Objective To examine the neuroprotective effects of amantadine(AMA),a non-competitive NMDA receptor an-tagonist,on the hypoxic-ischemic(HI)brain injury of neonatal rats and the possible mechanisms.Methods Hypoxic-ischemic encephalopathy(HIE)models were established in seven-day-old male and female Sprague-Dawley rats by ligating the right ce-phalic artery and then inhaling 8% oxygen for 2 h.All the rats were divided into 3 groups:control group(n=15),HIE group(n=15),and AMA group(n=45).Animals in AMA group were intranasally treated with AMA at 50 mg/kg 30 min before and 15 min after ligation and 30 min before inhalation(15 rats each used at the three time points).The right-to-left hemispheric weight ratio was calculated 7 days after the HI brain injury.The right hippocampus tissues of rats(n=45)were harvested 24 h after the HI brain injury and the concentrations of IL-1βand IL-6 were detected by ELISA.The outcomes of behavior tests(in-volving 45 rats)including Barnes maze test,motor coordination test and fear conditioning test,were evaluated 30 days after the HI brain injury.Results Intranasal AMA significantly increased the right-to-left hemispheric weight ratio,lowered the concen-trations of IL-1βand IL-6 in the right hippocampus of rats and promoted the behavior functions 15 min after ligation(P<0.05) . Conclusion Intranasal AMA can provide neuroprotection partially by reducing the hippocampal inflammation in the neonatal rats with HI brain injury.

ObjectiveTo observe the effect of penehyclidine hydrochloride (PHC) on serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α ) concentrations following tourniquet deflation in patients undergoing lower limb surgery.Methods Thirty adult patients,scheduled for unilateral lower limb surgery,ASA classification [ - Ⅱ grades,were divided into control group and research group by random number table,each group of 15 cases.Before anesthesia 30 min,PHC in intravenous infusion of 0.01-0.02 mg/kg in research group,the corresponding volume in intravenous infusion of 0.9% sodium chloride in control group.Peripheral venous blood samples were collected immediately before tourniquet inflation (T0,baseline),immediately before tourniquet deflation(T1),30 min (T2) and 60 min (T3) after tourniquet deflation.Serum IL-6 and TNF- α concentrations were measured by enzyme linked immunosorbentassay.ResaltsSerum TNF- α change at the same time point after tourniquet deflation was not statistically significant between two groups (P ＞ 0.05).Serum IL-6 concentration was decreased at each time point after tourniquet deflation compared with T0 in research group,while increased in control group.Serum IL-6concentration difference of T3 and T0 had statistically significant between research group and control group [ (-8.8 ± 5.6) ng/L vs.( 10.2 ± 6.7) ng/L,P＜ 0.05].ConclusionsPHC in advance can decrease serum IL-6 concentration after tourniquet deflation in patients undergoing lower limb surgery.

Objective To evaluate the role of ATP-sensitive potassium (KATP) channel in spinal dorsal horn neurons in hyperalgesia after thoracotomy in rats.Methods Twenty-eight Sprague-Dawley rats,aged 7-9 weeks,weighing 250-350 g,in which intrathecal catheters were successfully implanted without complications on 14th day after chronic post-thoracotomy pain was induced,were randomly divided into 4 groups (n =7 each):control group,the solvent dimethyl sulfoxide (DMSO) group,KATP channel opener pinacidil group (group P) and KATP channel blocker glibenclamide group (group G).10％ DMSO 10 μl,pinacidil 10 μg/10 μl and glibenclamide 50μg/10μ1 were injected intrathecally in groups DMSO,P and G at 5 day after the intrathecal catheter was implanted,respectively.Paw withdrawal threshold to von Frey filament stimulation was measured before intrathecal administration and at 10,30 and 60 min after intrathecal administration and the acetone test was performed.Coldinduced pain threshold was measured.Results There was no significant difference in paw withdrawal threshold to yon Frey filament stimulation at each time point among the four groups (P ＞ 0.05).Compared with C and DMSO groups,cold-induced pain threshold was significantly increased in group P and decreased in group G (P ＜ 0.05).There was no significant difference in cold-induced pain threshold between C and DMSO groups (P ＞ 0.05).Conclusion KATP channel in spinal dorsal horn neurons is involved in the maintenance of hyperalgesia after thoracotomy in rats.

