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 investigate the relationship between the single nucleotide polymorphisims in pre-miR-146a rs2910164 and miR-146a expression in rheumatoid arthritis(RA).MethodsPolymerase chain reaction- ligation detection reaction (PCR-LDR) was used to detect the pre-miR-146a rs2910164 single nucleotide polymorphisms in 123 patients with rheumatoid arthritis (RA) and 220 healthy controls.Expression of miR-146a in peripheral blood mononuclear cells was studied using quantitative realtime polymerase chain reaction (qRT-PCR) in 68 RA patients,10 osteoarthritis (OA) patients and 20 healthy controls.After application of glucocorticoid and NSAIDS combined with DMARDS for three months in 10 patients with active RA,miR-146a expression was again analyzed by qRT-PCR.Clinical characteristics including sex,age at onset,rheumatoid factor (RF),anti-cyclic citrullinated peptide (anti-CCP) antibody,RA activity (DAS28 ≥3.2) and bone erosion (X-ray ＞ Ⅰ stage) were taken into account.X2 test,One-Way ANOVA,t test and Pearson correlation were used for statistical analysis.ResultsThe polymorphisms of the pre-miR-146a rs2910164 were not correlated with susceptibility to RA (P＞0.05).There were no associations between pre-miR-146a rs2910164 genotypes and sex,age at onset,status of RF and antiCCP,RA activity,bone erosion and miR-146a expression in RA patients (P＞0.05 for each).MiR-146a expression was significantly higher in RA patients than that in OA patients and that in healthy controls( P＜0.01 for each) but did not differ between the latter two groups (P＞0.05).MiR-146a expression was significantly higher in active RA patients than that in inactive patients and that in healthy individuals (P＜0.01 for each).After treatment,miR-146a expression and DAS28 score were lower obviously (P＜0.05,P＜0.01,respectively).MiR-146a expression was positively correlated to ESR,CRP and DAS28 score (P＜0.01 for each),but not to RF titer and anti-CCP antibody titer (P＞0.05 for each).ConclusionThe polymorphisms of the pre-miR-146a rs2910164 are not associated with susceptibility to RA,and not correlated with clinical characteristics and miR-146a expression in RA patients.MiR-146a expression is upregulated in patients with RA,and may be a potentially useful marker of disease activity in these patients.

Objective To investigate the clinical efficacy of open abdomen management for severe abdominal infection.Methods The clinical data of 36 patients with severe abdominal infection who were admitted to the General Hospital of Lanzhou Military Command from January 2009 to January 2014 were retrospectively analyzed.After examination,patients received resuscitation and debridement according to the principle of damage control surgery.The surgery was divided into 2 stages.Open abdomen management was applied during the first stage,and 14 days later second stage surgery for abdominal closure was carried out when the abdominal infection was under control.Abdominal pus was collected during the operation for bacterial culture.Antishock,anti-infection,organ function protection,nutritional support and symptomatic treatment were applied after the operation.Patients were followed up via phone call and out-patient examination till March 2014.Results All the patients successfully received the first and the second stage surgeries.Six patients died of septic shock and multi-organ dysfunction syndrome,and 30 patients were cured.Eight patients underwent operation for 2 times.The operation time,volume of intraoperative blood loss,time for gastrointestinal function recovery,duration of postoperative hospital stay were (157 ±26) minutes,(230 ±64)mL,(44 ± 7) hours and (16 ± 5) days,respectively.Forty-eight bacterial strains were separated,including 31 gram-negative bacterial strains and 17 gram-positive bacterial strains.According to the results of drug sensitivity test,antibiotics including imipenem and cefoperazone were selected.Thirty patients were followed up with the median time of 6 months.Six patients were complicated with adhesive intestinal obstruction and 2 with incisional hernia,and they were cured after enterodialysis and hernia repair.No complications were detected in the other 22 patients.Conclusion The efficacy of open abdomen management and debridement is satisfactory for the treatment of severe abdominal infection in patients who can bear surgery.

