Traditional Chinese medicine （TCM） is an important part of the treatment of primary liver cancer （PLC） in China; however, the current instructions for the integrative use of traditional Chinese and Western medicin...Traditional Chinese medicine （TCM） is an important part of the treatment of primary liver cancer （PLC） in China; however, the current instructions for the integrative use of traditional Chinese and Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical prac-tice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the method- ological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy.展开更多
BACKGROUND In randomized controlled trials(RCTs),the placebo arm has often been ignored as the attention tends to be focused on the treatment arm.We undertook a meta-analysis based on the data from the placebo arm in ...BACKGROUND In randomized controlled trials(RCTs),the placebo arm has often been ignored as the attention tends to be focused on the treatment arm.We undertook a meta-analysis based on the data from the placebo arm in RCTs of hepatocellular carci-noma(HCC),the response rates and survival status,and adverse events(AEs)were summarized and evaluated.AIM To systematically evaluate the response rates,survival status and AEs in the placebo arms of RCTs for HCC.METHODS A systematic search was performed on PubMed,Ovid MEDLINE,Embase and Cochrane Library to identify relevant trials evaluating the efficacy of drugs for the treatment of HCC,published until December 31,2023.Statistical analysis was performed using R statistical software(version 4.3.2).RESULTS A total of 18 RCTs,involving 2390 patients,met the criteria for inclusion in the meta-analysis.The pooled overall disease control rate and objective response rate in the placebo group were 38%[95%confidence interval(CI):33%-42%]and 1%(95%CI:1%-2%),respectively.Overall survival and progression-free survival in the placebo group were 7.9 months(95%CI:7.6-8.31 months)and 1.9 months(95%CI:1.6-2.1 months),respectively.The incidence of grade 3 or 4 AEs was 37%(95%CI:30%-43%).Additionally,the incidence of interruptions or dose reductions due to AEs was 20%(95%CI:13%-27%),while the incidence of treatment discontinuation due to AEs was 9%(95%CI:6%-12%).CONCLUSION Over one-third of advanced HCC patients exhibit therapy-free disease control,with placebo-arm AEs observed.These findings guide single-arm trials design and enhance patient acceptance of anticancer therapies.展开更多
BACKGROUND Autoimmune gastritis(AIG)is frequently associated with one or more comorbid conditions,among which type I gastric neuroendocrine tumors(gNETs)warrant significant clinical concern.However,risk factors for th...BACKGROUND Autoimmune gastritis(AIG)is frequently associated with one or more comorbid conditions,among which type I gastric neuroendocrine tumors(gNETs)warrant significant clinical concern.However,risk factors for the development of gNETs in AIG populations remain poorly defined.AIM To characterize the clinical and endoscopic profiles of AIG and identify potential risk factors for gNETs development.METHODS In this single-center cross-sectional study carried out at a tertiary hospital,303 patients with AIG over an 8-year period were retrospectively categorized into gNETs(n=116)and non-gNETs(n=187)groups.Endoscopic and clinical pa-rameters were analyzed.Endoscopic features were systematically reevaluated according to the 2023 Japanese diagnostic criteria for AIG.Feature selection was performed using the Boruta algorithm,and the model discriminative ability was evaluated via receiver operating characteristic curve analysis.RESULTS Among the 303 patients with AIG,116 had gNETs and 187 did not.Compared with the non-gNETs group,patients in the gNETs group were younger(54.3 years vs 60.6 years,P<0.001),had higher rate of vitamin B12 deficiency(77.2%vs 55.8%,P<0.001),lower pepsinogen I(4.3 ng/mL vs 7.4 ng/mL,P<0.001)and pepsinogen I/II ratios(0.7 vs.1.1,P<0.001),and lower prior Helicobacter pylori infection rate(3.4%vs 21.4%,P<0.001).Endoscopically,the gNETs group showed a lower incidence of oxyntic mucosal remnants,hyperplastic polyps,and patchy antral redness.The predictive model incorporating age,prior Helicobacter pylori infection,vitamin B12 level,gastric hy-perplastic polyps,and patchy antral redness showed an area under the curve of 0.830.CONCLUSION Patients with AIG or gNETs exhibit specific clinical and endoscopic features.The predictive model demonstrated favorable discriminative ability and may facilitate risk stratification of gNETs in patients with AIG.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
Background: Chemotherapy?induced nausea and vomiting adversely affects the quality of life of patients who receive chemotherapy via intravenous infusion or transcatheter arterial chemoembolization(TACE). This study ai...Background: Chemotherapy?induced nausea and vomiting adversely affects the quality of life of patients who receive chemotherapy via intravenous infusion or transcatheter arterial chemoembolization(TACE). This study aimed to investigate the clinical effects of transcutaneous electrical acupoint stimulation(TEAS) on nausea and vomiting after TACE.Methods: A total of 142 patients who received TACE with cisplatin for primary or metastatic liver cancer were assigned to the active?acupuncture(n = 72) or placebo?acupuncture(n Hegu(LI4), Neiguan(P6), an= 70) groups using a covariate?adaptive randomization at a ratio of 1:1. The acupointsd Zusanli(ST36) were stimulated twice daily for 6 days. The effects of TEAS on nausea and vomiting were assessed by using occurrence rate and severity of these symptoms. Anorexia scale and M. D. Anderson Symptom Inventory(MDASI) scores were secondary endpoints and were used to assess the effect of TEAS on patient appetite and quality of life. The safety of the treatments was also monitored.Results: Between the two groups, the differences in occurrence rates and severities of nausea and vomiting after TACE were not significant(all P > 0.05). From the second day after TACE, anorexia scores were significantly lower in the active?acupuncture group than in the placebo?acupuncture group and continued to decrease over time with treat?ment(all P values less than 0.01). On days 0, 1, and 2, the mean MDASI scores for the active?acupuncture group were slightly lower than those for the placebo?acupuncture group, but the differences were not statistically significant(all P > 0.05). No significant differences were found between the two groups in the occurrence rate of any adverse event(P > 0.05).Conclusion: TEAS appears to be a safe and effective therapy to relieve patients' gastrointestinal discomfort after chemotherapy.展开更多
AIM: To investigate the efficacy and safety of capecitabine and oxaliplatin (CapeOx) for extrahepatic metastasis after local treatment of hepatocellular carcinoma (HCC). METHODS: Thirty-two patients with extrahepatic ...AIM: To investigate the efficacy and safety of capecitabine and oxaliplatin (CapeOx) for extrahepatic metastasis after local treatment of hepatocellular carcinoma (HCC). METHODS: Thirty-two patients with extrahepatic metastasis of HCC after local treatment were prospectively enrolled. The CapeOx regimen consisted of capecitabine 1000 mg/m 2 taken orally twice daily on days 1-14, and oxaliplatin was administered at a total dose of 100 mg/m 2 on day 1. The treatment was repeated every 3 wk until disease progression or unaccetablle toxicity. Efficacy and safety were assessable for all enrolled patients. The primary objective of this study was to assess the overall response rate. The secondary objectives were to evaluate the overall survival (OS), the time to tumor progression (TTP) and the toxicity profile of the combined strategy. TTP and OS were assessed by the Kaplan-Meier method and differences between the curves were analyzed using the log-rank test. The statistical software SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, United States) was used for statistical analysis. All P values were 2-tailed, with statistical significance defined byP ≤ 0.05. RESULTS: Thirty-two patients were assessable for efficacy and toxicity. The median follow-up duration was 15 mo (range, 12-20 mo). At the cut-off date of March 31, 2012, 27 patients died due to tumor progression and one patient died of myocardial infarction. Four patients were still alive (three patients with disease progression). OR was 21.9% (n = 7), the stabilization rate was 40.6% (n = 13), and the disease control rate was 62.5%. The responses lasted from 4 to 19 mo (median, 6 mo). Median TTP was 4.2 mo (95%CI: 2.5-7.4), and the median OS time was 9.2 mo (95%CI: 6.5-17.8). The 1-year survival rate was 43.6% (95%CI: 29.0-66.0). In a multivariate analysis, OS was significantly longer in patients with a Child-Pugh class A compared with class B patients (P = 0.014), with a median OS of 10.1 mo vs 5.4 mo, and there were trends towards longer OS (P = 0.065) in patients without portal vein tumor thrombosis. There were no significant effects of age, gender, performance status, cirrhosis, metastatic sites, and level of alpha fetoprotein (AFP) or hepatitis B virus-DNA on OS. Among the 22 patients with elevated AFP levels at baseline (≥ 400 ng/mL), the level fell by more than 50% during treatment in 6 patients (27.3%). The most frequent treatment-related grade 3 to 4 toxicities included leucopenia/neutropenia, transient elevation of aminotransferases, handfoot syndrome and fatigue. CONCLUSION: CapeOx showed modest anti-tumor activity in metastatic HCC. However, the manageable toxicity profile and the encouraging disease control rate deserve further study for these patients.展开更多