Pancreatic cancer is a devastating disease with the worst prognosis among all the major human malignancies. The propensity to rapidly metastasize contributes significantly to the highly aggressive feature of pancreatic cancer. The molecular mechanisms underlying this remain elusive, and proteins involved in the control of pancreatic cancer cell motility are not fully characterized. In this study, we find that histone deacetylase 6 (HDAC6), a member of the class II HDAC family, is highly expressed at both protein and mRNA levels in human pancreatic cancer tissues. HDAC6 does not obviously affect pancreatic cancer cell proliferation or cell cycle progression. Instead, it significantly promotes the motility of pancreatic cancer cells. Further studies reveal that HDAC6 interacts with cytoplasmic linker protein 170 (CLIP-170) and that these two proteins function together to stimulate the migration of pancreatic cancer cells. These findings provide mechanistic insight into the progression of pancreatic cancer and suggest HDAC6 as a potential target for the management of this malignancy.
Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Knockdown Techniques ; Histone Deacetylase 6 ; Histone Deacetylases ; metabolism ; Humans ; Microtubule-Associated Proteins ; metabolism ; Neoplasm Proteins ; metabolism ; Pancreatic Neoplasms ; enzymology ; metabolism ; pathology ; Protein Binding

Objective:To explore the diagnostic value of clinical, multi-parameter magnetic resonance imaging (MP-MRI) combined with transrectal ultrasound elasticity data for prostate cancer.Methods:A retrospective analysis was conducted on patient data from November 2021 to March 2023 when transrectal prostate two-dimensional ultrasound, real-time strain elastography of the prostate, MP-MRI examination of the prostate, and prostate biopsy were performed simultaneously at the Meizhou People′s Hospital. We collected patient age, height, weight, free serum prostate specific antigen (fPSA), total prostate specific antigen (tPSA), fPSA/tPSA, MRI prostate imaging report and data system (PI-RADS) scores, and ultrasound elasticity values. Four predictive models for prostate cancer diagnosis were constructed using multivariate logistic regression for comparison, and the optimal model was selected to construct a column chart. The diagnostic performance of different models was evaluated using receiver operating characteristic (ROC) curves, and the diagnostic performance of column charts was evaluated using calibration curves.Results:This study included a total of 117 patients with 117 prostate lesions, 47 benign prostate lesions, and 70 prostate cancer lesions. There were statistically significant differences in age, fPSA, tPSA, fPSA/tPSA, PI-RADS scores, and ultrasound elasticity values between benign and malignant lesions patients (all P<0.01). The area under the curve (AUC) of the clinical model (age+ tPSA+ fPSA+ fPSA/tPSA), MRI model (PI-RADS score), ultrasound elastic model, and clinical+ MRI+ ultrasound elastic combined model for diagnosing prostate cancer were 0.86, 0.86, 0.92, and 0.98, respectively. Conclusions:Compared with a single diagnostic model, the combination of age, tPSA, fPSA/tPSA, PI-RADS scores, and ultrasound elasticity value model can improve the diagnostic rate of prostate cancer.

Histone deacetylase 6 (HDAC6), a predominantly cytoplasmic protein deacetylase, participates in a wide range of cellular processes through its deacetylase activity. However, the diverse functions of HDAC6 cannot be fully elucidated with its known substrates. In an attempt to explore the substrate diversity of HDAC6, we performed quantitative proteomic analyses to monitor changes in the abundance of protein lysine acetylation in response to HDAC6 deficiency. We identified 107 proteins with elevated acetylation in the liver of HDAC6 knockout mice. Three cytoplasmic proteins, including myosin heavy chain 9 (MYH9), heat shock cognate protein 70 (Hsc70), and dnaJ homolog subfamily A member 1 (DNAJA1), were verified to interact with HDAC6. The acetylation levels of these proteins were negatively regulated by HDAC6 both in the mouse liver and in cultured cells. Functional studies reveal that HDAC6-mediated deacetylation modulates the actin-binding ability of MYH9 and the interaction between Hsc70 and DNAJA1. These findings consolidate the notion that HDAC6 serves as a critical regulator of protein acetylation with the capability of coordinating various cellular functions.
Acetylation ; Actins ; chemistry ; metabolism ; Animals ; Cell Line ; Chromatography, High Pressure Liquid ; HSC70 Heat-Shock Proteins ; metabolism ; HSP40 Heat-Shock Proteins ; metabolism ; Histone Deacetylase 6 ; Histone Deacetylases ; metabolism ; Isotope Labeling ; Liver ; metabolism ; Lysine ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microscopy, Confocal ; Nonmuscle Myosin Type IIA ; metabolism ; Protein Binding ; Proteomics ; Substrate Specificity ; Tandem Mass Spectrometry

