Objective To analyze the gene expression profiles in relation to the migration ability of adult human bone marrow-derived neural stem cells (Md-NSCs), and identify the genetic basis of the high migration potential of Md-NSCs in the central nervous system (CNS). Methods Adult human bone marrow stromal celIs(BMSCs) obtained from adult healthy volunteers were induced to differentiate into Md-NSCs in vitro, and the expressions of the genes related to cell invasiveness and metastasis were investigated by microarray analysis. Quantitative real-time PCR (RT-PCR) was used to verify the microarray results. Results The results of microarray analysis revealed significant overexpressions of the genes MMP1, MMP2, MMP17, ITGA3, RhoB, RhoC and RhoD in the Md-NSCs as compared with the expressions in fresh normal human adult bone marrow cells depleted of red blood cells. Quantitative RT-PCR verified the overexpression ofMMP2 gene by 2.84×100 folds, ITGA3 gene by 2.22×102folds, and RhoC gene by 4.92×100 folds. Conclusion The high migration potential of the Md-NSCs in the CNS is probably associated with the overexpression of the genes that promote cell invasiveness and metastasis. These overexpressed genes are also important oncogenes, and therefore the tumorigenicity of the Md-NSCs warrants further investigation.

OBJECTIVETo establish the triple-transgenic mouse model and study their biological characteristics by molecular biology, behavior and pathology.

METHODSHybrid the Tau and amyloid precursor protein (APP)/presenilins (PS1) transgenic mouse, the genotype of offspring mice were identified by PCR. Transcribed target genes were detected by RT-PCR. The protein expression of exogenous genes was detected by Western-blot. The pathological change of neurofibrillary tangles and senile plaque were observed by Bielschowsky silver staining and ABC immunohistochemical method. The changes time of learning and memory were observed by Morris water maze.

RESULTSAPP, PS1 and Tau genes were transcript in Tau/APP/PS1 mice. In 6 to 8 months old Tau/APP/PS1 mice, the neurofibrillary tangles and senile plaque could be found in cortex and hippocampus. In 6 months old Tau/APP/PS1 mice, the learning and memory abilities were worse.

CONCLUSIONWith the behavior change and pathological changes in Tau and beta-amyloid protein (AP), the Tau/APP/PS1 triple-transgenic mice can be used as a further study animal model of AD's pathogenesis and the target of drug treatment.

Alzheimer Disease ; pathology ; Amyloid beta-Protein Precursor ; genetics ; Animals ; Brain ; pathology ; Disease Models, Animal ; Learning ; Male ; Memory ; Mice ; Mice, Transgenic ; Neurofibrillary Tangles ; pathology ; Plaque, Amyloid ; pathology ; Presenilin-1 ; genetics ; tau Proteins ; genetics

OBJECTIVETo evaluate causes and clinical management of postoperative pain after total knee arthroplasty (TKA).

METHODSFrom January 2004 to June 2009, 41 patients (44 knees) with knee pain post TKA were treated. There were 9 male and 32 female patients aging from 51 to 84 years with a mean of 63.5 years. The diagnosis followed to Brown diagnostic system. One case of extraarticular pain was complex regional pain syndrome type 1 (CRPS-1) and underwent conservative treatment, the remaining 5 cases were treated by surgery. Three cases of joint instability, 1 case of patellar baja, 2 cases of soft tissue impingement caused by overhang of the prosthesis, 1 case of popliteal tendon impact underwent conservative treatment, the other 27 cases underwent surgical intervention. The patients were followed up and the Knee Society Score (KSS) knee score, pain visual analog scale (VAS) score were recorded.

RESULTSForty-one cases were followed up for 1 to 6 years. At the last time of follow-up, the 5 cases received surgical treatment to extra-articular pain showed VAS score as 2.5 ± 0.2, KSS clinical and functional score as 92.8 ± 2.6 and 89.0 ± 3.4. There was significantly difference compared with preoperative (P < 0.05). One case of CRPS-1 performed conservative treatment, the therapy was effective. In the infected 12 cases of intra-articular pain, 1 case received amputation, 3 cases received antibiotic bone cement insert, 8 cases received two stage revision. All infections were cured, and VAS score was 3.8 ± 0.2, KSS clinical score was 88.3 ± 4.6, function score was 85.0 ± 4.6 postoperatively, with significantly difference compared with preoperative (P < 0.05). In the 8 cases received conservative treatment in non-infected group, at the last time of follow-up, VAS score was 4.5 ± 0.4, KSS clinical and functional score was 85.4 ± 4.2 and 84.2 ± 2.3, with significantly difference compared with preoperative (P < 0.05). Fifteen cases underwent surgical treatment, at the last time of follow-up, VAS score was 3.4 ± 0.1, KSS clinical and functional score was 86.6 ± 5.4 and 87.1 ± 2.4, with significantly difference compared with preoperative (P < 0.05).

