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Gastrointestinal tumors(GT)are characterized by both high malignancy and high mortality and have become the major diseases for prevention in the elderly.GT often present detectable changes, including bleeding and abnormal mucosal morphology.However, many technical difficulties remain in accurately monitoring the tumor itself and related abnormal lesions mentioned above, which are the key factors affecting the early detection rate of gastrointestinal tumors.In recent years, with progresses in artificial intelligence(AI)applications for digestive endoscopy image analysis, biosensors, new biomarkers and other areas, AI holds promise for the detection of bleeding, morphological and structural abnormalities of the mucosa, tumors and other major disorders.Here we review the progress of AI applications in geriatric digestive diseases affecting digestive organs and the mucosa in light of morphology and function, to provide a reference for reducing the incidence of both geriatric emergencies and GT.
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Blockchain technology has the advantages of decentralization, secure sharing and tamper resistance, and high privacy, which can solve the current problem of sharing electronic medical records in medical institutions in China. A tertiary hospital established an electronic medical record sharing services convenience service platform based on blockchain in collaboration with China mobile gansu company in September 2021. The hardware architecture of the platform consisted of a hospital data warehouse, a local front-end computer and a blockchain platform. The functional architecture included platform front-end services, the blockchain electronic medical record archiving and service platform. The technical architecture included the underlying blockchain, service layer, interface layer and application layer, which was embedded with asymmetric encryption technology, hash algorithm, smart contract and other technical means, ensuring data ownership and on-demand, controllable, real-time and secure sharing of data. Since the operation of the platform in September 2021, as of October 2022, a tertiary hospital had accumulated 21 545 patient medical records on the chain. The overall operation of the platform was smooth, achieving reliable storage and secure sharing of patient electronic medical records, providing reference for further promoting the interconnection trusted sharing of electronic medical records in medical institutions in China.
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Objective:To evaluate the effectiveness and safety of concurrent chemoradiotherapy combined with nimotuzumab in the treatment of patients with inoperable esophageal squamous cell carcinoma (ESCC).Methods:A retrospective analysis was conducted on the clinical data of 503 patients with inoperable ESCC who underwent concurrent chemoradiotherapy in the Department of Radiation Oncology, Changzhou No. 2 People′s Hospital Affiliated to Nanjing Medical University and Department of Radiation Oncology, Affiliated Hospital of Jiangnan University from 2014 to 2020. Among these patients, 69 received concurrent chemoradiotherapy combined with nimotuzumab (the combined therapy group) and 434 received concurrent chemoradiotherapy alone (the concurrent chemoradiotherapy group). Patients of both groups were matched at a ratio of 1∶2 using the propensity score matching (PSM) method. As a result, 168 patients were determined for clinical analysis, including 61 in the combined therapy group and 107 in the concurrent chemoradiotherapy group. The short-term efficacy and adverse reactions of both groups were compared. The overall survival (OS) curves and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method for the Log-rank test.Results:The two groups showed no statistical difference ( P > 0.05) in clinical baseline characteristics after the PSM. The objective response rate (ORR) of the combined therapy group was significantly higher than that of the concurrent chemoradiotherapy group with statistically significant differences (85.2% vs. 71.0%, χ2 = 4.33, P = 0.037). There was no statistical difference (98.4% vs. 91.6%, P > 0.05) in the disease control rate (DCR) between the two groups. The combined therapy group had median PFS of 28.07 months and 1-, 3-, and 5-year PFS ratios of 78.2%, 37.5% and 29.1%, respectively. The concurrent chemoradiotherapy group had mPFS of 19.54 months and 1-, 3-, and 5-year PFS ratios of 72.9%, 28.3% and 21.3%, respectively. Both groups showed statistically significant differences in PFS ( χ2 = 4.49, P = 0.034). The combined group had median OS of 34.93 months and 1-, 3-, and 5-year OS ratios of 88.5%, 46.8% and 37.4%, respectively. The concurrent chemoradiotherapy group had mOS of 24.30 months and 1-, 3-, and 5-year OS ratios of 81.3%, 35.2% and 28.0%, respectively. Both groups showed statistically significant differences in OS (χ 2= 5.11, P = 0.024), but did not show statistical differences ( P > 0.05) in the severity degree of each adverse effect during the treatment. Conclusions:Concurrent chemoradiotherapy combined with nimotuzumab can improve the ORR and prolong the PFS and OS of patients with inoperable ESCC compared with concurrent chemoradiotherapy alone. Furthermore, combining with nimotuzumab does not increase adverse effects and can be tolerated by patients with high safety.
