Objective To evaluate the effect of small-dose ketamine on the onset time and course of modified electroconvulsive therapy (MECT) in mentally depressed rats.Methods Sixty SPF adult male SpragueDawley rats,aged 2-3 months,weighing 220-250 g,were randomly divided into 6 groups (n =10 each) using a random number table:normal control group (group C),depression group (group D),ECT group,propofol + ECT group (group PE),ketamine + ECT group (group KE) and ketamine + propofol + ECT group (group KPE).The depression model was established by chronic unpredictable mild stress (CUMS).Mter CUMS,C,D and ECT groups received intraperitoneal normal saline 8 ml/kg,group PE received intraperitoneal propofol 100 ml/kg,group KE received intraperitoneal ketamine 10 ml/kg,and group KPE received intraperitoneal ketamine 10 ml/kg + propofol 80 ml/kg.All the groups received ECT once a day for 7 consecutive days starting from the time point when righting reflex was lost except C and D groups.Open-field test was performed before CUMS,at 1 day after CUMS and at the end of each ECT (T0 8).The total distance and the number of standing on the back legs were recorded.Morris water maze test was performed at 2 days after CUMS and 1 day after the end of therapy,and the escape latency and time of staying at the original platform quadrant were recorded.Results Compared with group C,the total distance was shortened and the number of standing on the back legs was reduced,the escape latency was prolonged,and the time of staying at the original platform quadrant was shortened at T1-8 in D,ECT,PE and KE groups and at T1 5 in KPE group,and no significant was found in KPE group in the total distance,number of standing on the back legs,escape latency,and time of staying at the original platform quadrant at T6-8.Compared with group D,the total distance was prolonged and the number of standing on the back legs was increased at T6-8 in ECT and PE groups and at T4-8 in KE and KPE groups,the escape latency was prolonged,and the time of staying at the original platform quadrant was shortened in ECT group,and the escape latency was shortened,and the time of staying at the original platform quadrant was prolonged in KPE group.Compared with ECT and PE groups,the total distance was prolonged and the number of standing on the back legs was increased at T4-7 in group KE and at T4-8 in group KPE,and the escape latency was shortened,and the time of staying at the original platform quadrant was prolonged in KPE group.Compared with group KE,the total distance was prolonged and the number of standing on the back legs was increased at T6.7,the escape latency was shortened,and the time of staying at the original platform quadrant was prolonged in KPE group.Conclusion Small-dose ketamine can shorten the onset time and course of MECT in mentally depressed rats.

Objective:To discuss the type, treatment and results of different therapies of biliary fistula after orthotopic liver tansplantation(OLT).Methods:Data of 24 patients who developed biliary fistula after OLT in the First Affiliated Hospital of Xi′an Jiaotong University from January 2000 to March 2019 were retrospectively analyzed. Patients with biliary fistula were classified into 4 types according to presence or absence of stricture. All patients were treated by endoscopic retrograde cholangiopancreatography (ERCP) or interventional therapy, including endoscopic nasobiliary drainage (ENBD), endoscopic retrograde biliary drainage (ERBD) or percuteneous transhepatic cholangial drainage (PTCD). Main outcome measurements were the onset time of biliary fistula, the site of biliary fistula, the complications of ERCP or PTCD, the time of removing abdominal or biliary drainage tube, and the onset of new biliary stricture.Results:Biliary fistula was found in (46.5±36.6) days (6-122 days) after OLT. The numbers of patients in four types of biliary fistula were 6, 14, 2 and 2, respectively. Biliary fistula was cured in 22 patients, with clinical cure rate of 91.7%. All patients underwent ERCP first, and the technical success rate and clinical cure rate were 87.5% (21/24) and 85.7% (18/21), respectively. The clinical cure rates of ERCP forⅠ-Ⅳ biliary fistula were 6/6, 84.6%(11/13), 1/2, and 0, respectively. The clinical cure rates of ENBD and ERBD were 8/10 and 6/8, respectively. Five cases in whom ERCP failed, underwent PTCD, with technical success and clinical cure rates of 4/5 and 3/4 respectively. Eight patients(33.3%)developed cholangitis after treatment, and the incidence rate seemed higher in type Ⅱ biliary fistula than that in type Ⅰ [35.7% (5/14) VS 16.7% (1/6)]. Incidence of cholangitis was higher in patients with non-anastomotic stricture than those with anastomotic stricture [83.3%(5/6) VS 16.7%(3/18)].Conclusion:The first line treatment for biliary fistula after OLT is ERCP, followed by PTCD. The best procedures of biliary fistula typeⅠ-Ⅳ were ENBD, ENBD combined with ERBD, ENBD and PTCD, respectively.

