BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHO...BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHODS SW480 and DLD-1 CRC cell lines were used to investigate the mechanism of apoptosis by western blotting,flow cytometry,confocal microscopy,and other methods.RESULTS DCA significantly induced apoptosis,with rates increasing to 7.2%±1.5%in SW480 cells and 14.3%±0.6%in DLD-1 cells after treatment,compared to 4.7%±1.0%and 11.6%±0.8%in controls(P<0.05).Western blot analysis showed upregulation of pro-apoptotic proteins Bax and Cleaved-PARP,with a significant increase in the Cleaved-PARP/PARP ratio(P<0.001).DCA treatment also increased the intracellular reactive oxygen species(ROS)levels of SW480 and DLD-1 cells to 1.2-fold and 1.3-fold,respectively(P<0.01),while the increase of mitochondrial ROS levels in these cells was statistically significant under confocal microscopy.Additionally,cytosolic and mitochondrial Ca^(2+)levels increased 1.3-fold and 1.2-fold,respectively,in SW480 cells(P<0.01),and 1.1-fold and 1.1-fold,respectively,in DLD-1 cells compared with controls(P<0.05).p-CaMKII protein levels were also elevated(P<0.01),indicating activation of the Ca^(2+)-CaMKII signaling pathway.Pharmacological inhibition with BAPTAAM(1μM)reduced mitochondrial Ca^(2+)accumulation and ROS levels in SW480 cells(P<0.05),and suppressed apoptosis.CONCLUSION DCA activates the Ca^(2+)-CaMKII pathway,leading to ROS-mediated apoptosis in CRC cells,providing insights for potential therapeutic targets.展开更多
AIM:To investigate the clinicopathologic parameters of pulmonary metastasis in colorectal cancer(CRC) patients after lung operation of indeterminate pulmonary nodules(IPNs).METHODS:From a prospective database of CRCpa...AIM:To investigate the clinicopathologic parameters of pulmonary metastasis in colorectal cancer(CRC) patients after lung operation of indeterminate pulmonary nodules(IPNs).METHODS:From a prospective database of CRCpatients,40 cases that underwent lung operation between November 2008 and December 2012 for suspicious metastatic pulmonary nodules on chest computed tomography(CT)were enrolled.The decision to perform a lung operation was made if the patient met the following criteria:(1)completely resected or resectable primary CRC;(2)completely resectable IPNs;(3)controlled or controllable extrapulmonary metastasis;and(4)adequate general condition and pulmonary function to tolerate pulmonary operation.Lung operation was performed by a thoracic surgeon without CT-guided biopsy for pathologic confirmation.RESULTS:A total of 40 cases of lung resection was performed in 29 patients.Five patients underwent repeated lung resection.The final pathology result showed metastasis from the CRC in 30 cases(75%)and benign pathology in 10 cases(25%).The primary tumor site was the rectum in 26/30(86.6%)cases with pulmonary metastasis,but only 3/10(30%)cases in the benign group had a primary rectal cancer(P=0.001).Positron emission tomography(PET)-CT was performed for 22/30(73.4%)patients in the lung metastasis group and for 6/10(60.0%)patients in the benign group.PET-CT revealed hot uptake of18fluorine 2-fluoro-2-deoxy-D-glucose with all IPNs in both groups.The group with pulmonary metastasis had a higher incidence of primary rectal cancer(P=0.001),a more advanced tumor stage(P=0.011),and more frequent lymphatic invasion of tumor cells(P=0.005).Six cases with previous liver metastasectomy were present in the lung metastasis group.Serum carcinoembryonic antigen levels before lung operation were not elevated in any of the patients.CONCLUSION:The stage and location of the primary tumor and tumor cell infiltration of lymphatics provide useful indicators for deciding on lung resection of IPNs in CRC.展开更多
BACKGROUND With advanced age and chronic illness,the life expectancy of a patient with colorectal cancer(CRC)becomes less dependent on the malignant disease and more on their pre-morbid condition.Justifying major surg...BACKGROUND With advanced age and chronic illness,the life expectancy of a patient with colorectal cancer(CRC)becomes less dependent on the malignant disease and more on their pre-morbid condition.Justifying major surgery for these elderly patients can be challenging.An accurate tool demonstrating post-operative survival probability would be useful for surgeons and their patients.AIM To integrate clinically significant prognostic factors relevant to elective colorectal surgery in the elderly into a validated pre-operative scoring system.METHODS In this retrospective cohort study,patients aged 70 and above who underwent surgery for CRC at Singapore General Hospital between 1 January 2005 and 31 December 2012 were identified from a prospectively maintained database.Patients with evidence of metastatic disease,and those who underwent emergency surgery or had surgery for benign colorectal conditions were excluded from the analysis.The primary outcome was overall 3-year overall survival(OS)following surgery.A multivariate model predicting survival was derived and validated against an equivalent external surgical cohort from Kyungpook National University Chilgok Hospital,South Korea.Statistical analyses were performed using Stata/MP Version 15.1.RESULTS A total of 1267 patients were identified for analysis.The median post-operative length of stay was 8[interquartile range(IQR)6-12]d and median follow-up duration was 47(IQR 19-75)mo.Median OS was 78(IQR 65-85)mo.Following multivariate analysis,the factors significant for predicting overall mortality were serum albumin<35 g/dL,serum carcinoembryonic antigen≥20μg/L,T stage 3 or 4,moderate tumor cell differentiation or worse,mucinous histology,rectal tumors,and pre-existing chronic obstructive lung disease.Advanced age alone was not found to be significant.The Korean cohort consisted of 910 patients.The Singapore cohort exhibited a poorer OS,likely due to a higher proportion of advanced cancers.Despite the clinicopathologic differences,there was successful validation of the model following recalibration.An interactive online calculator was designed to facilitate post-operative survival prediction,available at http://bit.ly/sgh_crc.The main limitation of the study was selection bias,as patients who had undergone surgery would have tended to be physiologically fitter.CONCLUSION This novel scoring system generates an individualized survival probability following colorectal resection and can assist in the decision-making process.Validation with an external population strengthens the generalizability of this model.展开更多
BACKGROUND Breast cancer(BC)metastasis to the gastrointestinal tract is uncommon,colonic metastasis from BC(CMBC)is even rarer.CASE SUMMARY This report describes a 44-year-old female patient with metastatic triple-neg...BACKGROUND Breast cancer(BC)metastasis to the gastrointestinal tract is uncommon,colonic metastasis from BC(CMBC)is even rarer.CASE SUMMARY This report describes a 44-year-old female patient with metastatic triple-negative BC in the ascending colon who underwent laparoscopic radical right hemicolectomy.The patient had undergone left modified radical mastectomy only 15 months ago and stopped chemotherapy just 3 months ago.The diagnosis of CMBC was made based on the previous history of BC and positive results of several specific immunohistochemical markers(gross cystic disease fluid protein 15,mammaglobin,GATA-binding protein 3,and cytokeratin 7)for breast carcinoma.CONCLUSION CMBC should be highly cautious in patients with a previous history of BC,especially triple-negative BC,and further examination to aid in diagnosis.展开更多