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Objective:To evaluate the effect of niraparib, the poly (ADP-ribose) polymerase (PARP) inhibitor, on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) and to preliminarily investigate its mechanism.Methods:Human esophageal squamous cell carcinoma cells ECA-109 and KYSE-150 were divided into the control, niraparib, single irradiation, combined (niraparib+irradiation) groups. Cell proliferation was measured by CCK-8 assay. The changes of cell survival rate were detected by colony formation assay. The changes of cell cycle and apoptosis were analyzed by flow cytometry. The number of γH2AX foci was detected by immunofluorescence, and the expression levels of PARP-1, cleaved-PARP, RAD51, mitogen-activated protein kinase (MAPK) [extracellular signal-regulated kinase 1 and 2 (ERK1/2) ] and p-MAPK (ERK1/2) proteins were determined by Western blot. All data were expressed as Mean±SD. Data between two groups conforming to normal distribution through the normality test were subject to independent sample t-test and multiple groups were analyzed using one-way ANOVA. Results:In human ESCC cells ECA-109 and KYSE-150, the proliferation of ESCC cells was significantly inhibited by niraparib combined with irradiation, and the values of average lethal dose (D 0), quasi-threshould dose(D q), survival fraction after 2 Gy irradiation (SF 2) in the combined group were decreased compared with those in the single irradiation group. The effect of irradiation alone on apoptosis of ECA-109 and KYSE-150 cells was limited. Compared to single irradiation group, irradiation combined with niraparib further increased the apoptosis rate in ESCC cells ( P=0.015, P=0.006). In ECA-109 cells, G 2/M phase arrest was significantly increased in combined group compared with irradiation alone group ( P<0.001). In ECA-109 cells, the number of γH2AX foci in combined group was higher than that in the single irradiation group after 2 h, and showed a significantly slower decay of γH2AX foci ( P<0.001). Moreover, niraparib combined with irradiation enhanced the radiation-induced cleavage of PARP-1 and down-regulated the expression of Rad51 and p-MAPK(ERK1/2). Conclusion:Niraparib can increase the radiosensitivity of esophageal cancer cells by inhibiting cell proliferation, promoting cell apoptosis, inhibiting the repair of DNA damage and regulating the MARK-ERK signaling pathway.
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Objective:To study the effects of poly adenosine diphosphate ribose polymerase (PARP) inhibitors niraparib and pamiparib on the radiosensitivity of breast cancer cell lines MCF-7 and MDA-MB-436, and to explore its mechanism.Methods:MCF-7 and MDA-MB-436 cells were divided into control group, niraparib group, pamiparib group, radiation group, combination group treated with niraparib and radiation, and combination group treated with pamiparib and radiation, respectively. The effects of drugs on cell proliferation and radiosensitivity were measured by CCK-8 assay and colony formation assay, respectively. The effect of drugs combined with radiation on cell cycle and apoptosis were detected by flow cytometry. Immunofluorescence method was used to detect the changes of γ-H2AX focal number of cells. The expressions of FANCG, Bax and Bcl-2 mRNA and protein were detected by qPCR and Western blot, respectively.Results:Both niraparib and pamiparib inhibited the proliferation of breast cancer cells MCF-7 and MDA-MB-436 in a time-dose dependent manner. With the increase of irradiation dose, D0, Dq, SF2 value of MCF-7 and MDA-MB-436 cells decreased, and SER D0 and SER Dq value increased. Compared with control group, the percentages of cells in G 2/M phase were increased ( tMCF-7=41.66, 44.08, P<0.05; t436=24.69, 18.91, P<0.05), the percentage of cells in G 0/G 1 phase were decreased ( tMCF-7=8.67, 29.61, P<0.05; t436=26.39, 29.12, P<0.05), and the cell apoptosis rate was significantly increased ( tMCF-7=11.17, 11.71, P<0.05; t436=42.68, 15.89, P<0.05) in the combination group. Compared with control group, the number of γ-H2AX foci of MCF-7 cells in the radiation group and combination group treated with niraparib and radiation increased significantly at 2 h after irradiation ( t=8.89, 21.72, P<0.05). At 24 h after irradiation, the number of γ-H2AX foci basically returned to normal level in the radiation group but remained at a higher level in the combination group ( t=8.82, P<0.05). Compared with control group, the expressions of FANCG and Bcl-2 mRNA decreased ( tFANCG=14.07, P<0.05; tBcl-2=29.21, P<0.05), the expression of Bax mRNA increased ( t=8.90, P<0.05), and the expression of FANCG and Bcl-2 proteins decreased ( tFANCG=7.09, P<0.05; tBcl-2=10.24, P<0.05), while the expression of Bax protein increased ( t=2.90, P<0.05) in the combination group. Conclusions:PARP inhibitors niraparib and pamiparib can increase the radiosensitivity of breast cancer MCF-7 and MDA-MB-436 cells probably through down-regulating the expression of FANCG in FA-BRCA pathway, up-regulating apoptosis-related genes and inhibiting DNA damage repair.
