microvascular invasion(MVI).The ACT group also demonstrated a lower risk of mortality than the non-ACT group(hazard ratio=0.36,P=0.017).It was consistent across sensitivity analyses utilizing propensity score adjustment and match-ing.There was a significant stronger association between ACT and recurrence-free benefit in patients with grade M2 of MVI compared to patients with grade M0/1(P for interaction=0.002).Conclusions:ACT with mFOLFOX-6 regimen decreased the recurrence and mortality risks following LT for HCC patients.ACT may be considered in HCC patients with high risk of recurrence and mortality after LT.
文摘While exerting their metabolic activities in the gastrointestinal milieu,probiotics impact the host well-being by boosting immunity,treating metabolic disorders,and modulating microbiota and metabolome.Due to the high incidence of gluten-based disorders,the present work aims to deeply explore the metabolism of two selected microbial consortia(MCs)during gluten digestion under simulated gastrointestinal conditions.Featured by high protease and peptidase activity,both MCs accounted for different lactic acid bacteria and Bacillus strains that were combined with two commercial protease enzymes.Gluten substrates were used as purified extracts,white and whole wheat breads.Control samples,instead,relied onto the microbial enzyme lack.Twenty-four hours of simulated digestion were sufficient to completely hydrolyze gluten in one of the two MC-containing experimental sets,and the relative 48 h-digested extract did not alter the cytokine expression in duodenal biopsies from celiac disease(CeD)patients.When digested samples were assayed for antioxidant and phytase activities,microbial enzymes demonstrated to significantly improve both 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS)and 1,1-diphenyl-2-picrylhydrazyl(DPPH)scavenging activity and to decrease the phytic acid concentration.The inspection of the free amino acid profiles allowed for distinguishing the two MCs,whereas the detection of a heterogeneous panel of volatile organic compounds supported the presence/activity of microbial enzymes without statistically significant differences between MCs.As functional contribution,digested extracts with MCs also proved to reduce the inflammatory cytokine concentrations in cell lines exposed to lipopolysaccharide trigger.Therefore,in line with studies exploring novel adjuvant therapies,the present innovative probiotic consortium featured by high gluten-hydrolyzing metabolism also showed the capability to improve various parameters usually found to be altered in patients affected by gluten-based disorders or CeD.
基金work was supported by grants from the National Natural Science Foundation of China(No.82073346)Doctoral Through Train Scien-tific Research Project of Chongqing(No.CSTB2022BSXM-JCX0004)+1 种基金Famous Teachers section of the Chongqing Talents Program(No.4246ZP112)Special Projects of Army Medical University for Improving Scientific and Technological Innovation Capabilities(No.2019XLC1009).
文摘Hepatocellular carcinoma(HCC)is a lethalmalignancy.Formany years,chemotherapeutic regimens have served as the foundation of sys-temic therapies for advanced HCCdespite their limited efficacy and significant adverse effects.In recent decades,novel systemic therapies such as immunotherapy and targeted therapy have profoundly transformed HCC management.Although some patients with advanced HCC exhibit dramatically improved outcomes,the efficacy of immunotherapy and targeted therapy,either asmonotherapy or in combina-tion,remains limited.Numerous trials have indicated that locoregional therapies,including transarterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),and transarterial radioembolization(TARE),may synergize with systemic therapies to enhance ad-vanced HCC treatment.However,further studies are required to optimize these combination regimens.In contrast,curative treatments,such as surgical resection,liver transplantation,or local ablation,are typically recommended for patients with early-stage HCC.Although these treatments have achieved an impressivemedian overall survival(OS)exceeding 60months,more than half of the patients experience recurrence within 5 years.Consequently,the development of effective perioperative neoadjuvant or adjuvant therapies is urgently needed to reduce the incidence of recurrence and metastasis.It provides a comprehensive overview of recent advances in systemic therapies for advanced HCC,as well as adjuvant or neoadjuvant immunotherapies for early HCC.Additionally,emerging clinical trials and trial designs for future investigations into systemic therapies for HCC management are critically analyzed.