The inflammatory process plays a central role in the development and progression of numerous pathological situations,such as inflammatory bowel disease(IBD),autoimmune and neurodegenerative diseases,metabolic syndrome...The inflammatory process plays a central role in the development and progression of numerous pathological situations,such as inflammatory bowel disease(IBD),autoimmune and neurodegenerative diseases,metabolic syndrome,and cardiovascular disorders.IBDs involve inflammation of the gastrointestinal area and mainly comprise Crohn's disease(CD)and ulcerative colitis(UC).Both pathological situations usually involve recurring or bloody diarrhea,pain,fatigue and weight loss.There is at present no pharmacological cure for CD or UC.However,surgery may be curative for UC patients.The prescribed treatment aims to ameliorate the symptoms and prevent and/or delay new painful episodes.Flavonoid compounds are a large family of hydroxylated polyphenolic molecules abundant in plants,including vegetables and fruits which are the major dietary sources of these compounds for humans,together with wine and tea.Flavonoids are becoming very popular because they have many health-promoting and disease-preventive effects.Most interest has been directed towards the antioxidant activity of flavonoids,evidencing a remarkable free-radical scavenging capacity.However,accumulating evidence suggests that flavonoids have many other biological properties,including anti-inflammatory,antiviral,anticancer,and neuroprotective activities through different mechanisms of action.The present review analyzes the available data about the different types of flavonoids and their potential effectiveness as adjuvant therapy of IBDs.展开更多
OBJECTIVE： To investigate, in terms of Notch signaling pathway, the effect on pancreatic cancer of the extract of an anti-tumor prescription -- Qingyihuaji formula （QYHJ） -- from Traditional Chinese Medicine （TCM...OBJECTIVE： To investigate, in terms of Notch signaling pathway, the effect on pancreatic cancer of the extract of an anti-tumor prescription -- Qingyihuaji formula （QYHJ） -- from Traditional Chinese Medicine （TCM）.METHODS： Nude mice were implanted subcutaneously with human pancreatic cancer cell line SW1990 and then randomly divided into four groups： Control, QYHJ extract, Gemcitabine, and Combination of QYHJ extract and gemcitabine. Treatments were given for 21 days and tumor growth was evaluated simultaneously. Then, expression of Notch receptors （Notch-I, Notch-2, Notch-3, and Notch-4） and their Jagged ligands （Jagged-1 and Jagged-2） in dissected tumor tissue were detected by real-time quantitative reverse transcription-polymerase chain reaction and Western blot. Finally, immunohistochemistry was performed to detect CD133, a marker of pancreatic cancer stem cells （CSCs）, to evaluate the impact of QYHJ extract on pancreatic CSCs.RESULTS： QYHJ extract treatment effectively inhib- ited the tumor growth in nude mice. The expression of both Notch-4 and Jagged-1 were decreased significantly in QYHJ treatment groups （P 〈 0.05）, while gemcitabine alone had no significant effect in down-regulating Jagged-1 （P 〉 0.05）. No significant difference was observed in the ex- pression of Notch-1, Notch-2, Notch-3, and Jagged-2 between three treatment groups and control group （P 〉 0.05）. Moreover, immunohistochemical analysis showed that the number of CD133 positive cells was significantly reduced by QYHJ treatment （P 〈 0.05）, and the combined treatment was more effective than gemcitabine alone （P 〈 0.05）.CONCLUSION： The role of the extract in pancreatic cancer treatment was associated with down-regulation of Notch-4 and Jagged-1 in Notch signaling pathway. The extract could enhance the antitumor activity of gemcitabine and was more effective than gemcitabine in regulating Notch signaling pathway to some extent.展开更多
Objective：Early metastasis is a major biological feature of pancreatic cancer.The current study examined whether silencing Slc38a1,a gene involved in energy metabolism,using short hairpin RNA （shRNA） could inhibit ...Objective：Early metastasis is a major biological feature of pancreatic cancer.The current study examined whether silencing Slc38a1,a gene involved in energy metabolism,using short hairpin RNA （shRNA） could inhibit the growth,migration,and invasiveness of pancreatic cancer cells.Methods：A series of Slc38a1 shRNAs were designed and cloned into the pGPU6/GFP/Neo vectors.An shRNA with the most efficacious inhibitory action on SCL38A1 expression （65％ inhibition） upon screening in DH5α bacteria was used to transfect SW1990 human pancreatic cancer cells.Cell growth,migration,and invasiveness were examined using cell counting kit-8,Boyden chamber without and with Matrigel,respectively.Results：Transfection of SW1990 cells with the SLCs38A1 shRNA significantly decreased the proliferation （P＜0.0001） and migratory potential （by 46.7％,P=0.0399） of the cancer cells.Invasiveness,however,was not affected.Conclusions：Inhibiting Slc38a1 using shRNA technology could decrease the growth and migration of representative pancreatic cancer cells.However,the fact that invasiveness was not affected suggested that SLC38A1 is unlikely to be responsible for early metastasis.展开更多
AIM:To investigate the clinical characteristics,diagnosis,treatment,and prognosis of primary adenosquamous carcinoma(ASC)of the esophagus.METHODS:A total of 4015 patients with esophageal carcinoma underwent surgical r...AIM:To investigate the clinical characteristics,diagnosis,treatment,and prognosis of primary adenosquamous carcinoma(ASC)of the esophagus.METHODS:A total of 4015 patients with esophageal carcinoma underwent surgical resection between January 1995 and June 2012 at the Cancer Hospital of Shantou University Medical College.In 37 cases,the histological diagnosis was primary ASC.Clinical data were retrospectively analyzed from these 37 patients,who underwent transthoracic esophagectomy with lymphadenectomy.Theχ2or Fisher’s exact test was used to compare the clinicopathological features between patients with ASC and those with squamous cell carcinoma(SCC).The Kaplan-Meier and Log-Rank methods were used to estimate and compare survival rates.A Cox proportional hazard regression model was used to identify independent prognostic factors.RESULTS:Primary esophageal ASC accounted for0.92%of all primary esophageal carcinoma cases(37/4015).The clinical manifestations were identical to those of other types of esophageal cancer.All of the 24patients who underwent preoperative endoscopic biopsy were misdiagnosed with SCC.The median survival time(MST)was 21.0 mo(95%CI:12.6-29.4),and the1-,3-,and 5-year overall survival rates were 67.5%,29.4%,and 22.9%,respectively.In multivariate analysis,only adjuvant radiotherapy(HR=0.317,95%CI:0.114-0.885,P=0.028)was found to be an independent prognostic factor.The MST for ASC patients was significantly lower than that for SCC patients[21.0 mo(95%CI:12.6-29.4)vs 46.0 mo(95%CI:40.8-51.2),P=0.001].In subgroup analyses,the MST for ASC patients was similar to that for poorly differentiated SCC patients.CONCLUSION:Primary esophageal ASC is a rare disease that is prone to be misdiagnosed by endoscopic biopsy.The prognosis is poorer than esophageal SCC but similar to that for poorly differentiated SCC patients.展开更多