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The thioredoxin system is composed of thioredoxin (Trx), thioredoxin reductase (TR) and reduced nicotinamide adenine dinucleotide phosphate. Trx is an important antioxidant molecule that can resist cell death caused by various stresses and plays a prominent role in redox reactions. TR is a protein containing selenium (selenocysteine), mainly in three forms, i.e. TR1, TR2 and TR3. TR1 mainly distributed in the cytoplasm, TR2 mainly distributed in the mitochondria, and TR3 mainly distributed in the testes. TR can regulate cell growth and apoptosis. After the cell becomes cancerous, the expression of TR increases to promote cell growth and metastasis. Trx system is closely related to neurodegenerative diseases, parasitic infections, acquired immunodeficiency syndrome, rheumatoid arthritis, hypertension, myocarditis and so on. The Trx system can remove the reactive oxygen species (ROS) in the body, keep the inside and outside of the cell in a balanced state, and it interacts with the thioredoxin interacting protein (TXNIP), which plays an important role in the regulation of glucose metabolism and tumor treatment. The Trx system is an important target for drug treatment of many diseases. In this paper, the research progress of the thioredoxin system was reviewed.
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Objective:To investigate the influencing factors for hepatic artery complica-tions of liver transplantation from donation after citizen's death.Methods:The retrospective cohort study was conducted. The clinicopathological data of 147 recipients who underwent liver transplan-tation from donation after citizen's death in Xijing Hospital of Air Force Military Medical University from January 2015 to June 2020 were collected. There were 109 males and 38 females, aged (46±12)years. All recipients underwent liver transplantation from donation after citizen's death. Observation indicators: (1) surgical situations; (2) occurrence of hepatic artery complications after liver transplantation; (3) analysis of donor related influencing factors for hepatic artery complications after liver transplantation; (4) analysis of recipient related influencing factors for hepatic artery complications after liver transplantation; (5) follow-up. Follow-up was conducted using outpatient examination or telephone interview to detect survival of recipients up to June 2021. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Univariate analysis was conducted using the Fisher exact probability, and multivariate analysis was conducted using the COX regression model. Kaplan-Meier method was used to calculate the cumulative survival rate and draw the survival curve. Results:(1) Surgical situations: of the 147 recipients, 108 cases underwent orthotopic liver transplantation, and 39 cases underwent piggyback liver transplantation. The operation time of 147 recipients was (458±101)minutes. (2) Occurrence of hepatic artery complications after liver transplantation: 4 of the 147 recipients had hepatic artery complications, including 3 cases with hepatic artery embolism and 1 case with hepatic artery stenosis. The time to occurrence of hepatic artery complications after liver transplantation was (5±2)days. (3) Analysis of donor related influencing factors for hepatic artery complications after liver transplantation: results of univariate analysis showed that age, atherosclerosis, fatty liver and arterial variation were not donor related factors influencing hepatic artery complications after liver transplantation ( P>0.05). (4) Analysis of recipient related influencing factors for hepatic artery complications after liver transplantation: results of multivariate analysis showed that insufficient hepatic artery blood flow in the recipient was an independent risk factor for hepatic artery complications after liver transplantation ( hazard ratio=10.13, 95% confidence interval as 1.05-97.42, P<0.05). (5) Follow-up: 146 of the 147 recipients were followed up for 1 to 77 months, with a median follow-up time of 34 months. The 1-year cumulative survival rate of the 146 recipients was 92.2%. Conclusion:Insufficient hepatic artery blood flow of the recipient is an independent risk factor for hepatic artery complications after liver transplantation from donation after citizen's death.
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Forty-three fowl adenovirus (FAdV) strains were isolated in China from 2007 to 2014 from poultry and ostriches with inclusion body hepatitis (IBH) and hydropericardium syndrome (HPS). Phylogenetic analysis showed that 28/43 strains clustered into Fowl aviadenovirus D (FAdV-D) and 9/43 strains clustered into FAdV-E. FAdV-C included three isolates of ostrich origin, one of goose origin and two of chicken origin. Based on hexon loop 1 gene sequencing analysis, these viruses were genetically related to FAdV-4, FAdV-8a, FAdV-8b and FAdV-11, of which FAdV-11 was dominant. The isolation in 2014 of three FAdV strains belonging to serotype 4 from ostrich flocks is to our knowledge the first finding of FAdV-4 infection and HPS cases in ostriches. Epidemiological analysis showed that FAdV has been circulating in northern and eastern China, where more than 50% of layers and broilers are raised. The hosts of this pathogen included broilers, layers, geese and ostriches. IBH and HPS cases had a sporadic or cluster distribution from 2007 to 2013; however, since 2014 the number of cases has increased sharply. To control FAdV, strict biosecurity protection measures are necessary and a multivalent vaccine may be needed.
