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OBJECTIVE@#To explore the regulatory mechanism of human hepatocyte apoptosis induced by lysosomal membrane protein Sidt2 knockout.@*METHODS@#The Sidt2 knockout (Sidt2-/-) cell model was constructed in human hepatocyte HL7702 cells using Crispr-Cas9 technology.The protein levels of Sidt2 and key autophagy proteins LC3-II/I and P62 in the cell model were detected using Western blotting, and the formation of autophagosomes was observed with MDC staining.EdU incorporation assay and flow cytometry were performed to observe the effect of Sidt2 knockout on cell proliferation and apoptosis.The effect of chloroquine at the saturating concentration on autophagic flux, proliferation and apoptosis of Sidt2 knockout cells were observed.@*RESULTS@#Sidt2-/- HL7702 cells were successfully constructed.Sidt2 knockout significantly inhibited the proliferation and increased apoptosis of the cells, causing also increased protein expressions of LC3-II/I and P62(P < 0.05) and increased number of autophagosomes.Autophagy of the cells reached a saturated state following treatment with 50 μmol/L chloroquine, and at this concentration, chloroquine significantly increased the expressions of LC3B and P62 in Sidt2-/- HL7702 cells.@*CONCLUSION@#Sidt2 gene knockout causes dysregulation of the autophagy pathway and induces apoptosis of HL7702 cells, and the latter effect is not mediated by inhibiting the autophagy-lysosomal pathway.
Subject(s)
Humans , Lysosome-Associated Membrane Glycoproteins/metabolism , Autophagy , Apoptosis , Hepatocytes , Lysosomes/metabolism , Chloroquine/pharmacology , Nucleotide Transport Proteins/metabolismABSTRACT
Objective To investigate the significance of The Maryland Aggregate Pathology Index in the evaluation of donation after citizens death (DCD) kidney by time-zero renal biopsy.Methods 124 kidney grafts were donated by 62 donors after cardiac death in First Hospital of Jilin University between Jan.2015 and Dec.2015.One kidney was deprecated after evaluation and 123 transplants were performed eventually.Time-zero renal biopsy was performed on 123 cases of DCD donor kidney,and rapid frozen pathological examination was performed.The pathological results of donor kidneys were graded by The Maryland Aggregate Pathology Index:low risk group (less than 7 points) (n =112 cases);the middle risk group (8-11 points) (n =11 cases),high the risk group (more than 12 points) (n =0).The incidence of delayed graft function (DGF),the incidence of perioperative acute rejection (AR),and the average creatinine level in the patients at different time points one year post-transplantation were observed.The median value of follow-up was 19 months,and the 1-year survival rate of patients and renal grafts was observed.Results All 123 cases of kidney transplantation from DCD were performed successfully.The incidence of DGF in low risk group and in middle risk group was 6.3％ (7/112) and 27.3％ (3/11),respectively (P =0.046).The incidence of perioperative acute rejection (AR) in low risk group and middle risk group was 9.8％ (11/112) and 27.3％ (3/11),respectively (P =0.112).The mean serum creatinine (Scr) levels at 7th day,1st month,3rd month,and 12th month after operation were 123.3 ± 79.7,104.4 ± 52.6,72.9 ± 32.0 and 107.6 ± 34.6 μmol/L in low risk group,and 321.0 ± 74.3,172.6 ± 59.9,142.9 ± 45.7 and 140.8 ± 63.6 μmol/L in middle risk group,respectively.The mean Scr levels in patients at different time points one year post-transplantation in low risk group were significantly lower than those in middle risk group (P＜0.000 1,=0.000 3,＜0.000 1,=0.012 respectively).The 1-year survival rate of patients and renal grafts was 98.2％ (10/112)/98.2 (110/112 in low risk group,and 81.8％ (9/11)/81.8％ (9/11) in middle risk group,respectively (P =0.040).Conclusion The Maryland aggregate pathology index obtained from time-zero renal biopsy of rapid frozen pathological examination can provide some guidance for the evaluation of the quality of DCD and the prognosis.Incidence of DGF was lower in low risk group than that in middle risk group,and the renal function of each time point was better within 1 year,and the 1-year survival rate of patients and renal grafts was higher.
