The glymphatic system plays a pivotal role in maintaining cerebral homeostasis. Chronic cerebral hypoperfusion, arising from small vessel disease or carotid stenosis, results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction. However, whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown. Here, we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis. We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glymphatic system function. The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization. Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function. Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury. Our research yields new insight into the relationship between hemodynamics, glymphatic transport, white matter injury, and cognitive changes after chronic cerebral hypoperfusion.
Animals ; Brain Ischemia ; Carotid Stenosis/drug therapy* ; Cognitive Dysfunction/etiology* ; Digoxin ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; White Matter

Objective To investigate the clinical treatment and outcomes of severe community-acquired pneumonia (CAP) complicated with mediastinal emphysema after renal transplantation. Methods Clinical data of9 patients with severe CAP complicated with mediastinal emphysema after renal transplantation were retrospectively analyzed. The acute physiology and chronic health evaluationⅡ(APACHEⅡ) and oxygenation index were recorded when the patients were admitted to the intensive care unit (ICU). The complications of mediastinal emphysema and corresponding treatment were observed. The treatment course during the ICU, mortality rate in ICU, ICU stay time and hospital stay time were recorded. All patients underwent pathogenic examinations. Results The APACHEⅡ score of9 patients with severe CAP complicated with mediastinal emphysema after renal transplantation was 14 (8-21) scores and the oxygenation index was 150 (133-189) mmHg. Among 9 patients, 3 cases were infected by bacteria alone, 3 cases were infected by bacterial infection combined with viral infection, 1 case was infected by mycobacterium tuberculosis complicated with other bacterial infection and 1 case was viral infection. No pathogenic evidence was detected in the remaining 1 patient. Mediastinal emphysema complicated with subcutaneous emphysema occurred in 7 cases and pneumothorax occurred in 6 cases. Treatment methods included anti-infection, modified immunosuppressive program, mediastinal drainage, thoracic closed drainage, subcutaneous incision and extracorporeal membrane oxygenation (ECMO) treatment. Six patients received invasive mechanical ventilation (IMV), 2 received non-invasive positive pressure ventilation (NIV) and 1 received high-flow nasal oxygen cannula (HFNC). Among 9 patients, the mortality rate in ICU was 6/9, the remaining 3 patients were recovered and discharged, the ICU stay time was 26 (17-40) d, and the total hospital stay time was 27-61 d. Conclusions Mediastinal emphysema is a serious complication of patients presenting with severe CAP after renal transplantation with a high mortality rate. For these patients, imaging evaluation, timely drainage and full sedation should be strengthened, and ECMO treatment should be delivered when necessary.