BACKGROUND Anastomotic leakage(AL)is a challenging complication following rectal cancer surgery,often leading to increased morbidity and healthcare costs.The use of reinforcement sutures is expected to reduce the rate...BACKGROUND Anastomotic leakage(AL)is a challenging complication following rectal cancer surgery,often leading to increased morbidity and healthcare costs.The use of reinforcement sutures is expected to reduce the rate of AL,their preventive effects are controversial.AIM To determine the efficacy of reinforcing sutures in preventing AL in rectal cancer.METHODS A systematic search of major medical databases was conducted to identify studies up to June 2024.Intraoperative and postoperative outcomes were assessed;the primary outcome assessed was the incidence of AL.Pooled odds ratios(ORs)and mean differences(MDs)with a 95%confidence interval(CI)were calculated using fixed-effect or random-effect models under heterogeneity.RESULTS This meta-analysis incorporated 20 studies involving 3726 patients.Pooled results demonstrated a statistically significant reduction AL incidence in the reinforced suture group(OR:0.26,95%CI:0.19-0.35,P<0.001)than the unreinforced suture group.The reinforced suture group also exhibited a shorter hospital stay(MD:-1.17,95%CI:-1.78 to-0.57,P<0.001),earlier anal exhaust(MD:-0.13,95%CI:-0.22 to-0.05,P=0.002),longer operative time(MD:15.25,95%CI:10.71-19.80,P<0.001),lower infection rate(OR:0.54,95%CI:0.29-1.00,P=0.05)and lower reoperation rate(OR:0.19,95%CI:0.08-0.45,P<0.001).CONCLUSION The results substantiate the clinical value of anastomotic reinforcement sutures in reducing AL incidence postrectal cancer surgery.Nevertheless,these conclusions warrant verification through additional high-quality randomized controlled trials.展开更多
BACKGROUND Gastric cancer is the fifth most common cancer and the fourth leading cause of death worldwide.Most cases of newly diagnosed gastric cancer involve not only locally advanced tumor growth and regional lymph ...BACKGROUND Gastric cancer is the fifth most common cancer and the fourth leading cause of death worldwide.Most cases of newly diagnosed gastric cancer involve not only locally advanced tumor growth and regional lymph node metastases but also distant metastases.We report a rare case finding of a mass in the right inguinal area which is derived from gastric cancer.CASE SUMMARY A 68-year-old male initially diagnosed with an inguinal hernia presented with a 2 cm mass in the right inguinal area.Gastrointestinal symptoms led to the discovery of a stomach tumor.Biopsy confirmed gastrointestinal adenocarcinoma.The diagnosis was advanced gastric cancer with peritoneal dissemination,and the inguinal mass was due to direct infiltration.Due to gastrointestinal bleeding,the patient underwent palliative gastrectomy and lymph node dissection.Postoperatively,the patient received hyperthermic intraperitoneal chemotherapy and localized radiation therapy.CONCLUSION This case indicates that a systematic evaluation should be conducted during the initial consultation to explore the potential connection between unrecognized distant masses and the primary tumor.展开更多
Objective:The plastic role of regulatory factor X1(RFX1)in colon cancer progression and its impact on the tumor microenvironment remain poorly understood.The study aimed to clarify the molecular and clinical role of R...Objective:The plastic role of regulatory factor X1(RFX1)in colon cancer progression and its impact on the tumor microenvironment remain poorly understood.The study aimed to clarify the molecular and clinical role of RFX1 in colon cancer.Methods:We classified colon cancers into subgroups with high and low RFX1 expression and characterized their immune profiles,mutational profiles,cancer immunotherapy and drug sensitivity.By combining RFX1 expression with persistent tumor mutational burden,we proposed a novel nomogram clinical prediction model and validated its predictive performance,and the correlation between high expression and poor prognosis.Results:Compared to tumor mutational burden(TMB),persistent tumor mutational burden(pTMB)is an independent predictor of prognosis in patients with colon cancer.The predictive efficacy of the combination of RFX1 expression and pTMB was superior to and sensitive than the combination of RFX1 expression with TMB.Among them,patients in the RFX1^(high)/pTMB^(high) subgroup had the worst quality of survival and prognosis,whereas those in the RFX1low/pTMBlow subgroup had a relatively better prognosis(p<0.0001).Univariate Cox regression revealed a significant association between high RFX1 expression and increased risk in colon cancer patients(Hazard Ratio[HR]=1.58,95%Confidence Interval[CI]:1.10–2.25,p=0.012),which remained independently predictive in multivariate analysis after covariate adjustment(HR=1.52,95%CI:1.04–2.22,p=0.031).Conclusion:A nomogram model based on RFX1 combined with pTMB provides an alternative approach for the diagnosis and treatment of colon cancer.展开更多
AIM:To investigate the distribution pattern of lymphatic vessels and microvessels in sporadic colorectal carcinoma(SCRC)and their relationship to metastasis and prognosis.METHODS:The lymphatic vessel density(LVD)and m...AIM:To investigate the distribution pattern of lymphatic vessels and microvessels in sporadic colorectal carcinoma(SCRC)and their relationship to metastasis and prognosis.METHODS:The lymphatic vessel density(LVD)and microvessel density(MVD)in tumor tissue obtained from 132 patients with primary SCRC,including 74 with metastases and 58 without metastases,were evaluated by immunohistochemistry using antibodies directed against D2-40 and yon Willebrand factor(vWF).RESULTS:(1)The lymphatic vessels and microvessels at central portions of SCRC often had a reticular architecture with numerous tiny and ill-defined lumina,while those at tumor borders had large and open lumina.The LVD and MVD were both obviously higher in colorectal cancer patients with metastases than in those without(P〈0.001).(2)For each one lymphatic vessel increased,there was a 1.45-fold increase in the risk of metastasis in SCRC.The specificity and sensitivity of LVD in predicting metastasis or non-metastasis in SCRC were 71.62%and 56.90%,respectively,and the corresponding LVD was 5.For each one microvessel increased,there was a 1.11-fold increase in the risk of metastasis in SCRC.The specificity and sensitivity of MVD were 66.22%and 51.72%,respectively.(3)Double labeling immunohistochemistry showed D2-40 immunoreactivity to be specific for lymphatic vessels.(4)Univariate analysis indicated that high LVD,high MVD,as well as co-accounting of high LVD and high MVD were associated with patient's poor disease-free survival(Puni〈0.05);multivariate analysis indicated that co-accounting of LVD and MVD was an independent prognostic factor of colorectal cancer,CONCLUSION:D2-40 is a new specific antibody for lymphatic endothelial cells.Lymphogenesis and angiogenesis are commonly seen in SCRC,especially at tumor borders.The detection of LVD and MVD at tumor borders may be useful in predicting metastasis and prognosis in patients with SCRC,and,in particular,coaccounting of LVD and MVD might be a useful prognostic factor in SCRC.展开更多
BACKGROUND In recent years,the predictive role of YKL-40 for long-term survival in colorectal cancer patients has been gradually investigated.However,whether it is a reliable and valuable prognostic indicator for pati...BACKGROUND In recent years,the predictive role of YKL-40 for long-term survival in colorectal cancer patients has been gradually investigated.However,whether it is a reliable and valuable prognostic indicator for patients with colorectal carcinoma has not been verified.AIM To identify the prognostic value of serum/plasma concentration of YKL-40 or expression status of YKL-40 in tumor cells in colorectal carcinoma patients.METHODS Several electronic databases including the PubMed,EMBASE,Web of Science,CNKI,VIP and WanFang were searched for relevant studies.The hazard ratios(HR)and 95%confidence intervals(CI)were combined and the primary and secondary outcomes were overall survival(OS)and progression-free survival(PFS),respectively.All statistical analysis were conducted by STATA 15.0 software.RESULTS A total of nine studies involving 2545 patients were included.The pooled results indicated that YKL-40 was significantly associated with poor OS(HR=1.80,95%CI:1.32-2.45,P<0.001)and PFS(HR=1.62,95%CI:1.22-2.16,P=0.001).Subgroup analysis stratified by the treatment,tumor type and source of YKL-40 showed similar results.CONCLUSION Elevated serum/plasma concentration of YKL-40 or positive expression in tumor cells was related with worse prognosis of colorectal carcinoma patients.YKL-40 might serve as a novel and reliable indicator for the evaluation of prognosis in colorectal cancer.展开更多