Objective: The coronavirus disease 2019(COVID-19) pandemic has had a serious impact on health all over the world. Cancer patient, whose immunity is often compromised, faces a huge challenge.Currently, some COVID-19 va...Objective: The coronavirus disease 2019(COVID-19) pandemic has had a serious impact on health all over the world. Cancer patient, whose immunity is often compromised, faces a huge challenge.Currently, some COVID-19 vaccines are being developed and applied on general population;however,whether cancer patients should take COVID-19 vaccine remains unknown. Our study aimed to explore the knowledge, attitude, acceptance, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China.Methods: A cross-sectional study was conducted in Eastern China from June 17 th to September 3 rd, 2021.Patients were selected using a convenience sampling method. A self-report questionnaire was developed to assess knowledge about the COVID-19 vaccine, attitude towards the vaccine and acceptance of the vaccine;following a review of similar studies previously published in the scientific literature, multivariate logistic regression analysis was used to determine the predictors associated with COVID-19 vaccine acceptance.Results: A total of 2158 cancer patients were enrolled in this study. The rate of vaccine hesitancy was 24.05%(519/2158);further, among the participants of vaccine acceptance, 767 had taken COVID-19 vaccine(35.54%), and 872 were willing to get vaccinated(40.01%). A total of 24 variables including demographic characteristics, clinical status of cancer, impact of COVID-19 pandemic on study participants,patients’ knowledge about the COVID-19 vaccine, and attitude towards the vaccine, had significant differences between the ‘‘vaccine hesitancy" population and ‘‘vaccine acceptance" population.Multivariate logistic regression analysis indicated that parameters including alcohol consumption(odds ratio [OR] = 1.849;95% confidence interval [CI]: 1.375–2.488;P-reference [P-Ref] < 0.001 vs nondrinkers), income impacted by COVID-19 pandemic(OR = 1.930, 2.037 and 2.688 for mild, moderate,and severe impact, respectively;all P-Ref < 0.01 vs no impact), knowledge of how the vaccine was developed(OR = 1.616;95% CI: 1.126–2.318;P-Ref = 0.009 vs unknown), believing in the safety of the vaccine(OR = 1.502;95% CI: 1.024–2.203;P-Ref = 0.038 vs denying the safety of vaccine), willingness to pay for the vaccine(OR = 3.042;95% CI: 2.376–3.894;P-Ref < 0.001 vs unwilling), and willingness to recommend families and friends to get vaccinated(OR = 2.744;95% CI: 1.759–4.280;P-Ref < 0.001 vs do not recommend) were contributors to vaccine acceptance. While such as being retired(OR = 0.586;95% CI: 0.438–0.784;P-Ref < 0.001 vs unemployed), undergoing multiple therapies of cancer(OR = 0.408;95% CI: 0.221–0.753;P-Ref = 0.004 vs no ongoing treatment), and worrying that the vaccine might deteriorate the prognosis of cancer(OR = 0.393;95% CI: 0.307–0.504;P-Ref < 0.001 vs might not) were contributors to vaccine hesitancy.Conclusion: This study provided preliminary estimates of the rates of vaccine acceptance and vaccine hesitancy among cancer patients in Eastern China. The intention to receive the COVID-19 vaccine was impacted by factors such as patient occupation, alcohol consumption, and some parts of knowledge about and attitude towards COVID-19 vaccine. It is recommended to develop individualized vaccination plans that meet the healthcare needs of cancer patients.展开更多
BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incid...BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incidence has increased over the past few decades.However,the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.AIM To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs.METHODS The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.RESULTS Among the 232 patients with PDGNENs,191(82.3%)were male,with an average age of 62.83±9.11 years.One hundred and thirteen(49.34%)of 229 patients had a stage III disease and 86(37.55%)had stage IV disease.Three(1.58%)of 190 patients had no clinical symptoms,while 187(98.42%)patients presented clinical symptoms.The tumors were mainly(89.17%)solitary and located in the upper third of the stomach(cardia and fundus of stomach:115/215,53.49%).Most lesions were ulcers(157/232,67.67%),with an average diameter of 4.66±2.77 cm.In terms of tumor invasion,the majority of tumors invaded the serosa(116/198,58.58%).The median survival time of the 232 patients was 13.50 mo(7,31 mo),and the overall 1-year,3-year,and 5-year survival rates were 49%,19%,and 5%,respectively.According to univariate analysis,tumor number,tumor diameter,gastric invasion status,American Joint Committee on Cancer(AJCC)stage,and distant metastasis status were prognostic factors for patients with PDGNENs.Multivariate analysis showed that tumor number,tumor diameter,AJCC stage,and distant metastasis status were independent prognostic factors for patients with PDGNENs.CONCLUSION The overall prognosis of patients with PDGNENs is poor.The outcomes of patients with a tumor diameter>5 cm,multiple tumors,and stage IV tumors are worse than those of other patients.展开更多
BACKGROUND For the rarity of type 3 gastric neuroendocrine tumours(g-NETs),their clinicopathological characteristics and prognosis are not well illustrated.AIM To describe the clinicopathological features and outcome ...BACKGROUND For the rarity of type 3 gastric neuroendocrine tumours(g-NETs),their clinicopathological characteristics and prognosis are not well illustrated.AIM To describe the clinicopathological features and outcome of type 3 g-NETs in the Chinese population.METHODS Based on the 2019 WHO pathological classification,the clinicopathological characteristics and prognosis of patients with type 3 g-NETs in China were retrospectively analysed.RESULTS A total of 77 patients(55.8%of females)with type 3 g-NETs were analysed,with a median age of 48 years(range:28-79 years).The tumours were mainly located in the gastric fundus/body(83.1%)and were mostly solitary(83.1%),with a median size of 1.5 cm(0.8-3.5 cm).Of these,there were 37 G1 tumours(48.1%),31 G2(40.3%),and 9 G3(11.7%).Ten(13.0%)and 24(31.2%)patients had lymph node and distant metastasis,respectively.In addition,type 3 g-NETs were heterogeneous.Compared with G1 NETs,G2 NETs had a higher lymph node metastasis rate,and G3 NETs had a higher distant metastasis rate.G1 and G2 NETs with stage I/II disease(33/68)received endoscopic treatment,and no tumour recurrence or tumour-related death was observed within a median follow-up time of 36 mo.Grade and distant metastasis were identified to be independent risk factors for prognosis in multivariable analysis.CONCLUSION Type 3 g-NETs are obviously heterogeneous,and the updated WHO 2019 pathological classification may be used to effectively evaluate their biological behaviors and prognosis.Also,endoscopic treatment should be considered for small(<2 cm),low grade,superficial tumours.展开更多
Proteomic characterization of plasma is critical for the development of novel pharmacodynamic biomarkers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeol...Proteomic characterization of plasma is critical for the development of novel pharmacodynamic biomarkers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the“masking”effect caused by high-abundance proteins.The relative abundance of middleand low-abundance proteins increased substantially from 2.54%to 54.41%,and the top 20 highabundance proteins decreased from 83.63%to 25.77%.Notably,our method can quantify approximately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins identified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.展开更多
OBJECTIVE:To investigate the therapeutic effect of the Jianpi Liqi Fang(健脾理气方,JPLQF)combined with transcatheter arterial chemoembolization(TACE)in patients with hepatocellular carcinoma(HCC)and spleen deficiency ...OBJECTIVE:To investigate the therapeutic effect of the Jianpi Liqi Fang(健脾理气方,JPLQF)combined with transcatheter arterial chemoembolization(TACE)in patients with hepatocellular carcinoma(HCC)and spleen deficiency syndrome(SDS)and identify a potential indicator of efficacy.METHODS:Ninety-nine patients with HCC who were diagnosed with SDS,non-spleen deficiency syndrome(NSDS),or no syndrome(NS)were treated with JPLQF combined with TACE for three periods.Therapeutic efficacy was compared among the groups.Plasma proteins were screened using label-free discovery analysis and verified via enzyme-linked immunosorbent assay(ELISA).Furthermore,receiver operating characteristic(ROC)curves were analyzed to evaluate therapeutic indicators.RESULTS:After treatment,the Karnofsky Performance Status was significantly improved in the SDS group and significantly better than that in the NS group.The Traditional Chinese Medicine(TCM)syndrome scores were lower in the SDS group after treatment and lower than those in the NSDS group.However,alanine aminotransferase,carbohydrate antigen 19-9,alpha-fetoprotein,and carcinoembryonic antigen levels and white blood cell and platelet counts did not differ among the groups.Serum aspartate aminotransferase levels in the SDS group were significantly lower after treatment than before treatment,and total bilirubin levels were significantly lower in the SDS group than in the NSDS group.Label-free analysis identified 24 differentially expressed proteins(DEPs)between the SDS and NS groups,including 17 and 7 upregulated and downregulated proteins,respectively.Fibulin-5(FBLN5)displayed the largest difference in expression between the groups.ELISA confirmed that FBLN5 levels were significantly lower in the NSDS and NS groups than in the SDS group.Following treatment with JPLQF and TACE,FBLN5 expression was upregulated only in the SDS group.Furthermore,ROC curve analysis indicated that FBLN5 may serve as a potential indicator of the efficacy of JPLQF combined with TACE in patients with HCC and SDS.CONCLUSION:JPLQF combined with TACE improved quality of life,clinical TCM symptoms,and liver function in patients with HCC and SDS.FBLN5 expression was significantly altered by treatment with JPLQF and TACE in patients with HCC and SDS.展开更多