Objective To investigate the genetic diversity of MICA, and to analyze the correlation between genetic polymorphisms of MICA and T1DM in population of Han and Li nationalities in Hainan province.Methods This study was performed as a case-control study.Fifty-five individuals with T1DM and Fifty-five healthy controls of Han and Li nationalities from Wuzhishan, Lingshui, Qiongzhong, Baisha, Ledong,Changjiang, Dongfang and Haikou regions in Hainan province(35 Male,20 Female of T1DM of Han;28 Male,27 Female of healthy controls of Han; 33 Male,22 Female of T1DM of Li; 28 Male, 27 Female of healthy controls of Li), were enrolled for the study.MICA allelic variation was analyzed by sequencing-based typing(PCR-SBT).Fisher′s exact test was performed to determine the statistical significance of the distribution and allele frequency of MICA.Results In healthy population,11 MICA-sequence and 5 MICA-STR alleles were found in Han nationality, while 13 MICA-sequence and 5 MICA-STR alleles were detected in Li nationality.The MICA-sequence allele MICA*008:01 and the MICA-STR allele MICA-A5 were most frequently observed in Han nationality[30.85%(29/94)and 41.49%(39/94), respectively],while MICA*002:01 and A4 were the most common in Li nationality[21.57%(22/102) and 36%(36/100), respectively].Among patients with T1DM, 10 MICA-sequence and 5 MICA-STR alleles were detected in Han, and 9 MICA-sequence and 5 MICA-STR alleles were found in Li.MICA*002:01 and A9 were most frequently observed in Han[29%(29/100),29.29%(29/99),respectively], while MICA*012:01, MICA*002:01 and the A4 were the most common in Li[21.15%(22/104), 21.15%(22/104),38.24%(39/102), respectively].The allelic frequency of MICA*002:01, MICA*010, MICA-A5, MICA-A6 and MICA-A9 between the healthy population and T 1DM patients of Han nationality(5.32%,22.34%,41.49 %,9.58%,6.38%, respectively in healthy population;29%,7%, 26.26%,2.02%,29.29%, respectively in T1DM patients), exist significant difference(χ2value were 18.799,9.233,5.218,5.197,16.762, respectively.P value were 0.000,0.002, 0.025,0.024,0.000, respectively.all P<0.05),while no significant difference(all P>0.05)between the healthy population and T1DM patients of Li nationality.Conclusions The most common MICA alleles were MICA*008:01 and MICA-A5 in healthy population of Han nationality, while MICA*002:01 and MICA-A4 in healthy population of Li nationality.MICA*002:01 and MICA-A9 were high frequency in T1DM patients of Han population,while the MICA*010,MICA-A5 and MICA-A6 were low frequency.There was not any MICA alleles associated with T1DM in Li nationality.

Objective It has been confirmed that Epstein-Barr virus ( EBV) is associated with the occurrence and development of the nasopharyngeal carcinoma ( NPC ) . We investigated the clinical significance of plasma concentrations of EBV-DNA in patients with NPC. Methods Since October,2013 to December,2016,471 patients were analyzed. The significantly associated between EBV-DNA before treatment and staging, tumor burden was analyzed. The survival rate of EBV-DNA before and after treatment was calculated. Results The median copies of pretreatment plasma EBV-DNA in patients is 137 copies,( range 0-494000) ,which is correlated with T stage,N stage,M stage,clinical stage and tumor burden load and that is statistically significant. Overall survival ( OS,P=0. 007) ,progression-free survival ( PFS,P=0. 011) and distant metastasis-free survival ( DMFS,P=0. 003) were significantly lower among patients with pretreatment plasma EBV-DNA more than 1300 copies/ml. Patients with detectable plasma EBV-DNA had significantly worse OS (P=0. 016),PFS (P=0. 000) and DMFS (P=0. 000) than patients with undetectable EBV-DNA after treatment. Cox multivariate analyze suggests that T stage and EBV-DNA after treatment were independent prognostic factors for OS,however the plasma EBV-DNA after treatment ( P=0. 006,0. 001) and N stage ( P=0. 037,0. 017) were independent prognostic factors for PFS and DMFS. Conclusions The plasma EBV-DNA level was significantly correlated with staging and tumor load before treatment in patients with NPC,and the prognosis of patients with higher copies before treatment could be worse. The plasma EBV-DNA after treatment is predictive for OS,PFS and DMFS.