Objective To evaluate the effect of continuous transversus abdominis plane (TAP) block on postoperative systemic inflammatory responses of patients undergoing laparoscopic radical surgery for colorectal cancer.Methods Ninety-eight patients,aged 45-64 yr,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,weighing 50-75 kg,scheduled for elective laparoscopic radical surgery for colorectal cancer under general anesthesia,were divided into continuous patient-controlled epidural analgesia (PCEA) group (group PCEA) and continuous TAP block group (group TAPB) using a random number table,with 49 patients in each group.An epidural catheter was placed at L1,2 interspace,a test dose of 3 ml of 2％ lidocaine was given,and morphine 2 mg (in 10 ml of normal saline) was injected into the epidural space at the end of surgery in group PCEA.PCEA solution contained 0.15％ ropivacaine and sufentanil 2 μg/ml (diluted to 300 ml in normal saline).PCA pump was set up with a 2 ml bolus dose,a 20 min lockout interval and background infusion at a rate of 4 ml/h.Catheterization of bilateral transversus abdominis plane was accomplished under ultrasound guidance,and 0.3％ ropivacaine 20 ml was injected in group TAPB.TAP block solution contained 0.15％ ropivacaine (diluted to 300 ml in normal saline).PCA pump was set up with a 6 ml bolus dose,a 30 min lockout interval and background infusion at a rate of 6 ml/h.Analgesia lasted until 48 h after surgery,and visual analogue scale score was maintained less than or equal to 3 in both groups.Parecoxib sodium 40 mg was intravenously injected as a rescue analgesic when visual analogue scale score was more than 3.Blood samples were collected from the right internal jugular vein at 24 h before operation (T0) and 48 h after operation (T1) for determination of the expression of CXCL8 mRNA in serum (by real-time polymerase chain reaction) and expression of CXCL8 and STAT3 in serum (by Western blot).The development of requirement for rescue analgesia,sensory motor dysfunction of lower extremities and nausea and vomiting after surgery was recorded.Results Compared with the baseline at T0,the expression of serum CXCL8 mRNA,CXCL8 and STAT3 was significantly up-regulated at T1 in the two groups (P＜ 0.05).Compared with group PCEA,the expression of serum CXCL8 mRNA and STAT3 was significantly down-regulated at T1,the incidence of sensory motor dysfunction of lower extremities was decreased (P＜0.05),and no significant change was found in the expression of serum CXCL8,requirement for rescue analgesia or incidence of nausea and vomiting in group TAPB (P＞0.05).Conclusion Continuous TAP block can reduce postoperative systemic inflammatory responses of patients undergoing laparoscopic radical surgery for colorectal cancer.

Objective To analyze and investigate the risk factors for intraoperative and postoperative bleeding complications of stent implantation for ruptured intracranial aneurysms(from rupture to operation time ≤14 d). Methods A total of 249 consecutive patients with aneurysmal subarachnoid hemorrhage (aSAH)treated with stent intravascular interventional therapy at the Department of Neurosurgery,Tangdu Hospital,the Second Hospital Affiliated to Air Force Medical University(the Fourth Military Medical University)from August 2014 to July 2017 were enrolled retrospectively.According to whether having intraoperative and postoperative bleeding complications,they were divided into either a hemorrhage complication group(n=33)or a non-complication group(n=216).The baseline data,clinical data,and aneurysm characteristics,including age,sex,hypertension,Glasgow Coma Scale(GCS)score,aSAH to the patients were documented and analyzed,and multivariate logistic regression analysis was used to analyze the risk factors for bleeding complications. Results (1)The incidence of perioperative bleeding complications was 13. 3% (33 /249). (2)There was significant difference in GCS scores between the bleeding complication group and the non-complication group (P < 0. 05). There were no significant differences in age,male,hypertension,and aSAH to operation time between the two groups (all P >0. 05). (3)There were significant differences in Hunt-Hess grade (χ2 = 10. 392,P = 0. 001),Fisher score (χ2 = 7. 370,P =0. 007),number of aneurysms (χ2 = 4. 825,P = 0. 028),and aneurysm location (χ2 = 6. 818, P = 0. 033)between the bleeding complication group and the non-complication group. There were no significant differences in Raymond grade between the two groups (P > 0. 05). (4)Taking the occurrence of bleeding complications as a dependent variable,a further multivariate logistic regression analysis on Hunt- Hess grades Ⅲ-Ⅴ and multiple aneurysms was performed after variable screening,the results showed that Hunt-Hess grades Ⅲ-Ⅴ(OR,3. 658,95% CI 1. 660 -8. 061)and multiple aneurysms (OR,2. 667,95% CI 1.178-6.036)were the independent risk factors for stent placement in the treatment of bleeding complications of ruptured intracranial aneurysms(all P <0.05). Conclusions The single stent and stent-assisted coils can be used for endovascular treatment of rupture intracranial aneurysms,but preoperative Hunt-Hess grades Ⅲ-Ⅴ and multiple aneurysms are easy to cause perioperative bleeding complications in patients with aSAH.