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Objective To investigate the clinical value of preoperative nutritional support (PNS) therapy in the hepatectomy of patients with nutritional risk.Methods The prospective study was conducted.The clinical data of 133 patients with nutritional risk who were admitted to the Drum Tower Hospital Affiliated to Nanjing University Medical School from August 2012 to June 2016 were collected.All the patients undergoing PNS and traditional therapy were divided into the PNS group and the control group by random number table method,respectively.Observation indicators:(1) comparisons of laboratory indexes between groups;(2) comparisons of postoperative situations between groups;(3) comparisons of postoperative complications between groups.Measurement data with normal distribution were represented as-x±s.Comparisons between groups were evaluated with the independent-sample t test.Comparisons of count data were analyzed using the chi-square test,and repeated measures data were analyzed by the repeated measures ANOVA.Results All the 133 patients were screened for eligibility,including 68 in the PNS group and 65 in the control group.(1) Comparisons of laboratory indexes between groups:alanine transaminase (ALT),aspartate transaminase (AST),total bilirubin (TBil),cholinesterase,albumin (Alb),prealbumin,transferrin and C-reactive protein (CRP) in the PNS group were respectively (36± 13) U/L,(29± 10) U/L,(18.5±2.4) mmol/L,(5 738± 1 824) U/L,(37.4±5.1) g/L,(155±48) mg/L,(2.2±0.5)g/L,(10±4) g/L at admission and (33 ± 9) U/L,(27 ± 8) U/L,(17.9± 1.8) mmol/L,(5 796± 2 016) U/L,(38.5 ± 4.7) g/L,(181 ± 40) mg/L,(2.4± 0.5) g/L,(8± 4) g/L before operation and (285±100)U/L,(218±93)U/L,(33.5±6.3)mmol/L,(4 847±1 044)U/L,(32.6±3.8)g/L,(105±34)mg/L,(1.3±0.4) g/L,(55±28) g/L at 1 day postoperatively and (149±84) U/L,(76±42) U/L,(22.7±4.9) mmol/L,(3 866±893) U/L,(34.2±2.4) g/L,(125±30) mg/L,(1.6±0.4) g/L,(51±34) g/L at 3 days postoperatively and (64±33) U/L,(44±18) U/L,(19.4±2.8) mmol/L,(4 257± 1 032) U/L,(37.0±2.1) g/L,(148±42) mg/L,(1.9±0.4)g/L,(16±11)g/L at 7 days postoperatively;ALT,AST,TBil,cholinesterase,Alb,prealbumin,transferrin and CRP in the control group were respectively (36± 15)U/L,(31± 12)U/L,(18.3±2.9)mmol/L,(5 762±1 693)U/L,(37.3±6.1)g/L,(162±51)mg/L,(2.3±0.5)g/L,(10±4)g/L at admission and (36±11)U/L,(30±11)U/L,(18.2±2.8)mmol/L,(5 789±1 673)U/L,(37.8±7.1)g/L,(166±57) mg/L,(2.3±0.6) g/L,(9±5) g/L before operation and (305±127) U/L,(246± 104) U/L,(34.2±7.8) mmol/L,(4 842±1 173)U/L,(32.0±4.1) g/L,(83±32) mg/L,(1.2±0.4) g/L,(61 ±31) g/L at 1 day postoperatively and (163±104)U/L,(82±62)U/L,(23.1±6.0)mmol/L,(3 672±937) U/L,(33.8±3.6) g/L,(106±30)mg/L,(1.4±0.4)g/L,(61±40)g/L at 3 days postoperatively and (77±48) U/L,(52±27) U/L,(20.2±3.5) mmol/L,(3 925±987) U/L,(36.6±2.8) g/L,(125±40) mg/L,(1.7±0.4) g/L,(22± 12) g/L at 7 days postoperatively,showing no statistically significant difference in changing trends of above indicators between groups (F =1.007,2.223,0.579,0.014,0.235,3.533,2.970,2.143,P＞0.05).Results of further analysis showed that there were statistically significant differences in the levels of ALT,AST and cholinesterase at 7 days postoperatively between groups (t=1.832,2.073,1.899,P＜0.05),and in the levels of prealbumin before operation and at 1,3 and 7 days postoperatively between groups (t =1.698,3.738,3.625,3.178,P＜0.05) and in the levels of transferrin and CRP at 3 and 7 days postoperatively between groups (t=2.917,2.709,1.667,2.990,P＜0.05).(2) Comparisons of postoperative situations between groups:time to initial exsufflation,time of initial defecation,infused volume of exogenous albumin and duration of postoperative hospital stay were respectively (46± 15)hours,(64±16)hours,(23±10)g,(9.2±2.6)days in the PNS group and (55±18)hours,(78±21)hours,(39±25)g,(11.7±5.3) days,with statistically significant differences in the above indicators between groups (t =2.830,4.157,5.044,3.497,P＜0.05).(3) Comparisons of postoperative complications between groups:23 and 33 patients in the PNS and control groups had postoperative complications,showing a statistically significant difference between groups (x2=3.915,P＜0.05).Eight and 17 patients in the PNS and control groups were respectively complicated with peritoneal effusion,with a statistically significant difference between groups (x2 =4.508,P＜ 0.05).Conclusion PNS therapy in the hepatectomy of patients with nutrition risk can effectively improve pre-and post-operative nutrition statuses,reduce liver damage,accelerate recoveries of liver and gastrointestinal functions,reduce complications,shorten duration of postoperative hospital stay and accelerate patients' recovery.
