Objective To investigate the effects of a highly selective protein kinase A (PKA) inhibitor, H89, injected intrathecally (IT) on hyperalgesia and phosphorylation of cAMP element binding protein(pCREB) in the dorsal horn neurons of the spinal cord induced by chronic constriction injury (CCI) to the sciatic nerve.Methods Fifty-eight adult female SD rats weighing 230-270 g were used in this study. CCI was produced by 4 loose ligatures place on the sciatic nerve of right hind leg at 1 mm interspace with 3-0 silk suture. The experiment was carried out in two parts. In part Ⅰ 28 animals were randomized to receive H89 1 (group H1), 2 (group H2 ) or 4 nmol (group H4) or 10 ?l of DMSO (the solvent) 10mmol?L-1 (control group) intrathecally (IT) (n = 7 each) 7 days after surgery. The paw-withdrawal latency following mechanical (MWL) and thermal stimulation (TWL) were recorded before (baseline) and 15, 30 and 60 min after drug administration. In part Ⅱ 24 rats were randomized to receive H89 1, 2 or 4 nmol or 10 ?l of DMSO 10 mmol?L-1 IT as in part Ⅰ (group H1, H2, H4 and control group, n = 6 each) . Another 6 animals received 10 ?l of DMSO 10 mmol?L IT 7 days after sham operation. The animals were killed 30 min after drug administration and lumbar (L4.5) segment of spinal cord was removed for determination of pCREB expression in the dorsal horn neurons of spinal cord using immuno-histochemical technique. Results MWL and TWL were significantly increased after drug administration in group H2(at 15min) and group H4(at 15 and 30 min) as compared to the baseline values(P

Objective To determine whether chronic constriction injury (CCI) to sciatic nerve is associated with changes in the phosphorylation of CREB in dorsal root ganglia ( DRG) and superficial dorsal horn neurons of the spinal cord.Methods Thirty-two adult female SD rats weighing 230-270 g were randomly divided into 4 groups (n = 8 each): Ⅰ blank control;Ⅱ sham operation; Ⅲ CCI 2w and Ⅳ CCI 4w. The animals were anesthetized with intraperitoneal pentobarbital 40 mg?kg-1. Right sciatic nerve was exposed and 4 ligatures were placed on the right sciatic nerve at 1 mm interspace with 3-0 silk suture. Paw withdrawal threshold to mechanical stimulation (von Frey filament) applied to plantar surface ( MWT) and paw withdrawal latency to thermal stimulation (radiant heat) (TWL) were measured before operation (baseline) and 14 days (group Ⅰ,Ⅱ and Ⅲ) or 28 days (group Ⅳ) after nerve ligation. The animals were killed the next day and the L4,5 segment of the spinal cord and L5 dorsal root ganglion were removed for determination of expression of phosphorylated-CREB-immuno-reaction(pCREB-IR) using immuno-histochemistry. The pCREB-IR cells both in DRG and superficial dorsal horn neurons were quantified and analyzed. Results The animals developed mechanical and thermal hyperalgesia on the 14th day after CCI (in group CCI 2w) . The hyperalgesia was greatly attenuated on the 28th day after CCI. Interestingly enough the animals in sham operation group (Ⅱ) also developed mechanical hyperalgesia to some extent on the 14th day after operation. The number of pCREB-IR cells was significantly increased in the ipsilateral L5 DRG and superficial dorsal horn in group Ⅲ(CCI 2w) as compared to sham operation group ( P

Objectives：To observe the effect of eukaryotic expression vectors coding IL-2 and IL-12 on immune responses induced by DNA immunization of HBV surface antigen（pCR3.1-S）in BABL/c(H-2d) and the protection against P815 mastocytoma cells stable expressing HBV surface antigen in mice after immunized with HBV gene vaccine.Methods：The immunization was performed by intramuscular injection,three weeks later,we directly inoculated P815-HBV-S into mice by subcutaneous injection .Tumor growth was measured every five days.Anti-HBs in serum was detected by ELISA and HBsAg specific cytotoxic T lymphocytes (CTLs) activity was measured by 51 Chromium release assay.Results：Eight weeks after immunization,the A value of mice serum in 450 nm and CTLs activity of mice codiog IL-2 and IL-12 eukaryotic expression vectors were significant higher(P<0.05) than that of mice intramuscular injected HBV-S DNA vaccine,these values are significant higher than that of mice injected pCR3.1(P<0.05).The spleen cells CTLs activity have decreased obviously after treated with anti-CD8+ monoclonal antibody and have no significant change after treated with anti-CD4+ monoclonal antibody.The HBV-S gene vaccine could evidently inhibit the tumor growth,prolong the survival period (>38.2 days) and improve the survival rate in mice.Conclusions：The DNA vaccine of HBV ( pCR3.1-S) had strong antigenicity in cellular and humoral immunity and had marked killing effect on HBV infected cells in vivo，which could be promoted by vector coding murine IL-2 or IL-12.CTLs activity was performed by CD8+ cells.