Apolipoprotein A-I(Apo A-I),the main protein component of high-density lipoprotein(HDL),plays a pivotal role in reverse cholesterol transport(RCT).Previous studies indicated a reduction of serum Apo A-I levels in vari...Apolipoprotein A-I(Apo A-I),the main protein component of high-density lipoprotein(HDL),plays a pivotal role in reverse cholesterol transport(RCT).Previous studies indicated a reduction of serum Apo A-I levels in various types of cancer,suggesting Apo A-I as a potential cancer biomarker.Herein,ectopically overexpressed Apo A-I in MDA-MB-231 breast cancer cells was observed to have antitumor effects,inhibiting cell proliferation and migration.Subsequent studies on the mechanism of expression regulation revealed that estradiol(E2)/estrogen receptorα(ERα)signaling activates Apo A-I gene transcription in breast cancer cells.Mechanistically,our Ch IP-seq data showed that ERαdirectly binds to the estrogen response element(ERE)site within the Apo A-I gene and establishes an acetylation of histone 3 lysine 27(H3 K27 ac)-enriched chromatin microenvironment.Conversely,Fulvestrant(ICI 182780)treatment blocked ERαbinding to ERE within the Apo A-I gene and downregulated the H3 K27 ac level on the Apo A-I gene.Treatment with p300 inhibitor also significantly decreased the Apo A-I messenger RNA(m RNA)level in MCF7 cells.Furthermore,the analysis of data from The Cancer Genome Atlas(TCGA)revealed a positive correlation between ERαand Apo A-I expression in breast cancer tissues.Taken together,our study not only revealed the antitumor potential of Apo A-I at the cellular level,but also found that ERαpromotes the transcription of Apo A-I gene through direct genomic effects,and p300 may act as a co-activator of ERαin this process.展开更多
Objective:The membrane-linking protein Ezrin is highly expressed in several types of human cancers.The cor-relations between its immunoreactivity and histopathological data as well as patient outcome have previously b...Objective:The membrane-linking protein Ezrin is highly expressed in several types of human cancers.The cor-relations between its immunoreactivity and histopathological data as well as patient outcome have previously been shown.However,the role played by Ezrin in the carcinogenesis,progression and metastasis of primary sporadic colorectal carcinoma(SCRC)is still under investigation.This study assessed Ezrin protein expression in a series of clinical specimens.Methods:Immunohistochemical analysis was used to characterize patterns of Ezrin expression in 132 cases of SCRC,including 74 metastatic cases and 58 non-metastatic cases and 43 adjacent normal colorectal mucosa.Results:(1)The expression rate of Ezrin in SCRC(79.5%)was significantly higher than in adjacent normal colorectal mucosa(11.6%)(P<0.001);(2)The total expression rate of Ezrin was 86.5%and 70.7%in metastatic group and non-metastatic group,respectively(P=0.026);the membrane expression rate of Ezrin was 31.1%and 6.9%in the two groups,respectively(P<0.01);(3)There was no relation-ship between the expression of Ezrin with age,gender,tumor size,location,degree of differentiation and invasive depth;(4)In the cases with followed-up data,univariate analysis demonstrated that Ezrin expression and its membrane translocation was correlated with worse patient’s disease-free survival(DFS)(Puni<0.05).Conclusion:Ezrin was expressed in the majority of SCRC and associated with adverse prognostic factors.The increase expression and the switch of Ezrin localization from the cytoplasm to the membrane were closely correlated with metastasis in SCRC.It might be served as an important parameter for determining tumor biological behavior.展开更多
The number of new cancer cases in China is increasing rapidly,and China now ranks first in the world for the number of cancer patients.Traditional oncology treatment is based on surgery,radiotherapy and chemotherapy,b...The number of new cancer cases in China is increasing rapidly,and China now ranks first in the world for the number of cancer patients.Traditional oncology treatment is based on surgery,radiotherapy and chemotherapy,but all three treatments are often accompanied by a poor quality of life,impaired physical function,and significant anxiety and depression.Exercise therapy can provide both prognostic improvement and a better quality of life for cancer patients,and can be adapted to serve patients at all stages from perioperative recovery to hospice.Although the impact of exercise alone is difficult to assess given the influence of lifestyle and other factors,data suggest that consistent exercise can improve the prognosis of cancer patients.Exercise enhances cardiopulmonary function,induces protein synthesis,improves physiological performance and increases physiological reserves;it also helps to improve the metabolic and immune functions,creating an anti-cancer environment in the body.An appropriate exercise plan can reduce adverse effects associated with cancer treatment,improve patients'physiological function,reduce fatigue and improve quality of life.Of note,exercise may also reduce the risk of cancer recurrence and metastasis.In recent years,exercise oncology has received increasing attention,thus,this article reviews the progress made in the clinical application of exercise therapy in oncology patients.展开更多
Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and c...Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.展开更多
Objective：To evaluate the efficacy and safety of Yiqi Zhuyu Decoction（益气逐瘀汤,YZD） combined with oxaliplatin plus 5-flurouracil/leucovorin（FOLFOX-4） in the patients with metastatic colorectal cancer（MCRC）.Me...Objective：To evaluate the efficacy and safety of Yiqi Zhuyu Decoction（益气逐瘀汤,YZD） combined with oxaliplatin plus 5-flurouracil/leucovorin（FOLFOX-4） in the patients with metastatic colorectal cancer（MCRC）.Methods：A total of 120 patients with MCRC were randomly divided into the experimental group（FOLFOX-4 plus YZD,60 cases） and the control group（FOLFOX-4 plus placebo,60 cases）,according to the sequence of hospitalization from January 2005 to December 2007.The treatment was supposed to be continued until disease progression（PD） or for 48 weeks（i.e.,up to 24 cycles of FOLFOX-4）.Response rate （RR）,progression-free survival（PFS）,overall survival（OS） and adverse events（AEs） were observed.Results： RR was 41.5%in the experimental group and 34.0%in the control group[odds ratio（OR）：1.18,95%CI：0.77 to 1.82,P=0.432].Median PFS were 9.0 months and 8.0 months,respectively[hazard ratio（HR）：0.78,95% CI：0.53 to 1.15,P=0.215].Median OS were 21.0 months and 18.0 months（HR：0.65,95%CI：0.43 to 0.99, P=0.043） and grade 3/4 AEs were 56.6%and 76.7%（OR：0.61,95%CI：0.18 to 0.87,P=0.020）,respectively. Conclusions：YZD combined with FOLFOX-4 chemotherapy significantly improved OS in this first-line trial in the patients with MCRC and significantly decreased grade 3/4 AEs.However,RR was not improved,and PFS did not reach statistical significance by the addition of YZD.The treatment of YZD combined with FOLFOX-4 may be necessary in order to optimize efficacy and safety.展开更多