Objective To compare the effects of propofol combined with fentanyl or dezocine on painless abortion and the influence on body movement.Methods From July 2016 to May 2017,240 patients with voluntary painless abortion who aged 19-45 years old in the Second People's Hospital of Linhai,were randomly divided into 3 groups according to the digital table ,with 80 cases in each group.D group was given propofol and dezocine ;F group was given propofol combined with fentanyl ;C group was the control group and was treated with propofol intravenous anesthesia,the three groups were given propofol added according to the specific situation.The operative time,recovery time and the total amount of propofol were compared among the three groups ;and the pain visual analogue scale (VAS) at 0min,15min,30min,1h,3h were comparedamong the three groups ;The incidence of respiratory depression and other adverse reactions were statistically analyzed in three groups.Results The operation time,recovery time,the total dosage of propofol in D group were (4.5 ±0.7)min,(1.2 ±0.3)min and (136.8 ±14.5)mg,respectively, which in F group were (4.6 ±0.8)min,(1.3 ±0.2)min and (139.6 ±12.1)mg,respectively,there were no statisti-cally significant differences between the two groups (all P＞0.05).The recovery time and total dosage of propofol in D group and F group were lower than those of C group [(2.4 ±0.6) min,(168.7 ±18.9) mg](t＝25.298,27.287, 11.977,27.287,all P＜0.05).The VAS scores at postoperative 0min,15min,30min,1h,3h in D group were lower than those in F group and group (t＝34.785,25.044,25.043,22.349,28.622,48.809,42.278,40.000,42.278, 40.000,all P＜0.05).The VAS scores at postoperative 0min,15min,30min,1h in F group were lower than those of C group(t＝36.978,24.406,19.846,24.406,all P ＜0.05).The incidence rates of nausea,sedentary,respiratory depression,hypotension in D group were 1.3%(1case),2.5%(2cases),1.3%(1case),0.0%(0cases), resperctively,which in F group were 0.0%(0cases),3.8%(3cases),3.8%(3cases),2.5%(2cases),which in D group,F group were lower than those in C group [6.3%(5cases),16.3%(13cases),11.3%(9cases),15.0%(12cases)](χ2＝3.925,3.657,3.925,3.657,5.889,3.152,3.152,3.657,all P＜0.05).Conclusion Propofol combined with dezocine and fentanyl used in painless abortion have good effect ,and the body movement is less ,but propofol combined with dezocine has less postoperative pain degree.

Objective To investigate the safety and feasibility of intraluminal brachytherapy using iodine-125 seed strand for locally advanced pancreatic ductal adenocarcinoma with obstructive jaundice.Methods Clinical data of 17 consecutive patients,from January 2010 to February 2015,diagnosed with pancreatic ductal adenocarcinoma (4 cases of T4 N0 M0 and 13 of T4 N1M0) with obstructive jaundice and received intraluminal brachytherapy using iodine-125 seed strand were collected and analyzed retrospectively.Liver function was evaluated using paired-samples t test.The iodine-125 seed strand radiation doses were calculated using iodine-125 radiation field distribution calculation software (version 0.1,Institute of Radiation Medicine,Fudan University,Shanghai,China) based on the American Association of Physicists in Medicine TG43U1 brachytherapy formula.Obstruction free survival and overall survival were calculated using the Kaplan-Meier method.Complications were assessed according to the CTCAE 4.0 criteria.Results The estimated mean accumulating dose (r =5 mm,240 days) was 167.2Gy,from 164.19Gy to 170.05Gy.The mean and median obstruction free survival time were (9.62 ± 1.47) months (95％CI:6.73-12.50) and (7.26 ± 1.71) months (95 ％CI:3.90-10.62).The mean and median overall survival time were (9.89 ± 1.59) months (95％CI:6.78-13.00) and (7.26 ± 1.71) months (95 ％ CI:3.90-10.62),retrospectively.Total bilirubin and conjugated bilirubin decreased significantly after the therapy.Two patients had adverse event of Grade 3,one of Grade 4.Stent dysfunction occurred in 1/17 (5.9 ％) patients.Conclusions Intraluminal brachytherapy using iodine-125 seed strand might be considered as a safe treatment option for the locally advanced pancreatic duct adenocarcinoma complicated by obstructive jaundice.