Objective To analyze the clinical features,methods of treatment and prognosis of primary neurogenic tumors of mediastinum in patients taking surgical intervention.Methods A database was maintained retrospectively of all patients undergoing surgery for tumor and pathologically diagnosed with primary neurogenic tumors of mediastinum,managed in the Department of Thoracic Surgery,Zhongshan Hospital,Fudan University,Shanghai between Jan.,2008 and Dec.,2014.This work analyzed retrospectively the information about clinical and imaging features,surgical techniques and outcome extracted from medical records.Results Among the 131 cases,78 cases (59.5％) were males,53 cases (40.5％) were females;72 cases were diagnosed incidentally (55.0％),while the other 59 cases (45.0 ％) suffered from different symptoms.The posterior mediastinum was the most principal location with 61 cases in the left and 69 cases in the right,and 1 case remained in the anterior mediastinum.Total 98 cases (74.8％) underwent surgeries via video-assisted thoracic surgery (VATS),5 cases (3.8％) took VATS surgery with small incision,and 28 cases (21.4％) experienced open thoracotomy,with no mortality during perioperative period.Gross total resection was obtained in 130 patients (99.2％).The remaining patient underwent a palliative resection for malignant schwannomas.Of the patients,98 cases had benign schwannomas (74.8％),24 cases had gangliocytomas (18.3％),2 cases had malignant schwannomas (1.5％),2 cases had neurofibromas (1.5％),2 cases had paragangliomas (1.5％),2 cases hadprimitive neurotodermal tumor (PNET) (1.5％) and 1 case had neuroblastomas (0.8％).All patients were followed up from 12 to 95 months with an average of 53 months.A patient with PNET died of tumor metastasis,a patient with malignant schwannomas died after palliative ectomy,and 2 cases died of other reasons.The rest survived until Jan.,2016 with tumor free.Conclusions Nearly no specific clinical symptoms occur in neurogenic tumors of mediastinum.Most of neurogenic tumors of mediastinum are benign with optimistic prognosis after surgical treatment.While malignant neurogenic tumorsusually come with poor prognosis,which places special emphasis on early diagnose together with surgical treatment.

Objective To study the effect of corrected TIMI frame count (CTFC) of infarction related artery on systolic function of infarct area of myocardium after primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Methods One hundred and six patients with AMI having undergone successful PCI in Cangzhou Central Hospital were selected, and they were divided into two groups (each, 53 cases). The standard of fast or slow flow was in accord to the CTFC of infarction related artery (IRA) measured soon after successful PCI. The patients with greater value of CTFC were enrolled in the slow flow group, while the patients with smaller such value were assigned in the fast flow group. At 6, 12, 24 and 48 hours after PCI, the venous plasma MB isoenzyme of creatine kinase (CK-MB) level was measured. And at 1 week, 1 month and 3 months after PCI, the left ventricular ejection fraction (LVEF) was measured by cardiac ultrasound, and the levels of radial strain (RS) and longitudinal strain (LS) of the infarct area were measured via speckle tracking imaging (STI). The differences in CTFC, CK-MB, RS and LS between the two groups were analyzed, and the correlations between the strains and CTFC, CK-MB were analyzed by Pearson linear correlation method. Results After successful PCI, the CK-MB of fast flow group was higher than that of the slow flow group at 6 hours. However, the CK-MB of slow flow group was higher than that of the fast flow group after 12 hours, appearing separate phenomenon, and the statistical significance occurred beginning from 24 hours after PCI (U/L, 24 hours:98.43±11.65 vs. 86.43±18.97, 48 hours:51.09±8.94 vs. 49.80±6.92, both P<0.05). CTFC in fast flow group was significantly lower than that of slow flow group (frame: 22.69±4.83 vs. 26.14±5.67, P < 0.01). After 3 months of follow-up, LVEF in fast flow group was higher than that of the slow flow group, but the difference had no significance (P > 0.05). RS and LS in fast flow group were higher than those in slow flow group, and the statistically significant difference appeared from 1 month after PCI (1 month RS:29.74±6.66 vs. 26.86±5.61, LS:-16.37±3.91 vs. -15.27±3.22, 3 months RS: 30.03±6.31 vs. 27.63±5.67, LS: -17.74±3.96 vs. -15.75±4.17, all P < 0.05). Pearson linear correlation showed:the strains (both RS and LS) and CK-MB had no significant relation (both P>0.05). Both RS and LS at 1 week, 1 month and 3 months were of significantly positive correlation with CTFC of each group (fast flow group:r value of CTFC and RS was respectively-0.526,-0.515,-0.532, r value of CTFC and LS was respectively-0.532,-0.541,-0.572;slow flow group:r value of CTFC and RS was respectively-0.691,-0.685,-0.702, r value of CTFC and LS was respectively-0.621,-0.584,-0.605, all P<0.01). Conclusion CTFC has some relationship with the recovery of the systolic function in area of infarct myocardium after PCI, and can be regarded as an important index to predict the long-term prognosis in patients with AMI.

