Nerve injury produces a long lasting neuropathic pain, manifested as allodynia, a decrease in pain threshold and hyperalgesia, an increase in response to noxious stimuli. The mechanism underlying the lasting abnormal pain is not well understood. Our previous works have shown that electrical tetanic stimulation of the sciatic nerve induces long-term potentiation (LTP) of C-fiber evoked field potentials in the spinal dorsal horn, which is considered as a synaptic model of pathological pain. In the present study we tested if nerve injury, which is proved to produce neuropathic pain, induced the spinal LTP in intact rats. C-fiber evoked field potentials in spinal dorsal horn produced by electrical stimulation (10-20 V, 0.5 ms, 1/min) of the sciatic nerve were recorded. For induction of LTP of C-fiber evoked field potentials, three types of noxious stimuli were applied. (1) Electrical tetanic stimulation (40 V, 0.5 ms pulses at 100 Hz for 1 s repeated four times at 10 s intervals). (2) Transection of the sciatic nerve at 4-5 mm distal to the stimulation electrode. (3) Crushing the sciatic nerve with a forceps four times at 4-5 mm distal to stimulation electrode (from distal to proximal with 1 mm spacing at 10 s intervals), which simulated electrical tetanic stimulation. Acute nerve injury was made by either transection of the sciatic nerve at the distal to the stimulating electrode or crushing the sciatic nerve. We found that nerve injury by cutting or crushing the sciatic nerve produced LTP of C-fiber evoked field potentials lasting until the end of the experiments (3-9 h), and that pretreatment of the sciatic nerve with lidocaine 10 min prior to the nerve transectoin completely blocked LTP induced by nerve transection. The nerve transection-induced LTP was blocked by NMDA receptor antagonist AP5. LTP produced by nerve transection could not be further potentiated by electrical tetanic stimulation, while LTP induced by single electrical tetanic stimulation could be further potentiated by transection of the sciatic nerve. However, when LTP was saturated by several times of electrical tetanic stimulation, nerve transection did not affect the spinal LTP. We conclude that acute nerve injury induces LTP of C-fiber evoked field potentials in intact animals and that nerve transection is more powerful than electrical tetanic stimulation for induction of the spinal LTP. The results further support the notion that LTP of C-fiber evoked field potentials may underlie neuropathic pain.
Animals ; Evoked Potentials ; physiology ; Long-Term Potentiation ; physiology ; Male ; Nerve Fibers, Unmyelinated ; physiology ; Neural Pathways ; drug effects ; physiology ; Nociceptors ; physiology ; Posterior Horn Cells ; enzymology ; physiology ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; injuries ; physiology ; Spinal Cord ; physiology

Objective To detect the expression of matrix metallproteinases(MMPs) in aortic valve of children who suffered from rheumatic heart disease(RHD) and to explore the pathological role of MMPs in children′s rheumatic aortic valve disease.Methods RHD group composed of 18 aortic valves from children suffered from RHD.Controls were 8 children who were died accidentally without cardiovascular system diseases.Hematoxylin and eosin stain observing the histological characteristic of the 2 groups.Immunohistochemistry was used to detect expression of MMP2 and MMP9 on aortic valves in 2 groups.Results Hematoxylin and eosin stain showed:in RHD the valves′ structure were destroyed along with fibrous tissue proliferation,mucinous degeneration,collagen and fiber hyalinization,blood vessel and blood capillary proliferation,lymphocyte,plasmocyte,monocyte infiltration.Immunohistochemistry showed that MMP2 and MMP9 expression were significantly higher than those in the aortic of RHD(68.85?13.08,64.35?9.59) compared with control group(107.31?23.39,116.28?6.99)(t=3.92,10.18 all P

OBJECTIVETo evaluate the transhiatus esophagectomy for patients with esophageal cancer.

METHODSClinicopathological data of 46 patients with esophageal cancer undergone transhiatus esophagectomy by single surgeon team from May 2000 to July 2007 were analyzed retrospectively.