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Anseriformes , Aviadenovirus/genética , Enfermedades de las Aves/virología , Pollos , Struthioniformes , Animales , Enfermedades de las Aves/epidemiología , China/epidemiología , FilogeniaRESUMEN
Objective:To observe the effect and underlying mechanism of down-regulation of VEGFA on the radiosensitivity of esophageal cancer ECA-109 cells.Methods:Esophageal cancer cells were divided into four groups: sh-VEGFA group, vector control group, X-ray plussh-VEGFA group and X-ray plus vector group. The expressions of VEGFA gene and protein were detected by qPCR and Western blot, respectively. Cell proliferation and survival was measured by CCK8 assay and cloning formation, respectively. Cell apoptosis was detected by flow cytometry, and γ-H2AX foci were detected by immune-fluorescence assay.Results:Compared with the vector group, the expression of VEGFA gene was decreased in sh-VEGFA group ( t=11.98, P<0.05), and the expression of VEGFA protein was also reduced( t=12.38, P<0.05). After VEGFA being down-regulated, the cell proliferation( A450)was obviously inhibited( t=2.78, 7.25, 21.93, 13.21, P<0.05), and the cell clone formation of the sh-VEGFA group was significantly decreased so that D0, Dqand SF2 of sh-VEGFA group were decreased( t=5.83, 8.56, 7.68, P<0.05), and SERD0and SERDqwere increased. Compared with the vector group, the apoptosis rate in the sh-VEGFA group and the X-ray group was significantly increased and further increased in the sh-VEGFA plus X-ray group( t=17.63, 22.48, 33.87, P<0.05), and the number of γ-H2AX foci in both sh-VEGFA and vector groups were significantly increased within 2 h after X-ray irradiation. At 24 h after irradiation, the number of γ-H2AX foci returned to normal level in the vector group but remained at a higher level in the sh-VEGFA group ( t=7.00, P<0.05). Conclusions:Down-regulation of VEGFA inhibits the proliferation and colony formation, promotes apoptosis and hence increases the radiosensitivity of esophageal carcinoma cells via a pathway related to DNA damage repair.
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Objective@#To investigate the adverse effects and clinical efficacy of the intensive modulated radiotherapy(IMRT)and intravaginal brachytherapy combined with versus without chemotherapy in elderly patients with cervical cancer, and to analyze its prognostic factors.@*Methods@#Clinical data and follow-up results of 214 patients with cervical cancer aged ≥60 years undergoing IMRT and intravaginal brachytherapy combined with or without chemotherapy were retrospectively analyzed.The overall survival(OS)rate was calculated by using the Kaplan-Meier method.Prognostic factors were analyzed by Log-rank single factor test and Cox multivariate analysis.@*Results@#The rates of myelosuppression(≥grade 3)was higher in the concurrent chemo-radiotherapy group than in simple radiotherapy group(48.6% vs.15.8%, χ2=27.372, P<0.05). The complete response(CR)rate was higher in the concurrent chemo-radiotherapy group than in the simple radiotherapy group(83.0% vs.68.3%, χ2=5.993, P=0.014). The 1-, 3- and 5-year OS rate were 92.2%, 79.3% and 65.6%, respectively in all patients.Univariate analysis showed that the staging, lymph node metastasis status, pathological type and short-term efficacy of cervical cancer(based on FIGO guideline)were influencing factors for the prognosis(χ2=4.321-30.316, all P<0.05). Multivariate analysis showed that the FIGO staging, lymph node metastasis status and short-term efficacy were independent influencing factors for the prognosis(χ2=5.284-14.261, all P<0.05).@*Conclusions@#The intensive modulated radiotherapy and intravaginal brachytherapy combined with chemotherapy have a good efficacy and favorable long-term survival rate for the treatment of cervical cancer in elderly patients, and its major adverse effects can be tolerated.The FIGO staging, lymph node metastasis status and short-term efficacy are independent influencing factors for the prognosis in elderly patients with cervical cancer.
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Objective To investigate the adverse effects and clinical efficacy of the intensive modulated radiotherapy (IMRT)and intravaginal brachytherapy combined with versus without chemotherapy in elderly patients with cervical cancer,and to analyze its prognostic factors.Methods Clinical data and follow-up results of 214 patients with cervical cancer aged ≥60 years undergoing IMRT and intravaginal brachytherapy combined with or without chemotherapy were retrospectively analyzed.The overall survival(OS) rate was calculated by using the Kaplan-Meier method.Prognostic factors were analyzed by Log-rank single factor test and Cox multivariate analysis.Results The rates of myelosuppression(≥grade 3)was higher in the concurrent chemo-radiotherapy group than in simple radiotherapy group(48.6%% vs.15.8 %,x2 =27.372,P < 0.05).The complete response (CR)rate was higher in the concurrent chemo-radiotherapy group than in the simple radiotherapy group (83.0% vs.68.3%,x 2=5.993,P=0.014).The 1-,3-and 5-year OS rate were 92.2 %,79.3 % and 65.6 %,respectively in all patients.Univariate analysis showed that the staging,lymph node metastasis status,pathological type and short-term efficacy of cervical cancer (based on FIGO guideline)were influencing factors for the prognosis (x2 =4.321-30.316,all P < 0.05).Multivariate analysis showed that the FIGO staging,lymph node metastasis status and short-term efficacy were independent influencing factors for the prognosis(x2 =5.284-14.261,all P<0.05).Conclusions The intensive modulated radiotherapy and intravaginal brachytherapy combined with chemotherapy have a good efficacy and favorable long-term survival rate for the treatment of cervical cancer in elderly patients,and its major adverse effects can be tolerated.The FIGO staging,lymph node metastasis status and short-term efficacy are independent influencing factors for the prognosis in elderly patients with cervical cancer.