Objective:To investigate the ultrasonographic features of internal jugular venous vein pseudo-aneurysm.Methods:The ultrasonographic and clinical features of a patient with internal jugular venous vein pseudo-aneurysm in Union Hospital Affiliated to Huazhong University of Science and Technology were retrospectively analyzed. These characteristics of this patient combined with cases from literatures were summarized.Results:Ultrasound showed that the 38.6 mm×14.0 mm×29.9 mm anechoic area in the soft tissue layer of the left neck communicated with the left internal jugular vein through the 3.8 mm wide breach, and a 12.9 mm×6.6 mm slightly hyperechoic mass was found in the anechoic area. Color Doppler flow imaging showed that the internal jugular vein communicated with the anechoic area through the crevasse. There was no obvious blood flow signal in slightly hyperechoic mass. The bidirectional burr-like blood flow signal could be detected by pulse-wave Doppler. Contrast enhanced ultrasound showed that the contrast agent flowed into the mass from the internal jugular vein through the breach, and the slightly hyperechoic mass appeared the contrast filling defect, and contrast agent was well filled in the rest of the anechoic area. Ultrasound diagnosis: left internal jugular vein pseudoaneurysm with thrombosis. 35 cases of cervical vein pseudo-aneurysm patients were finally included in 23 documents, including 12 males, 23 females, 15 cases on the left side, 20 cases on the right side, 6 cases of the internal jugular vein, 27 cases of the external jugular vein; one case only describes the neck veins and supraclavicular vein in another one case. Among them, 34 cases showed subcutaneous anechoic masses on ultrasound, 1 case showed slightly hyperechoic masses, and 35 cases showed venous wall breaches.Conclusions:Ultrasound examination has high diagnostic value for vein pseudo-aneurysm owing to its convenience, fast and serial observation. Therefore, it is the preferred method and can be widely used in clinical practice. Contrast-enhanced ultrasound can clearly show the blood perfusion, and help to improve the diagnostic confidence of the operator.