文摘In a recent study by He et al,the nomogram integrates postoperative serum tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen,thereby improving the accuracy of identifying high-risk patients compared to relying solely on preoperative markers,which has significant implications for customizing adjuvant therapy and potentially improving outcomes for this aggressive form of cancer.However,the study’s single-center design and short follow-up period may limit the generalizability of its findings and potentially introduce reporting bias.Future studies could consider additional confounding factors,such as adjuvant chemotherapy and variations in surgical techniques,to improve the model’s accuracy.Furthermore,it would be valuable to validate the nomogram in broader,prospective cohorts and explore the inclusion of additional markers like circulating tumor DNA to refine further its predictive power and applicability across diverse patient populations.
文摘This study reviews the findings of a recent study by Li et al,which demonstrated that perioperative chemotherapy benefits patients with diffuse-type gastric cancer compared to surgery alone.Despite potential biases,the study supports the inclusion of perioperative chemotherapy in treatment guidelines.Neoadjuvant and adjuvant chemotherapy may also provide similar survival outcomes,allowing for flexible treatment planning.
文摘BACKGROUND Gastric cancer(GC)is an aggressive malignancy of the gastrointestinal tract characterized by high recurrence rates following radical gastrectomy.To enhance treatment efficacy,reduce recurrence,and improve patient survival,adjuvant chemotherapy is commonly administered based on established postoperative guidelines.Despite advancements in chemotherapy delivery,the overall response rate remains below 50%,primarily due to the lack of targeted therapies tailored to specific patient populations.AIM To explore sensitive biomarkers to assess the efficacy of postoperative adjuvant chemotherapy in appropriate patient subgroups.METHODS This study retrospectively analyzed 1628 patients who underwent radical gastrectomy for GC at our hospital in 2017 and 2018,with a subsequent five-year follow-up.Patients were divided based on whether they received postoperative adjuvant chemotherapy.The study aimed to determine optimal cutoff values for various biomarkersneutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio,carcinoembryonic antigen(CEA),carbohydrate antigen(CA)199,CA724,and CA242-using receiver operating characteristic(ROC)curves.Based on the optimal ROC cut-off,a novel combined metric,NLR-CEA,was developed to assess the efficacy of adjuvant chemotherapy following GC surgery.RESULTS Cox subgroup analysis demonstrated that postoperative adjuvant chemotherapy significantly improved overall survival in the NLR-CEA_Low group with a rate of 0.41(0.26-0.63).In the NLR-CEA_Middle group,the protective effect was observed at 0.69(0.54-0.87),while in the NLR-CEA_High group,it was 0.73(0.53-0.99).Notably,a 32%difference in the efficacy of chemotherapy was observed between the NLR-CEA_Low and NLR-CEA_High groups.CONCLUSION NLR-CEA is an effective biomarker for evaluating the efficacy of postoperative adjuvant chemotherapy in GC.Patients with NLR-CEA_Low exhibit significantly better responses to chemotherapy compared to those with NLRCEA_High.
文摘We read with great interest the article by Sun et al addressing the prognostic role of tumor deposits(TDs)and negative lymph nodes in N1c colorectal cancer.Their proposal of the NLNTD index is a valuable step toward refining risk stratification in this subgroup.In our recently published population-based cohort of 111106 patients with early-stage colon cancer,TD positivity,classified as N1c according to AJCC definitions,was independently associated with significantly worse overall and disease-specific survival,even after propensity score matching.Taken together,these findings show that TDs are adverse prognostic factors across stages.They should inform treatment planning and follow-up,rather than be regarded as incidental.
文摘Pterygium,a common ocular surface disorder characterized by the abnormal growth of conjunctival tissue onto the cornea,often necessitates surgical excision as its primary treatment.While effective,pterygium surgery is frequently associated with a spectrum of postoperative complications that significantly impact patient prognosis and quality of life.This comprehensive review systematically analyzes the classification,underlying pathophysiological mechanisms,and associated risk factors of these complications,with a particular focus on less commonly explored entities such as postoperative granuloma(PPG),corneal dellen,and scleral necrosis,alongside the more prevalent issue of recurrence.We delineate these complications based on their temporal presentation(early,intermediate,and late),and provide an in-depth analysis of general and specific contributing factors,including surgical trauma,individual patient characteristics,surgical technique,and perioperative management.Furthermore,this review synthesizes advancements in preventive strategies and therapeutic interventions,encompassing refined surgical techniques[e.g.,femtosecond laser-assisted pterygium surgery(FLAPS),pterygium extended removal followed by extended conjunctival transplant(P.E.R.F.E.C.T.)technique,Tissue Tuck technique],judicious application of adjuvant therapies[e.g.,mitomycin C(MMC),5-fluorouracil(5-FU),corticosteroids,anti-vascular endothelial growth factor(VEGF)agents],and optimized postoperative care protocols.By consolidating current evidence and identifying future research priorities,this review aims to provide ophthalmologists with a valuable theoretical foundation to guide individualized surgical planning,dynamic postoperative management,and ultimately minimize complications and improve patient satisfaction.