BACKGROUNDAs a time-dependent antibiotic, the time of cefazedone concentration exceeds the minimum inhibitory concentration (MIC) is the key pharmacokinetic-pharmacodynamic (PK-PD) variable associated with the killing of pathogens. The purpose of the study was to evaluate the clinical regimen rationality of intravenous cefazedone sodium in the treatment of community-acquired pneumonia (CAP) by PK/PD study.

METHODSTen patients with mild to moderate CAP were enrolled to receive intravenous cefazedone sodium (2 g q12 h) for 7-14 days. Blood samples were collected in any day during day 5-7. Sputum specimens were collected before treatment for bacteria isolated, and susceptibility to cefazedone determined. PK-PD analysis was performed using the noncompartmental analysis of Phoenix WinNolin software (version 6.1, Pharsight Corporation, CA, USA). The maximal time above MIC (ƒT > MIC) was calculated, and its correlation with clinical efficacy was analyzed.

RESULTSAll 10 patients completed the study and 8 of them were cured. Six strains were isolated from patients before treatment (one for each patient) and all susceptible to cefazedone. Five patients of six in culture positive group were cured. All pathogens were cleared at the end of therapy. The MICs were between 0.25 and 1 mg/L. The main PK parameters were C max 175.22 ± 36.28 mg/L; T½ 1.52 ± 0.23 h; AUC (0-∞) 280.51 ± 68.17 mg·L -1·h -1 ; CL 7.37 ± 1.84 L/h; Vd 16.06 ± 4.42 L. The average ƒT > MIC was 55.45 ± 8.12%.

CONCLUSIONSIntravenous injection of cefazodone sodium with 2 g q12 h dosage regimen is used in the treatment of CAP caused by sensitive bacteria, either ƒT > MIC or clinical efficacy shows that such dosing regimen is reasonable.

Administration, Intravenous ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; administration & dosage ; pharmacokinetics ; therapeutic use ; Cefazolin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; therapeutic use ; Community-Acquired Infections ; drug therapy ; metabolism ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Young Adult