Objective: To evaluate the short-term efficacy of R-type jejunal interposition and esophagojejunostomy by delta-shaped anastomosis after totally laparoscopic radical gastrectomy for gastric stump carcinoma. Methods:Data on 10 patients with gas-tric stump cancer were analyzed retrospectively from January 2013 to August 2014. All the patients received R-type jejunal interposi-tion and esophagojejunostomy by delta-shaped anastomosis after totally laparoscopic radical gastrectomy for gastric stump carcinoma (laparoscope group) in the Lanzhou General Hospital of the Lanzhou Military Area. Laparotomy was performed on 18 cases that com-prised the control group (laparotomy group). The intraoperative and postoperative indicators between these two groups were then com-pared. All the patients were followed-up from 14 to 21 months after the operations. Results:The operations were successfully carried out in all 10 patients (laparoscope group), without performing open operation. The mean operative times, volumes of the intraoperative blood loss, numbers of dissected lymph nodes, frequencies of leaving the bed, days marking the first liquid diet intake, days marking the recovery of gastrointestinal function, and days of hospitalization of the laparoscope group and the laparotomy group were (210.0 ± 30.9) min and (283.9 ± 50.9) min, (90.0 ± 26.7) mL and (277.8 ± 79.1) mL, (19.0 ± 3.6) and (18.8 ± 3.7), (17.3 ± 3.6) h and (75.8 ± 15.7) h, (1.6 ± 0.4) d and (5.7 ± 1.3) d, (3.0 ± 0.8) d and (7.2 ± 1.3) d, and (7.6 ± 1.2) d and (20.8 ± 3.9) d, respectively. Anastomotic stricture, reflux esophagitis, bleeding, leakage, dumping syndrome, or intestinal obstruction was not detected in the laparoscope group. There was no perioperative death. All of the cases exhibited good nutrition situation, and no choking or esophagus burning was reported. Conclusion:R-type jejunal interposition and esophagojejunostomy by delta-shaped anastomosis after totally laparoscopic radical gastrectomy is safe and feasible. The operation can improve the quality of life of patients and induce positive short-term therapeutic effects. Laparo-scopic-assisted radical gastrectomy for gastric stump cancer has the same effect as laparotomy.

Angiogenesis, the expansion of preexisting blood vessels, is a complex process required for tumor growth and metastasis. Although current antiangiogenic strategies have shown promising results in several cancer types, identification of additional antiangiogenic targets is required to improve the therapeutic response. Herein, we show that the microtubule-binding protein CLIP-170 (cytoplasmic linker protein of 170 kDa) is highly expressed in breast tumor samples and correlates positively with blood vessel density. Depletion of CLIP-170 significantly impaired vascular endothelial tube formation and sprouting in vitro and inhibited breast tumor growth in mice by decreasing tumor vascularization. Our data further show that CLIP-170 is important for the migration but not the proliferation of vascular endothelial cells. In addition, CLIP-170 promotes the polarization of endothelial cells in response to the angiogenic stimulus. These findings thus demonstrate a critical role for CLIP-170 in tumor angiogenesis and suggest its potential as a novel antiangiogenic target.
Animals ; Breast Neoplasms ; blood supply ; metabolism ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Polarity ; Female ; Human Umbilical Vein Endothelial Cells ; Humans ; MCF-7 Cells ; Mice ; Mice, Nude ; Microtubule-Associated Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Microtubules ; metabolism ; Neoplasm Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Neovascularization, Pathologic ; RNA Interference ; RNA, Small Interfering ; metabolism ; Transplantation, Heterologous

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.

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.

Adenomatous Polyposis Coli Protein ; chemistry ; metabolism ; Amino Acid Sequence ; Chromatography, High Pressure Liquid ; HeLa Cells ; Humans ; Kinesin ; chemistry ; metabolism ; Microtubule-Associated Proteins ; chemistry ; metabolism ; Microtubules ; metabolism ; Molecular Sequence Data ; Phosphopeptides ; analysis ; Phosphorylation ; Protein Multimerization ; Tandem Mass Spectrometry

Paclitaxel is a microtubule-targeting agent widely used for the treatment of many solid tumors. However, patients show variable sensitivity to this drug, and effective diagnostic tests predicting drug sensitivity remain to be investigated. Herein, we show that the expression of end-binding protein 1 (EB1), a regulator of microtubule dynamics involved in multiple cellular activities, in breast tumor tissues correlates with the pathological response of tumors to paclitaxel-based chemotherapy. In vitro cell proliferation assays reveal that EB1 stimulates paclitaxel sensitivity in breast cancer cell lines. Our data further demonstrate that EB1 increases the activity of paclitaxel to cause mitotic arrest and apoptosis in cancer cells. In addition, microtubule binding affinity analysis and polymerization/depolymerization assays show that EB1 enhances paclitaxel binding to microtubules and stimulates the ability of paclitaxel to promote microtubule assembly and stabilization. These findings thus reveal EB1 as a critical regulator of paclitaxel sensitivity and have important implications in breast cancer chemotherapy.
Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Female ; Humans ; MCF-7 Cells ; Microtubule-Associated Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Microtubules ; chemistry ; metabolism ; Paclitaxel ; pharmacology ; therapeutic use ; RNA Interference ; RNA, Small Interfering ; metabolism