Osteoporosis caused by aging is characterized by reduced bone mass and accumulated adipocytes in the bone marrow cavity. How the balance between osteoblastogenesis and adipogenesis from bone marrow mesenchymal stem ce...Osteoporosis caused by aging is characterized by reduced bone mass and accumulated adipocytes in the bone marrow cavity. How the balance between osteoblastogenesis and adipogenesis from bone marrow mesenchymal stem cells(BMSCs) is lost upon aging is still unclear. Here, we found that the RNA-binding protein Musashi2(Msi2) regulates BMSC lineage commitment. Msi2 is commonly enriched in stem cells and tumor cells. We found that its expression was downregulated during adipogenic differentiation and upregulated during osteogenic differentiation of BMSCs. Msi2 knockout mice exhibited decreased bone mass with substantial accumulation of marrow adipocytes, similar to aging-induced osteoporosis. Depletion of Msi2 in BMSCs led to increased adipocyte commitment. Transcriptional profiling analysis revealed that Msi2 deficiency led to increased PPARγ signaling.RNA-interacting protein immunoprecipitation assays demonstrated that Msi2 could inhibit the translation of the key adipogenic factor Cebpα, thereby inhibiting PPAR signaling. Furthermore, the expression of Msi2 decreased significantly during the aging process of mice, indicating that decreased Msi2 function during aging contributes to abnormal accumulation of adipocytes in bone marrow and osteoporosis. Thus, our results provide a putative biochemical mechanism for aging-related osteoporosis, suggesting that modulating Msi2 function may benefit the treatment of bone aging.展开更多
Dear Editor,To date,the effect of colorectal cancer(CRC)-derived extracellular vesicles(EVs)on liver pre-metastatic niche(PMN)remain incompletely understood.1 To investigate the role of CRC-derived EVs in the remodeli...Dear Editor,To date,the effect of colorectal cancer(CRC)-derived extracellular vesicles(EVs)on liver pre-metastatic niche(PMN)remain incompletely understood.1 To investigate the role of CRC-derived EVs in the remodeling of the liver PMN,we isolated EVs from CT26 cell culture supernatant.The characteristics of EVs(the morphology,size,and markers)were identified by transmission electron microscopy(TEM),Nanoparticle Tracking Analysis(NTA),and western blotting(Supplementary Fig.S1a–e).Then,BALB/c mice with an intact liver immune status were pretreated with CRCderived EVs and phosphate-buffered saline(PBS)for one month,and a liver metastasis model was established via spleen injection of tumor cells to determine whether EVs influence liver metastasis(Fig.1a).Two hours after the operation,in vivo imaging indicated that the animal model was successfully established,and the tumor fluorescence intensity in the liver was consistent between the two groups(Supplementary Fig.S2a,b).Amazingly,the liver tumor fluorescence intensity in the EVs group was significantly stronger than that in the PBS group after 24 h(Fig.1b;Supplementary Fig.S2c,d).The number of liver tumor nodules in the EVs group was also significantly higher than that in the PBS group on day 4(Fig.1c;Supplementary Fig.S2e,f).展开更多
Magnesium(Mg)deficiency is associated with increased risk and malignancy in colorectal cancer(CRC),yet the underlying mechanisms remain elusive.Here,we used genomic,proteomic,and phosphoproteomic data to elucidate the...Magnesium(Mg)deficiency is associated with increased risk and malignancy in colorectal cancer(CRC),yet the underlying mechanisms remain elusive.Here,we used genomic,proteomic,and phosphoproteomic data to elucidate the impact of Mg deficiency on CRC.Genomic analysis identified 160 genes with higher mutation frequencies in Low-Mg tumors,including key driver genes such as KMT2C and ERBB3.Unexpectedly,initiation driver genes of CRC,such as TP53 and APC,displayed higher mutation frequencies in High-Mg tumors.Additionally,proteomic and phosphoproteomic data indicated that low Mg content in tumors may activate epithelial–mesenchymal transition(EMT)by modulating inflammation or remodeling the phosphoproteome of cancer cells.Notably,we observed a negative correlation between the phosphorylation of DBN1 at S142(DBN1S142p)and Mg content.A mutation in S142 to D(DBN1S142D)mimicking DBN1S142p up-regulated MMP2 and enhanced cell migration,while treatment with MgCl2 reduced DBN1S142p,thereby reversing this phenotype.Mechanistically,Mg2þattenuated the DBN1–ACTN4 interaction by decreasing DBN1S142p,which in turn enhanced the binding of ACTN4 to F-actin and promoted F-actin polymerization,ultimately reducing MMP2 expression.These findings shed new light on the crucial role of Mg deficiency in CRC progression and suggest that Mg supplementation may be a promising preventive and therapeutic strategy for CRC.展开更多
BACKGROUND Robot-assisted gastrointestinal and liver surgery has been an important development direction in the field of surgery in recent years and it is also one of the fastest developing and most concerning fields ...BACKGROUND Robot-assisted gastrointestinal and liver surgery has been an important development direction in the field of surgery in recent years and it is also one of the fastest developing and most concerning fields in surgical operations.AIM To illustrate the major areas of research and forward-looking directions over the past twenty-six years.METHODS Using the Web of Science Core Collection database,a comprehensive review of scholarly articles pertaining to robot-assisted gastrointestinal and liver surgery was researched out between 2000 and 2023.We used Citespace(Version 6.2.4)and Bibliometrix package(Version 4.3.0)to visualize the analysis of all publications including country,institutional affiliations,authors,and keywords.RESULTS In total,346 articles were retrieved.Surgical Endoscopy had with the largest number of publications and was cited in this field.The United States was a core research country in this field.Yonsei University was the most productive institution.The current focus of this field is on rectal surgery,long-term prognosis,perioperative management,previous surgical experience,and the learning curve.CONCLUSION The scientific interest in robot-assisted gastrointestinal and liver surgery has experienced a significant rise since 1997.This study provides new perspectives and ideas for future research in this field.展开更多
Background and Objectives:Patients with gastrointestinal(GI)malignancies are at high risk for malnutrition because of reduced food intake,poor digestion,and altered absorption.Methods and Study Design:In a retrospecti...Background and Objectives:Patients with gastrointestinal(GI)malignancies are at high risk for malnutrition because of reduced food intake,poor digestion,and altered absorption.Methods and Study Design:In a retrospective review of medical records for patients admitted to urban hospitals in an Asian nation for GI tumor surgery(gastric,colon,or anorectal cancers),we found that malnutrition was common yet often overlooked.Our review identified records for 349 adult GI-tumor surgery patients.The Nutrition Risk Screening-2002(NRS-2002)was the most frequently used screening instrument.In further review,we compared outcomes for malnourished GI tumor surgery patients given daily oral nutritional supplements(ONS)to outcomes for patients who were not given ONS.Results:Review of results revealed that only 20%of patients in our sample underwent nutritional screening or assessment on admission.Of those who did,nearly 60%were malnourished.Although due to small sample sizes,no statistically significant differences were observed,malnourished patients who received ONS had fewer complications and shorter lengths of stay by 1-day.Such findings reveal many missed opportunities to improve patient outcomes and to avert excess healthcare costs for treatment of complications,slowed recovery,longer hospital stays,and readmissions.Conclusions:Based on our findings,nutritional training for professionals is necessary to address the serious problems of under-recognition and inadequate treatment of malnutrition in hospitalized patients.展开更多
Esophageal cancer(EC)is one of the most lethal cancers in the world[1].Esophageal squamous cell carcinoma(ESCC)is the dominant subtype of EC in China,with a poor prognosis and low survival rate[1].Currently,surgical r...Esophageal cancer(EC)is one of the most lethal cancers in the world[1].Esophageal squamous cell carcinoma(ESCC)is the dominant subtype of EC in China,with a poor prognosis and low survival rate[1].Currently,surgical resection,radiotherapy,and chemotherapy are the primary clinical treatments for EC[2,3].展开更多
基金Supported by the Key Discipline of Zhejiang Province in Medical Technology(First Class,Category A)Wenzhou Science&Technological Project,No.Y20240103.