RESULTSThese 46 patients included 44 esophageal squamous cell carcinomas,1 esophageal adenocarcinoma and 1 esophageal carcinoid. The lesions of 11 patients located at neck segment, 21 at upper segment, 5 at middle segment, and 9 at lower segment. All the patients were classified according to UICC TNM stage classification: 3 cases as stage 0, 6 cases as stage I, 17 cases as stage II a, 2 cases as stage II b, 16 cases as stage III. Six patients received preoperative chemotherapy and pathological complete response was seen in 2 cases. Reconstruction with stomach was performed in 42 cases and with colon interposition in 4 cases.All the tumors were resected, and there was no perioperative death. All the resected margins were pathologically clear. Postoperative complications occurred in 12 cases and were successfully treated, including 2 cases of hoarseness, 3 cases of cardiac arrhythmia,1 case of bilateral pleural effusion, and 6 cases of small anastomotic leakage at neck.

CONCLUSIONTranshiatus esophagectomy is an ideal choice in surgical treatment for patients with esophageal cancer, especially for the ones of aged, poor cardiac or pulmonary function, who can not afford the thoracotomy.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; surgery ; Esophageal Neoplasms ; surgery ; Esophagectomy ; methods ; Esophagus ; surgery ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVE: To explore the inhibitive effects of 1,3,8-trihydroxy-5-methoxyxanthone (TMX) on cytochrome P450s (CYP450s) in human liver microsomes. METHODS: Probe drugs were incubated with and without adding TMX to determine the changes of enzyme activities. The concentration ratio of metabolites to probe drugs was used to present enzyme activities. Concentrations of the probe drugs and their metabolites in the incubated mixture were detected by high performance liquid chromatography. RESULTS: The variations (mean, 95%CI) of the activities of CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 were 2.95 x 10(-3) (2.03 x 10(-3), 3.88 x 10(-3)), 3.14 x 10(-2) (1.87 x 10(-2), 4.42 x 10(-2)), 2.27 x 10(-3) (-1.4 x 10(-2),1.81 x 10(-2)), 7.72 x 10(-2) (-0.83 x 10(-2), 0.2374), and -0.2548 (-2.9802, 2.4707), respectively. The activities of CYP1A2 and CYP2C9 were significantly reduced in the present of TMX. CONCLUSION TMX (10 micromol/L) has significant inhibitive effect on the activities of CYP1A2 and CYP2C9, but no significant inhibitive effect on the activities of CYP2C19, CYP2E1 and CYP3A4.
Cytochrome P-450 Enzyme System ; metabolism ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; Xanthones ; pharmacology

Objective To study the cell toxicity of thrombin in astrocytes in vitro and the protective effect of hirudo extract liquid (HEL) on the injured astrocytes. Methods Astrocytes were isolated from Wistar rats' cerebral cortex and cultured in vitro, and observed under a phase contrast microscope for growth status. Cell activity was measured with MTT assay. The survival of astrocytes was investigated after exposed to a selected concentration of thrombin ranging from 0.1 to 100 U/mL or to HEL ranging from 0.25 to 4 mg/μL by observing cell morphology under an inverted phase-contrast microscope and measuring the lactate dehydrogenase (LDH) activity (a marker of cell death) in cell supernatant. Expressions of HSP70 and TGFβ-1 protein in astrocytes were investigated by immunohistochemistry. Results (1) Thrombin (1-100 U/mL) had toxicity on astrocytes in vitro in a dose-dependent manner (F=118.65, P=0.000). (2) HEL (0.25-4 mg/μL) could significantly reduce the cell toxicity of 10 U/mL thrombin in astrocytes (F=156.08, P=0.000). With the increasing concentration of HEL, the protection of HEL was accordingly enhanced, and it even increased the expressions of HSP70and TGFβ-1. Conclusions HEL could accelerate the proliferation of astrocytes, enhance the expressions of HSP70 and TGFβ-1 protein, so as to significantly depress the cell toxicity of thrombin to astrocytes.