CONCLUSIONSPatients with knee pain post TKA need systematic assessment to identify the causes. Appropriate treatment due to the positive diagnosis generally lead to satisfactory results, surgical intervention with indefinite causes is strictly prohibited.

Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Knee ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pain, Postoperative ; etiology ; therapy ; Retrospective Studies

ObjectiveThe objective of the present study was to compare the pregnancy and perinatal outcomes in women of advanced age between autologous fresh ET and FET cycles. MethodsA retrospective cohort study was conducted， which included 1 622 transfer cycles of 1 622 patients with ≥35 years of age. Patients who received their first embryo transfer cycle （IVF/ICSI treatment） between October 2015 and May 2020 in the center of reproductive medicine of the Third Affiliated Hospital of Sun Yat-sen University were included. Among them， 903 patients had 903 fresh ET cycles， and 719 freeze-all patients received 719 FET cycles. The baseline characteristics， pregnancy outcomes， complication rates， and perinatal outcomes were compared between the two groups. Logistic regression was performed to adjusted for confounding factors. ResultsWomen with advanced age and fresh embryo transfer had significantly higher clinical pregnancy rate ［40.2% vs. 36.6%，OR 95%CI：1.66 （1.323，2.078），P＜0.001］， live birth rate ［29.7% vs. 23.8%，OR 95%CI：1.93 （1.505，2.484），P＜0.001］， and multiple pregnancy rate ［25.1% vs. 12.2%，OR 95%CI：1.89 （1.114，3.190），P＝0.018］ than those with FET cycles. Fresh embryo transfer had significantly decreased miscarriage rate ［25.1% vs. 33.5%，OR 95%CI：0.53 （0.356，0.794），P＝0.002］， Caesarean delivery rate ［70.5% vs. 76.6%，OR 95%CI：0.60 （0.362，0.987），P＝0.044］， and hypertensive disorders of pregnancy ［2.2% vs. 4.6%，OR 95%CI：0.35 （0.128，0.947），P＝0.039］ than those of FET group. There were no significant differences in the rate of ectopic pregnancy， preterm delivery rate， gestational diabetes mellitus. and preterm premature rupture between the two groups （P＞0.05）. FET group had significantly higher mean new born birth weight ［（3 133 ± 612） g vs. （2 977 ± 609） g，P=0.006］. Further age-stratified analysis showed that the clinical pregnancy rate of fresh transfer was significantly higher than that of frozen embryo transfer in patients aged 35-37 years ［47.8% vs. 45.4%，OR 95%CI：1.68 （1.176，2.391），P =0.004］. The live birth rate of fresh embryo transfer in patients aged 35-37 years and 38-39 years was higher than that of frozen embryo transfer ［39.3% vs. 32.9%，OR 95%CI： 1.79 （1.239，2.581），P =0.002］， ［35.5% vs. 30.4%，OR 95%CI： 1.70 （1.023，2.809），P =0.040］ . ConclusionsPatients with advanced age obtain better pregnancy and neonatal outcomes by fresh embryo transfer than by frozen embryo transfer. Patients without contraindications should preferentially choose fresh embryo transfer to improve their pregnancy outcome， reduce the waiting time for embryo transfer， and to avoid the adverse outcomes which increase over time with advanced age.

BACKGROUNDPancreatic beta-cell apoptosis induced by lipotoxicity, to a large extent, contributes to the progression of type 2 diabetes. To investigate the mechanism of free fatty acid induced apoptosis, we aimed to study the effects of palmitic acid (PA) on the apoptosis and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression in βTC3 cells as well as the possible role of nuclear factor-κB (NF-κB) in this process.

METHODSHoechst 33258 was used to detect βTC3 cell apoptosis, which was induced by PA stimulation for 12 hours. PGC-1α expression was analyzed by reverse transcription polymerase chain reaction, IκB kinase β (IKKβ), IκBα, NF-κB-inducing kinase (NIK) and Rel-B expressions were analyzed by Western blotting. MG132 was employed to block the endogenous IκBα degradation before PA administration, and then its effect on PA-inducing cell apoptosis and PGC-1α mRNA expression was analyzed.

