Objectives:To analyze the long-term prognosis of patients with locally advanced gastric cancer in the stage of ypT0~2N0M0 after neoadjuvant chemotherapy.Methods:The clinical data of 78 patients with locally advanced gastric cancer who underwent neoadjuvant chemotherapy and radical resection at ypT0~2N0M0 stage from January 2012 to December 2019 in the Department of Abdominal Surgery/Pancreatic and Gastric Surgery of the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. Kaplan-Meier method was used to calculate the overall survival and disease-free survival, and the survival difference between patients with postoperative ypT0N0M0 and ypT1~2N0M0 was compared. Multivariate Cox proportional hazards regression analysis was performed on clinical, pathologic and treatment measures that may affect survival.Results:Among the 78 patients, there were 18 cases (23.1%) with ypT0N0M0, 14 cases (17.9%) with ypT1aN0M0, 17 cases (21.8%) with ypT1bN0M0, and 29 cases (37.2%) with ypT2N0M0. Median follow-up time was 74.1 (19.8~132.5) months. Fourteen patients (17.9%) had tumor recurrence and metastasis, and 9 patients died from tumor recurrence and metastasis. The 5-year disease-free survival and overall survival rates were 84.4% and 87.8%, respectively. There was no statistically significant difference in 5-year overall survival (86.9% vs 87.8%) or 5-year disease-free survival (88.9% vs 83.2%) between patients with ypT0N0M0 and ypT1~2N0M0. Analysis of factors that may affect prognosis revealed that signet ring cell carcinoma, nerve invasion, and lymph node dissection of fewer than 16 were significantly associated with prognosis ( P＜0.05). Multivariate Cox analysis including these three factors showed that only lymph node dissection of fewer than 16 was an independent risk factor affecting prognosis (OS: HR=10.44 ,95% CI: 2.15-50.72, P=0.004; DFS: HR=11.47, 95% CI: 2.85-46.20, P=0.001). Conclusions:The long-term prognosis of patients with locally advanced gastric cancer at ypT0~2N0M0 stage after neoadjuvant chemotherapy is relatively good, and the long-term survival time of patients with ypT1~2N0M0 and ypT0N0M0 is similar. Lymph node dissection of less than 16 nodes may be an independent risk factor affecting prognosis. During surgery, efforts should be made to increase the number of lymph node dissections. For patients with less than 16 nodes dissected, postoperative treatment and follow-up should be strengthened.

Objectives:To analyze the long-term prognosis of patients with locally advanced gastric cancer in the stage of ypT0~2N0M0 after neoadjuvant chemotherapy.Methods:The clinical data of 78 patients with locally advanced gastric cancer who underwent neoadjuvant chemotherapy and radical resection at ypT0~2N0M0 stage from January 2012 to December 2019 in the Department of Abdominal Surgery/Pancreatic and Gastric Surgery of the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. Kaplan-Meier method was used to calculate the overall survival and disease-free survival, and the survival difference between patients with postoperative ypT0N0M0 and ypT1~2N0M0 was compared. Multivariate Cox proportional hazards regression analysis was performed on clinical, pathologic and treatment measures that may affect survival.Results:Among the 78 patients, there were 18 cases (23.1%) with ypT0N0M0, 14 cases (17.9%) with ypT1aN0M0, 17 cases (21.8%) with ypT1bN0M0, and 29 cases (37.2%) with ypT2N0M0. Median follow-up time was 74.1 (19.8~132.5) months. Fourteen patients (17.9%) had tumor recurrence and metastasis, and 9 patients died from tumor recurrence and metastasis. The 5-year disease-free survival and overall survival rates were 84.4% and 87.8%, respectively. There was no statistically significant difference in 5-year overall survival (86.9% vs 87.8%) or 5-year disease-free survival (88.9% vs 83.2%) between patients with ypT0N0M0 and ypT1~2N0M0. Analysis of factors that may affect prognosis revealed that signet ring cell carcinoma, nerve invasion, and lymph node dissection of fewer than 16 were significantly associated with prognosis ( P＜0.05). Multivariate Cox analysis including these three factors showed that only lymph node dissection of fewer than 16 was an independent risk factor affecting prognosis (OS: HR=10.44 ,95% CI: 2.15-50.72, P=0.004; DFS: HR=11.47, 95% CI: 2.85-46.20, P=0.001). Conclusions:The long-term prognosis of patients with locally advanced gastric cancer at ypT0~2N0M0 stage after neoadjuvant chemotherapy is relatively good, and the long-term survival time of patients with ypT1~2N0M0 and ypT0N0M0 is similar. Lymph node dissection of less than 16 nodes may be an independent risk factor affecting prognosis. During surgery, efforts should be made to increase the number of lymph node dissections. For patients with less than 16 nodes dissected, postoperative treatment and follow-up should be strengthened.