Our previous studies have shown that long-term potentiation (LTP) of C-fiber-evoked field potentials in the spinal dorsal horn is NMDA receptor dependent. It is known that elevation of Ca(2+) in the postsynaptic neurons through NMDA receptor channels during high-frequency stimulation of the afferent fibers is crucial for LTP induction, but how this leads to a prolonged potentiation of synaptic transmission in the spinal dorsal horn is not clear. In the hippocampus, a rise of Ca(2+) activates calcium/calmodulin-dependent protein kinase II (CaMK II) through autophosphorylation. Once this occurs, the kinase remains active, even when Ca(2+) concentration returns to baseline level. Phosphorylated CaMK II potentiates synaptic transmission by enhancement of AMPA receptor channel function via phosphorylation of GluR1 subunit of the receptor and the addition of AMPA receptors to synapses. Up to now, the role of CaMK II in the induction and maintenance of LTP of the C-fiber-evoked field potentials in spinal dorsal horn has not been evaluated. In the present study, we examined the expression of CaMK II and phospho-CaMK II in the lumbar segments (L4-L6) of the rat spinal dorsal horn at 30 min and 3 h after the establishment of LTP induced by tetanic electrical stimulation of the sciatic nerve (40 V, 0.5 ms pulses at 100 Hz for 1 s repeated four times at 10 s intervals) by using Western blot and electrophysiological techniques. To determine the role of the phospho-CaMK II in the induction and maintenance of the spinal LTP, a selective CaMK II inhibitor KN-93 (100 micromol/L) was applied directly onto the spinal cord at the recording segments before and after LTP induction. We found that (1) the protein level of phospho-CaMKII increased at both 30 min and 3 h after LTP induction, while the total protein level of CaMK II increased at 3 h but not at 30 min after LTP induction. (2) Spinal application of KN-93 at 30 min prior to the tetanus blocked both LTP induction and the increase in phospho-CaMK II. (3) 30 min after LTP induction, spinal application of KN-93 depressed LTP and the level of phospho-CaMK II (n=3). (4) Spinal application of KN-93 at 3 h after LTP, however, affected neither the amplitude of the spinal LTP nor the level of phospho-CaMK II in the spinal dorsal horn. These results suggest that activation of CaMK II is probably crucial for the induction and the early-phase maintenance of LTP of C-fiber-evoked field potentials in the spinal dorsal horn.
Animals ; Evoked Potentials ; Long-Term Potentiation ; physiology ; Male ; Nerve Fibers, Unmyelinated ; physiology ; Neural Pathways ; drug effects ; physiology ; Phosphoprotein Phosphatases ; metabolism ; Phosphorylation ; Posterior Horn Cells ; enzymology ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; Spinal Cord ; enzymology ; physiology

By using stereological morphometric techniques, we examined the ultrastructure of synapses in lamine II of the spinal dorsal horn of Sprague Dawley rats 30 min, 3 h and 5 h after long-term potentiation (LTP) induction. We found that the numerical density per unit volume (Nv) of total synapses, the thickness of the postsynaptic density (PSD), width of the synaptic cleft increased significantly after the establishment of LTP. (1) Thirty minutes after the formation of LTP, the thickness of the PSD increased from 0.029 +/-0.0064 microm (control) to 0.036 +/-0.009 microm (P<0.05) and the width of the synaptic cleft increased from 0.0181+/-0.0024 microm (control) to 0.0197+/-0.0029 microm (P< 0.05); the number of synaptic vesicles decreased from 0.122 +/-0.011/microm(2) to 0.085 +/-0.010/microm(2) (P<0.05); (2) 3 h after the formation of LTP, the thickness of PSD and the width of the synaptic cleft had no difference compared with those 30 min after LTP. The number of synaptic vesicles increased from 0.122 +/-0.011/microm(2) to 0.138 +/-0.015/microm(2); the curvature of the synaptic interface increased from 1.153+/-0.195 to 1.386 +/-0.311 (P<0.05, compared with control). Nv of negative synapses increased from 0.0187 +/-0.0056 to 0.0543 +/-0.0152 (P<0.05, compared with control), Nv of perforated synapses also increased from 0.0135 +/-0.0053 to 0.0215 +/-0.0076 (P<0.05, compared with control). These data suggest that the increase in thickness of PSD might be the major morphological change during the induction of LTP, while the increase in curvature of the synaptic interface, and the number of perforated synapses might be responsible for the maintenance of the spinal LTP.
Animals ; Long-Term Potentiation ; physiology ; Male ; Posterior Horn Cells ; physiology ; ultrastructure ; Rats ; Spinal Cord ; anatomy & histology ; physiology ; Synapses ; ultrastructure ; Synaptic Transmission ; Synaptic Vesicles ; ultrastructure

OBJECTIVETo evaluate the efficacy and safety of nateglinide, a new antidiabetic agent, in the treatment of type 2 diabetes.

