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Objective:To explore the effect of Helicobacter pylori(HP)eradication on development of metachronous gastric cancer(MGC)after endoscopic submucosal dissection(ESD)in elderly patients with early gastric cancer.Methods:From January 2014 to December 2019, 748 early gastric cancer patients aged 60 years or older, receiving ESD in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, were included.According to the situation of HP infection and eradication efficacy within 1 year postoperatively, patients were divided into three groups.The patients with HP infection and successful HP-eradication were enrolled into successful eradication group, those without eradicating or with eradication failure were enrolled into eradication failure group, those with HP negative were enrolled into HP-negative group.And then the occurrence and risk factors of MGC after ESD among the three groups were statistically analyzed.Results:MGC were detected in 58 cases(7.7%)in elderly patients with early gastric cancer after ESD.The median follow-up time was 39 months.The multivariate regression analysis results of MGC showed that no HP-eradication or HP eradication of failure( HR=2.231, 95% CI: 1.054-4.722, P=0.036)and multiple lesions( HR=1.857, 95% CI: 1.076-3.204, P=0.026)were independent risk factors.Non-smoking was a protective factor for the occurrence of MGC( HR=0.409, 95% CI: 0.234-0.716, P=0.002). After adjusting for confounding factors, Cox proportional risk regression analysis showed that the incidence of MGC was significantly higher in group of no HP-eradicating or HP-eradicating of failure than in group of successful HP-eradicating group( χ2=37.877, P<0.001). Conclusions:HP eradication can effectively prevent MGC in elderly patients with early gastric cancer after ESD.Multiple lesions and smoking are independent risk factors for MGC.
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Alanine-serine-cysteine transporter 2 (ASCT2) is reported to participate in the progression of tumors and metabolic diseases. It is also considered to play a crucial role in the glutamate-glutamine shuttle of neuroglial network. However, it remains unclear the involvement of ASCT2 in neurological diseases such as Parkinson's disease (PD). In this study, we demonstrated that high expression of ASCT2 in the plasma samples of PD patients and the midbrain of MPTP mouse models is positively correlated with dyskinesia. We further illustrated that ASCT2 expressed in astrocytes rather than neurons significantly upregulated in response to either MPP+ or LPS/ATP challenge. Genetic ablation of astrocytic ASCT2 alleviated the neuroinflammation and rescued dopaminergic (DA) neuron damage in PD models in vitro and in vivo. Notably, the binding of ASCT2 to NLRP3 aggravates astrocytic inflammasome-triggered neuroinflammation. Then a panel of 2513 FDA-approved drugs were performed via virtual molecular screening based on the target ASCT2 and we succeed in getting the drug talniflumate. It is validated talniflumate impedes astrocytic inflammation and prevents degeneration of DA neurons in PD models. Collectively, these findings reveal the role of astrocytic ASCT2 in the pathogenesis of PD, broaden the therapeutic strategy and provide a promising candidate drug for PD treatment.
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Objective:To analyze the clinicopathological characteristics of differentiated early cardia cancer and to evaluate the short-term and long-term efficacy of endoscopic submucosal dissection (ESD).Methods:A total of 329 patients (331 lesions) who underwent ESD at Nanjing Drum Tower Hospital from October 2014 to December 2019 and were pathologically confirmed as differentiated early cardia cancer were included in the study and followed up. The endoscopic and pathological data of patients were reviewed to analyze the clinicopathological characteristics of differentiated early cardia cancer. The short-term (including en bloc resection rate, curative resection rate and incidence of short-term complications) and long-term efficacy (including incidence of metachronous cancer, recurrence and distant metastasis, and overall survival rate) of ESD was evaluated.Results:The ratio of male to female in 329 patients with differentiated early cardia cancer was 4∶1, and their age was 65.69±8.02 years. Tumor diameter of ≤2.0 cm accounted for 65.9% (218/331). Most lesions were located on the posterior wall (50.5%, 167/331), followed by the minor curve (36.3%, 120/331). The endoscopic morphology of 0-Ⅱc type accounted for 49.5% (164/331). There were 69.8% (231/331) lesions confined to the mucosal layer. The en bloc resection rate was 100.0% (329/329), and the curative resection rate was 83.3% (274/329). Short-term complications occurred in 28 patients (8.5%). With a median follow-up time of 39 months, 11 patients (3.3%) developed metachronous cancer, 2 (0.6%) developed distant metastasis, and no recurrence occurred. Seven patients died, and the overall survival rate during the follow-up period was 97.9% (322/329). The survival rate of patients with curative resection and additional surgery was 100.0% (3/3), while that without additional surgery was 99.3% (269/271). The survival rate of patients with non-curative resection and additional surgery was 96.0% (24/25), and that without additional surgery was 86.7% (26/30).Conclusion:Most differentiated early cardia cancers are well-differentiated adenocarcinomas, with less than 2 cm in diameter at the time of diagnosis with a low rate of ulcer and vascular invasion. ESD is safe and effective for the treatment of differentiated early cardia cancer with a high rate of curative resection, fewer intraoperative and postoperative complications, low incidences of metachronous cancer, distant metastasis and recurrence, and a high overall survival rate. However, additional surgical treatment is recommended for patients with non-curative resection.