Humans ; Stomach Neoplasms/pathology* ; Neoadjuvant Therapy ; Chemotherapy, Adjuvant ; Gastrectomy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

OBJECTIVE To reveal the role of the basal forebrain(BF)GABAergic neurons in the regulation of isoflurane anesthesia and to elucidate the underlying neural pathways.METHODS The activity of BF GABAer-gic neurons was monitored during isoflurane anesthesia using a genetically encoded calcium indicator in Vgat-Cre mice of both sexes.The activity of BF GABAer-gic neurons was manipulated by chemogenetic and opto-genetic approaches.Sensitivity,induction time and emer-gence time of isoflurane anesthesia were estimated by righting reflex.The electroencephalogram(EEG)power and burst-suppression were monitored by EEG recording.The effects of activation of GABAergic BF-thalamic reticu-lar nucleus(TRN)pathway on isoflurane anesthesia were investigated with optogenetics.RESULTS The activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia,obviously decreased during the induction of anesthesia and gradually restored during the emergence from anesthesia.Activation of BF GABAergic neurons with chemogenetics and optogenetics promoted behavioral emergence from isoflurane anesthesia,with decreased sensitivity to isoflurane,delayed induction and accelerated emergence from isoflurane anesthesia.Optogenetic activation of BF GABAergic neurons prom-oted cortical activity during isoflurane anesthesia,with decreased EEG delta power and burst suppression ratio during 0.8%and 1.4%isoflurane anesthesia,respectively.Similar to the effects of activating BF GABAergic cell bod-ies,photostimulation of BF GABAergic terminals in the TRN also strongly promoted cortical activation and behav-ioral emergence from isoflurane anesthesia.CONCLU-SION The GABAergic neurons in the BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthe-sia via the BF-TRN pathway.

Background The primary management for nasolacrimal duct obstruction is the combination of lacrimal duct probing with lacrimal duct stent implantation.However,conventional implant is undegradable.New degradable lacrimal duct prosthesis based on biopolymer materials is a research hotspot.Objective This study described herein a preparation method of novel degradable lacrimal duct prosthesis and its application.Methods A new degradable lacrimal tube stent was prepared with compound of poly L lactic acid (PLLA) and polycaprolactone (PCL) (6:4) and 15％ polyethylene glycol (PEG).Thirty-two Japanese rabbits aged 3-4 months were randomized into postoperative 1-week group,postoperative 4-week group,postoperative 8-week group and postoperative 16-week group.The degradable lacrimal tube stents were inserted into the lacrimal ducts of the left eyes of the rabbits.The prosthesis was removed in corresponding time points according to grouping,and the integrity and weight of the prosthesis were evaluated.The mucosal findings of the operative eyes were examined under the endoscope,and the histopathological and inflammatory reaction was observed by hematoxylin & eosin stain.The ultrastructure of the lacrimal mucosal surface was examined under the scanning electron microscope.The use and care of the rabbits complied with the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results The new degradable PLLA:PCL+15％ PEG lacrimal duct stents were smooth,flexible and hydrophilic tubes.The removed tubes were intact in the postoperative 1-week group,however,the rupture of the tubes appeared in the postoperative 4-week group,while discrete pieces of the tubes were seen in the postoperative 16-week group.The weight-loss rates of the tubes were (13.44±6.59)％,(23.96±6.33)％,(55.08-± 6.55) ％ and (78.00±8.74) ％ in the postoperative 1-week group,postoperative 4-week group,postoperative 8-week group and postoperative 16-week group,respectively,and the weight-loss rate of the tubes was significantly higher in the postoperative 16-week group than those in the postoperative 8-week group (q =4.27,P＜0.05).No significant difference was found in the weight-loss rate of the tubes between postoperative 1-week group and postoperative 4-week group (q =1.71,P＞0.05).The edema,hyperemia and mild proliferation of the lacrimal mucosal were exhibited in the eyes of the postoperative 4-and 8-week groups,and the mucosal findings were almost normal in the eyes of the postoperative 16-week group under the endoscope.Histopathological examination showed a large number of inflammatory cells in the postoperative 1-,4-and 8-week groups.However,few inflammatory cells were seen in the postoperative 16-week group.Mucosal folds,microvillus decrease and disorder were displayed in the lacrimal duct of the postoperative 8-week group,and no evident abnormality was seen in the lacrimal duct mucosal surface.No postoperative complication occurred in all the rabbits.Conclusions PLLA:PCL+15％ PEG lacrimal duct stent has an appropriate degradation speed and good biocompatibility after implant in rabbits,and its decay period of mechanical strength could match lacrimal duct healing period.