Objective To observe the effects of recombinant human B-type natriuretic peptide (rhBNP) on cardiac function and heart rate variability (HRV) in patients with heart failure after acute myocardial infarction (AMI). Methods One hundred and twenty patients with heart failure after AMI admitted to the Department of Cardiology of Cangzhou Central Hospital of Hebei Province from January 2015 to January 2018 were enrolled. The patients were divided into a conventional treatment group and an rhBNP treatment group according to random number table method, with 60 cases in each group. The two groups were treated according to the AMI guidelines, the conventional treatment group received west medicine anti-myocardial ischemia and anti-heart failure treatment; the rhBNP treatment group received rhBNP on the basis of routine treatment; the first load dose was 2 μg/kg intravenous injection impact treatment, followed by maintaining dose 8.5 ng·kg-1·min-1 intravenous drip for 7 days. The changes of hypersensitivity C-reactive protein (hs-CRP), N-terminal B-type natriuretic peptide precursor (NT-proBNP), left ventricular ejection fraction (LVEF) and HRV index were observed before and after treatment in the two groups [HRV indexes including the changes of average normal RR interval standard deviation (SDNN), the average value of the normal RR interval standard deviation (SDANN), the root mean square (RMSSD) of the adjacent RR interval difference, and the percentage of adjacent RR interval difference > 50 ms (PNN50)]; the incidences of adverse reactions in the two groups were observed. Results After treatment, the levels of hs-CRP and NT-proBNP in the two groups were significantly lower than those before treatment (all P < 0.05). LVEF, SDNN, SDANN, RMSSD and PNN50 were higher than those before treatment, and the changes of the above indicators in the rhBNP treatment group were more significant than those in the conventional treatment group [hs-CRP (mg/L): 6.2±3.3 vs. 11.8±5.5, NT-proBNP (ng/L): 2.5±2.0 vs. 6.4±4.3, LVEF: 0.49±0.02 vs. 0.44±0.04, SDNN (ms): 93.3±18.1 vs. 79.1±16.0, SDANN (ms): 87.3±17.8 vs. 70.9±14.9, RMSSD: 30.3±11.0 vs. 23.8±10.4, PNN50: (15.9±7.3)% vs. (9.6±5.5)%, all P < 0.05]; No significant adverse reactions occurred during the treatment of the two groups. Conclusion rhBNP can significantly improve the heart function of patients with heart failure after AMI, reduce the levels of inflammatory response indicators and improve HRV;since its clinical efficacy is good, and its application safe, it is worthy to promote its clinical use.

Objective To observe the effect of low-dose dabigatran etexilate on the clinical efficacy of elderly patients with venous thromboembolism (VTE). Methods Seventy-five elderly (≥ 80 years old) VTE patients admitted to Cangzhou Central Hospital from October 2016 to June 2018 were enrolled, they were treated according to the VTE guidelines, and low dose dabigatran etexilate was the anticoagulant therapy selected, 110 mg once daily for 6 months. After treatment for 6 months, the thrombus regression situation with color Doppler ultrasonography;clinical efficacy was evaluated by clinical symptoms and ultrasonographic results, the changes in platelet count (PLT), coagulation parameters [international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (Fib)] before and after treatment were detected and the occurrence of adverse reactions were recorded and safety of drug was evaluated. Results There were no significant differences in PLT, INR and Fib before and after treatment [PLT (×109/L): 197.88±58.00 vs. 199.88±65.15, INR: 1.02±0.10 vs. 1.05±0.13, Fib (g/L): 2.89±0.67 vs. 2.84±0.70, all P > 0.05], the APTT after treatment was significantly prolonged compared with that before treatment (seconds:40.9±7.34 vs. 26.2±3.16), the difference being statistically significant (P < 0.05), the amount of APTT prolongation after treatment did not exceed 2 times [average (1.75±0.24) times] of the baseline value before treatment. The total effective rate of low-dose dabigatran etexilate for treatment of elderly patients with VTE for 6 months was 90.7% (68/75);no obvious adverse reactions occurred during the treatment. Conclusion Low-dose dabigatran etexilate for treatment of elderly patients with VTE is safe and effective without any obvious adverse reactions, and is worthy to be promoted for clinical use.