Objective To explore the variation and clinical value of the degradation of endothelial glycocalyx in the patients with septic shock. Methods A prospective case control study was conducted. Patients of 18 years or older diagnosed with septic shock and admitted to Department of Critical Care Medicine of Affiliated Hospital of Binzhou Medical University from June 2014 to May 2015 were enrolled. The levels of degradation products, including hyaluronic acid (HA) and heparin sulfate (HS), at 0, 6, 12, 24, 48 hours were determined, while 20 healthy people were enrolled and served as controls. The changes of HA and HS were analyzed in the patients with septic shock. The differences of HA and HS between survival group and death group after 28 days were also analyzed. The relationships between HA, HS and tumor necrosis factor-α (TNF-α), sequential organ failure assessment (SOFA) score, arterial blood lactate (Lac), platelet, albumin were analyzed by Pearson correlation analysis. The receiver-operating characteristic (ROC) curve was plotted to assess the prognostic value of HA and HS for patients with septic shock. Results Thirty-one patients diagnosed as septic shock were enrolled, among whom 17 patients died after 28 days, with a mortality of 54.8%. The levels of HA and HS in patients with septic shock were increased significantly as compared with those of health control group, peaked at 48 hours, and the levels of HA and HS at 48 hours were significantly higher than those at 0 hour [HA (μg/L): 119.47±32.44 vs. 94.84±23.63, HS (μg/L): 72.83±19.03 vs. 58.83±16.63, both P < 0.05]. The levels of HA and HS at 0 hour and 48 hours in death group were significantly higher than those of the survival group [HA (μg/L): 130.42±27.67 vs. 93.29±29.80, 105.14±19.18 vs. 70.82±13.24; HS (μg/L): 67.23±25.01 vs. 39.23±14.58, 79.74±19.84 vs. 56.17±14.53, all P < 0.05]. The levels of HA and HS in patients with septic shock were remarkably positively correlated with the levels of TNF-α, SOFA score, Lac, and platelet, but were remarkably negatively correlated with albumin levels (r value of HA was 0.595, 0.462, 0.545, 0.466, -0.534, respectively; r value of HS was 0.607, 0.468, 0.563, 0.547, -0.455, respectively; all P < 0.05). It was demonstrated by ROC curves that the areas under ROC curve (AUC) of HA and HS at 0 hour and 48 hours for predicting the prognosis of patients with septic shock were 0.881, 0.940 and 0.833, 0.821, respectively, the sensitivities of HA and HS were 87.5%, 100.0% and 83.3%, 81.3%, respectively, and the specificities of HA and HS were 82.6%, 78.3% and 91.3%, 78.3%, respectively. Conclusions The concentrations of degradation products generated by endothelial glycocalyx in the blood of the patients with septic shock are remarkably increased. The elevated levels of the degradation products are closely associated with the severity of septic shock, microcirculation disturbance, and the levels of inflammatory factors.

Objective To evaluate the effects of exendin-4 on glial brillary acidic protein (GFAP ) and interleukin-1β(IL-1β) expression in hippocampi of aged rats .Methods Forty-eight healthy male Sprague-Dawley rats ,aged 22-24 weeks ,weighing 500-700 g ,were randomly divided into 4 groups (n=12 each) using a random number table:control group (group C ) ,exendin-4 group (group E ) ,operation group (group O ) and exendin-4 plus operation group (group OE) .The rats were anesthetized with intraperitoneal fentanyl and droperidol .Groups C and E did not receive anesthesia or splenectomy .In O and OE groups ,splenectomy was carried out .In E and OE groups , exendin-4 5 μg/kg was injected intraperitoneally at 30 min before skin incision and 12 h after operation .C and O groups received the equal volume of normal saline instead of exendin-4 .Learning and memory function was assessed using Morris water maze test (escape latency (EL) and total swimming distance (TSD) at 1 day before operation (T0 ) .The fasting blood glucose was measured after anesthesia (T1 ) ,at the end of operation (T2 ) and on postoperative day 1 (T3 ) .The rats were sacrificed after assessment of the cognitive function at T 3 and the hippocampi were removed for determination of the expression of GFAP (by immuno-histochemistry ) and IL-1β(by Western blot ) .Results There was no significant difference in the EL and TSD at T0 between the four groups ( P>0.05) .Compared with group C ,the EL and TSD were significantly prolonged at T3 and fasting blood glucose was increased at T2 ,3 ,and the expression of IL-1βand GFAP was up-regulated at T3 in O and OE groups ( P<0.05) .Compared with group O ,the EL and TSD were significantly prolonged at T3 and fasting blood glucose was decreased at T2 ,3 ,and the expression of IL-1βand GFAP was down-regulated at T3 in group OE ( P<0.05) . Conclusion Exendin-4 can improve the postoperative cognitive function of aged rats by inhibiting inflammatory responses in hippocampi and maintaining stable perioperative blood glucose .