Objective:To investigate the application value of Clavien-Dindo classification in evaluation of postoperative short-term complications of Da Vinci robotic-assisted or laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy. Methods:The retrospective cohort study was conducted. The clinicopathological data of 262 patients with gastric cancer who were admitted to the 940th Hospital of Joint Logistic Support Force of Chinese People′s Liberation Army from January 2016 to January 2019 were collected. There were 214 males and 48 females, aged (58±11) years, with a range from 17 to 81 years. Of 262 patients, 120 cases undergoing Da Vinci robotic-assisted total gastrectomy + D 2 lymphadenectomy + Roux-en-Y anastomosis were divided into robotic group, and 142 cases undergoing laparoscopic-assisted total gastrectomy + D 2 lymphadenectomy + Roux-en-Y anastomosis were divided into laparoscopic group. Observation indicators: (1) intraoperative and postoperative situations; (2) postoperative pathological examination; (3)complications; (4) stratified analysis; (5) follow-up. Follow-up using outpatient examination and telephone interview was performed to detect complications, tumor recurrence and survival of patients within postoperative 2 months. The follow-up was up to May 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ranked data between groups was analyzed using the rank sum test. Results:(1) Intraoperative and postoperative situations: cases undergoing conversion to open surgery, the operation time, volume of intraoperative blood loss, the number of lymph node dissected, time to first flatus, time to initial fluid diet intake, duration of postoperative hospital stay of the robotic group were 1, (243±42)minutes, 100 mL(range, 100-150 mL), 38±15, (2.8±1.0)days, 3 days(range, 3-4 days), 11 days(range, 9-13 days), respectively. The above indicators of the laparoscopic group were 2, (244±38)minutes, 100 mL(range, 100-150 mL), 34±14, (3.2±1.0)days, 4 days(range, 3-5 days), 10 days(range, 9-13 days), respectively. There were significant differences in the number of lymph node dissected, time to first flatus, time to initial fluid diet intake between the two groups ( t=2.068, -3.030, Z=-3.370, P<0.05), and there was no significant difference in cases undergoing conversion to open surgery, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay between the two groups ( χ2=0.000, t=-0.158, Z=-1.824, -0.088, P>0.05). (2) Postoperative pathological examination: cases with well differentiated tumor, moderately differentiated tumor, poorly differentiated tumor, signet ring cell carcinoma or other types of tumor, cases in stage T1b, T2, T3 or T4a (pT staging), cases in stage N0, N1, N2, N3a or N3b (pN staging), cases in stage ⅠB, ⅡA, ⅡB, ⅢA, ⅢB or ⅢC (pTNM staging) of the robotic group were 6, 50, 55, 9, 10, 22, 63, 25, 42, 19, 19, 24, 16, 17, 22, 23, 20, 23, 15, respectively. The above indicators of the laparoscopic group were 4, 42, 84, 12, 6, 18, 81, 37, 39, 27, 32, 19, 25, 13, 19, 28, 39, 16, 27, respectively. There was no significant difference in the above indicators between the two groups ( Z=-1.880, -1.827, -0.140, -1.460, P>0.05). (3) Complications: cases with complication classified as grade Ⅰ, grade Ⅱ, grade Ⅲa, grade Ⅲb, grade Ⅳa, grade Ⅳb of Clavien-Dindo classification, cases with death, cases with overall complications, cases with severe complications of the robotic group were 9, 6, 3, 2, 2, 0, 0, 22, 7, respectively. The above indicators of the laparoscopic group were 12, 15, 9, 6, 3, 1, 1, 47, 20, respectively. There were significant differences in cases with overall complications, cases with severe complications between the two groups ( χ2=7.309, 4.790, P<0.05), and there was no significant difference in cases with complication classified as grade Ⅰ, grade Ⅱ, grade Ⅲa, grade Ⅲb, grade Ⅳa, grade Ⅳb of Clavien-Dindo classification, cases with death between the two groups ( χ2=0.080, 2.730, 1.042, 0.704, 0.000, 0.000, 0.000, P>0.05). (4) Stratified analysis: of the patients with overall complications in robotic group, cases of male or female, cases aged ≥65 years or <65 years, cases with body mass index (BMI) ≥24 kg/m 2 or <24 kg/m 2, cases with tumor diameter ≥5 cm or <5 cm, cases with or without abdominal surgery, cases with tumor located at upper stomach or middle stomach, cases in Ⅰ-Ⅱ grade or Ⅲ grade of American Society of Anesthesiologists (ASA) classification, cases with well differentiated tumor or undifferentiated tumor, cases in stage Ⅰ-Ⅱ or stage Ⅲ (pTNM staging), cases with operation time ≥250 minutes or <250 minutes, cases with volume of intraoperative blood loss ≥150 mL or <150 mL, cases with the number of lymph node dissected ≥25 or <25 were 15, 7, 14, 8, 11, 11, 16, 6, 4, 18, 19, 3, 15, 7, 7, 15, 8, 14, 12, 10, 12, 10, 14, 8, respectively. The above indicators of patients with overall complications in the laparoscopic group were 33, 14, 17, 30, 16, 31, 36, 11, 11, 36, 27, 20, 31, 16, 13, 34, 14, 33, 24, 23, respectively. Of the patients with overall complication, there were significant differences in cases of male, cases aged ≥65 years or <65 years, cases with BMI<24 kg/m 2, cases with tumor diameter≥5 cm, cases without abdominal surgery, cases with tumor located at middle stomach, cases in Ⅰ-Ⅱ grade or Ⅲ grade of ASA classification, cases with well differentiated tumor, cases in stage Ⅲ (pTNM staging), cases with operation time ≥250 minutes, cases with volume of intraoperative blood loss <150 mL, cases with the number of lymph node dissected ≥25 between the two groups ( χ2=6.683, 4.207, 6.761, 7.438, 4.297, 6.325, 9.433, 3.970, 4.850, 4.911, 3.952, 3.915, 6.865, 4.128, P<0.05) and there was no significant difference in cases of female, cases with BMI≥24 kg/m 2, cases with tumor diameter <5 cm, cases with abdominal surgery, cases with tumor located at upper stomach, cases with undifferentiated tumor, cases in stage Ⅰ-Ⅱ (pTNM staging), cases with operation time < 250 minutes, cases with volume of intraoperative blood loss ≥150 mL, cases with the number of lymph node dissected <25 between the two groups ( χ2=0.277, 1.052, 1.996, 1.552, 2.172, 2.594, 2.244, 3.771, 1.627, 3.223, P>0.05). (5) Follow-up: 262 patients were followed up postoperatively for 2 months. During the follow-up, no patient was diagnosed with tumor recurrence, and one patient in the laparoscopic group died of severe infection. Conclusions:The Clavien-Dindo classification can be used in evaluating postoperative short-term complications of Da Vinci robotic-assisted or laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy. Compared with laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy, Da Vinci robotic-assisted total gastrectomy with D 2 lymphadenectomy has the advantages of minimally invasiveness, low incidence of overall and severe complication.