RESULTSSignificant increased cell apoptosis was found at the concentration of 0.5 mmol/L and 1.0 mmol/L PA administration. PA (0.5 mmol/L) could extensively reduced the expression of PGC-1α mRNA. After exposing βTC3 cells to 0.5 mmol/L PA for different time periods (0, 4, 6, 8, 10 and 12 hours), IKKβ protein expression increased while IκBα, NIK and Rel-B protein expression declined in a time-dependent manner. Pretreatment with MG132 to inhibit the degradation of IκBα, partially prevented the down-regulation of PGC-1α mRNA expression after 12-hour PA treatment in accordance with the decrease of PA induced apoptosis.

CONCLUSIONSNF-κB canonical pathway was activated in PA-mediated βTC3 cell apoptosis, whereas non-canonical pathway was inhibited. Reduced PGC-1α expression by PA in βTC3 cells could involve the activation of canonical NF-κB pathway, so as to deteriorate the PA induced apoptosis.

Apoptosis ; drug effects ; Cell Line ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Insulin-Secreting Cells ; drug effects ; metabolism ; Leupeptins ; pharmacology ; NF-kappa B ; genetics ; metabolism ; Palmitic Acid ; pharmacology ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects ; Transcription Factors ; genetics ; metabolism

Nicotine enhances the function of learning and memory, but the underlying mechanism still remains unclear. Hippocampal long-term potentiation (LTP) is assumed to be a cellular mechanism of learning and memory. Our previous experiments showed that with the single pulses evoking 80% of the maximal population spike (PS) amplitude, nicotine (10 μmol/L) induced LTP-like response in the hippocampal CA1 region. In the present study, the nicotinic acetylcholine receptor (nAChR) subtypes and relevant neurotransmitter releases involved in LTP-like response induced by nicotine were investigated by extracellularly recording the PS in the pyramidal cell layer in the hippocampal CA1 region in vitro. LTP-like response induced by nicotine was blocked by mecamylamine (1 μmol/L) or κ-bungarotoxin (0.1 μmol/L), but not by dihydro-β-erythtroidine (DHβE, 10 μmol/L). Moreover, it was inhibited by propranolol (10 μmol/L), but not by phentolamine (10 μmol/L) or atropine (10 μmol/L). The results suggest that noradrenaline release secondary to the activation of κ-bungarotoxin-sensitive nAChRs participates in LTP-like response induced by nicotine in the hippocampal CA1 region.
Animals ; Bungarotoxins ; CA1 Region, Hippocampal ; physiology ; Long-Term Potentiation ; drug effects ; Nicotine ; pharmacology ; Norepinephrine ; secretion ; Receptors, Nicotinic ; metabolism

OBJECTIVETo explore the anti-tumor efficacy of anti- vascular endothelial growth factor (VEGF) McAb 5-fluorouracil (5-FU) loaded polylactic acid (PLA) nanoparticles (NPS) in human gastric carcinoma xenografts of nude mice.

METHODSAnti-VEGF McAb 5-FU loaded PLA NPS were made by ultrasound emulsification. Nude mice model of human gastric carcinoma xenografts was established. Therapeutic effects of drugs on human gastric carcinoma xenografts and side effects concerned were observed.

RESULTSThe tumor inhibition rates of control group, nanosphere without 5-FU group, 5-FU (20 mg/kg) group, anti-VEGF McAb nanosphere without 5-FU group, anti-VEGF McAb group, nanosphere with 5-FU group, 5-FU (20 mg/kg) combined with anti-VEGF McAb group, anti-VEGF McAb 5-FU loaded nanosphere group was 0, 6.61%, 24.26%, 27.94%, 35.29%, 37.50%, 39.71% and 52.21% respectively, and there were no significant differences between anti-VEGF McAb 5-FU loaded nanosphere group and nanosphere group without 5-FU in WBC count, serum alanine transferase level or creatinine level. Compared with control group and anti-VEGF McAb 5-FU loaded nanosphere group, the 5-FU group decreased by 34.43% and 37.38% respectively in WBC count (P< 0.05), and increased by 93.17% and 66.56% respectively in alanine transferase. There were significant differences between experimental groups and control group in apoptosis index, especially between anti-VEGF McAb 5-FU loaded nanosphere group and control group (P< 0.05). The microvessel density (MVD) of experimental groups containing anti-VEGF McAb was significantly lower than that of control group or groups containing 5-FU (P< 0.05).