Objective:The presence of complex components in Chinese herbal medicine(CHM)hinders identification of the primary active substances and understanding of pharmacological principles.This study was aimed at developing a ...Objective:The presence of complex components in Chinese herbal medicine(CHM)hinders identification of the primary active substances and understanding of pharmacological principles.This study was aimed at developing a big-data-based,knowledgedriven in silico algorithm for predicting central components in complex CHM formulas.Methods:Network pharmacology(TCMSP)and clinical(GEO)databases were searched to retrieve gene targets corresponding to the formula ingredients,herbal components,and specific disease being treated.Intersections were determined to obtain diseasespecific core targets,which underwent further GO and KEGG enrichment analyses to generate non-redundant biological processes and molecular targets for the formula and each component.The ratios of the numbers of biological and molecular events associated with a component were calculated with a formula,and entropy weighting was performed to obtain a fitting score to facilitate ranking and improve identification of the key components.The established method was tested on the traditional CHM formula Danggui Sini Decoction(DSD)for gastric cancer.Finally,the effects of the predicted critical component were experimentally validated in gastric cancer cells.Results:An algorithm called Chinese Herb Medicine-Formula vs.Ingredients Efficacy Fitting&Prediction(CHM-FIEFP)was developed.Ferulic acid was identified as having the highest fitting score among all tested DSD components.The pharmacological effects of ferulic acid alone were similar to those of DSD.Conclusions:CHM-FIEFP is a promising in silico method for identifying pharmacological components of CHM formulas with activity against specific diseases.This approach may also be practical for solving other similarly complex problems.The algorithm is available at http://chm-fiefp.net/.展开更多
BACKGROUND Neuroendocrine carcinoma of the breast(NECB)is a rare type of malignant tumor.Due to the rarity of NECB,the relevant literature mostly comprises case reports.Available data on treatment options for NECB are...BACKGROUND Neuroendocrine carcinoma of the breast(NECB)is a rare type of malignant tumor.Due to the rarity of NECB,the relevant literature mostly comprises case reports.Available data on treatment options for NECB are very limited.CASE SUMMARY A 62-year-old woman presented to our hospital in October 2016 for intermittent vomiting and diarrhea and masses in the liver found on abdominal computed tomography(CT)imaging.She was diagnosed in July 2012 with neuroendocrine carcinoma of the right breast in local hospital.The patient initially presented with a painful lesion of the right breast.She then undergone surgical resection and adjuvant chemotherapy with pirarubicin and paclitaxel for four cycles as well as endocrine therapy.She was regularly followed every 3 mo after surgery.Enhanced abdominal CT imaging at our hospital revealed multiple suspicious masses in the liver with the largest lesion measuring 8.4 cm×6.3 cm.Chest CT revealed masses in the anterior chest wall and lung.Core needle biopsy of the lesion revealed liver metastases of NECB.A bone scan showed right second anterior rib metastases.Upper endoscopy and colonoscopy did not provide any evidence of another possible primary tumor.She stopped receiving endocrine therapy and then received etoposide and cisplatin(EP)chemotherapy as a firstline treatment regimen for six cycles at our hospital after liver,bone,and lung metastases.On October 2017,the chemotherapy regimen was changed to S-1(40mg twice daily,days 1-14)combined with temozolomide(200 mg once daily,days 10-14)(STEM)every 21 d as a second-line treatment regimen due to disease progression.Progression-free survival(PFS)and adverse effects after treatment were analyzed,and the efficacy of the STEM regimen was assessed using RECIST version 1.1.This patient achieved a partial response after using the STEM regimen,with a PFS of 23 mo.Adverse effects included only grade 1 digestive tract reactions with no need for a reduction in chemotherapy.CONCLUSION This case report suggests that the STEM regimen may be effective and well tolerated as the second-line treatment for advanced NECB.STEM is still highly effective in patients who show disease progression with the EP regimen.More evidence is needed to prove the validity of STEM.展开更多
The main task of cancer vaccines is to deliver tumorspecifc antigens to antigen-presenting cells for immune recognition that can lead to potent and durable immune response against treated tumor. Using photodynamic the...The main task of cancer vaccines is to deliver tumorspecifc antigens to antigen-presenting cells for immune recognition that can lead to potent and durable immune response against treated tumor. Using photodynamic therapy （PDT）-generated vaccines as an example of autologous whole-cell cancer vaccines, the importance is discussed of the expression of death-associated molecules on cancer vaccine cells. This aspect appears critical for the optimal capture of vaccine cells by host’s sentinel phagocytes in order that the tumor antigenic material is processed and presented for immune recognition and elimination of targeted malignancy. It is shown that changing death pattern of vaccine cells by agents modulating apoptosis, autophagy or necrosis can significantly alter the therapeutic impact of PDT-generated vaccines. Improved therapeutic effect was observed with inhibitors of necrosis/necroptosis using IM-54, necrostatin-1 or necrostatin-7, as well as with lethal autophagy inducer STF62247. In contrast, reduced vaccine potency was found in case of treating vaccine cells with apoptosis inhibitors or lethal autophagy inhibitor spautin-1. Therefore, PDT-generated cancer vaccine cells undergoing apoptosis or lethal autophagy are much more likely to produce therapeutic benefit than vaccine cells that are necrotic. These fndings warrant further detailed examination of the strategy using cell death modulating agents for the enhancement of the efficacy of cancer vaccines.展开更多
Owing to significantly prolonged survival,targeted therapy has become standardized recommendation for advanced non-small cell lung cancer patients with mutated driver genes.However,the genetic status of lung cancer pa...Owing to significantly prolonged survival,targeted therapy has become standardized recommendation for advanced non-small cell lung cancer patients with mutated driver genes.However,the genetic status of lung cancer patients is dynamic.By dynamically monitoring the evolution of genes status,differential genes and concomitant genes related to progressive disease could be confirmed early,so as to achieve a more accurate and comprehensive insight of the whole process management of targeted therapy for lung cancer patients.Under the guidance of accurate genetic testing results,it is helpful to provide patients with more effective,long-term,and stable individualized targeted therapy.展开更多
Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chin...Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chinese medicine syndrome diagnoses(also called syndrome differentiation)in pancreatic ductal adenocarcinoma.Methods:128 pancreatic ductal adenocarcinoma patients with different syndrome diagnoses were retrospectively reviewed in this study.Long RNA sequencing was conducted to analyze the EV long RNA profile of plasma samples.Differentially regulated EV long RNAs were annotated and assessed for Gene Ontology pathway enrichment using DAVID.The online program xCell were used to perform the cell-type enrichment analysis.Results:An average of 15,000 annotated genes,mainly including messenger RNAs,were stably detected per sample.Different syndrome diagnoses exhibited unique EV mRNA expression profiles and therefore different enriched pathways.Gene Set Enrichment Analysis discovered transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation as the hallmarks of cancer with Shi-Re syndrome.Cell-type enrichment analysis also revealed a varied inflammation/immune cell type distribution among patients with or without Shi-Re diagnosis.Mast cells,platelets and Tregs were significantly enriched but basophils,common lymphoid progenitors,dendritic cells,and conventional dendritic cells were decreased in patients with Shi-Re diagnosis compared with patients without Shi-Re diagnosis.Conclusion:We identified the hallmarks of cancer with different syndrome diagnoses based on plasma EV long RNA sequencing.In particular,transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation were the hallmarks of Shi-Re syndrome,which contribute to shape an inflammatory/immune-suppressive tumor microenvironment in pancreatic ductal adenocarcinoma.展开更多
基金funded by the Shanghai Municipal Commission of Health and Family Planning(Grant Number ZY3-LCPT-2-1004)National Natural Science Foundation of China(Grant Number81503459)E-Institutes of Shanghai Municipal Education Commission(Grant Number E03008)
文摘Traditional Chinese medicine （TCM） is an important part of the treatment of primary liver cancer （PLC） in China; however, the current instructions for the integrative use of traditional Chinese and Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical prac-tice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the method- ological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy.