OBJECTIVE: To investigate the effect of ulinastatin pretreatment on isoflurane-induced mitochondria-dependent neuronal apoptosis in the hippocampus of rats. METHODS: Thirty-six male SD rats were randomly assigned into control group, isoflurane group and ulinastatin group. In the latter two groups, the rats were subjected to acute exposure to 0.75% isoflurane for 6 h and pretreated with 50 000 U/kg of ulinastatin before isoflurane exposure, respectively. After the treatments, apoptosis of the hippocampal neurons was detected using TUNEL assay, and the mitochondrial membrane potential (△ ψm) was measured using JC-1 mitochondrial membrane potential kit; cytochrome C release and caspase-3 activity were examined with Western blotting, and intracellular reactive oxygen species (ROS) was detected using the fluorescent probe H2DCFDA. RESULTS: Compared with those in the control group, the rats with acute exposure to isoflurane showed markedly increased TUNEL-positive cells in the hippocampus ( < 0.05), which were obviously reduced by ulinastatin pretreatment ( < 0.05). The △ψm of the hippocampal neurons was significantly reduced after isoflurane exposure ( < 0.05), and was partly recovered by ulinastatin pretreatment ( < 0.05). Acute exposure to isoflurane resulted in obviously increased cellular ROS, cytochrome C release and caspase-3 activity in the hippocampal neurons ( < 0.05), and these changes were significantly inhibited by ulinastatin pretreatment ( < 0.05). CONCLUSIONS Ulinastatin pretreatment provides neuroprotection against isoflurane-induced apoptosis of the hippocampal neurons in rats possibly by inhibiting mitochondria-dependent apoptosis pathway.
Animals ; Apoptosis ; Glycoproteins ; Hippocampus ; Isoflurane ; Male ; Rats ; Rats, Sprague-Dawley