基金supported by the National Key Research and Development Program of China(Grant No.2021YFA1201100)the Projects of Tianjin Science and Technology Bureau National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine(Grant Nos.24ZXZSSS00440 and 22ZXJBSY00030)+1 种基金the Science&Technology Development Fund of Tianjin Education Commission for Higher Education(Grant No.2022ZD067)the Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A).
文摘Objective:The aim of the current study was to identify independent prognostic factors,evaluate differential adjuvant chemotherapy efficacy across clinicopathologic subgroups,and define adjuvant chemotherapy-sensitive populations.Methods:A retrospective analysis of 168 AAC patients undergoing curative pancreaticoduodenectomy(2011-2020)was performed.Cases were classified into intestinal(28.0%),pancreatobiliary(30.4%),and mixed subtypes(18.5%)per NCCN(v2.2025)criteria.Independent prognostic factors for AAC patients were identified through uni-and multi-variable Cox proportional hazards modeling and subgroup analyses were stratified by age range,gender,differentiation,T stage,N stage,BVI,TDs,and PNI.Results:The pancreatobiliary signature(HR=2.884,P<0.001)and BVI(HR=2.330,P=0.001)were independent poor prognostic factors.Adjuvant chemotherapy improved overall survival(OS)in the following AAC patients:T3-T4 stage(HR=0.485,P=0.050);N1-N2 stage(HR=0.365,P=0.008);and TD-positive(HR=0.401,P=0.026).The median OS increased from 22.3-51.3 months with adjuvant chemotherapy in TD-positive patients(P=0.019).TD positivity conferred a worse prognosis in BVI-negative subgroups(OS:HR=3.840,95%CI:2.058-7.166,P<0.001;and progression-free survival(PFS):HR=2.950,95%CI:1.550-5.617,P=0.002).Conclusions:The pancreatobiliary signature and BVI constitute critical high-risk pathologic features in AAC.TD status identified high-risk cohorts,thus enabling postoperative risk-stratified treatment strategies.In patients negative for pancreatobiliary signature or BVI,TD positivity predicted significantly worse survival.
基金supported by the 2022 Traditional Chinese Medicine Scientific Research Special Project of Henan Province,China(2022ZY1048)2023 Traditional Chinese Medicine Scientific Research Special Project of Henan Province,China(2023YZ2043)General Program of Natural Science Foundation of Henan Province,China(232300421183).
文摘Objective This study aims to explore the correlation between traditional Chinese medicine(TCM)syndromes and the expression status of estrogen receptor(ER)and progesterone receptor(PR)in breast cancer patients before and after adjuvant chemotherapy.Methods A total of 222 breast cancer patients with consistent ER and PR expression scheduled to undergo adjuvant chemotherapy were classified according to TCM syndrome differentiation before and after chemotherapy.The data were analyzed using chi-square tests and binary logistic regression with SPSS 26.0 software,and compared with ER/PR expression results.Results(i)In the ER-positive/PR-positive group,compared with prechemotherapy,syndromes of spleen qi deficiency,spleen deficiency with dampness-phlegm,and spleen–kidney deficiency significantly increased during mid-chemotherapy and after chemotherapy.Compared with mid-chemotherapy,spleen yang deficiency syndrome significantly increased after chemotherapy,with statistical significance(p<0.05).(ii)In the ER-negative/PR-negative group,compared with prechemotherapy,syndromes of spleen qi deficiency and spleen deficiency with dampness-phlegm significantly increased during mid-chemotherapy,while spleen qi deficiency,spleen yang deficiency,and spleen–kidney deficiency significantly increased after chemotherapy.Compared with mid-chemotherapy,spleen–kidney deficiency and spleen yang deficiency syndromes significantly increased after chemotherapy,with statistical significance(p<0.05).(iii)The distribution of spleen qi deficiency syndrome during mid-chemotherapy and after chemotherapy was significantly higher in the ER-positive/PR-positive group than in the ER-negative/PR-negative group,with statistical significance(p<0.05).(iv)ER and PR were not independent influencing factors for the various syndrome types before and after adjuvant chemotherapy(p>0.05).Conclusion After chemotherapy initiation,syndromes of spleen qi deficiency,spleen yang deficiency,and spleen–kidney deficiency significantly increased in both ER-positive/PR-positive and ER-negative/PR-negative groups.The distribution of spleen qi deficiency during mid-chemotherapy and after chemotherapy was significantly higher in the ER-positive/PR-positive group than in the ER-negative/PR-negative group.ER and PR were not independent influencing factors for the syndrome types before and after adjuvant chemotherapy.