文摘BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHODS SW480 and DLD-1 CRC cell lines were used to investigate the mechanism of apoptosis by western blotting,flow cytometry,confocal microscopy,and other methods.RESULTS DCA significantly induced apoptosis,with rates increasing to 7.2%±1.5%in SW480 cells and 14.3%±0.6%in DLD-1 cells after treatment,compared to 4.7%±1.0%and 11.6%±0.8%in controls(P<0.05).Western blot analysis showed upregulation of pro-apoptotic proteins Bax and Cleaved-PARP,with a significant increase in the Cleaved-PARP/PARP ratio(P<0.001).DCA treatment also increased the intracellular reactive oxygen species(ROS)levels of SW480 and DLD-1 cells to 1.2-fold and 1.3-fold,respectively(P<0.01),while the increase of mitochondrial ROS levels in these cells was statistically significant under confocal microscopy.Additionally,cytosolic and mitochondrial Ca^(2+)levels increased 1.3-fold and 1.2-fold,respectively,in SW480 cells(P<0.01),and 1.1-fold and 1.1-fold,respectively,in DLD-1 cells compared with controls(P<0.05).p-CaMKII protein levels were also elevated(P<0.01),indicating activation of the Ca^(2+)-CaMKII signaling pathway.Pharmacological inhibition with BAPTAAM(1μM)reduced mitochondrial Ca^(2+)accumulation and ROS levels in SW480 cells(P<0.05),and suppressed apoptosis.CONCLUSION DCA activates the Ca^(2+)-CaMKII pathway,leading to ROS-mediated apoptosis in CRC cells,providing insights for potential therapeutic targets.
文摘AIM:To investigate the clinicopathologic parameters of pulmonary metastasis in colorectal cancer(CRC) patients after lung operation of indeterminate pulmonary nodules(IPNs).METHODS:From a prospective database of CRCpatients,40 cases that underwent lung operation between November 2008 and December 2012 for suspicious metastatic pulmonary nodules on chest computed tomography(CT)were enrolled.The decision to perform a lung operation was made if the patient met the following criteria:(1)completely resected or resectable primary CRC;(2)completely resectable IPNs;(3)controlled or controllable extrapulmonary metastasis;and(4)adequate general condition and pulmonary function to tolerate pulmonary operation.Lung operation was performed by a thoracic surgeon without CT-guided biopsy for pathologic confirmation.RESULTS:A total of 40 cases of lung resection was performed in 29 patients.Five patients underwent repeated lung resection.The final pathology result showed metastasis from the CRC in 30 cases(75%)and benign pathology in 10 cases(25%).The primary tumor site was the rectum in 26/30(86.6%)cases with pulmonary metastasis,but only 3/10(30%)cases in the benign group had a primary rectal cancer(P=0.001).Positron emission tomography(PET)-CT was performed for 22/30(73.4%)patients in the lung metastasis group and for 6/10(60.0%)patients in the benign group.PET-CT revealed hot uptake of18fluorine 2-fluoro-2-deoxy-D-glucose with all IPNs in both groups.The group with pulmonary metastasis had a higher incidence of primary rectal cancer(P=0.001),a more advanced tumor stage(P=0.011),and more frequent lymphatic invasion of tumor cells(P=0.005).Six cases with previous liver metastasectomy were present in the lung metastasis group.Serum carcinoembryonic antigen levels before lung operation were not elevated in any of the patients.CONCLUSION:The stage and location of the primary tumor and tumor cell infiltration of lymphatics provide useful indicators for deciding on lung resection of IPNs in CRC.
文摘BACKGROUND With advanced age and chronic illness,the life expectancy of a patient with colorectal cancer(CRC)becomes less dependent on the malignant disease and more on their pre-morbid condition.Justifying major surgery for these elderly patients can be challenging.An accurate tool demonstrating post-operative survival probability would be useful for surgeons and their patients.AIM To integrate clinically significant prognostic factors relevant to elective colorectal surgery in the elderly into a validated pre-operative scoring system.METHODS In this retrospective cohort study,patients aged 70 and above who underwent surgery for CRC at Singapore General Hospital between 1 January 2005 and 31 December 2012 were identified from a prospectively maintained database.Patients with evidence of metastatic disease,and those who underwent emergency surgery or had surgery for benign colorectal conditions were excluded from the analysis.The primary outcome was overall 3-year overall survival(OS)following surgery.A multivariate model predicting survival was derived and validated against an equivalent external surgical cohort from Kyungpook National University Chilgok Hospital,South Korea.Statistical analyses were performed using Stata/MP Version 15.1.RESULTS A total of 1267 patients were identified for analysis.The median post-operative length of stay was 8[interquartile range(IQR)6-12]d and median follow-up duration was 47(IQR 19-75)mo.Median OS was 78(IQR 65-85)mo.Following multivariate analysis,the factors significant for predicting overall mortality were serum albumin<35 g/dL,serum carcinoembryonic antigen≥20μg/L,T stage 3 or 4,moderate tumor cell differentiation or worse,mucinous histology,rectal tumors,and pre-existing chronic obstructive lung disease.Advanced age alone was not found to be significant.The Korean cohort consisted of 910 patients.The Singapore cohort exhibited a poorer OS,likely due to a higher proportion of advanced cancers.Despite the clinicopathologic differences,there was successful validation of the model following recalibration.An interactive online calculator was designed to facilitate post-operative survival prediction,available at http://bit.ly/sgh_crc.The main limitation of the study was selection bias,as patients who had undergone surgery would have tended to be physiologically fitter.CONCLUSION This novel scoring system generates an individualized survival probability following colorectal resection and can assist in the decision-making process.Validation with an external population strengthens the generalizability of this model.
基金The Science and Technology Bureau of Wuhu,Anhui Province,China,Under The Key Research and Development and Achievement Transformation Project,No.2023yf099.
文摘BACKGROUND Breast cancer(BC)metastasis to the gastrointestinal tract is uncommon,colonic metastasis from BC(CMBC)is even rarer.CASE SUMMARY This report describes a 44-year-old female patient with metastatic triple-negative BC in the ascending colon who underwent laparoscopic radical right hemicolectomy.The patient had undergone left modified radical mastectomy only 15 months ago and stopped chemotherapy just 3 months ago.The diagnosis of CMBC was made based on the previous history of BC and positive results of several specific immunohistochemical markers(gross cystic disease fluid protein 15,mammaglobin,GATA-binding protein 3,and cytokeratin 7)for breast carcinoma.CONCLUSION CMBC should be highly cautious in patients with a previous history of BC,especially triple-negative BC,and further examination to aid in diagnosis.
文摘BACKGROUND Anastomotic leakage(AL)is a challenging complication following rectal cancer surgery,often leading to increased morbidity and healthcare costs.The use of reinforcement sutures is expected to reduce the rate of AL,their preventive effects are controversial.AIM To determine the efficacy of reinforcing sutures in preventing AL in rectal cancer.METHODS A systematic search of major medical databases was conducted to identify studies up to June 2024.Intraoperative and postoperative outcomes were assessed;the primary outcome assessed was the incidence of AL.Pooled odds ratios(ORs)and mean differences(MDs)with a 95%confidence interval(CI)were calculated using fixed-effect or random-effect models under heterogeneity.RESULTS This meta-analysis incorporated 20 studies involving 3726 patients.Pooled results demonstrated a statistically significant reduction AL incidence in the reinforced suture group(OR:0.26,95%CI:0.19-0.35,P<0.001)than the unreinforced suture group.The reinforced suture group also exhibited a shorter hospital stay(MD:-1.17,95%CI:-1.78 to-0.57,P<0.001),earlier anal exhaust(MD:-0.13,95%CI:-0.22 to-0.05,P=0.002),longer operative time(MD:15.25,95%CI:10.71-19.80,P<0.001),lower infection rate(OR:0.54,95%CI:0.29-1.00,P=0.05)and lower reoperation rate(OR:0.19,95%CI:0.08-0.45,P<0.001).CONCLUSION The results substantiate the clinical value of anastomotic reinforcement sutures in reducing AL incidence postrectal cancer surgery.Nevertheless,these conclusions warrant verification through additional high-quality randomized controlled trials.