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Objective:To study the safety and efficacy of endoscopic submucosal dissection (ESD) for early gastric cardia cancer (EGCC) in elderly patients.Methods:A retrospective analysis was performed on data of 499 EGCC patients who underwent ESD from January 2011 to June 2018 in Nanjing Drum Tower Hospital. The patients were divided into two groups by age, the young/middle-aged group (<65 years old) and the elderly group (≥65 years old). The baseline data, lesion features, postoperative complications, short-term efficacy and long-term efficacy of the two groups were compared.Results:The elderly group included 272 patients (283 lesions) and the young/middle-aged group included 227 patients (229 lesions). Except that there were significant differences in the age ( P<0.001) and body mass index ( P=0.002) between the elderly group and the young/middle-aged group, there were no significant differences in the baseline data or pathological features between the two groups. The rate of curative resection in the elderly group was 77.0%, lower than that in the young/middle-aged group (84.3%, P=0.045). No significant differences were found in en bloc resection rate (100.0% VS 99.6%, P=1.000), complete resection rate (94.7% VS 93.9%, P=0.705), postoperative complications incidence (6.4% VS 5.7%, P=0.747), operation time (64.02±39.24 min VS 66.16±44.62 min, P=0.566) or hospitalization time (6.76±2.06 d VS 6.47±1.74 d, P=0.092]. After the median follow-up of 47.9 months, 13.4% patients in the elderly group received additional surgery, which was slightly lower than that in the young/middle-aged group ( P=0.891). There were no significant differences in postoperative recurrence, lymph node metastasis, distant metastasis, overall mortality and disease-related mortality between the two groups. The survival analysis showed that five-year overall survival rates were 94.41% and 96.34% in the elderly group and the young/middle-aged group respectively ( P=0.156), and five-year disease-specific survival rate were 99.18% and 99.03% in the two groups respectively ( P=0.858). Conclusion:ESD is safe and effective for EGCC in elderly patients with satisfactory short-term and long-term efficacy.
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Objective:To investigate the clinicopathological characteristics and cost-effectiveness of endoscopic resection and surgical resection for gastric schwannomas arising from the muscularis propria layer.Methods:Thirty-eight consecutive cases of gastric schwannomas diagnosed by histopathology between October 2011 and July 2016 were divided into the endoscopy group(including endoscopic submucosal excavation and endoscopic full-thickness resection) and the surgery group. Complications, complete resection rate and cost-effectiveness were analyzed.Results:The age was 52±10 years (range, 41-63 years) with 11(28.9%) males and 27(71.1%) females. The most common site of gastric schwannomas was the body (71.1%) and the antrum (21.1%). All 38(100%) lesions were protruded. The maximum diameter of the lesions was 2.5±1.2 cm (range 0.6-4.5 cm). Under endoscopic ultrasonography (EUS), 60.5% lesions were heterogeneous hypoechoic, and 15 (39.5%) hypoechoic. The complete resection rate of endoscopy group was 100.0% (17/17). The median operation time of the endoscopy group was 54 minutes. Perforations occurred in 11 patients (64.7%, 11/17), and metal clips or the nylon rope combined with metallic clips were used to close the defect in the endoscopy group. Compared with the surgery group, the length of hospital stay was significantly shorter (4.6±0.6 d VS 9.6±4.4 d, P<0.001); the time to the first fluid diet was significantly shorter (1.2±0.4 d VS 2.7±0.7 d, P<0.001), and the costs were significantly lower (21 965.0±9 342.4 yuan VS 34 253.3±10 520.9 yuan, P<0.001) in the endoscopy group. S100 immunoreactivity was present in all tumors. Local recurrence and distant metastasis did not occur during the median 34 months of follow-up. Conclusions:Endoscopic resection appears to be safe and effective for diagnosis and treatment of gastric schwannomas from the muscularis propria layer. The cost-effectiveness of endoscopic resection is significantly higher than surgical resection.