Objective To evaluate the safety and efficacy of brachytherapy with 125I seed strand in treating implanted main portal vein tumor thrombus (MPVTT) in experimental rabbits.Methods VX2 tumor cell line was implanted in the main portal vein (MPV) of 32 New Zealand white rabbits to establish MPVTT models.The rabbits were randomly divided into the treatment group (group T,n=16) and the control group (group C,n=16).125I seed strand was implanted in the MPVTT of the rabbits of group T,while blank seed strand was implanted in the MPVTT of the rabbits of group C.After the implantation,the changes in general condition,body weight and laboratory testing results were recorded.Two weeks after the treatment,every 8 rabbits from each group were sacrificed,and the specimens were collected and sent for pathological examination.The remaining rabbits were fed till they died,and then autopsy was conducted.Multi-slice spiral CT manifestations,histopathological findings,Ki-67 labeling index and apoptosis index were used to assess the curative effect,and the results were compared between the two groups.Results At each observation time point after brachytherapy,the weight loss of the experimental rabbits was more obvious in group C than in group T.No statistically significant differences in liver functions and white blood cell count existed between the two groups (P＞0.05).The mean MPVTT volume of group T and group C were (565.40±220.90) mm3 and (2 269.90±437.00) mm3 respectively (P＜0.001);the Ki-67 labeling indexes were (4.14±1.84)％ and (33.82± 6.07)％ respectively (P=0.001);the median survival days were (39.50±2.37) d and (27.38±1.22) d respectively (P=0.001).Conclusion For the treatment of implanted MPVTT in experimental rabbits,brachytherapy with 125I seed strand is safe and effective.

Objective To evaluate the prognostic value of blood lactate (Lac) level in sepsis patients with or without diabetes.Methods 106 patients admitted to intensive care unit (ICU) of Zhongshan Hospital Affiliated to Fudan University from April 2015 to November 2016 were enrolled. The patients with age > 18 years and the length of hospital stay > 24 hours were included. Records including blood Lac, serum creatinine (SCr), white blood cell count (WBC), platelet count (PLT), sequential organ failure assessment (SOFA) on the first day of admission; minimum oxygen index (PaO2/FiO2) in 3 days after admission; mechanical ventilation, whether there was a history of diabetes, usage of biguanides, etiology control treatment, usage of continuous renal replacement therapy (CRRT) were collected. According to the level of blood Lac patients were divided into high Lac group (Lac > 2 mmol/L) and low Lac group (Lac ≤ 2 mmol/L);based on their diabetic history, sepsis patients were divided into the diabetes group and non-diabetes group. The survival curve of each group was analyzed by Kaplan-Meier regression analysis, and the factors influencing the prognosis were analyzed by multivariate Cox regression analysis.Results There were 76 males and 30 females sepsis patients, with an average age of (68.1±14.7) years old. In the 51 patients of low Lac group, there were 7 patients who suffered from diabetes. While in the 55 patients of high Lac group, there were 12 patients who suffered from diabetes. Compared with low Lac group, high Lac group had a higher age, higher SOFA score, and a lower proportion of patients who had the treatment of etiology control (allP < 0.05). There was no significant difference of blood Lac in sepsis patients with diabetes and those without diabetes (mmol/L: 3.03±2.73 vs. 2.81±2.40,P > 0.05). Kaplan-Meier survival curve analysis showed that the 90-day survival rate in the high Lac group was significantly lower than that in the low Lac group (56.36% vs. 90.20%,χ2 = 0.697,P = 0.008). The high Lac group without diabetes had lower survival rate, and the 90-day survival rate was significantly lower than that of the low Lac group without diabetes (58.14% vs. 90.90%,χ2 = 7.152,P = 0.007); there was no significant difference in 90-day survival rate between the high Lac group and the low Lac group with diabetes (50.00% vs. 85.71%,χ2 = 0.012,P = 0.914). Multivariate Cox regression analysis showed that blood Lac was an independent risk factor for the prognosis of sepsis patients [odds ratio (OR) = 3.863, 95% confidence interval (95%CI) = 1.237-12.060,P = 0.020]. After stratification according to their diabetic history, the blood Lac was an independent risk factor for the prognosis of sepsis patients without diabetes (OR = 4.816, 95%CI = 1.407-15.824, P = 0.010), but the blood Lac had no effect on the prognosis of sepsis patients with diabetes (OR = 0.000, 95%CI =0.000-1.103,P = 0.270).Conclusions The predictive value of blood Lac on sepsis patients with or without diabetes was different. The blood Lac was related with the prognosis of sepsis patients without diabetes, while further study should be conducted for the prognostic value of blood Lac in sepsis patients with diabetes, and it's possible to increase the cut-off-point of Lac level in these patients.