文摘BACKGROUND Gastric cancer is the fifth most common cancer and the fourth leading cause of death worldwide.Most cases of newly diagnosed gastric cancer involve not only locally advanced tumor growth and regional lymph node metastases but also distant metastases.We report a rare case finding of a mass in the right inguinal area which is derived from gastric cancer.CASE SUMMARY A 68-year-old male initially diagnosed with an inguinal hernia presented with a 2 cm mass in the right inguinal area.Gastrointestinal symptoms led to the discovery of a stomach tumor.Biopsy confirmed gastrointestinal adenocarcinoma.The diagnosis was advanced gastric cancer with peritoneal dissemination,and the inguinal mass was due to direct infiltration.Due to gastrointestinal bleeding,the patient underwent palliative gastrectomy and lymph node dissection.Postoperatively,the patient received hyperthermic intraperitoneal chemotherapy and localized radiation therapy.CONCLUSION This case indicates that a systematic evaluation should be conducted during the initial consultation to explore the potential connection between unrecognized distant masses and the primary tumor.
基金sponsored by the National Natural Science Foundation of China(82002507)Shanghai Sailing Program(20YF1430100)Shanghai Hospital Development Center(SHDC2023CRT004).
文摘Objective:The plastic role of regulatory factor X1(RFX1)in colon cancer progression and its impact on the tumor microenvironment remain poorly understood.The study aimed to clarify the molecular and clinical role of RFX1 in colon cancer.Methods:We classified colon cancers into subgroups with high and low RFX1 expression and characterized their immune profiles,mutational profiles,cancer immunotherapy and drug sensitivity.By combining RFX1 expression with persistent tumor mutational burden,we proposed a novel nomogram clinical prediction model and validated its predictive performance,and the correlation between high expression and poor prognosis.Results:Compared to tumor mutational burden(TMB),persistent tumor mutational burden(pTMB)is an independent predictor of prognosis in patients with colon cancer.The predictive efficacy of the combination of RFX1 expression and pTMB was superior to and sensitive than the combination of RFX1 expression with TMB.Among them,patients in the RFX1^(high)/pTMB^(high) subgroup had the worst quality of survival and prognosis,whereas those in the RFX1low/pTMBlow subgroup had a relatively better prognosis(p<0.0001).Univariate Cox regression revealed a significant association between high RFX1 expression and increased risk in colon cancer patients(Hazard Ratio[HR]=1.58,95%Confidence Interval[CI]:1.10–2.25,p=0.012),which remained independently predictive in multivariate analysis after covariate adjustment(HR=1.52,95%CI:1.04–2.22,p=0.031).Conclusion:A nomogram model based on RFX1 combined with pTMB provides an alternative approach for the diagnosis and treatment of colon cancer.
基金Supported by the a grant from the Sciences and Techni-que Development Foundation of Shanghai,No.064119512,024119010
文摘AIM:To investigate the distribution pattern of lymphatic vessels and microvessels in sporadic colorectal carcinoma(SCRC)and their relationship to metastasis and prognosis.METHODS:The lymphatic vessel density(LVD)and microvessel density(MVD)in tumor tissue obtained from 132 patients with primary SCRC,including 74 with metastases and 58 without metastases,were evaluated by immunohistochemistry using antibodies directed against D2-40 and yon Willebrand factor(vWF).RESULTS:(1)The lymphatic vessels and microvessels at central portions of SCRC often had a reticular architecture with numerous tiny and ill-defined lumina,while those at tumor borders had large and open lumina.The LVD and MVD were both obviously higher in colorectal cancer patients with metastases than in those without(P〈0.001).(2)For each one lymphatic vessel increased,there was a 1.45-fold increase in the risk of metastasis in SCRC.The specificity and sensitivity of LVD in predicting metastasis or non-metastasis in SCRC were 71.62%and 56.90%,respectively,and the corresponding LVD was 5.For each one microvessel increased,there was a 1.11-fold increase in the risk of metastasis in SCRC.The specificity and sensitivity of MVD were 66.22%and 51.72%,respectively.(3)Double labeling immunohistochemistry showed D2-40 immunoreactivity to be specific for lymphatic vessels.(4)Univariate analysis indicated that high LVD,high MVD,as well as co-accounting of high LVD and high MVD were associated with patient's poor disease-free survival(Puni〈0.05);multivariate analysis indicated that co-accounting of LVD and MVD was an independent prognostic factor of colorectal cancer,CONCLUSION:D2-40 is a new specific antibody for lymphatic endothelial cells.Lymphogenesis and angiogenesis are commonly seen in SCRC,especially at tumor borders.The detection of LVD and MVD at tumor borders may be useful in predicting metastasis and prognosis in patients with SCRC,and,in particular,coaccounting of LVD and MVD might be a useful prognostic factor in SCRC.
文摘BACKGROUND In recent years,the predictive role of YKL-40 for long-term survival in colorectal cancer patients has been gradually investigated.However,whether it is a reliable and valuable prognostic indicator for patients with colorectal carcinoma has not been verified.AIM To identify the prognostic value of serum/plasma concentration of YKL-40 or expression status of YKL-40 in tumor cells in colorectal carcinoma patients.METHODS Several electronic databases including the PubMed,EMBASE,Web of Science,CNKI,VIP and WanFang were searched for relevant studies.The hazard ratios(HR)and 95%confidence intervals(CI)were combined and the primary and secondary outcomes were overall survival(OS)and progression-free survival(PFS),respectively.All statistical analysis were conducted by STATA 15.0 software.RESULTS A total of nine studies involving 2545 patients were included.The pooled results indicated that YKL-40 was significantly associated with poor OS(HR=1.80,95%CI:1.32-2.45,P<0.001)and PFS(HR=1.62,95%CI:1.22-2.16,P=0.001).Subgroup analysis stratified by the treatment,tumor type and source of YKL-40 showed similar results.CONCLUSION Elevated serum/plasma concentration of YKL-40 or positive expression in tumor cells was related with worse prognosis of colorectal carcinoma patients.YKL-40 might serve as a novel and reliable indicator for the evaluation of prognosis in colorectal cancer.
基金supported by the National Natural Science Foundation of China(Nos.81672785,31871291,and82073113 to Li TAN)the National Key R&D Project of China(No.2016YFA0101800 to Li TAN)supported by the Innovative Research Team of High-level Local University in Shanghai。
文摘Apolipoprotein A-I(Apo A-I),the main protein component of high-density lipoprotein(HDL),plays a pivotal role in reverse cholesterol transport(RCT).Previous studies indicated a reduction of serum Apo A-I levels in various types of cancer,suggesting Apo A-I as a potential cancer biomarker.Herein,ectopically overexpressed Apo A-I in MDA-MB-231 breast cancer cells was observed to have antitumor effects,inhibiting cell proliferation and migration.Subsequent studies on the mechanism of expression regulation revealed that estradiol(E2)/estrogen receptorα(ERα)signaling activates Apo A-I gene transcription in breast cancer cells.Mechanistically,our Ch IP-seq data showed that ERαdirectly binds to the estrogen response element(ERE)site within the Apo A-I gene and establishes an acetylation of histone 3 lysine 27(H3 K27 ac)-enriched chromatin microenvironment.Conversely,Fulvestrant(ICI 182780)treatment blocked ERαbinding to ERE within the Apo A-I gene and downregulated the H3 K27 ac level on the Apo A-I gene.Treatment with p300 inhibitor also significantly decreased the Apo A-I messenger RNA(m RNA)level in MCF7 cells.Furthermore,the analysis of data from The Cancer Genome Atlas(TCGA)revealed a positive correlation between ERαand Apo A-I expression in breast cancer tissues.Taken together,our study not only revealed the antitumor potential of Apo A-I at the cellular level,but also found that ERαpromotes the transcription of Apo A-I gene through direct genomic effects,and p300 may act as a co-activator of ERαin this process.