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Objective:To investigate the analgesic effect of nalbuphine combined with sufentanil on elderly patients with colorectal cancer after laparoscopic surgery.Methods:From January 2017 to December 2019, 106 elderly patients with colorectal cancer underwent laparoscopic surgery in Jiangshan People's Hospital were divided into observation group (53 cases) and control group (53 cases) according to the random digital table method.The control group was given sufentanil analgesia, and the observation group was given nalbuphine analgesia on the basis of the control group.The recovery time and catheter extubation time, pain visual analogue score (VAS) scores at 3, 12 and 24 hours after operation, changes of stress response before and 24h after operation, and adverse reactions were compared between the two groups.Results:The recovery time [(9.87±1.42)min] and catheter extubation time [(13.24±3.51)min] in the observation group were shorter than those in the control group [(17.34±2.98)min and (21.83±5.62)min] ( t=16.474, 9.438, all P<0.05). The postoperative 12h VAS score[(1.63±0.19)points] and 24h VAS score[(1.06±0.13)points] in the observation group were lower than those in the control group [(2.37±0.27)points and (1.83±0.32)points] ( t=16.318, 16.230, all P<0.05). The serum levels of Cor [(234.18±19.98)μg/L] and NE [(1.59±0.21)mmol/L] in the observation group were lower than those in the control group [(287.24±14.26)μg/L and (1.97±0.16)mmol/L] ( t=15.737, 10.479, all P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusion:Nalbuphine combined with sufentanil has good analgesic effect on elderly patients with colorectal cancer after laparoscopic surgery, and can reduce the postoperative stress response.
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Objective To investigate the impact of low intensity pulsed ultrasound (LIPUS) with different intensities on the migration of bone marrow mesenchymal stem cells (BMSCs) in vitro.Methods BMSCs were divided into control group,30 mW/cm2 group,60 mW/cm2 group and 90 mW/cm2 group.Control group was treated by sham LIPUS exposure,and the other three groups were treated by LIPUS with corresponding intensities.The impact of LIPUS on scratch healing was tested with scratch assay,and the interference of proliferation was eliminated with MTT assay.The migration of BMSCs were evaluated with transwell migration assay.The expression of F-actin was analyzed with fluorescein isothiocyanate (FITC) fluorescent coloration.Results 24 h and 48 h after LIPUS exposure,there were statistical differences of scratch area among groups (F=26.559,106.110,both P＜0.001),and the scratch area of control group was the largest ([0.93 ± 0.26)mm2 of 24 h after LIPUS exposure and [0.70 ± 0.11]mm2 of 48 h after LIPUS exposure),while that of 30 mW/cm2 group was the smallest ([0.47 ±0.21]mm2 of 24 h after LIPUS exposure and [0.19±0.10]mm2 of 48 h after LIPUS exposure).There was no statistical difference of scratch area among the four groups immediately after LIPUS exposure (F=2.921,P=0.063).MTT assay results showed there was no statistical difference of absorbance among the four groups immediately,nor 24 h,48 h after LIPUS exposure (F=1.616,0.720,1.408;P=0.196,0.544,0.378).Significant difference was found in the number of cells migrated through the transwell chamber among the four groups (F=43.145,P＜0.001),and the cell number of 30 mW/cm2 group was the largest (212.53±35.32),while that of the control group was the least (89.53±19.27).F-actin fluorescence staining results showed the morphology of F-actin was changed after LIPUS exposure.The cytoskeleton became narrow and elongated.Statistical difference of relative fluorescence intensity was found among the four groups (F 64.350,P＜0.001).The relative fluorescence intensity of 30 mW/cm2 group was the largest (125.43 ± 17.43),while that of control group was the least (51.94± 12.76).Conclusion LIPUS can promote the migration ability of BMSCs in vitro with the best intensity was 30 mW/cm2.