Objective To evaluate the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP)-based comprehensive minimally invasive treatment for biliary anastomotic stenosis (BAS) after liver transplantation. Methods Clinical data of 60 BAS recipients after liver transplantation were retrospectively analyzed, 54 male and 6 female, aged (48±10) years. ERCP was initially carried out. If it succeeded, plastic or metallic stents were placed into the biliary tract. If it failed, percutaneous transhepatic cholangial drainage (PTCD) or single-operator cholangioscopy (SpyGlass) was adopted to pass through the stenosis. If all these procedures failed, magnetic anastomosis or other special methods were delivered. The incidence and treatment of BAS after liver transplantation were summarized. The efficacy, stent removal and recurrence were observed. Results The median time of incidence of BAS after liver transplantation was 8 (4, 13) months. Within postoperative 1 year, 1-2 years and over 2 years, 39, 16 and 5 recipients were diagnosed with BAS, respectively. All 60 BAS recipients after liver transplantation were successfully treated, including 56 cases initially receiving ERCP, and 41 completing BAS treatment, with a success rate of 73%. The failure of guide wire was the main cause of ERCP failure. The success rates of PTCD, SpyGlass and magnetic anastomosis were 5/9, 5/7 and 7/8, respectively. Two recipients were successfully treated by percutaneous choledochoscope-assisted blunt guide wire technique and stent placement in the biliary and duodenal fistula. After 3 (3, 4) cycles of ERCP and 13 (8, 18) months of stent indwelling, 38 recipients reached the stent removal criteria, including 25 plastic stents and 13 metallic stents. The indwelling time of plastic stents was longer than that of metallic stents (P < 0.05). Six cases suffered from stenosis recurrence at 12 (8, 33) months after stent removal, and the recurrence rate was 16%. Six patients were treated with ERCP, and 5 of them did not recur after the stents were successfully removed. Multivariate analysis showed that delayed diagnosis of stenosis and frequent ERCP before stent removal were the independent risk factors for BAS recurrence (both P < 0.05). Conclusions ERCP-based comprehensive minimally invasive treatment may improve the success rate of BAS treatment after liver transplantation and yield satisfactory long-term efficacy. Delayed diagnosis of BAS and high frequent ERCP required for stent removal are the independent risk factors for BAS recurrence.

DNA Polymerase gamma ; DNA-Directed DNA Polymerase ; genetics ; Diffuse Cerebral Sclerosis of Schilder ; diagnosis ; drug therapy ; etiology ; genetics ; Heterozygote ; Humans ; Infant ; Male ; Mutation

Objective We aimed to investigate the effect of ferroptosis on Shenling Baizhu Powder,a compound prescription of Chinese herbal medicine,in improving testicular spermatogenic function in hyperuricemic mice with spermatogenic dysfunction. Methods Sixty BALB/c mice were randomly divided into normal group,model group,Shenling Baizhu Powder high-,medium-,and low-dose groups (20.14,10.07,5.04 g/kg,by gavage),and ferrostatin-1(Fer-1) group (0.8 mg/kg,by tail vein injection),with 10 mice each group. Except for the normal group,the other groups were intraperitoneally injected with potassium oxonate suspension[600mg/(kg·d)]for 7 days to establish the hyperuricemic model,and then the corresponding intervention was given for consecutive 14 days. Content of serum uric acid (UA),testicular Fe2+,reduced glutathione (GSH),malondialdehyde (MDA) and superoxide dismutase (SOD) activity were detected by biochemical method. Epididymal and testicular indices were measured. The spermatogenic function of testes was evaluated by eosin-hematoxylin staining. Sperm quality was detected by an automatic animal sperm analyzer. Prussian blue staining was used to detect iron deposition in testicular tissue. Immunohistochemistry was used to detect the related protein expressions of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) in testicular tissue. Western blotting was used to detect the related protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1)/GPX4 signaling pathway in testicular tissue. Results Compared with the normal group,the contents of serum UA,MDA,and Fe2+in the testis tissue of the model group were increased,the GSH content and SOD activity were decreased,the epididymal and testicular index,testicular spermatogenic function,sperm density and activity rate were decreased,and the iron deposition and ACSL4 protein expression in the testis tissue were increased. The expressions of kelch-like ECH-associated protein-1 (Keap1) and Nrf2 were increased. The expressions of nuclear Nrf2,HO-1,GPX4,and recombinant solute carrier family 7 member 11 (SLC7A11) protein were decreased (P<0.01). Compared with the model group,the above indexes in the Shenling Baizhu Powder groups and the Fer-1 group were improved to varying degrees (P<0.05,P<0.01). Conclusion Shenling Baizhu Powder can inhibit the ferroptosis of testicular cells through the Nrf2/HO-1/GPX4 signaling pathway,and improve the testicular spermatogenic function of mice with hyperuricemia spermatogenic dysfunction.