METHODSA total of 219 treatment-naïve patients with type 2 diabetes from 6 centers were enrolled in this study and blindly divided into nateglinide group (n = 105) and repaglinide group (n = 114). In all patients, the disease was confirmed for at least three months. The whole observation lasted for 12 weeks. The efficacy indicators measured include glycohemoglobin A1c (HbA1c), fasting blood glucose, and 2 hours postprandial blood glucose, and the safety parameters measured included renal and hepatic function, serum lipids, and blood and urea profiles.

RESULTSSimilar decreases in fasting blood glucose, 2 hours postprandial blood glucose, and HbA1 c were found in both nateglinide group and repaglinide group without significant differences. No severe adverse events were noted. The hypoglycemia event reports were not significantly different between these two groups.

CONCLUSIONNateglinide is an effective and safe drug in treating type 2 diabetes.

Blood Glucose ; drug effects ; Cyclohexanes ; administration & dosage ; adverse effects ; therapeutic use ; Diabetes Mellitus, Type 2 ; drug therapy ; Drug Administration Schedule ; Female ; Humans ; Hypoglycemic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Phenylalanine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Treatment Outcome

Objective: To evaluate the prostate health index (PHI) as a tool for the diagnosis of PCa with a PSA level of 4－10 μg/L and determine the best cut-off value of PHI. METHODS: Fifty-eight patients with a PSA level of 4－10 μg/L underwent transrectal ultrasound-guided prostatic biopsy in our hospital between April 2017 and June 2019. We constructed receiver operating characteristic (ROC) curves for the relationship of the biopsy results with the level of PSA, the ratio of ［－2］ proPSA to fPSA and PHI, and calculated the area under the ROC curves (AUC). RESULTS: Prostatic biopsy revealed 18 cases of PCa in the 58 patients (31.0%). Statistically significant differences were observed between the PCa and non-PCa groups in ［－2］ proPSA, %［－2］ proPSA and PHI, but not in tPSA, % fPSA and PSA-density. The AUCs of PSA, % fPSA, PSA-density, ［－2］ proPSA, %［－2］ proPSA and PHI were 0.556, 0.407, 0.533, 0.746, 0.751 and 0.774, respectively. The specificity of PHI was 27.50% (95% CI: 14.6%－43.9%), the highest among the above predictors at 90% sensitivity. By applying PHI to this cohort, 13 cases (22.4%) of unnecessary biopsy could be avoided. CONCLUSIONS The application of PHI can increase the accuracy of PCa prediction and reduce unnecessary prostatic biopsy.、.
Asians ; Humans ; Macau ; Male ; Prostate ; Prostate-Specific Antigen ; Prostatic Neoplasms/diagnosis*

OBJECTIVE: To report an overview of bariatric & metabolic surgery performed in 2018 in North China. METHODS: Based on prospective and observational North China Bariatric & Metabolic Surgery Clinical Database(NC-BMD), the study of evaluating the number and the type of bariatric &metabolic surgery procedures was performed in North China. Demographic characteristic, obesityrelated diseases and operational information were also analyzed. RESULTS: In 2018, 17 centers from 7 regions in North China contributed a total of 728 registration data. Valid data were analyzed from 16 centers. The patients' median (minimum, maximum) BMI pre-surgery was 38.4(24.7,95.2). The overall proportion of female patients was 74.7%, and mean±SD age was(32.5±8.29) years, while male patients was 25.3%, and mean±SD age was (32.7±9.90) years. According the data 93.9% laparoscopic sleeve gastrectomy(LSG), 4.4% laparoscopic Roux-en-Y gastric bypass (LRYGB) and 1.7% other operation types. 29.2% of patients had a history of type 2 diabetes, 69.4% had sleep apnea, and 22.6% had polycystic ovary syndrome before operation. CONCLUSION: The establishment of NC-BMD has laid a solid foundation for data registration in North China. Based on current data, LSG is the mainstream of bariatric and metabolic surgery in North China this year.