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Objective To investigate the effects of intrathecal different doses of dexmedetomidine hydrochloride in spinal block by ropivacaine hydrochloride . Methods Forty lower limb surgery scheduled for elective under spinal anesthesia, were randomly divided into 2 groups (n = 20 each): the control and the treatment groups.The control and the treatment group were intrathecally injected with 4,12 μg dexmedetomidine hydrochloride respectively.The 0.75% ropivacaine hydrochloride 1.5 mL was injected for spinal anesthesia.SBP,DBP,HR,SpO2 and Ramsay Sedation Score were recorded before the spinal anesthesia conduct and thereafter every five minutes. And the onset and duration of block were recorded,adverse reaction like nausea, vomiting and respiratory depression were also observed. Results Compared with the control group,the onset of sensory block was shorter [(6.9±2.6) min vs (8.7±2.9) min] (P<0.05),and the duration of sensory and motor block was longer in the treatment group[(130.8±30.1) min vs (115.9±23.9) min] (P<0.05) and [(145.9±29.0) min vs (130.0±30.1) min] (P<0.05). Conclusion Intrathecal dexmedetomidine hydrochloride at 12 μg improves anesthesia via shortening the sensory block onset and prolonging sensory and motor block,which maintains hemodynamically stable,and does not generate adverse reactions as nausea,vomiting,bradycardia and respiratory depression.
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Objective To investigate the effects of different anesthesia methods on immunity in patients underwent radical resection of rectal carcinoma.Methods 82 patients underwent radical resection of rectal carcinoma were divided into two groups,each group had 41 cases.A group received total intravenous anesthesia while B group received total intravenous anesthesia combined with eqidural anesthesia.CD3+,CD4+,CD4+/CD8+,CD3+HLA-DR+and NK cells were inspected before induction of anesthesia(T0),2 h after skin incision(T1),2 h(T2) and 24 h(T3) after the end of operation.The T-lymphocyte subsets,activated T cells and NK cells were measured by flow cytometry. Visual analogue scale(VAS) was observed at T2 and T3.Results The VAS score of T2,T3 in A group[(3.86 ± 0.46)points,(3.62 ±0.26)points]were higher than those in B group[(1.67 ±0.57)points,(1.94 ±0.42)points] (all P<0.05).The percentages of CD3+,CD4+,CD4+/CD8+,CD3+HLA-DR+and NK cells of T1,T2,T3 were lower than those of T0 in A group(all P<0.05);The percentages of CD3+,CD4+,CD4+/CD8+,CD3+HLA-DR+and NK cells of T1, T2 were lower than those of T0 in B group ( all P <0.05 );The percentages of CD3+, CD4+, CD4+/CD8+, CD3+HLA-DR+ and NK cells of T1, T2, T3 in A group were lower than those in B group ( all P <0.05 ). Conclusion Total intravenous anesthesia combined with eqidural anesthesia produces less immune suppression than total intravenous anesthesia.
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Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous and immature myeloid-derived cells,which accumulate largely in blood,lymphoid organs,spleen and tumor tissue and so on under the different pathogenic conditions such as infection,trauma,hematosepsis,especially tumor and so on.MDSCs can suppress tumor immune through many mechanisms.The number of MDSCs in periphery blood of patients is closely related with tumor stage,tumor burden,remote metastasis and prognosis.The major results are from laboratory mice.Because of the complexity of MDSCs in patients with tumor,there are many difficulties and debate on the research of them,and the researches of human MDSCs progress slowly.
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Objective: To study the effects of deguelin on proliferation and apoptosis of human breast cancer cell line MCF-7 and on phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Methods: After treatment with 0, 1, 5, 10, 15 and 20 μmol/L of deguelin for 6, 24, 48 and 72 hours, the proliferation inhibition rate of MCF-7 cells was measured by cell counting kit-8 assay. Apoptosis rate of MCF-7 cells was detected with Annexin V-fluorescein isothiocyanate/propidium iodide double staining by flow cytometry and the apoptotic morphology was observed under a transmission electron microscope. After treatment with 0, 1 and 5 μmol/L of deguelin for 6 hours, 5 proteins involved in the PI3K/Akt signaling pathway were examined by Western blot analysis. Results: Deguelin at doses of 5, 10, 15 and 20 μmol/L inhibited the proliferation of MCF-7 cells at 6, 24, 48 and 72 hours. There was a significant difference in each group compared with the control group (P0.05). Deguelin at doses of 5, 10, 15 and 20 μmol/L induced apoptosis of MCF-7 cells at 6 hours. There were significant differences (P<0.01) in the early and late apoptosis rate between the treated groups and the control group. The typical apoptotic MCF-7 cells were observed under the transmission electron microscopy. However, 1 μmol/L of deguelin had no apparent effect in inducing apoptosis of MCF-7 cells at 6 hours. After treatment with 5 μmol/L of deguelin for 6 hours the expression of phosphorylated phosphatase and tensin homologue deleted on chromosome 10 (PTEN) (Ser380), phosphorylated 3-phosphoinositide-dependent protein kinase 1 (PDK1) (Ser241), phosphorylated Akt (Thr308) and phosphorylated glycogen synthase kinase-3β (GSK-3β) (Ser9) proteins were significantly reduced in MCF-7 cells, while there was no significant change in the expression of total Akt protein. However, after treatment with 1 μmol/L of deguelin for 6 hours, there was no apparent change in the expression of these 5 proteins. Conclusion: Deguelin can inhibit the phosphorylation of GSK-3β (Ser9) via inhibition of the phosphorylation of PTEN (Ser380) and PDK1 (Ser241) pathway, thus inducing apoptosis and inhibiting proliferation of MCF-7 cells.