CONCLUSIONAnti-VEGF McAb 5-FU loaded nanosphere can increase the tumor inhibitory rate of 5-FU, induce apoptosis by inhibiting tumor angiogenesis with less side effect, and then enhance therapeutic effect, which indicate its potential as a novel, safe nano-tumor-targeting drug.

Animals ; Antibodies, Monoclonal ; administration & dosage ; pharmacology ; Antimetabolites, Antineoplastic ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Drug Carriers ; Fluorouracil ; administration & dosage ; pharmacology ; Humans ; Lactic Acid ; administration & dosage ; pharmacology ; Mice ; Mice, Nude ; Nanoparticles ; Neovascularization, Pathologic ; Polyesters ; Polymers ; administration & dosage ; pharmacology ; Stomach Neoplasms ; drug therapy ; pathology ; Vascular Endothelial Growth Factor A ; administration & dosage ; pharmacology ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the toxicity of cationic liposome Lipofectamine 2000 (Lipo) in human pancreatic cancer Capan-2 cells.

METHODSCapan-2 cells were cultured in the presence of Lipo at toxic concentrations, and the cell growth, apoptosis and cell cycle changes were evaluated by cell counting and flow cytometry.

RESULTSThe concentrations of both Lipo and siRNA affected the transfection efficiency. In a transfection volume of 2 ml, the presence of 5 microl Lipo resulted in slowed growth of Capan-2 cells, which was especially obvious after 3 days (P<0.001). Prolonged culture of the transfected cells caused significant increases in early apoptotic cells (P<0.05) and in the damaged or necrotic cells (P<0.001), and resulted in reduced viable cells (P<0.01); these changes became obvious after a 48-hour culture, which also increased the ratio of G(0)/G(1) phase cells (P<0.05) and decreased those of G(2)/M phase cells (P<0.01), S phase cells (P<0.01), and the late apoptotic cells (P<0.05).

CONCLUSIONToxic concentrations of Lipo can affect the growth, apoptosis and cell cycles of Capan-2 cells in vitro, and this urges careful concentration selection when using Lipo for gene transfer into different cells.

Apoptosis ; drug effects ; Cations ; toxicity ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Humans ; Lipids ; genetics ; toxicity ; Liposomes ; toxicity ; Pancreatic Neoplasms ; pathology ; RNA, Small Interfering ; genetics ; Transfection

Background::Ophthalmic ambulatory surgery is preferred to be performed under general anesthesia either by total intravenous anesthesia (TIVA) or by inhalational anesthesia to increase the patient comfort. However, anesthesia-controlled time (ACT) can cause increased non-operative operating room (OR) time which may adversely affect the ORs efficiency. This study was aimed to compare the ACT of desflurane with that of propofol-remifentanil in strabismus ambulatory surgery.Methods::From November 2016 to December 2017, a total of 200 strabismus patients (aged 18-60 years old, and scheduled for elective ambulatory surgery at Zhongshan Ophthalmic Center) were randomly assigned to receive either propofol-based TIVA (group TIVA) or desflurane anesthesia (group DES) for maintenance of anesthesia. The primary outcome was the extubation time. Secondary outcomes included surgical time, anesthetic time, OR exit time, and Phase I and II recovery time. The intraoperative incidences of hypotension, bradycardia and oculocardiac reflex (OCR), and the incidences of any post-operative complications were recorded. Mann-Whitney U test and Chi-square or Fisher exact tests were used to compare the two groups. Results::We found that the extubation time (5.5 [3.9-7.0] vs. 9.7 [8.5-11.4] min, P < 0.001) and the incidence of prolonged time to extubation (0 vs. 6%, P = 0.029) in the DES group were significantly decreased compared with those in the TIVA group. The patients in the DES group displayed shorter OR exit time as compared with that in the TIVA group (7.3 [5.5-8.7] vs. 10.8 [9.3-12.3] min, P < 0.001). The patients using desflurane exhibited more stable hemodynamics during surgery than the patients using propofol-based TIVA, as demonstrated by lower incidences of hypotension (1% vs. 22%, P < 0.001), bradycardia (2% vs. 13%, P = 0.002), and OCR (17% vs. 44%, P < 0.001). Conclusion::DES enhanced the ophthalmic OR efficiency by reducing the extubation time and OR exit time, and provided more stable hemodynamics intra-operatively than TIVA in patients undergoing strabismus ambulatory surgery.Trial registration::ClinicalTrials.gov, No. NCT02922660; https://clinicaltrials.gov/ct2/show/NCT02922660?id=NCT02922660&draw=2&rank=1

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.