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Objective@#To investigate the adverse events and efficacy in cervical cancer patients receiving intensity modulated radiationtherapy (IMRT) plusbrachytherapy with or without chemotherapy, and to indentify the factors that may affect the prognosis.@*Methods@#In this retrospective analysis, we analyzed the clinical and follow-up data of the 422 cervical cancer patients, who received IMRT plus brachytherapy with or without chemotherapy.Among these patients, 353 cases received concurrent chemoradiotherapy and the other 69 cases received radiotherapy alone. Kaplan-Meier method was utilized to calculate the overall survival (OS) rates. Log-rank-test and Cox regression were performed to executing the univariate and multivariate analysis of the OS, respectively.@*Results@#The rate of complete response (CR) in the patients receiving concurrent chemoradiotherapy was significantly higher than that of the patients who received single radiotherapy (77.6% vs. 65.2%, χ2=4.812, P<0.05). The 1-, 3-, and 5-year OS rates were 93.4%, 79.4%, and 65.0%, respectively. Univariate analysis showed that age, Federation International of Gynecology and Obstetr(FIGO)2009 staging, lymph node metastasis, pathological type, chemotherapy experiences concurrent with radiotherapy, short-term efficiency, and sequential chemotherapy could affect the OS (χ2=6.375-613.123, P<0.05). Multivariate analysis showed that FIGO staging, lymph node metastasis, pathological type, chemotherapy experiences concurrent with radiotherapy, and the short-term efficacy were the independent determinants for the prognosis (χ2=3.930-42.994, P<0.05). For patients with positive pelvic lymph node, there were no statistical differences in the para-aortic lymph node (PALN) metastasis whether undergoing prophylactic extended field irradiation of the PALN or not(PALN metastasis rates: 6.1% vs. 16.8%, P>0.05). The OS for the patients receiving prophylactic extended field irradiation of the PALN was higher than that of patients without prophylactic radiation (χ2=3.953, P<0.05).@*Conclusions@#Cervical cancer patients receiving IMRT plus brachytherapy with or without chemotherapy had achieved promising prognosis. Prophylactic extended field irradiation of the PALN contributed to the improved OS in the patients with pelvic lymph node metastasis. FIGO staging, pathology type, lymph node metastasis, radiotherapy concurrent with chemotherapy or not, and short-term efficiency were independent factors for the prognosis.
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Objective@#To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms.@*Methods@#The esophageal cancer cells, KYSE-150 and ECA-109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 μmol/L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR-2 was measured by real-time quantitative PCR (qRT-PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme-linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p-MEK, p-ERK, JAK2, STAT3 and p-STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor-bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively. Tumor inhibition rates of different groups were calculated. And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining.@*Results@#In the presence of 20 μmol/L and 40 μmol/L of apatinib for 24 hours, the migration cell numbers of KYSE-150 and ECA-109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33±26.84, respectively, that were significantly lower than control group (P<0.05 for all). In addition, after treatment with 10 μmol/L, 20 μmol/L and 40 μmol/L of apatinib for 7 days on KYSE-150 and ECA-109, the colony formation rates were (65.12±25.48)%, (58.19±24.73)% and (29.10±22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 μmol/L and 40 μmol/L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P<0.05). The cell cycle ratio of G2/M phase and apoptosis rate of control group and 20 μmol/L apatinib group in KYSE-150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65±1.54)%, respectively. The corresponding ratios in ECA-109 cells were (3.44±0.57)% and (6.31±1.43)% as well as (22.64±2.36)% and (49.26±1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G2/M phase and induced cell apoptosis in both KYSE-150 and ECA-109 cells (P<0.05 for all). In the presence of 20 μmol/L and 40 μmol/L of apatinib in KYSE-150 cells, the relative levels of VEGF mRNA were (42.57±10.43)% and (25.69±1.24)%, and those of VEGF-2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P<0.05 for all). For ECA-109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P<0.05 for all). Moreover, after treatment with 20 μmol/L and 40 μmol/L of apatinib in KYSE-150 cells, the VEGF concentrations were (766.48±114.27) pg/ml and (497.40±102.18)pg/ml, which were significantly decreased compared to control group [(967.41±57.75) pg/ml, P<0.05)]. The results in ECA-109 were consistent (P<0.05). Furthermore, after treatment with 40 μmol/L of apatinib in KYSE-150 and ECA-109, the relative expression of p-MEK and p-ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66±0.07 as well as 1.03±0.20 and 1.76±0.20; P<0.05). The relative expression of STAT3, p-STAT3 in control group and experimental group were 0.96±0.15 and 0.85±0.16 as well as 0.62±0.09 and 0.36±0.13, respectively. The results showed that the protein levels of STAT3 and p-STAT3 were significantly lower than the control group (P<0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg/ml, (16.40±2.81) pg/ml and (15.04±4.88)pg/ml for control, 250 mg and 500 mg treatment groups, respectively.@*Conclusions@#Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras/Raf/MEK/ERK pathway and JAK2/STAT3 pathway.