基金the Sciences and Technique Development Foundation of Shanghai(No.024119010).
文摘Objective:The membrane-linking protein Ezrin is highly expressed in several types of human cancers.The cor-relations between its immunoreactivity and histopathological data as well as patient outcome have previously been shown.However,the role played by Ezrin in the carcinogenesis,progression and metastasis of primary sporadic colorectal carcinoma(SCRC)is still under investigation.This study assessed Ezrin protein expression in a series of clinical specimens.Methods:Immunohistochemical analysis was used to characterize patterns of Ezrin expression in 132 cases of SCRC,including 74 metastatic cases and 58 non-metastatic cases and 43 adjacent normal colorectal mucosa.Results:(1)The expression rate of Ezrin in SCRC(79.5%)was significantly higher than in adjacent normal colorectal mucosa(11.6%)(P<0.001);(2)The total expression rate of Ezrin was 86.5%and 70.7%in metastatic group and non-metastatic group,respectively(P=0.026);the membrane expression rate of Ezrin was 31.1%and 6.9%in the two groups,respectively(P<0.01);(3)There was no relation-ship between the expression of Ezrin with age,gender,tumor size,location,degree of differentiation and invasive depth;(4)In the cases with followed-up data,univariate analysis demonstrated that Ezrin expression and its membrane translocation was correlated with worse patient’s disease-free survival(DFS)(Puni<0.05).Conclusion:Ezrin was expressed in the majority of SCRC and associated with adverse prognostic factors.The increase expression and the switch of Ezrin localization from the cytoplasm to the membrane were closely correlated with metastasis in SCRC.It might be served as an important parameter for determining tumor biological behavior.
基金the National Natural Science Foundation of China(No.82171565).
文摘The number of new cancer cases in China is increasing rapidly,and China now ranks first in the world for the number of cancer patients.Traditional oncology treatment is based on surgery,radiotherapy and chemotherapy,but all three treatments are often accompanied by a poor quality of life,impaired physical function,and significant anxiety and depression.Exercise therapy can provide both prognostic improvement and a better quality of life for cancer patients,and can be adapted to serve patients at all stages from perioperative recovery to hospice.Although the impact of exercise alone is difficult to assess given the influence of lifestyle and other factors,data suggest that consistent exercise can improve the prognosis of cancer patients.Exercise enhances cardiopulmonary function,induces protein synthesis,improves physiological performance and increases physiological reserves;it also helps to improve the metabolic and immune functions,creating an anti-cancer environment in the body.An appropriate exercise plan can reduce adverse effects associated with cancer treatment,improve patients'physiological function,reduce fatigue and improve quality of life.Of note,exercise may also reduce the risk of cancer recurrence and metastasis.In recent years,exercise oncology has received increasing attention,thus,this article reviews the progress made in the clinical application of exercise therapy in oncology patients.
基金funded by Chinese NSFC(Grant Nos.:82373336,82303238,and U22A20311,Sichuan Science and Technology Department,China(GrantNos.:2024NSFSC1945,,and 2023NSFSC0667)the Third People's Hospital of Chengdu Clinical Research Program,China(Grant Nos.:CSY-YN-01-2023-013,CSYYN-01-2023-005,and CSY-YN-03-2024-003)+1 种基金Sichuan University“From O to 1”Innovative Research Project,China(Project No.:2023SCUH0024)Health Commission of Chengdu,China(Grant No.:2024291).
文摘Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.
文摘Objective：To evaluate the efficacy and safety of Yiqi Zhuyu Decoction（益气逐瘀汤,YZD） combined with oxaliplatin plus 5-flurouracil/leucovorin（FOLFOX-4） in the patients with metastatic colorectal cancer（MCRC）.Methods：A total of 120 patients with MCRC were randomly divided into the experimental group（FOLFOX-4 plus YZD,60 cases） and the control group（FOLFOX-4 plus placebo,60 cases）,according to the sequence of hospitalization from January 2005 to December 2007.The treatment was supposed to be continued until disease progression（PD） or for 48 weeks（i.e.,up to 24 cycles of FOLFOX-4）.Response rate （RR）,progression-free survival（PFS）,overall survival（OS） and adverse events（AEs） were observed.Results： RR was 41.5%in the experimental group and 34.0%in the control group[odds ratio（OR）：1.18,95%CI：0.77 to 1.82,P=0.432].Median PFS were 9.0 months and 8.0 months,respectively[hazard ratio（HR）：0.78,95% CI：0.53 to 1.15,P=0.215].Median OS were 21.0 months and 18.0 months（HR：0.65,95%CI：0.43 to 0.99, P=0.043） and grade 3/4 AEs were 56.6%and 76.7%（OR：0.61,95%CI：0.18 to 0.87,P=0.020）,respectively. Conclusions：YZD combined with FOLFOX-4 chemotherapy significantly improved OS in this first-line trial in the patients with MCRC and significantly decreased grade 3/4 AEs.However,RR was not improved,and PFS did not reach statistical significance by the addition of YZD.The treatment of YZD combined with FOLFOX-4 may be necessary in order to optimize efficacy and safety.
基金supported by the National Natural Science Foundation of China(NSFC)[81672119 and 81725010 to W.Z.]W Z is a scholar of‘the National Science Fund for Distinguished Young Scholars’(NSFC)[81725010]+4 种基金the Strategic Priority Research Program of the Chinese Academy of Science(XDA16020400 to P.H.)Ministry of Science and Technology of China(2017YFA0102700 to P.H.)National Natural Science Foundation of China(32170804 to PH)P.H.the fellowship of China Postdoctoral Science Foundation(2021TQ0207,2021M702184 to J.S.)the‘Basic research project of Shanghai Sixth People’s Hospital’(ynqn202102 to J.S.)。
文摘Osteoporosis caused by aging is characterized by reduced bone mass and accumulated adipocytes in the bone marrow cavity. How the balance between osteoblastogenesis and adipogenesis from bone marrow mesenchymal stem cells(BMSCs) is lost upon aging is still unclear. Here, we found that the RNA-binding protein Musashi2(Msi2) regulates BMSC lineage commitment. Msi2 is commonly enriched in stem cells and tumor cells. We found that its expression was downregulated during adipogenic differentiation and upregulated during osteogenic differentiation of BMSCs. Msi2 knockout mice exhibited decreased bone mass with substantial accumulation of marrow adipocytes, similar to aging-induced osteoporosis. Depletion of Msi2 in BMSCs led to increased adipocyte commitment. Transcriptional profiling analysis revealed that Msi2 deficiency led to increased PPARγ signaling.RNA-interacting protein immunoprecipitation assays demonstrated that Msi2 could inhibit the translation of the key adipogenic factor Cebpα, thereby inhibiting PPAR signaling. Furthermore, the expression of Msi2 decreased significantly during the aging process of mice, indicating that decreased Msi2 function during aging contributes to abnormal accumulation of adipocytes in bone marrow and osteoporosis. Thus, our results provide a putative biochemical mechanism for aging-related osteoporosis, suggesting that modulating Msi2 function may benefit the treatment of bone aging.
