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Objective:To evaluate the efficacy of bupivacaine pamoate for sciatic nerve block in rats.Methods:Forty-eight SPF healthy male Sprague-Dawley rats, weighing 300-400 g, were divided into 6 groups using a random number table method: bupivacaine pamoate vehicle group (group VE), bupivacaine HCl group (group BH), liposomal bupivacaine group (group BL), low-dose bupivacaine pamoate group (group HL), moderate-dose bupivacaine pamoate group (group HM) and high-dose bupivacaine pamoate group (group HH), with 8 animals in each group.In VE, BH, BL, HL, HM and HH groups, bupivacaine pamoate vehicle 0.4 ml, bupivacaine HCl solution 0.4 ml, liposomal bupivacaine suspension 0.4 ml, and 1, 3 and 10 mg/ml bupivacaine pamoate suspension 0.4 ml were injected around the left sciatic nerve, respectively.The thermal paw withdrawal latency were measured before administration (T 0) and at 0.5, 1.5, 3, 5, 8, 12, 16, 24 and 48 h after injection (T 1-9). The percentage of maximum possible effect (MPE) of thermal paw withdrawal latency was calculated, and motor function score was simultaneously performed to evaluate the efficacy of sensory and motor block.Five and three rats in each group were sacrificed at 2 and 7 days after administration (T 9, 10), respectively, and the sciatic nerve at the injection site and the surrounding muscle tissues were harvested for microscopic examination (with a light microscope) after Luxol fast blue and HE staining.Nerve damage and inflammatory responses were assessed and scored to evaluate neurotoxicity. Results:Compared with group VE, the MPE was significantly increased at T 1-4 in group HL, at T 1-8 in group HM and at T 1-8 in group HH, the motor function scores were decreased at T 1-4 in group HL, at T 1-5 in group HM and at T 1-7 in group HH ( P<0.05), and no significant change was found in inflammatory response scores for the sciatic nerve and surrounding muscles at each time point in HL, HM and HH groups ( P>0.05). Compared with group BH, the MPE was significantly increased at T 3-8, motor function scores were decreased at T 3-5, and inflammatory response scores for the muscles around the sciatic nerve were decreased at T 9 in group HM ( P<0.05). Compared with group BL, the MPE was significantly increased at T 3-7, motor function scores were decreased at T 4, 5, and inflammatory response scores for the sciatic nerve and surrounding muscles were decreased at T 9 in group HM ( P<0.05). The nerve damage score was 0 in the six groups. Conclusion:Bupivacaine pamoate can block the sciatic nerve of rats, the duration of block is prolonged with the increase in the concentration, and the duration of motor block is not longer than that of sensory block; compared with the same concentration and equal volume of bupivacaine HCl and liposomal bupivacaine, bupivacaine pamoate produces longer duration of sciatic nerve block and less neurotoxicity.
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Purpose@#Effective predictors of the response to neoadjuvant chemotherapy (NAC) are still insufficient. This study aimed to investigate the predictive value of serum lipid profiles for the response to NAC in breast cancer patients. @*Methods@#A total of 533 breast cancer patients who had received NAC were retrospectively studied. The pretreatment of serum lipids, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein-α, and clinicopathological characteristics were collected to assess their predictive roles. @*Results@#Breast cancer patients had significantly lower TC, TG, HDL-C, and LDL-C levels than normal individuals. Among these indicators, TG and LDL-C levels and HDL-C level increased and decreased significantly after NAC, respectively. In estrogen receptor (ER)-positive patients, increased LDL-C level was associated with better outcomes. Moreover, the receiver operating characteristic curve analyses suggested that TG and HDL-C levels at diagnosis can be used as predictors of the response to NAC only in the ER-positive subgroup.According to univariate analyses, patients with low TG level (< 1.155 mmol/L) or high HDL-C level (≥ 1.305 mmol/L) in the ER-positive subgroup had more favorable clinical responses than the other patients in the subgroup. Furthermore, according to multivariate analyses, a high HDL-C level (≥ 1.305 mmol/L, p = 0.007) was an independent predictor of NAC efficacy. @*Conclusion@#High HDL-C level (≥ 1.305 mmol/L) before NAC and increased LDL-C level after NAC were associated with the better treatment response in ER-positive breast cancer patients.These results are potentially considered beneficial in establishing treatment decisions.