文摘BACKGROUND In randomized controlled trials(RCTs),the placebo arm has often been ignored as the attention tends to be focused on the treatment arm.We undertook a meta-analysis based on the data from the placebo arm in RCTs of hepatocellular carci-noma(HCC),the response rates and survival status,and adverse events(AEs)were summarized and evaluated.AIM To systematically evaluate the response rates,survival status and AEs in the placebo arms of RCTs for HCC.METHODS A systematic search was performed on PubMed,Ovid MEDLINE,Embase and Cochrane Library to identify relevant trials evaluating the efficacy of drugs for the treatment of HCC,published until December 31,2023.Statistical analysis was performed using R statistical software(version 4.3.2).RESULTS A total of 18 RCTs,involving 2390 patients,met the criteria for inclusion in the meta-analysis.The pooled overall disease control rate and objective response rate in the placebo group were 38%[95%confidence interval(CI):33%-42%]and 1%(95%CI:1%-2%),respectively.Overall survival and progression-free survival in the placebo group were 7.9 months(95%CI:7.6-8.31 months)and 1.9 months(95%CI:1.6-2.1 months),respectively.The incidence of grade 3 or 4 AEs was 37%(95%CI:30%-43%).Additionally,the incidence of interruptions or dose reductions due to AEs was 20%(95%CI:13%-27%),while the incidence of treatment discontinuation due to AEs was 9%(95%CI:6%-12%).CONCLUSION Over one-third of advanced HCC patients exhibit therapy-free disease control,with placebo-arm AEs observed.These findings guide single-arm trials design and enhance patient acceptance of anticancer therapies.
文摘BACKGROUND Autoimmune gastritis(AIG)is frequently associated with one or more comorbid conditions,among which type I gastric neuroendocrine tumors(gNETs)warrant significant clinical concern.However,risk factors for the development of gNETs in AIG populations remain poorly defined.AIM To characterize the clinical and endoscopic profiles of AIG and identify potential risk factors for gNETs development.METHODS In this single-center cross-sectional study carried out at a tertiary hospital,303 patients with AIG over an 8-year period were retrospectively categorized into gNETs(n=116)and non-gNETs(n=187)groups.Endoscopic and clinical pa-rameters were analyzed.Endoscopic features were systematically reevaluated according to the 2023 Japanese diagnostic criteria for AIG.Feature selection was performed using the Boruta algorithm,and the model discriminative ability was evaluated via receiver operating characteristic curve analysis.RESULTS Among the 303 patients with AIG,116 had gNETs and 187 did not.Compared with the non-gNETs group,patients in the gNETs group were younger(54.3 years vs 60.6 years,P<0.001),had higher rate of vitamin B12 deficiency(77.2%vs 55.8%,P<0.001),lower pepsinogen I(4.3 ng/mL vs 7.4 ng/mL,P<0.001)and pepsinogen I/II ratios(0.7 vs.1.1,P<0.001),and lower prior Helicobacter pylori infection rate(3.4%vs 21.4%,P<0.001).Endoscopically,the gNETs group showed a lower incidence of oxyntic mucosal remnants,hyperplastic polyps,and patchy antral redness.The predictive model incorporating age,prior Helicobacter pylori infection,vitamin B12 level,gastric hy-perplastic polyps,and patchy antral redness showed an area under the curve of 0.830.CONCLUSION Patients with AIG or gNETs exhibit specific clinical and endoscopic features.The predictive model demonstrated favorable discriminative ability and may facilitate risk stratification of gNETs in patients with AIG.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
基金supported by grants from the Shanghai Municipal Health Bureau Programs (No.2010L058A)the National Natural Science Foundation of China (No.81403248, No.81273955)
文摘Background: Chemotherapy?induced nausea and vomiting adversely affects the quality of life of patients who receive chemotherapy via intravenous infusion or transcatheter arterial chemoembolization(TACE). This study aimed to investigate the clinical effects of transcutaneous electrical acupoint stimulation(TEAS) on nausea and vomiting after TACE.Methods: A total of 142 patients who received TACE with cisplatin for primary or metastatic liver cancer were assigned to the active?acupuncture(n = 72) or placebo?acupuncture(n Hegu(LI4), Neiguan(P6), an= 70) groups using a covariate?adaptive randomization at a ratio of 1:1. The acupointsd Zusanli(ST36) were stimulated twice daily for 6 days. The effects of TEAS on nausea and vomiting were assessed by using occurrence rate and severity of these symptoms. Anorexia scale and M. D. Anderson Symptom Inventory(MDASI) scores were secondary endpoints and were used to assess the effect of TEAS on patient appetite and quality of life. The safety of the treatments was also monitored.Results: Between the two groups, the differences in occurrence rates and severities of nausea and vomiting after TACE were not significant(all P > 0.05). From the second day after TACE, anorexia scores were significantly lower in the active?acupuncture group than in the placebo?acupuncture group and continued to decrease over time with treat?ment(all P values less than 0.01). On days 0, 1, and 2, the mean MDASI scores for the active?acupuncture group were slightly lower than those for the placebo?acupuncture group, but the differences were not statistically significant(all P > 0.05). No significant differences were found between the two groups in the occurrence rate of any adverse event(P > 0.05).Conclusion: TEAS appears to be a safe and effective therapy to relieve patients' gastrointestinal discomfort after chemotherapy.
基金Supported by Shanghai Municipal Health Bureau Outstanding Young Clinical Personal Training Project, No. ZYSNXD-YLYSZK025
文摘AIM: To investigate the efficacy and safety of capecitabine and oxaliplatin (CapeOx) for extrahepatic metastasis after local treatment of hepatocellular carcinoma (HCC). METHODS: Thirty-two patients with extrahepatic metastasis of HCC after local treatment were prospectively enrolled. The CapeOx regimen consisted of capecitabine 1000 mg/m 2 taken orally twice daily on days 1-14, and oxaliplatin was administered at a total dose of 100 mg/m 2 on day 1. The treatment was repeated every 3 wk until disease progression or unaccetablle toxicity. Efficacy and safety were assessable for all enrolled patients. The primary objective of this study was to assess the overall response rate. The secondary objectives were to evaluate the overall survival (OS), the time to tumor progression (TTP) and the toxicity profile of the combined strategy. TTP and OS were assessed by the Kaplan-Meier method and differences between the curves were analyzed using the log-rank test. The statistical software SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, United States) was used for statistical analysis. All P values were 2-tailed, with statistical significance defined byP ≤ 0.05. RESULTS: Thirty-two patients were assessable for efficacy and toxicity. The median follow-up duration was 15 mo (range, 12-20 mo). At the cut-off date of March 31, 2012, 27 patients died due to tumor progression and one patient died of myocardial infarction. Four patients were still alive (three patients with disease progression). OR was 21.9% (n = 7), the stabilization rate was 40.6% (n = 13), and the disease control rate was 62.5%. The responses lasted from 4 to 19 mo (median, 6 mo). Median TTP was 4.2 mo (95%CI: 2.5-7.4), and the median OS time was 9.2 mo (95%CI: 6.5-17.8). The 1-year survival rate was 43.6% (95%CI: 29.0-66.0). In a multivariate analysis, OS was significantly longer in patients with a Child-Pugh class A compared with class B patients (P = 0.014), with a median OS of 10.1 mo vs 5.4 mo, and there were trends towards longer OS (P = 0.065) in patients without portal vein tumor thrombosis. There were no significant effects of age, gender, performance status, cirrhosis, metastatic sites, and level of alpha fetoprotein (AFP) or hepatitis B virus-DNA on OS. Among the 22 patients with elevated AFP levels at baseline (≥ 400 ng/mL), the level fell by more than 50% during treatment in 6 patients (27.3%). The most frequent treatment-related grade 3 to 4 toxicities included leucopenia/neutropenia, transient elevation of aminotransferases, handfoot syndrome and fatigue. CONCLUSION: CapeOx showed modest anti-tumor activity in metastatic HCC. However, the manageable toxicity profile and the encouraging disease control rate deserve further study for these patients.