基金Supported by Xiamen Natural Science Foundation of China,No.3502Z20227347.
文摘BACKGROUND Despite emerging evidence from studies on other malignancies that support early adjuvant chemotherapy(AC)initiation,the feasibility and oncologic benefits of this therapy remain underexplored in patients receiving gastric resection.AIM To evaluate the feasibility,safety,and oncologic outcomes of early postoperative AC in advanced gastric cancer patients.METHODS In this retrospective cohort study,219 stage Ⅱ/Ⅲ gastric adenocarcinoma patients who underwent laparoscopic gastrectomy between 2016 and 2021 were analyzed.Patients were stratified by AC initiation timing:Early(10-13 days,n=21)vs conventional(4-6 weeks,n=198).Propensity score matching(1:2)was performed,with balance assessed via standardized mean differences.Recurrence-free sur-vival,overall survival,and safety were compared between the two groups.Sensi-tivity analyses were conducted to assess the robustness of the findings.RESULTS After 1:2 matching(21 patients vs 42 patients),early AC demonstrated comparable 3-year recurrence-free survival(53.7%vs 61.6%,hazard ratio=0.89,P=0.562)and overall survival(69.1%vs 66.3%,P=0.874)rates to conventional timing.Peritoneal recurrence was significantly lower in the early group(4.8%vs 26.2%,P=0.048),although Cox regression did not confirm a significant difference(hazard ratio=0.418,P=0.257).Early initiation correlated with a 2.18-fold greater proportion of patients requiring dose reductions(57.1%vs 26.2%,P=0.026)but similar grade 3/4 toxicity(42.9%vs 57.1%,P=0.285).CONCLUSION Early AC initiation appears feasible in selected patients but necessitates individualized dose management.Our findings challenge traditional timing paradigms while highlighting the need for molecularly guided treatment sequencing strategies.
文摘Gallbladder cancer is an aggressive malignancy notorious for its poor prognosis and treatment challenges,even at early stages.In their recent work,Kim et al utilized data from the National Cancer Database to explore whether adding chemotherapy to surgical intervention could improve survival outcomes for patients diagnosed with stage II gallbladder cancer.The use of adjuvant chemotherapy following curative surgery in this patient population has been a longstanding source of debate.Historically,the lack of clear guidelines for managing stage II gallbladder cancer has resulted in inconsistent,sometimes contradictory findings from various studies regarding the effectiveness of postoperative chemotherapy.Consequently,many clinicians have relied on studies involving other biliary tract cancers to justify the routine use of prophylactic chemotherapy after surgery,aiming to minimize recurrence risk.Given the rarity,high mortality rate,and the small sample sizes typical in gallbladder cancer studies,Kim et al’s contribution represents a significant and commendable effort to address these challenges.Kim et al designed a retrospective cohort study with well-defined inclusion criteria and clear treatment classifications.Notably,their findings suggested that in stage II gallbladder cancer,adjuvant chemotherapy did not yield a meaningful survival benefit over surgery alone.These results therefore casted doubt on the routine practice of administering chemotherapy to all patients postoperatively,prompted clinicians to reconsider their approach.Furthermore,this controversy directly influences clinical decisionmaking and guideline recommendations,as uncertainty regarding the benefit of adjuvant chemotherapy may lead to heterogeneous practices across different institutions and regions.This article critically assessed the research design,methodology,and clinical implications of the study by Kim et al.It also provided an in-depth exploration of the broader question regarding the appropriateness of adjuvant chemotherapy following surgery for stage II gallbladder cancer,highlighting the necessity of rigorous study designs to produce reliable evidence.