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Objective To observe the efficacy of percutaneous transhepatic biliary drainage (PTBD) combined with transarterial chemoembolization (TACE) in treatment of malignant obstructive jaundice, and to evaluate its application value in clinic. Methods A total of 82 patients with malignant obstructive jaundice who received PTBD from January 2017 to January 2019 in Taiyuan Central Hospital were collected. The patients were divided into the experimental group who received TACE (41 cases) and the control group who could not receive TACE (41 cases) after PTBD. Clinical symptoms, liver function, tumor markers, drainage tube patency rate and survival time of the two groups were compared before and after the treatment. T-test and chi-square test were used for statistical analysis, and Kaplan-Meier method was used for survival analysis. Results A total of 93 drainage tubes were placed in 82 patients, and 109 TACE treatments were performed in the experimental group. PTBD and TACE both had successful results. After PTBD, 72 patients felt jaundiceand obvious alleviation of other clinical symptoms. There were no serious complications after PTBD and TACE. Postoperative follow-up results showed that compared with the total bilirubin (TBIL) [(269±113)μmol/L], the direct bilirubin (DBIL) [(159 ±74) μmol/L], alanine transaminase (ALT) [(118 ±40) U/L] and aspartate aminotransferase (AST) [(111±55) U/L] before the operation, the TBIL [(46±11)μmol/L], DBIL [(28±10)μmol/L], ALT [(35±12) U/L] and AST [(33±12) U/L] in the experimental group were decreased significantly 3 months after the operation, and the differences were statistically significant (all P<0.05). TBIL [(48±9)μmol/L], DBIL [(25±10) μmol/L], ALT [(32±9) U/L] and AST [(30±12) U/L] in the control group were decreased significantly compared with TBIL [(291±114)μmol/L, DBIL [(171±66)μmol/L], ALT [(129±54) U/L] and AST [(114±43) U/L] before the operation, and the differences were statistically significant (all P< 0.05). There was no significant difference in liver function between the two groups before the operation and 3 months after the operation (both P>0.05). The level of carbohydrate antigen-199 in the experimental group at 6 months after PTBD was lower than that in the control group [(426 ±136) U/ml vs. (569 ±204) U/ml; t = 19.457, P < 0.05]. There were statistical differences in the patency rate of the both groups at 6, 9 and 12 months after PTBD (all P< 0.05). The median survival time in the experimental group was longer than that in the control group (310.4 d vs. 234.5 d; χ2= 12.678, P< 0.05). Conclusion The effect of PTBD in patients with malignant obstructive jaundice is obvious. The combination with TACE after PTBD can prolong the survival of patients and it is worthy of clinical application.
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Objective To improve the understanding of cutaneous intravascular natural killer/T-cell lymphoma (CIVNKTC). Methods Clinical data on five cases of CIVNKTC were collected. The histopathological feature, treatment and prognosis of CIVNKTC were retrospectively analyzed and discussed. Results Of the 5 patients, 1 was male and 4 were female. The age of onset ranged from 38 to 83 years (average, 56.2 years). All the patients presented with multiple plaques and nodules as the primary symptoms. Histopathological examination revealed vasodilatation in the dermis and subcutaneous tissue, as well as atypical lymphoid cells with large hyperchromatic nuclei containing 1-2 small nucleoli in dilated veins. Immunohistochemical studies of tumor cells showed positive staining for CD3ε, cytotoxic proteins (including T cell-restricted intracellular antigen-1, granzyme B and perforin)and Epstein-Barr virus(EBV)-encoded microRNA, but negative staining for cytokeratin, CD20, CD79a, CD4 and CD8. Furthermore, the tumor cells stained positive for CD56 in two patients. Among the 5 patients, only 2 received chemotherapy and the remaining received no treatment. During a 24-month follow-up, 4 patients died, and only 1 survived with the tumor. Conclusion CIVNKTC is a rare extranodal Hodgkin′s lymphoma with distinct histologic manifestations and immunophenotypes, rapid and aggressive clinical course, and poor prognosis.