文摘The inflammatory process plays a central role in the development and progression of numerous pathological situations,such as inflammatory bowel disease(IBD),autoimmune and neurodegenerative diseases,metabolic syndrome,and cardiovascular disorders.IBDs involve inflammation of the gastrointestinal area and mainly comprise Crohn's disease(CD)and ulcerative colitis(UC).Both pathological situations usually involve recurring or bloody diarrhea,pain,fatigue and weight loss.There is at present no pharmacological cure for CD or UC.However,surgery may be curative for UC patients.The prescribed treatment aims to ameliorate the symptoms and prevent and/or delay new painful episodes.Flavonoid compounds are a large family of hydroxylated polyphenolic molecules abundant in plants,including vegetables and fruits which are the major dietary sources of these compounds for humans,together with wine and tea.Flavonoids are becoming very popular because they have many health-promoting and disease-preventive effects.Most interest has been directed towards the antioxidant activity of flavonoids,evidencing a remarkable free-radical scavenging capacity.However,accumulating evidence suggests that flavonoids have many other biological properties,including anti-inflammatory,antiviral,anticancer,and neuroprotective activities through different mechanisms of action.The present review analyzes the available data about the different types of flavonoids and their potential effectiveness as adjuvant therapy of IBDs.
基金Supported by the National Natural Science Foundation of China(No.81173461)China Scholarship Council(No.201306100055)
文摘OBJECTIVE： To investigate, in terms of Notch signaling pathway, the effect on pancreatic cancer of the extract of an anti-tumor prescription -- Qingyihuaji formula （QYHJ） -- from Traditional Chinese Medicine （TCM）.METHODS： Nude mice were implanted subcutaneously with human pancreatic cancer cell line SW1990 and then randomly divided into four groups： Control, QYHJ extract, Gemcitabine, and Combination of QYHJ extract and gemcitabine. Treatments were given for 21 days and tumor growth was evaluated simultaneously. Then, expression of Notch receptors （Notch-I, Notch-2, Notch-3, and Notch-4） and their Jagged ligands （Jagged-1 and Jagged-2） in dissected tumor tissue were detected by real-time quantitative reverse transcription-polymerase chain reaction and Western blot. Finally, immunohistochemistry was performed to detect CD133, a marker of pancreatic cancer stem cells （CSCs）, to evaluate the impact of QYHJ extract on pancreatic CSCs.RESULTS： QYHJ extract treatment effectively inhib- ited the tumor growth in nude mice. The expression of both Notch-4 and Jagged-1 were decreased significantly in QYHJ treatment groups （P 〈 0.05）, while gemcitabine alone had no significant effect in down-regulating Jagged-1 （P 〉 0.05）. No significant difference was observed in the ex- pression of Notch-1, Notch-2, Notch-3, and Jagged-2 between three treatment groups and control group （P 〉 0.05）. Moreover, immunohistochemical analysis showed that the number of CD133 positive cells was significantly reduced by QYHJ treatment （P 〈 0.05）, and the combined treatment was more effective than gemcitabine alone （P 〈 0.05）.CONCLUSION： The role of the extract in pancreatic cancer treatment was associated with down-regulation of Notch-4 and Jagged-1 in Notch signaling pathway. The extract could enhance the antitumor activity of gemcitabine and was more effective than gemcitabine in regulating Notch signaling pathway to some extent.
文摘Objective：Early metastasis is a major biological feature of pancreatic cancer.The current study examined whether silencing Slc38a1,a gene involved in energy metabolism,using short hairpin RNA （shRNA） could inhibit the growth,migration,and invasiveness of pancreatic cancer cells.Methods：A series of Slc38a1 shRNAs were designed and cloned into the pGPU6/GFP/Neo vectors.An shRNA with the most efficacious inhibitory action on SCL38A1 expression （65％ inhibition） upon screening in DH5α bacteria was used to transfect SW1990 human pancreatic cancer cells.Cell growth,migration,and invasiveness were examined using cell counting kit-8,Boyden chamber without and with Matrigel,respectively.Results：Transfection of SW1990 cells with the SLCs38A1 shRNA significantly decreased the proliferation （P＜0.0001） and migratory potential （by 46.7％,P=0.0399） of the cancer cells.Invasiveness,however,was not affected.Conclusions：Inhibiting Slc38a1 using shRNA technology could decrease the growth and migration of representative pancreatic cancer cells.However,the fact that invasiveness was not affected suggested that SLC38A1 is unlikely to be responsible for early metastasis.
文摘AIM:To investigate the clinical characteristics,diagnosis,treatment,and prognosis of primary adenosquamous carcinoma(ASC)of the esophagus.METHODS:A total of 4015 patients with esophageal carcinoma underwent surgical resection between January 1995 and June 2012 at the Cancer Hospital of Shantou University Medical College.In 37 cases,the histological diagnosis was primary ASC.Clinical data were retrospectively analyzed from these 37 patients,who underwent transthoracic esophagectomy with lymphadenectomy.Theχ2or Fisher’s exact test was used to compare the clinicopathological features between patients with ASC and those with squamous cell carcinoma(SCC).The Kaplan-Meier and Log-Rank methods were used to estimate and compare survival rates.A Cox proportional hazard regression model was used to identify independent prognostic factors.RESULTS:Primary esophageal ASC accounted for0.92%of all primary esophageal carcinoma cases(37/4015).The clinical manifestations were identical to those of other types of esophageal cancer.All of the 24patients who underwent preoperative endoscopic biopsy were misdiagnosed with SCC.The median survival time(MST)was 21.0 mo(95%CI:12.6-29.4),and the1-,3-,and 5-year overall survival rates were 67.5%,29.4%,and 22.9%,respectively.In multivariate analysis,only adjuvant radiotherapy(HR=0.317,95%CI:0.114-0.885,P=0.028)was found to be an independent prognostic factor.The MST for ASC patients was significantly lower than that for SCC patients[21.0 mo(95%CI:12.6-29.4)vs 46.0 mo(95%CI:40.8-51.2),P=0.001].In subgroup analyses,the MST for ASC patients was similar to that for poorly differentiated SCC patients.CONCLUSION:Primary esophageal ASC is a rare disease that is prone to be misdiagnosed by endoscopic biopsy.The prognosis is poorer than esophageal SCC but similar to that for poorly differentiated SCC patients.