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Objective: To investigate the clinical efficacy of needling Danzhong(CV 17) in the treatment of postpartum hypogalactia and provide clinical evidence for indications of the point. Methods: A multi-centre single-blind randomized controlled trial was carried out. Two hundred and seventy-six puerperal women with postpartum hypogalactia were randomly allocated into acupuncture group and herb group, and respectively treated for three consecutive days. The degree of mammary fullness, the amount of milk secreted, prolactin, baby weight, the frequency and volume of artificial feeding, the number of infant urination events, and the duration of baby crying were observed. The clinical curative effects on postpartum hypogalactia were compared. Results: Hypogalactia was effectively treated in both acupuncture and herb groups. There were statistically significant differences in degree of mammary fullness, amount of milk secreted, baby weight, the frequency and amount of artificial feeding, and the number of infant urination events between pretreatment and post-treatment, but no difference between the two groups. There was no significant difference in prolactin in the acupuncture group and there was a difference in prolactin in the herb group between pretreatment and posttreatment. Conclusion: Needling Danzhong(CV 17) can effectively promote lactation.
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Objective:To establish a method for isolating tumor infiltrating dendritic cells(TIDC)from mice models of Lewis lung cancer by positive selection using anti-CD11c magnetic beads.Methods:A total of 1.0?10~6 Lewis lung cancer cells were subcutaneously injected into a C57BL/6 mice at the lateral abdominal wall to establish the mouse model of lung cancer.TIDC were isolated positively using anti-mouse CD11c magnetic beads;they were labeled by anti-mouse CD11c,and then the purity of the isolated cells was tested by FACScan flow cytometer.The cells were also double labeled by PE-conjugated MHC-ⅡmAb and FITC-conjugated CD83 mAb or FITC-conjugated CD86 mAb to analyze the phenotype of cells by FACScan flow cytometer.Results:The positive selection using anti-CD11 c magnetic beads isolated(1.73?0.31)?10~6 TIDC from each gram of Lewis lung cancer tissue,which accounted for(2.18?0.29)%of the cells in the tumor tissues.The purity of TIDC was 96.49%.Electron microscope showed that the isolated TIDC had the typical character of DC cells.The positive rates of MHC-Ⅱ,CD83 and CD86 molecules in TIDC surface were(51.25?4.21)%, (3.48?0.34)%and(3.07?0.65)%,respectively.Conclusion:The positive selection using anti-CD11c magnetic beads is highly effective,simple,and economic,and is worth popularizing.
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Objective:Investigate the relation between the phosphorylation of FOXO1 and the apoptosis and the proliferation of lymphoma cells and to clarify its specific mechanism.Methods:The lymphoma cells Namalwa and Jurkat were treated with PI3K inhibitor wort mannin or etoposide or Wortmannin plus etoposide for different times-pan and at different concentration.The inhibition rates for cell growth of lymphoma cells were examined by XTT assay.Apoptosis were detected by flow cytometry.The expressions of p-Akt,p-FOXO1,FOXO1 and Bim were determined by Western blot analysis.Results:Wortmannin induced apoptosis of Jurkat cells and Namalwa cells and inhibited their survival effectively.The growth inhibition rate and the apoptosis rate of lymphoma cells induced by Wortmannin plus etoposide were higher than those induced by etoposide alone.After treated with Wortmannin,phosphorylation of FOXO1 remarkably reduced and bim markedly increased.Conclusion:The dephosphorylation of FOXO1 inhibits proliferation of Jurkat cells and Namalwa cells,promotes their apoptosis and enhanced the sensitivity of Non-Hodgkin lymphoma cells to etoposide.Bim activated by FOXO1 promotes cell apoptosis.