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Objective To compare the clinical effects of sodium valproate separately combined with ziprasi -done and olanzapine in the treatment of bipolar disorder type Ⅰ .Methods 100 patients with bipolar disorder type Ⅰ were chosen.According to the digital table ,the patients were randomly divided into two groups ,including A group (50 children) with olanzapine and B group (50 children) with ziprasidone on the basis of sodium valproate .The clinical effects,the BRMS score,digit symbol scores,TMT A/B scores,WCST score and TOH cognitive function scores before and after treatment of the two groups were compared .Results The total effective rates of A group and B group were 88.00%,92.00%,respectively.There was no statistically significant difference in clinical effects between the two groups(χ2 =8.14,P<0.05).The BRMS scores of both two groups after treatment were significantly lower than before treatment(t=3,74,4.06,all P<0.05).There was no statistically significant difference in BRMS score after treatment between the two groups (t =0.89,P >0.05).The digit symbol scores,WCST score and TOH cognitive function scores of B group after treatment were significantly higher than those of A group and before treatment ( t=3.17,4.03,3.96,3.54,2.86,3.81,4.66,4.29,3.81,3.43,all P<0.05).The TMT A/B scores of B group after treatment were significantly lower than those of A group and before treatment ( t=3.82,4.82,4.55,4.09,3.83,all P<0.05).Conclusion Sodium valproate separately combined with ziprasidone and olanzapine in the treatment of bipolar disorder type I possess the same clinical effects in manic symptoms relief ,and sodium valproate combined with ziprasidone can effectively promote the recovery process of cognitive function damage and improve the clinical prognosis for long-term.
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Objective To study the relationship between preoperative serum a-fetoprotein (AFP) level and early recurrence of patients with hepatocellular carcinoma (HCC) after partial hepatectomy.Methods 267 patients with hepatocellular carcinoma who underwent partial hepatectomy in Xijing Hospital,the Fourth Military Medical University from January 2011 to November 2015 were retrospectively studied.The patients were divided into the AFP-negative group (AFP ≤20 μg/L) and the AFP-positive group (AFP > 20 μg/L) according to the preoperative serum AFP levels.The risk factors of early recurrence of HCC in patients after partial hepatectomy were studied by multivariate regression analysis.The recurrence-free survival rates during 24 months after surgery between the AFP-negative group and the AFP-positive group were compared.Results In 267 patients,97 patients had low or negative AFP levels (AFP≤20 μg/L) and 170 patients had high or positive AFP levels (AFP > 20 μg/L).Patients in the AFP-positive group had significantly more well differentiated HCC on tumor histology when compared with patients in the AFP-negative group (x2 =17.050,P < 0.05).The proportion of patients with liver cirrhosis in the AFP-positive group was significantly higher than that of the AFP-negative group (x2 =4.374,P < 0.05).On the other hand,the numbers of patients with adjacent tissue invasion (x2 =4.374,P < 0.05) and early HCC recurrence (x2 =7.595,P < 0.05) in the AFP-positive group were significantly less than those of the AFP-negative group.Survival analysis showed that the recurrence-free survival rates in the AFP-positive and negative groups were 35.3%,52.6%,respectively.The results on univariate analysis showed that portal vein tumor thrombus,HBsAg positivity,tumor number,tumor diameter,tumor tissue differentiation,preoperative serum AFP level and adjacent tissue invasion were significantly associated with early recurrence of liver cancer (P < 0.05).Cox multivariate regression analysis revealed that serum AFP positivity (HR =1.605,P < 0.05),portal vein tumor thrombosis (HR =3.936,P < 0.05),HBsAg positivity (HR =1.621,P <0.05),tumor diameter (HR =1.977,P < 0.05) and tumor number (HR =1.991,P < 0.05) were significantly correlated with early recurrence of liver cancer after partial hepatectomy.Conclusion The preoperative serum AFP level had an important predictive value for early recurrence of primary hepatocellular carcinoma in patients after partial hepatectomy.