基金supported by National Administration of Traditional Chinese Medicine’s Traditional Chinese Medicine Inheritance and Innovation“Hundreds and Thousands”Talent Project(Qihuang Project)Qihuang Scholars Support FundNational Natural Science Foundation of China(No.82030117)。
文摘Objective: The coronavirus disease 2019(COVID-19) pandemic has had a serious impact on health all over the world. Cancer patient, whose immunity is often compromised, faces a huge challenge.Currently, some COVID-19 vaccines are being developed and applied on general population;however,whether cancer patients should take COVID-19 vaccine remains unknown. Our study aimed to explore the knowledge, attitude, acceptance, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China.Methods: A cross-sectional study was conducted in Eastern China from June 17 th to September 3 rd, 2021.Patients were selected using a convenience sampling method. A self-report questionnaire was developed to assess knowledge about the COVID-19 vaccine, attitude towards the vaccine and acceptance of the vaccine;following a review of similar studies previously published in the scientific literature, multivariate logistic regression analysis was used to determine the predictors associated with COVID-19 vaccine acceptance.Results: A total of 2158 cancer patients were enrolled in this study. The rate of vaccine hesitancy was 24.05%(519/2158);further, among the participants of vaccine acceptance, 767 had taken COVID-19 vaccine(35.54%), and 872 were willing to get vaccinated(40.01%). A total of 24 variables including demographic characteristics, clinical status of cancer, impact of COVID-19 pandemic on study participants,patients’ knowledge about the COVID-19 vaccine, and attitude towards the vaccine, had significant differences between the ‘‘vaccine hesitancy" population and ‘‘vaccine acceptance" population.Multivariate logistic regression analysis indicated that parameters including alcohol consumption(odds ratio [OR] = 1.849;95% confidence interval [CI]: 1.375–2.488;P-reference [P-Ref] < 0.001 vs nondrinkers), income impacted by COVID-19 pandemic(OR = 1.930, 2.037 and 2.688 for mild, moderate,and severe impact, respectively;all P-Ref < 0.01 vs no impact), knowledge of how the vaccine was developed(OR = 1.616;95% CI: 1.126–2.318;P-Ref = 0.009 vs unknown), believing in the safety of the vaccine(OR = 1.502;95% CI: 1.024–2.203;P-Ref = 0.038 vs denying the safety of vaccine), willingness to pay for the vaccine(OR = 3.042;95% CI: 2.376–3.894;P-Ref < 0.001 vs unwilling), and willingness to recommend families and friends to get vaccinated(OR = 2.744;95% CI: 1.759–4.280;P-Ref < 0.001 vs do not recommend) were contributors to vaccine acceptance. While such as being retired(OR = 0.586;95% CI: 0.438–0.784;P-Ref < 0.001 vs unemployed), undergoing multiple therapies of cancer(OR = 0.408;95% CI: 0.221–0.753;P-Ref = 0.004 vs no ongoing treatment), and worrying that the vaccine might deteriorate the prognosis of cancer(OR = 0.393;95% CI: 0.307–0.504;P-Ref < 0.001 vs might not) were contributors to vaccine hesitancy.Conclusion: This study provided preliminary estimates of the rates of vaccine acceptance and vaccine hesitancy among cancer patients in Eastern China. The intention to receive the COVID-19 vaccine was impacted by factors such as patient occupation, alcohol consumption, and some parts of knowledge about and attitude towards COVID-19 vaccine. It is recommended to develop individualized vaccination plans that meet the healthcare needs of cancer patients.
基金National Key R&D Program of China,No.2019YFB1309704。
文摘BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incidence has increased over the past few decades.However,the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.AIM To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs.METHODS The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.RESULTS Among the 232 patients with PDGNENs,191(82.3%)were male,with an average age of 62.83±9.11 years.One hundred and thirteen(49.34%)of 229 patients had a stage III disease and 86(37.55%)had stage IV disease.Three(1.58%)of 190 patients had no clinical symptoms,while 187(98.42%)patients presented clinical symptoms.The tumors were mainly(89.17%)solitary and located in the upper third of the stomach(cardia and fundus of stomach:115/215,53.49%).Most lesions were ulcers(157/232,67.67%),with an average diameter of 4.66±2.77 cm.In terms of tumor invasion,the majority of tumors invaded the serosa(116/198,58.58%).The median survival time of the 232 patients was 13.50 mo(7,31 mo),and the overall 1-year,3-year,and 5-year survival rates were 49%,19%,and 5%,respectively.According to univariate analysis,tumor number,tumor diameter,gastric invasion status,American Joint Committee on Cancer(AJCC)stage,and distant metastasis status were prognostic factors for patients with PDGNENs.Multivariate analysis showed that tumor number,tumor diameter,AJCC stage,and distant metastasis status were independent prognostic factors for patients with PDGNENs.CONCLUSION The overall prognosis of patients with PDGNENs is poor.The outcomes of patients with a tumor diameter>5 cm,multiple tumors,and stage IV tumors are worse than those of other patients.
基金Supported by National Natural Science Foundation of China,No.81673763Foundation of Guangzhou Science and Technology Plan,No.201804010078。
文摘BACKGROUND For the rarity of type 3 gastric neuroendocrine tumours(g-NETs),their clinicopathological characteristics and prognosis are not well illustrated.AIM To describe the clinicopathological features and outcome of type 3 g-NETs in the Chinese population.METHODS Based on the 2019 WHO pathological classification,the clinicopathological characteristics and prognosis of patients with type 3 g-NETs in China were retrospectively analysed.RESULTS A total of 77 patients(55.8%of females)with type 3 g-NETs were analysed,with a median age of 48 years(range:28-79 years).The tumours were mainly located in the gastric fundus/body(83.1%)and were mostly solitary(83.1%),with a median size of 1.5 cm(0.8-3.5 cm).Of these,there were 37 G1 tumours(48.1%),31 G2(40.3%),and 9 G3(11.7%).Ten(13.0%)and 24(31.2%)patients had lymph node and distant metastasis,respectively.In addition,type 3 g-NETs were heterogeneous.Compared with G1 NETs,G2 NETs had a higher lymph node metastasis rate,and G3 NETs had a higher distant metastasis rate.G1 and G2 NETs with stage I/II disease(33/68)received endoscopic treatment,and no tumour recurrence or tumour-related death was observed within a median follow-up time of 36 mo.Grade and distant metastasis were identified to be independent risk factors for prognosis in multivariable analysis.CONCLUSION Type 3 g-NETs are obviously heterogeneous,and the updated WHO 2019 pathological classification may be used to effectively evaluate their biological behaviors and prognosis.Also,endoscopic treatment should be considered for small(<2 cm),low grade,superficial tumours.
基金supported by the National Natural Science Foundation of China(Grant No:51773151)。
文摘Proteomic characterization of plasma is critical for the development of novel pharmacodynamic biomarkers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the“masking”effect caused by high-abundance proteins.The relative abundance of middleand low-abundance proteins increased substantially from 2.54%to 54.41%,and the top 20 highabundance proteins decreased from 83.63%to 25.77%.Notably,our method can quantify approximately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins identified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.
基金Supported by Key Program of National Science Foundation of China:study of’same syndrome in different diseases’and same treatment in different diseases’of hepatocellular carcinoma and colorectal cancer based on systems biology(No.81330084)。
文摘OBJECTIVE:To investigate the therapeutic effect of the Jianpi Liqi Fang(健脾理气方,JPLQF)combined with transcatheter arterial chemoembolization(TACE)in patients with hepatocellular carcinoma(HCC)and spleen deficiency syndrome(SDS)and identify a potential indicator of efficacy.METHODS:Ninety-nine patients with HCC who were diagnosed with SDS,non-spleen deficiency syndrome(NSDS),or no syndrome(NS)were treated with JPLQF combined with TACE for three periods.Therapeutic efficacy was compared among the groups.Plasma proteins were screened using label-free discovery analysis and verified via enzyme-linked immunosorbent assay(ELISA).Furthermore,receiver operating characteristic(ROC)curves were analyzed to evaluate therapeutic indicators.RESULTS:After treatment,the Karnofsky Performance Status was significantly improved in the SDS group and significantly better than that in the NS group.The Traditional Chinese Medicine(TCM)syndrome scores were lower in the SDS group after treatment and lower than those in the NSDS group.However,alanine aminotransferase,carbohydrate antigen 19-9,alpha-fetoprotein,and carcinoembryonic antigen levels and white blood cell and platelet counts did not differ among the groups.Serum aspartate aminotransferase levels in the SDS group were significantly lower after treatment than before treatment,and total bilirubin levels were significantly lower in the SDS group than in the NSDS group.Label-free analysis identified 24 differentially expressed proteins(DEPs)between the SDS and NS groups,including 17 and 7 upregulated and downregulated proteins,respectively.Fibulin-5(FBLN5)displayed the largest difference in expression between the groups.ELISA confirmed that FBLN5 levels were significantly lower in the NSDS and NS groups than in the SDS group.Following treatment with JPLQF and TACE,FBLN5 expression was upregulated only in the SDS group.Furthermore,ROC curve analysis indicated that FBLN5 may serve as a potential indicator of the efficacy of JPLQF combined with TACE in patients with HCC and SDS.CONCLUSION:JPLQF combined with TACE improved quality of life,clinical TCM symptoms,and liver function in patients with HCC and SDS.FBLN5 expression was significantly altered by treatment with JPLQF and TACE in patients with HCC and SDS.