Objective:To analyze the risk factors of stress perception in patients with systemic lupus erythematosus (SLE) , and construct and validate a risk prediction model for health risk stress perception in SLE patients.Methods:This study is a cross-sectional study. From October 2020 to March 2021, totals of 310 SLE inpatients and outpatients in the Department of Rheumatology and Immunology from 4 general hospitals in Anhui Province were selected as the modeling object. According to the patients' stress perception score, they were divided into the group with health risk stress ( n=132) and the group without health risk stress ( n=178) . The general data, SLE disease activity, general self-efficacy, emotional intelligence, resilience, sleep disturbance, anxiety, depression were compared between the two groups, and independent risk factors were screened out and Logistic regression was used to construct a risk prediction model. Hosmer-Lemeshow and receiver operator characteristic curve (ROC) area were used to test the fit and prediction effect of the model, respectively, and 206 patients were included for model validation. Results:Binary Logistic regression analysis showed that SLE disease activity, resilience, anxiety, payment type, and family monthly income were the influencing factors of stress perception in SLE patients, and the difference was statistically significant ( P<0.05) . Hosmer-Lemeshow fit test showed χ 2=6.123, P=0.633. Besides, the area under the ROC, maximum Youden index, predictive critical value, sensitivity and specificity were 0.903, 0.660, 0.497, 0.795 and 0.865 respectively. Conclusions:This study is based on five independent risk factors of SLE patients' stress perception, namely SLE disease activity, resilience, anxiety, payment type, and family monthly income. The risk prediction model has good sensitivity and specificity, which can provide a reference for clinical assessment of health risk stress perception in SLE patients.

OBJECTIVETo analyze the of risk factors of radius shortening in adult with distal radius fracture after conservative treatment by Logistic analysis.

METHODSFrom May 2009 to March 2015, 137 adults patients with distal radius fracture treated by conservative treatment were retrospective analyzed, and 36 patients occurred radius shortening, including 7 males and 29 females with an average age of (58.33±14.06) years old, 8 patients were type A, 34 patients were type B and 12 patients were type C according to fracture classification; 101 patients were without radius shortening, including 23 males and 78 females with an average age of (52.49±12.79) years old, 48 patients were type A, 34 patients were type B and 19 patients were type C according to fracture classification. Ages, gender, BMI , time from injuries to reduction, fracture classification, fixed form and loading time were collected and screened risk factors by Logistic analysis.

RESULTSAll patients were followed up from 8 to 16 months. Ages, time from injuries to reduction, fracture classification, earlier loading could obviously affect radius shortening by univariate analysis, multivariate logistic analysis revealed the risk factor including ages [=1.045(1.008-1.083),=0.015], time from injury to reduction[=2.853(1.178-6.909),=0.020], fracture classification(Type C fracture was more relevant to radius shortening than other two type fractures)[=4.854(1.506-15.640),=0.008], and earlier loading[=3.038(1.138-8.111),=0.027].

CONCLUSIONSAges, time from injury to reduction, fracture classification, and earlier load are the risk factors of radius shortening, so corresponding preventive measures and appropriate treatment should be applied to according to different risk factor.