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Objective To assess the long-term efficacy and adverse effects of three-dimensional radiotherapy (3-DCRT) for elderly patients with esophageal cancer,to investigate the effects of diabetes and hypertension on radiation esophagitis and pneumonitis and to analyze the prognostic factors.Methods A total of 233 patients aged 70 or over with esophageal squamous cell carcinoma were treated with 3-DCRT,and 27 of the patients had type-2 diabetes and 63 had hypertension.Radiation esophagitis and pneumonitis were monitored in patients with or without diabetes and in patients with or without hypertension.Potential prognostic factors were analyzed by Logrank single factor analysis and Cox multivariate analysis.Results The incidences of radiation esophagitis and pneumonitis in grade 3 or over were significantly higher in patients with diabetes than in those without diabetes (Z =-3.762,-2.972;P <0.001,0.003).The incidences of radiation esophagitis and pneumonitis in grade 3 or over in patients with hypertension were significantly higher than in those without hypertension (Z =-2.610,-2.209;P =0.009,0.027).The 1-,3 and 5-year overall survival (OS) rates were 70.6%,35.8% and 23.9%,respectively.The median OS was 23.0 months (95%CI:18.6-27.5).Univariate analysis showed that age (x2 =4.274,P =0.039),T stage (x2=9.376,P 0.025),N-stage (x2=8.504,P=0.014),TNM stage (x2=7.806,P=0.020),gross tumor volume (GTV) (x2 =5.209,P =0.022) and short-term therapeutic efficacy (x2 =25.276,P<0.001) had influenced OS.Multivariate analysis showed that T-stage (P =0.001),N-stage (P =0.007),TNM stage (P =0.002) and short term therapeutic efficacy (P < 0.001) were independent prognostic factors for OS.Conclusions 3-DCRT achieves favorable long-term efficacy in elderly patients with esophageal cancer.Diabetes and hypertension are potential risk factors for radiation esophagitis and pneumonitis.T-stage,N-stage,TNM stage,and short term therapeutic efficacy are independent prognostic factors.
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Objective To compare the prognostic factors and adverse effects of elderly patients with esophageal cancer between radiotherapy alone and concurrent chemoradiotherapy. Methods A total of 479 patients with esophageal squamous cell carcinoma aged 70 years or older were analyzed retrospectively at our institute, from January 2008 to December 2017. The patients were divided into radiotherapy alone group ( 359 cases ) and concurrent chemoradiotherapy group ( 120 cases ) . After Propensity Score Matching ( PSM) , data from matched patients with 102 cases in each group was analyzed. The overall survival (OS) rates, the prognostic factors and adverse effects were assessed. Results The 1, 3, 5-year of OS in radiotherapy alone group after PSM were 77. 4%, 40. 1%, 22. 7%, respectively, and median overall survival time (mOS) was 26. 9 months (95% CI:18. 7 - 35. 2 months). The chemoradiotherapy group after PSM were 79. 5%, 47. 6%, 35. 7% and 35. 6 months (95% CI:23. 2-48.0 months), respectively, while there was no significant difference between the groups (P >0. 05). Subgroup analysis showed that the 1, 3, 5-year of OS and mOS of the patients aged 70 -75 years in radiotherapy alone group were 79. 4%, 41. 0%, 26. 2% and 29. 2 months, respectively. The patients aged 70-75 years in chemoradiotherapy group were 86. 5%, 56. 1%, 47. 6% and 48. 9 months, respectively. There was statistically significance between the groups after PSM(χ2 =4. 746, P<0. 05). The univariate prognostic analysis showed that the age, T stage, N stage, clinical stage, short-term efficacy and performance status were influencing factors for OS (χ2 =6. 714-42. 900, P<0. 05). The clinical stage and short-term efficacy were independent prognostic factors for OS (χ2 =5. 007 -9. 181, P<0. 05). In addition , the risk of non-tumor related death of the patients aged 75 years or older in the chemoradiotherapy group was higher than those in the radiotherapy alone group(χ2 =5. 630, P<0. 05). The prevalence of toxicities (≥grade 3) including bone marrow suppression, radiation esophagitis and radiation pneumonia in the chemoradiotherapy group were higher than that in the radiotherapy alone group (χ2 =4. 701 -28. 318, P<0. 05). Conclusions Concurrent chemoradiotherapy, compared with radiotherapy alone, may improve the prognosis of patients aged 70-75 years with esophageal squamous cell carcinoma.
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Objective To evaluate the radiosensitivity effects of apatinib on the esophageal cancer cell line ECA-109 and its cancer stem-like cells,and to investigate the underlying mechanism.Methods A serum-free medium (SFM) was used to culture esophageal cancer stem cell line ECA-109 and enrich the esophageal stem-like spheres.ECA-109 and its stem-like cells were divided into control group,drug treatment group,radiation group and drug plus radiation group.Cell proliferations of ECA-109 and its stem-like cells were detected with CCK-8 method.The concentration of vascular endothelial growth factor (VEGF) in the cell culture medium was determined by enzyme linked immunosorbent assay(ELISA).Cell cycle and apoptosis were detected by flow cytometry method.The expressions of CHK2 and P-STAT3 proteins were detected by Western blot assay.Results With the administration with apatinib for 24,48 and 72 h,the half of the inhibitory concentration (IC50) of ECA-109 stem-like cells was significantly higher than that of the parent cells (t =8.17,9.29,18.85,P < 0.05) in a time dependent manner (parental cells:r2 =0.94-0.97,P <0.05;stem-like cells:r2 =0.94-0.98,P <0.05).After administration with different concentrations of apatinib (parental cells:10 and 20 μmol/L;stem-like cells:30 and 40 μmol/L) combined with different dose of X-rays (6 and 8 Gy),the proliferations of ECA-109 and its stem-like cells were significantly (t =5.20-39.68,P < 0.05) inhibited compared with radiation alone group.VEGF secretion from both ECA-109 cells and its stem like cells were significantly decreased in different manner (t =7.45,P < 0.05).Compared with control group,the cell apoptosis rate and the percentages of cells in G2/M phase were significantly increased in drug plus radiation group (t =8.83,11.59,P < 0.05),and the expressions of CHK2 and P-STAT3 were decreased in drug group (t =3.36,4.10,P < 0.05).Compared with radiation group,the expressions of CHK2 and P-STAT3 were decreased in drug plus radiation group (t =9.05,2.36,P < 0.05).Conclusions Apatinib enhanced the radiosensitivity of ECA-109 cells and its stem-like cells,which was much more effective on ECA-109 cells and may be related to the radiation-induced inhibition of VEGF signal pathway that can further inhibit cell proliferation,promote cell apoptosis and induce cell cycle redistribution.The higher intrinsic level of VEGF protein may contribute to radioresistance of ECA-109 stem-like cells.