基金funded by the National Natural Science Foundation of China(Grant Nos.82204694 and 81572416)the Tianjin Health and Family Planning Commission Program(Grant No.ZC20169)the Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A)。
文摘Objective:The presence of complex components in Chinese herbal medicine(CHM)hinders identification of the primary active substances and understanding of pharmacological principles.This study was aimed at developing a big-data-based,knowledgedriven in silico algorithm for predicting central components in complex CHM formulas.Methods:Network pharmacology(TCMSP)and clinical(GEO)databases were searched to retrieve gene targets corresponding to the formula ingredients,herbal components,and specific disease being treated.Intersections were determined to obtain diseasespecific core targets,which underwent further GO and KEGG enrichment analyses to generate non-redundant biological processes and molecular targets for the formula and each component.The ratios of the numbers of biological and molecular events associated with a component were calculated with a formula,and entropy weighting was performed to obtain a fitting score to facilitate ranking and improve identification of the key components.The established method was tested on the traditional CHM formula Danggui Sini Decoction(DSD)for gastric cancer.Finally,the effects of the predicted critical component were experimentally validated in gastric cancer cells.Results:An algorithm called Chinese Herb Medicine-Formula vs.Ingredients Efficacy Fitting&Prediction(CHM-FIEFP)was developed.Ferulic acid was identified as having the highest fitting score among all tested DSD components.The pharmacological effects of ferulic acid alone were similar to those of DSD.Conclusions:CHM-FIEFP is a promising in silico method for identifying pharmacological components of CHM formulas with activity against specific diseases.This approach may also be practical for solving other similarly complex problems.The algorithm is available at http://chm-fiefp.net/.
文摘BACKGROUND Neuroendocrine carcinoma of the breast(NECB)is a rare type of malignant tumor.Due to the rarity of NECB,the relevant literature mostly comprises case reports.Available data on treatment options for NECB are very limited.CASE SUMMARY A 62-year-old woman presented to our hospital in October 2016 for intermittent vomiting and diarrhea and masses in the liver found on abdominal computed tomography(CT)imaging.She was diagnosed in July 2012 with neuroendocrine carcinoma of the right breast in local hospital.The patient initially presented with a painful lesion of the right breast.She then undergone surgical resection and adjuvant chemotherapy with pirarubicin and paclitaxel for four cycles as well as endocrine therapy.She was regularly followed every 3 mo after surgery.Enhanced abdominal CT imaging at our hospital revealed multiple suspicious masses in the liver with the largest lesion measuring 8.4 cm×6.3 cm.Chest CT revealed masses in the anterior chest wall and lung.Core needle biopsy of the lesion revealed liver metastases of NECB.A bone scan showed right second anterior rib metastases.Upper endoscopy and colonoscopy did not provide any evidence of another possible primary tumor.She stopped receiving endocrine therapy and then received etoposide and cisplatin(EP)chemotherapy as a firstline treatment regimen for six cycles at our hospital after liver,bone,and lung metastases.On October 2017,the chemotherapy regimen was changed to S-1(40mg twice daily,days 1-14)combined with temozolomide(200 mg once daily,days 10-14)(STEM)every 21 d as a second-line treatment regimen due to disease progression.Progression-free survival(PFS)and adverse effects after treatment were analyzed,and the efficacy of the STEM regimen was assessed using RECIST version 1.1.This patient achieved a partial response after using the STEM regimen,with a PFS of 23 mo.Adverse effects included only grade 1 digestive tract reactions with no need for a reduction in chemotherapy.CONCLUSION This case report suggests that the STEM regimen may be effective and well tolerated as the second-line treatment for advanced NECB.STEM is still highly effective in patients who show disease progression with the EP regimen.More evidence is needed to prove the validity of STEM.
基金Supported by The Canadian Cancer SocietyNo.#701132
文摘The main task of cancer vaccines is to deliver tumorspecifc antigens to antigen-presenting cells for immune recognition that can lead to potent and durable immune response against treated tumor. Using photodynamic therapy （PDT）-generated vaccines as an example of autologous whole-cell cancer vaccines, the importance is discussed of the expression of death-associated molecules on cancer vaccine cells. This aspect appears critical for the optimal capture of vaccine cells by host’s sentinel phagocytes in order that the tumor antigenic material is processed and presented for immune recognition and elimination of targeted malignancy. It is shown that changing death pattern of vaccine cells by agents modulating apoptosis, autophagy or necrosis can significantly alter the therapeutic impact of PDT-generated vaccines. Improved therapeutic effect was observed with inhibitors of necrosis/necroptosis using IM-54, necrostatin-1 or necrostatin-7, as well as with lethal autophagy inducer STF62247. In contrast, reduced vaccine potency was found in case of treating vaccine cells with apoptosis inhibitors or lethal autophagy inhibitor spautin-1. Therefore, PDT-generated cancer vaccine cells undergoing apoptosis or lethal autophagy are much more likely to produce therapeutic benefit than vaccine cells that are necrotic. These fndings warrant further detailed examination of the strategy using cell death modulating agents for the enhancement of the efficacy of cancer vaccines.
基金National Natural Science Foundation of China(No.81873396)Capital Health Development Research Project(No.2018-2-4065)Project of China-Japan Friendship Hospital(No.2018-HX-26)。
文摘Owing to significantly prolonged survival,targeted therapy has become standardized recommendation for advanced non-small cell lung cancer patients with mutated driver genes.However,the genetic status of lung cancer patients is dynamic.By dynamically monitoring the evolution of genes status,differential genes and concomitant genes related to progressive disease could be confirmed early,so as to achieve a more accurate and comprehensive insight of the whole process management of targeted therapy for lung cancer patients.Under the guidance of accurate genetic testing results,it is helpful to provide patients with more effective,long-term,and stable individualized targeted therapy.
基金supported by the National Natural Science Foundation of China(82230122,82025035,82104612)Shanghai Municipal Health Commission program(ZY(2021-2023)-0205-02)the Science Foundation for Young Scholars of Zhongshan Hospital,Fudan University(grant No.2021ZSQN70).
文摘Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chinese medicine syndrome diagnoses(also called syndrome differentiation)in pancreatic ductal adenocarcinoma.Methods:128 pancreatic ductal adenocarcinoma patients with different syndrome diagnoses were retrospectively reviewed in this study.Long RNA sequencing was conducted to analyze the EV long RNA profile of plasma samples.Differentially regulated EV long RNAs were annotated and assessed for Gene Ontology pathway enrichment using DAVID.The online program xCell were used to perform the cell-type enrichment analysis.Results:An average of 15,000 annotated genes,mainly including messenger RNAs,were stably detected per sample.Different syndrome diagnoses exhibited unique EV mRNA expression profiles and therefore different enriched pathways.Gene Set Enrichment Analysis discovered transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation as the hallmarks of cancer with Shi-Re syndrome.Cell-type enrichment analysis also revealed a varied inflammation/immune cell type distribution among patients with or without Shi-Re diagnosis.Mast cells,platelets and Tregs were significantly enriched but basophils,common lymphoid progenitors,dendritic cells,and conventional dendritic cells were decreased in patients with Shi-Re diagnosis compared with patients without Shi-Re diagnosis.Conclusion:We identified the hallmarks of cancer with different syndrome diagnoses based on plasma EV long RNA sequencing.In particular,transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation were the hallmarks of Shi-Re syndrome,which contribute to shape an inflammatory/immune-suppressive tumor microenvironment in pancreatic ductal adenocarcinoma.