文摘This paper investigates the effects of graphene quantum dots and mesoporous silica as nanomaterial adjuvants on immune activity in mice both in vitro and in vivo.The two materials have distinct properties;graphene quantum dots possess unique optical and electrical characteristics,while mesoporous silica features a regular pore structure.In vitro experiments show differences in their effects on immune cell activation and cytokine secretion;in vivo experiments reveal varying performances in antibody production and immune cell function regulation.Their mechanisms of action and safety profiles also differ,offering distinct advantages in application prospects.These two nanomaterial adjuvants provide new directions for the development of immunology,warranting further exploration.
基金Supported by Natural Science Foundation of Guangdong Province of China,No.2023A1515010785Key Clinical Technique of Guangzhou,No.2023P-ZD01Clinical Research Program of Nanfang Hospital,Southern Medical University,No.2021CR003.
文摘BACKGROUND Duodenal adenocarcinoma(DA),a rare gastrointestinal malignancy,lacks clear natural history and management strategies.This study aimed to investigate the long-term outcomes of patients with DA,focusing on long-term survival and the impact of tumor characteristics,surgery,and adjuvant therapy.AIM To bridge this knowledge gap,we conducted a hospital-based cohort study in our 15-year experience with DA aimed at investigating the long-term outcomes of the patients with DA,along with analyzing the impact of the tumor characteristics,operations and adjuvant therapy on survival outcomes.METHODS A retrospective analysis of 208 patients diagnosed with non-ampullary DA at a single institution between 2009 and 2023 was performed.This study used SPSS 26.0 software to make a comprehensive statistical analysis of demographic characteristics,clinical presentation,treatment modalities,and survival outcomes.The effectiveness of surgical resection and adjuvant therapy in 5-year oval survival(OS)and disease-free survival was evaluated using Kaplan-Meier survival curves,the Cox proportional hazards model,and statistical comparisons of survival distributions.RESULTS The median OS time for the cohort was 39 months,with 3-and 5-year OS rates of 51.2%and 43.6%,respectively.Radical resection was performed in 82.6%of cases,and was significantly associated with an improved 5-year OS,with a rate of 57.8%.Adjuvant therapy showed a survival benefit in the specific patient subsets,particularly in tumor stage Ⅱ or Ⅲ tumors,with an improved OS.Adjuvant therapy(hazard ratio=2.71,95%confidence interval:1.30-5.62,P=0.008),pancreatic invasion and advanced tumor stage were identified as significant predictors of OS in multivariate analyses.CONCLUSION Radical operation for DA is associated with a remarkable improvement in the 5-year OS.Importantly,postoperative adjuvant therapy can significantly prolong the OS time in patients with radical operation,especially in patients with stage III.It highlights the necessity for early diagnosis,tailored surgical approaches,and a nuanced understanding of the role of adjuvant therapy.
文摘Objective:Radical nephroureterectomy(RNU)is considered the standard of care for patients with high-risk upper tract urothelial carcinoma.Current literature reveals a deficit in direct comparative studies evaluating the efficacy of different chemotherapeutic agents administered in single postoperative instillation following RNU.The primary aim of this study was to compare the bladder recurrence(BR)rates between patients receiving a single instillation of mitomycin C(MMC)versus gemcitabine(Gem)after RNU.Methods:The ROBUUST(ROBotic surgery for Upper tract Urothelial cancer STudy)2.0 is an international,multicenter registry that aggregates data on patients who have undergone curative surgery for upper tract urothelial carcinoma across participating centers from January 2015 to December 2022.Data including primary baseline variables of the patients,characteristics of the tumors,surgical management,and definitive histopathological characterizations were collected and stratified based on the type of postoperative bladder instillation:MMC(the MMC group)and Gem(the Gem group).We selected variables correlated with our primary outcome to conduct a propensity-score match analysis.Results:One hundred patients in the MMC group were matched 1:1 with 100 patients in the Gem group.At 36 months of follow-up,30 patients in the MMC group and 39 patients in the Gem group experienced BR,representing recurrence rates of 30%and 39%,respectively(p=0.2).The Cox proportional hazards model comparing BR between the groups revealed a hazard ratio of 1.58(95%confidence interval:0.98-2.55)with a non-statistically significant increased risk of BR in the Gem group compared with the MMC group(p=0.059).Conclusion:A single perioperative instillation of Gem or MMC seems to offer similar efficacy in reducing the risk of BR in patients undergoing RNU.Further research,ideally within the framework of prospective studies,is warranted to elucidate the optimal chemotherapeutic approach in this setting.