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Objective To observe the long-term prognosis and analyze the predictive factors of esophageal cancer patients treated with three-dimensional radiotherapy.Methods A total of 373 patients with esophageal squamous carcinoma who received three-dimensional radiotherapy were retrospectively enrolled in this study.Among these,231 cases received three dimensional conformal radiotherapy (3D-CRT) and the other 142 received intensity modulated radiotherapy (IMRT);202 cases received radiotherapy alone,and the other 171 received chemoradiotherapy;249 cases received involved-field irradiation(IFI),and the other 124 received elective nodal irradiation(ENI);60 cases received a total radiation dose of 50-60 Gy,and the other 313 received 60-70 Gy.Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS).The Logrank single factor analysis and Cox multivariate analysis were used to evaluate predictive factors of PFS and OS.Results The 1-,3-,5-year OS and PFS were 69.4%,33.7%,22.9% and 63.8%,32.8%,22.4%,respectively.The median OS and PFS were 22.7 months (95% CI 18.6-25.4 months) and 19.2 months (95% CI 16.7-21.3 months) respectively.Univariate analysis showed that age,gender,tumor location,three-dimensional technology (3D-CRT vs.IMRT),chemotherapy,prophylactic irradiation to lymphatic drainage area and irradiation dose did not influence OS and PFS (P > 0.05).T-stage,N-stage,TNM-stage and gross tumor volume (GTV) were significantly correlated to OS and PFS (x2 =5.836-14.526,P < 0.05).The multivariate analysis showed that N-stage and GTV were independent predictive factors of OS and PFS (x2 =5.345-12.216,P <0.05).The OS and PFS of patients with two fields of lymph node metastases were worse than those with only one lymph node field metastasis (x2 =4.467,4.169,P < 0.05).Conclusions The long-term efficacy for esophageal cancer patients could be significantly improved through 3D-CRT technology.N-stage and tumor volume were independent prognostic factors of OS and DFS.The number of lymph node metastasis field is significantly related to prognosis.
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Objective To investigate the risk factors for acute radiation esophagitis andpneumonitis after radiation therapy in esophageal cancer (EC) patients with diabetes or hypertension.Methods A total of 373 EC patients receiving three dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) were included in this study.Among these patients,42 showed concurrent with diabetes and 99 with hypertension.Radiation esophagitis or pneumonitis in patients with or without diabetes,and with or without hypertension were monitored in the 1-year follow up,respectively.Results The prevalence of grade 1,2,3 and 4 radiation esophagitis in diabetes and non-diabetes patients was 40.5%,38.1%,14.3%,4.8% and 66.2%,27.8%,2.7%,1.8%,respectively,while that of the grade 1,2 and 3 radiation pneumonitis in diabetes and non-diabetes patients was 31.0%,16.7%,9.5% and 30.8%,15.7%,1.2%,respectively.The prevalence of grade 3 or above radiation esophagitis and pneumonitis in patients with diabetes and was significantly higher than those with non-diabetes (x2 =13.573,12.279,P < 0.05).The prevalence of grade 1,2,3 and 4 radiation esophagitis in hypertension and non-hypertension patients was 49.5%,38.4%,8.1%,3.0% and 68.2%,25.5%,2.6%,1.8%,respectively,while that of the grade 1,2 and 3 radiation pneumonitis in hypertension and non-hypertension patients were 30.3%,18.2%,5.1% and 31.0%,15.0%,1.1%,respectively.The prevalence of grade 3 or above radiation esophagitis and pneumonitis in patients with hypertension was significantly higher than those with non-hypertension (x2 =5.695、5.422,P < 0.05).Diabetes is an independent risk factor for grade 3 or above acute radiation esophagitis and pneumonitis.Conclusions Diabetes or hypertension might be risk factors for severe radiation esophagitis and pneumonitis in EC patients receiving radiation therapy.