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Objective To evaluate the efficacy and safety of epalrestat, an aldose reductase inhibitor, and epalrestat plus methylcobalamine on diabetic peripheral neuropathy, as compared with methylcobalamine. Methods A total of 444 subjects with diabetic neuropathy were enrolled in the study, and divided into methylcobalamine group ( n= 145 ) , epalrestat group ( n = 143 ) , and methylcobalamine combined with epalrestat group ( n = 156 ) . Therapeutic efficacay was assessed in terms of clinical symptoms and physical examinations by using Michigan Neuropathy Screening Instrument ( MNSI ) , and electrophysiological assessments. Results After 4 to 12-weeks′treatment, symptoms and signs of neuropathy ( using MNSI ) are significantly improved in the three groups ( P0. 05). Conclusion Epalrestat is effective and safe in the treatment of diabetic neuropathy. Furthermore, epalrestat is more efficacious in ameliorating symptoms and MNCV of neuropathy than methylcobalamine. However, while no improved efficacy is shown with the combined treatment.
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Objective To explore the effects of penile erectile dysfunction (ED) on the quality of life in male renal transplant recipients.Methods 150 cases of male married recipients undergoing renal transplantation were selected randomly.The recipients were divided into ED group (n =63) and non-ED group (n =87) through the IIEF-5 score.The Short Form-36 Health Status Survey (SF-36)and Hamilton Anxiety Scale were used to compare their living quality and the state of mental health between the two groups,respectively.Results The SF-36 scores in ED group in General Health,Vitality,Social Function,Role Limitation due to Emotional Problems,Mental Health were significantly lower than those in non-ED group (P＜0.05).There were 13 cases in ED group with anxiety disorders (20.6％),significantly more than in non-ED group (3.4％),P＜0.05.Conclusion ED is an important influencing factor for the quality of life in male kidney transplant recipients.
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Objective To investigate the safety and clinical effect of renal hilum controlling during right retroperitoneal laparoscopic living donor nephrectomy (RPLDN).Methods From January 2009 to May 2012,62 cases of right RPLDN were performed in our department.The clinical data,including the general status of donors,operative time,blood loss,donor kidney warm ischemic time,hospital stays and complications,were analyzed retrospectively.Results Right RPLDN was performed successfully on all 62 cases without conversion to open procedure and apparent complications.The function of all the kidney grafts recovered well.Mean operative time was 73.5 ± 10.4 min,mean blood loss was 30.7 ± 10.4 ml,mean warm ischemic time was 107.2 ± 24.8 s,mean artery and vein lengths were 3.3 ± 0.5 cm and 2.0 ± 0.4 cm,vena cava incision suture time was 2.0 ± 0.5 min and mean hospital stay was 5.2 ± 1.6 days,respectively.Conclusion Right donor kidney with small part of vena cava can be harvested by using retroperitoneal laparoscopy plus open passage way.This technique of renal hilum controlling in RPLDN has good clinical effect and more advantages,including ensuring the safety of donors and kidney grafts,promoting the operation done smoothly,reducing the pain and financial burden of donors.