Objective Essential polyunsaturated fatty acids(PUFA) can not been synthesized by the body-self.Serum triglycerides n-6 and n-3 PUFAs directly or indirectly reflect the corresponding unsaturated fatty acids intake from meals.This study was to investigate the relationship of serum triglycerides polyunsaturated fatty acid composition with the ratio of n-6 to n-3 PUFA(n-6/n-3 PUFA) and magnetic resonance imaging measured intra-abdominal fat(MRI-IAF) with other body fat parameters of patients with metabolic syndrome.Methods Thirty-six patients with metabolic syndrome and 41 healthy controls were enrolled in this investigation.The relevance of serum triglycerides polyunsaturated fatty acids with MRI-IAF was observed.A stepwise regression analysis was applied to determine which kind of triglycerides polyunsaturated fatty acid could predict MRI-IAF,waist circumference and body mass index (BMI) more potent.Results In the metabolic syndrome group,blood sugar,lipid profiles,blood pressure,visceral fat accumulation-related parameters and serum triglycerides polyunsaturated fatty acid composition was worse than those in the control group.Compared with the healthy controls,n-6/n-3 PUFA was significantly increased(t=8.564,P＜0.05),although C18∶3 n-3,C20∶5 n-3(EPA),C22∶6 n-3(DHA) and n-3PUFA were significantly declined(t=-2.920,-7.034,all P＜0.05) in metabolic syndrome group.The difference of n-6 PUFA showed no statistically significant difference(t=-0.957,-1.494,P＞0.05).n-6/n-3 PUFA,n-3 PUFA,EPA and DHA were associated with MRI-IAF(r=-0.377,0.565,all P＜0.05); n-6/n-3 PUFA was correlated with the waist circumference(r=0.400,P=0.016) and BMI(r=0.357,P=0.033),while n6 PUFA showed no correlation with body fat parameters.N-6/n-3 PUFA was more potent to predict MRIIAF,waist circumference and BMI(adjusted R2=0.102,0.299,all P＜0.05) than other polyunsaturated fatty acids.Conclusions The ratio of n-6/n-3 PUFA and n-3 PUFA may be positively correlated with EPA and DHA could be inversely associated with MRI-IAF and other body fat-related parameters in patients with metabolic syndrome,while n-6 PUFA did not show such a relationship.The ratio of n-6/n-3 PUFA might be more potent to predict MRI-IAF and other body fat-related parameters.

Background Leber hereditary optic neuropathy (LHON) is mitochondrial DNA (mtDNA) disease and mainly leads to optical nerve degeneration.Its primary mechanism is synthesis disorder of DN4 protein due to variation of mtDNA 11778 locus.So to construct a vector with exogenous normal ND4 and transfect into mitochondria is a key of gene therapy for LHON.Objective This study was to investigate the in vitro transfection of adeno-associated virus (AAV)-ND4 gene into mitochondria.Methods Human renal epithelial cell lines transfected adenovirus E1A (293 cells) were regularly cultured and divided into two groups.Framework plasmids of recombinant AAV-ND4 or simple AAV2 were added to the cell medium respectively.The expression of ND4 in cells were located 12,24,36 and 48 hours after transfected by Y03 dual fluorescent quantum dots staining.The positive response for ND4 showed the green fluorescence.Results Cultured 293 cells grew well with 80％ confluence.Abundant green fluorescence particles were seen in cytoplasm in the AAV-ND4 transfected group,but only red fluorescence from mitochondrial protein was seen in the simple AAV transfected group under the fluorescence microscope.Conclusions Exogenous ND4 protein can been successfully transfected into mitochondria using the ND4 gene constructed AAV.This result provides experimental evidence for the further study on gene therapy of LHON.