Objective:To investigate the influence of admission to intensive care unit (ICU ) on the postoperative complications in patients with esophageal carcinoma .Methods :A total of 391 patients with esophageal carcinoma confirmed by surgery in Department of Thoracic Surgery ,Zhongshan Hospital ,Fudan University ,from Jan 2009 to Dec 2009 ,were chosen .All the patients had clinical data and postoperative follow‐up data in detail . Patients were divided into postoperative ICU group (treatment group) and postoperative general ward group(control group) .The control group was further classified into control group A(without unplanned ICU admission) and control group B(with unplanned ICU admission) based on whether unplanned admission to ICU was conducted .The occurrence rates of postoperative complications were compared among the three groups . Logistic regression was performed in multivariate analysis of postoperative complications .Results:On Day 1 after surgery ,the APACHE Ⅱ score was higher in treatment group than in control group I(P<0 .05) .However ,there was no increase on rate of postoperative complications in treatment group .The APACHE Ⅱ score ,as well as the occurrence rate of postoperative complications ,was lower in control group A than those in control group B (P<0 .01) .The APACHE Ⅱ score in treatment group was higher than that in control group B (P< 0 .05) .However ,the occurrence rate of postoperative complications in treatment group was lower than that in control group B (P<0 .01) .On Day 1 after surgery ,the higher the postoperative acute physiology and chronic health evaluation(APACHE)Ⅱ score was ,the higher the occurrence rate of postoperative complications was(HR= 0 .631 ,95% CI:0 .405~ 0 .983 ,P< 0 .05) .Postoperative planned ICU admission could diminish postoperative complications ,and it was the independent factor(HR= 1 .588 ,95% CI:1 .147‐2 .199 ,P< 0 .01).Conclusions :If prompt admission to ICU for comprehensive treatment was conducted after esophageal cancer operation , the occurrence rate of complications could be reduced in esophageal cancer patients .

OBJECTIVETo determine the optimal dose range (therapeutic window) of mycophenolate mofetil (MMF) for preventing acute graft rejection following renal transplantation.

METHODSThe trough concentration of MMF (MPA-C0) at 12 h after oral administration of the drug (two doses daily given at an interval of 12 h) was monitored in 110 renal transplant recipients within a month, in 2-3 months, and over 4 months after the transplantation using EMIT method. The occurrence of acute graft rejection and drug toxicity were observed in all the patients during the one-year follow-up.

RESULTSs The incidence of acute graft rejection after transplantation was 13.64% (15/110) in these patients. Drug toxicity and complications occurred in 32.73% (36/110) of the patients, including 12 cases with reduced white blood cell counts, 10 with MMF cid-associated diarrhea, 10 with infection, 4 with liver function damage. Acute rejection was successfully reversed after methylprednisolone treatment and drug toxicity was managed by corresponding treatment and adjustment of MMF dose. No deaths or graft removal occurred in these patients. The ROC curve showed that a MPA-C0 of 1.40-2.80 mg/L was optimal in preventing acute rejection after the transplantation and reducing adverse drug effects.

CONCLUSIONMonitoring MPA-C0 and individualized MMF dosing help to prevent acute graft rejection, reducing drug toxicity and complications, and improving graft survival rate after renal transplantation.

Graft Rejection ; drug therapy ; prevention & control ; Graft Survival ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Kidney Transplantation ; Methylprednisolone ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; therapeutic use ; Survival Rate ; Time Factors