基金the Department of Science and Technology of Sichuan Province(2019YFS03752021YFS0025+7 种基金2022YFS0162)1·3·5 project for disciplines of excellence,West China Hospital,Sichuan University(20HXJS003ZYGD18003)1·3·5 project for disciplines of excellence-Clinical Research Incubation Project,West China Hospital,Sichuan University(22HXFH001,2019HXFH031)a Post-Doctoral Research Project,West China Hospital,Sichuan University(2021HXBH033)a Post-Doctoral Research Project,Sichuan University(20826041E4084)the China Postdoctoral Science Foundation(2022M712264)the National Natural Science Foundation of China(82103541).
文摘Dear Editor,To date,the effect of colorectal cancer(CRC)-derived extracellular vesicles(EVs)on liver pre-metastatic niche(PMN)remain incompletely understood.1 To investigate the role of CRC-derived EVs in the remodeling of the liver PMN,we isolated EVs from CT26 cell culture supernatant.The characteristics of EVs(the morphology,size,and markers)were identified by transmission electron microscopy(TEM),Nanoparticle Tracking Analysis(NTA),and western blotting(Supplementary Fig.S1a–e).Then,BALB/c mice with an intact liver immune status were pretreated with CRCderived EVs and phosphate-buffered saline(PBS)for one month,and a liver metastasis model was established via spleen injection of tumor cells to determine whether EVs influence liver metastasis(Fig.1a).Two hours after the operation,in vivo imaging indicated that the animal model was successfully established,and the tumor fluorescence intensity in the liver was consistent between the two groups(Supplementary Fig.S2a,b).Amazingly,the liver tumor fluorescence intensity in the EVs group was significantly stronger than that in the PBS group after 24 h(Fig.1b;Supplementary Fig.S2c,d).The number of liver tumor nodules in the EVs group was also significantly higher than that in the PBS group on day 4(Fig.1c;Supplementary Fig.S2e,f).
基金supported by the National Key R&D Program of China(Grant No.2022YFA1303200)the National Natural Science Foundation of China(Grant Nos.82073221,31870826,and 82073246)+2 种基金the Sichuan Provincial Science and Technology Project(Grant No.2021YFS0134)the National Clinical Research Center for Geriatrics of West China Hospital(Grant No.Z2021JC005)the 135 Project for Disciplines of Excellence of West China Hospital(Grant Nos.ZYYC23013,ZYYC23025,ZYGD20006,and 2016105).
文摘Magnesium(Mg)deficiency is associated with increased risk and malignancy in colorectal cancer(CRC),yet the underlying mechanisms remain elusive.Here,we used genomic,proteomic,and phosphoproteomic data to elucidate the impact of Mg deficiency on CRC.Genomic analysis identified 160 genes with higher mutation frequencies in Low-Mg tumors,including key driver genes such as KMT2C and ERBB3.Unexpectedly,initiation driver genes of CRC,such as TP53 and APC,displayed higher mutation frequencies in High-Mg tumors.Additionally,proteomic and phosphoproteomic data indicated that low Mg content in tumors may activate epithelial–mesenchymal transition(EMT)by modulating inflammation or remodeling the phosphoproteome of cancer cells.Notably,we observed a negative correlation between the phosphorylation of DBN1 at S142(DBN1S142p)and Mg content.A mutation in S142 to D(DBN1S142D)mimicking DBN1S142p up-regulated MMP2 and enhanced cell migration,while treatment with MgCl2 reduced DBN1S142p,thereby reversing this phenotype.Mechanistically,Mg2þattenuated the DBN1–ACTN4 interaction by decreasing DBN1S142p,which in turn enhanced the binding of ACTN4 to F-actin and promoted F-actin polymerization,ultimately reducing MMP2 expression.These findings shed new light on the crucial role of Mg deficiency in CRC progression and suggest that Mg supplementation may be a promising preventive and therapeutic strategy for CRC.
基金Natural Science Foundation of Sichuan Province,No.2021YFS1834。
文摘BACKGROUND Robot-assisted gastrointestinal and liver surgery has been an important development direction in the field of surgery in recent years and it is also one of the fastest developing and most concerning fields in surgical operations.AIM To illustrate the major areas of research and forward-looking directions over the past twenty-six years.METHODS Using the Web of Science Core Collection database,a comprehensive review of scholarly articles pertaining to robot-assisted gastrointestinal and liver surgery was researched out between 2000 and 2023.We used Citespace(Version 6.2.4)and Bibliometrix package(Version 4.3.0)to visualize the analysis of all publications including country,institutional affiliations,authors,and keywords.RESULTS In total,346 articles were retrieved.Surgical Endoscopy had with the largest number of publications and was cited in this field.The United States was a core research country in this field.Yonsei University was the most productive institution.The current focus of this field is on rectal surgery,long-term prognosis,perioperative management,previous surgical experience,and the learning curve.CONCLUSION The scientific interest in robot-assisted gastrointestinal and liver surgery has experienced a significant rise since 1997.This study provides new perspectives and ideas for future research in this field.
基金supported by Abbott Laboratories(Chicago,IL,US).
文摘Background and Objectives:Patients with gastrointestinal(GI)malignancies are at high risk for malnutrition because of reduced food intake,poor digestion,and altered absorption.Methods and Study Design:In a retrospective review of medical records for patients admitted to urban hospitals in an Asian nation for GI tumor surgery(gastric,colon,or anorectal cancers),we found that malnutrition was common yet often overlooked.Our review identified records for 349 adult GI-tumor surgery patients.The Nutrition Risk Screening-2002(NRS-2002)was the most frequently used screening instrument.In further review,we compared outcomes for malnourished GI tumor surgery patients given daily oral nutritional supplements(ONS)to outcomes for patients who were not given ONS.Results:Review of results revealed that only 20%of patients in our sample underwent nutritional screening or assessment on admission.Of those who did,nearly 60%were malnourished.Although due to small sample sizes,no statistically significant differences were observed,malnourished patients who received ONS had fewer complications and shorter lengths of stay by 1-day.Such findings reveal many missed opportunities to improve patient outcomes and to avert excess healthcare costs for treatment of complications,slowed recovery,longer hospital stays,and readmissions.Conclusions:Based on our findings,nutritional training for professionals is necessary to address the serious problems of under-recognition and inadequate treatment of malnutrition in hospitalized patients.
基金supported by the National Key R&D Program of China(2022YFA1303200 and 2022YFA1303201)National Natural Science Foundation of China(32330062,31972933,82272166,32471498,and 81925012)+10 种基金Program of Shanghai Academic/Technology Research Leader(22XD1420100)Major Project of Special Development Funds of Zhangjiang National Independent Innovation Demonstration Zone(ZJ2019-ZD004)Shanghai Municipal Science and Technology Major Project(2023SHZDZX02)the Fudan Original Research Personalized Support Project,the New Cornerstone Science Foundation(NCI202242 and the Xplorer Prize)the Young Scientists Fund of the National Natural Science Foundation of China(32201212 and 32301236)Shanghai Sailing Program(23YF1402800)the Guiding Funds of Central Government for Supporting the Development of the Local Science and Technology(2022)the Science and Technology Commission of Shanghai Municipality(22ZR1426400)the Shanghai Municipal Science and Technology Major Projectthe Human Phenome Data Center of Fudan universityShanghai Phenomic precision measurement professional technical service platform(23DZ2290800)。
文摘Esophageal cancer(EC)is one of the most lethal cancers in the world[1].Esophageal squamous cell carcinoma(ESCC)is the dominant subtype of EC in China,with a poor prognosis and low survival rate[1].Currently,surgical resection,radiotherapy,and chemotherapy are the primary clinical treatments for EC[2,3].