Background Researchers are paying increasing attention to the effect of cellular senescence in vascular dysfunctional diseases,and it is hypothesized that cellular senescence may also be involved in the development of diabetes related vascular complications.The outstanding feature of cellular senescence is the upregulation of beta-galactosidase.Objective This study was to investigate the effects of high glucose on cell senescent in vitro and in vivo on bovine retinal endothelial cells (BRVECs) and mouse retina.Methods BRVECs were cultured and passaged,and the seventh generation of cells were employed in this study.The cells were divided into the control group and the high glucose culture group and cultivated using M199 medium containing 5.5 mmol/L or 25.0 mmol/L glucose,respectively.5-bromine-chlorine-4-3-indole-beta D galactose glucoside (X-Gal) staining was used to examine the expression of beta-galactosidase in the cells.Diabetic models were established in the SPF male C57BL/6J mice aged 8-10 weeks by intraperitoneal injection of streptozotocin (STZ),and the age-and gendermatched normal mice served as controls.The mouse retinas were collected and starched in the 48-well plates 3 months later.X-Gal staining was employed to calculate the positive cells.Results BRVECs grew well 24 hours after culture but showed irregular arrangement.Forty-eight hours later,the cells reached confluence with a tight connect.The ratios of positive BRVECs and total cells were (51.4±5.4) ％ and (36.6-±3.8) ％ in the high glucose culture group and the control group,with a significant difference between the two groups (t =-3.204,P =0.033).The number of positive cells for X-Gal in mouse retinas was (94.0± 15.1) /field in the diabetic group,which was higher than that in the control group ([60.0 ± 5.7]/field) (t =-2.974,P =0.041).Conclusions High glucose environment accelerates senescence of retinal cells,and high glucose induces premature cell senescence,which likely plays an important role in the pathogenesis of diabetic retinopathy.

Mobile learning has the characteristics of mobility,timeliness,network and virtu-ality. We developed virtual hospital suitable for mobile devices and organized students in to a network. Through early training,clinical case screen,learning objective fix,learning process and results evaluation,mobile devices were employed to do problem-based learning,which is conducive to the integration of theory with practice,the shifting from discipline-centered to system-based courses and the improving of utilization rate of learning resource.

Objective To study the regulation effect of estrogen in expression of matrix metalloproteinase-9 (MMP-9) in the central nervous system (CNS) in mice with experimental autoimmune encephalomyelitis ( EAE).Methods The 60 mice were overiectomized and 2 weeks later EAE was induced with MOG35-55 peptide in these mice.They were divided into a treatment group and a control group.The treatment group was treated with estrogen and the control group was given PBS.Clinical symptoms in these two groups were scored and compared.HE staining was used to observe inflammation in the brain and spinal cord.The MMP-9 expression in the CNS was examined by quantitative real-time PCR and immunofluorescence staining.Results The incidence of disease was lower (treatment and control group were 8/30 and 28/30 respectively) and clinical symptoms were milder (treatment and control group were 3.23±0.83 and 1.62 ±1.00 respectively,t=3.811 and P＜0.05) in the treatment group than those in the control group.HE staining showed the decreased infiltration of inflammatory cell in the treatment group (Treatment group:inflammatory score were 0.895 ±0.206,0.752 ±0.302,0.732 ±0.183 in acute,relief and chronic phase respectively;Control group:inflammatory score were 3.472 ±0.635,2.881 ±0.662,1.891 ± 0.482 in acute,relief and chronic phase respectively.t = 8.622,6.543 and 5.027,all P ＜ 0.05).The quantitative real-time PCR and immunofluorescence staining showed that the expression of MMP9 in the CNS was decreased in the treatment group.Conclusion Estrogen may decrease MMP-9 expression in the CNS,reduce inflammation and clinical symptoms in mice with EAE.