Objective:To investigate the impacts of stroke volume variation (SVV)-guided goal-directed fluid therapy on intraoperative signs, intestinal barrier function and prognosis in patients undergoing laparoscopic radical rectal cancer surgery.Methods:A total of 90 patients who underwent laparoscopic radical resection for rectal cancer in Peking University International Hospital from May 2020 to May 2022 were prospectively selected as subjects, and divided into SVV group (45 cases) and traditional infusion group (45 cases) by random number table method. The SVV group was given SVV-guided goal-directed fluid therapy, and the traditional infusion group was given central venous pressure (CVP)-guided goal-directed fluid therapy. The operation-related indicators (urine volume, crystalloid volume, colloid volume, total fluid volume, blood loss and operation time), intraoperative signs indicators[heart rate (HR), CVP, mean arterial pressure (MAP)], intestinal barrier function indicators [diamine oxidase (DAO), D-lactic acid], inflammatory factor levels [interleukin-10 (IL-10), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], and the incidence of complications were compared between the two groups.Results:There was no significant difference in the urine volume, blood loss and operation time between the two groups (all P>0.05), while the crystalloid volume, colloid volume and total fluid volume in the SVV group were greatly lower than those in the traditional infusion group (all P<0.05). There was no significant difference in HR between the two groups at different time points ( P>0.05). Compared with T 0, CVP at T 1 in the two groups was significantly decreased (all P<0.05), and increased at T 2 and T 3 compared with T 1 (all P<0.05). There was no significant difference in MAP at different time points in the SVV group (all P>0.05). The MAP at T 1, T 2 and T 3 in the traditional infusion group was significantly lower than that at T 0 (all P<0.05), and the MAP at T 1, T 2 and T 3 in the SVV group was significantly higher than that in the traditional infusion group (all P<0.05). Compared with T 0, DAO and D-lactic acid levels were significantly increased at T 1, T 3, T 4 and T 5 in the two groups (all P<0.05), and DAO and D-lactic acid levels at T 1, T 3, T 4 and T 5 in the SVV group were significantly lower than those in the traditional infusion group (all P<0.05). Compared with T 0, serum IL-10 level in the two groups was significantly decreased at T 4 ( P<0.05), and serum IL-6 and TNF-α levels were significantly increased at T 4 (all P<0.05). The serum levels of IL-10, IL-6 and TNF-α in the SVV group at T 4 were significantly different from those in the traditional infusion group (all P<0.05). Compared with T 4, the serum levels of IL-10 at T 5 were significantly increased (all P<0.05), while the levels of IL-6 and TNF-α were significantly decreased (all P<0.05), but there was no statistical significance between the two groups (all P>0.05). The incidence of postoperative infection, anastomotic fistula, vomiting and nausea in SVV group (13.33%) was significantly lower than that in traditional infusion group (35.33%) ( P<0.05). Conclusions:SVV-guided goal-directed fluid therapy for patients undergoing laparoscopic radical rectal cancer can effectively stabilize intraoperative vital signs, reduce inflammation, improve intestinal barrier function, and improve prognosis.

Objective To evaluate the effect of dexmedetomidine postconditioning on cardiac function after cardiac arrest-cardiopulmonary resuscitation in swine.Methods Twenty-eight healthy male white swine,weighing 33-41 kg,were divided into 4 groups (n=7 each) using a random number table:sham operation group (group S),cardiac arrest-cardiopulmonary resuscitation group (group CA-CPR),lowdose dexmedetomidine postconditioning group (group LDP) and high-dose dexmedetomidine postconditioning group (group HDP).Ventricular fibrillation was electrically induced and left untreated for 8 min,and then cardiopulmonary resuscitation was initiated and continued for 5 min.At 5 min after successful resuscitation,dexmedetomidine was infused via the femoral vein at a loading dose of 0.25 μg/kg followed by an infusion of 0.25 μg · kg-1 · h-1 for 6 h in group LDP,and dexmedetomidine was infused via the femoral vein at a loading dose of 0.50 μg/kg followed by an infusion of 0.50 μg · kg-1 · h-1for 6 h in group HDP.The equal volume of normal saline was given in S and CA-CPR groups.At 1,3,6 and 24 h after resuscitation,stroke volume (SV) and global ejection fraction (GEF) were measured using PiCCO,and the concentration of cardiac troponin Ⅰ (cTnⅠ) in serum was also measured by enzyme-linked immunosorbent assay.At 24 h after resuscitation,the animals were sacrificed,hearts were removed and myocardial tissues were obtained for determination of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) contents (by enzyme-linked immunosorbent assay),malondialdehyde (MDA) content (by thiobarbituric acid method),and superoxide dismutase (SOD) activity (using xanthine oxidase method).Results Compared with group S,the SV and GEF were significantly decreased,the cTnⅠ concentration in serum and contents of TNF-α,IL-6 and MDA in myocardial tissues were increased,and the activity of SOD in myocardial tissues was decreased in CA-CPR,LDP and HDP groups (P＜0.05).Compared with group CA-CPR,the SV and GEF were significantly increased,the cTnⅠ concentration in serum and contents of TNF-α,IL-6 and MDA in myocardial tissues were decreased,and the activity of SOD in myocardial tissues was increased in LDP and HDP groups (P＜0.05).Compared with group LDP,the SV and GEF were significantly increased,the cTnⅠ concentration in serum and contents of TNF-α,IL-6 and MDA in myocardial tissues were decreased,and the activity of SOD in myocardial tissues was increased in group HDP (P＜0.05).Conclusion Dexmedetomidine postconditioning can improve cardiac function after cardiac arrest-cardiopulmonary resuscitation in swine,and the mechanism may be related to inhibiting inflammatory responses and oxidative stress responses.