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Objective To evaluate the clinical effect of preservation of parotid masseter fascia and sternocleidomastoid muscle flap in preventing facial concave deformity and Frey’ s syndrome. Methods 110 patients with parotid gland benign tumor were selected and ran-domly divided into treatment group(56 cases) and control group(54 cases). The treatment group was filled with sternocleidomastoid muscle flap at once and remained parotid masseter fascia in operation. The control group got parotidectomy only. All the cases were followed-up. Re-sults All the cases were successful during a follow-up period of 3~24 months. The treatment group was better than the control group at pre-venting facial concave deformity and Frey’s syndrome (P<0. 01). Conclusion Preservation of parotid masseter fascia and sternocleido-mastoid muscle flap can be the priority selection in improving facial concave deformity and preventing Frey’ s syndrome.
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ObjectiveTo explore the effects of brucine on multiple myeloma (MM) and to compare the effects between brucine and bontezomib on MM.MethodsMTT method was used to determine the median inhibitory concentratiom (IC50) of brucine and bortezomib on the MM cell line U266.The supernatant of cultured U266 cell line was added to the culture system for inducing the differentiation of osteoblast cell line MC3T3-E1.After aseptic assay,RT-PCR was used to determine the RNA levels of alkaline phosphatase (ALP),osteocalcine (OC),osteoprotegerin (OPG) and recepter activator of NF-κB ligand (RANKL).Results IC50 of bortezomib on U266 cell line for 48 h was 22.4 nmol/L,and that of strychnine was 0.16 nmol/L.The mRNA levels of ALP,OC and OPG in osteoblast co-intervened by brucine combined with the supernatant of MM cells were higher than those in supernatant of U266 cells,while the level of RANKL mRNA was lower (P ＜0.05).The degree of increasing or reducing was greater than the level of control group intervened only by bortezomib (P ＜0.05).ConclusionThe therapeutic effects of brucine on MM might be carried out through the regulation of osteoclast by osteoblast,and the experiment confirmed that the therapeutic effect of brucine on MM was superior to that of bortezomib.
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Objective To investigate the mechanism of the apoptotic effect of brucine on human multiple myeloma. Methods MTT, morphology, flow cytometry, and RT-PCR were used to observe the apoptotic pathways of brucine on human multiple myeloma cell line-U266. Results The apoptotic effect of brucine showed a dose and time dependent manner, 48 hour IC50 0.16 mg/ml. The cells treated with brucine showed significant feature associated with apoptosis by Hoechst 33258 at fluorescence microscope.Mitochondrial membrance potential showed no statistical significant difference in different concentration with Rhodamine 123 by flow cytometry (P ＞0.05). The Caspase-3 expression detected by RT-PCR was increased at 12, 24 and 48 hours treated with brucine, and its gray value was (0.2597±-0.020), (0.5488±0.016), (0.6205±0.006), (0.6533±0.009) (P ＞ 0.05), detection of added z-IETD-fmk, z-LEHD-fmk (Caspase-8 and Caspase-9specific inhibitor) the expression of Caspase-3, the gray scale values were (0.7118±0.006), (0.2637±0.003)(P ＜0.01); and (0.7182±0.004) (0.7195±0.003) (P=0.836). Caspase-8 was activated. Conclusion Within the 0.4 mg/ml concentration brucine can induce apoptosis in U266 cells. Brucine induced apoptosis on cell line U266 through Caspase-8 activation by death-receptor pathway.
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Objective To study the changes of life span and pathology in superoxide dismutase 1 (SOD1)-G93A mice after intracardiac transplantation of human mesenchymal stem cells (hMSCs).Methods hMSCs were isolated from bone marrow cells obtained from healthy donors and cultured.The purity and morphology were assessed by flow cytometry (FCM).hMSCs (3×10~6) resuspended in 0.2 ml DMEM was injected into the heart of 8 week-old SOD1-G93A mice.In non-transplantion control SOD1-G93A mice, only DMEM was injected.The mice were evaluated for signs of motor deficit with 4-point scoring system previously described by Weydt et al.The age of onset and life span in mice were assessed.The pathological change including number of motor neurons was investigated by Nissl staining.Immunofluorescence staining with specific human nuclear antibody was used to confirm the transplant of hMSCs in mice.Results The onset symptoms in untreated SOD1-G93A mice appeared at (156.56±3.60) days of age and the average life span was (188.32±3.51) days.hMSCs transplantation delayed the onset of ALS type symptoms about 16 days (x~2=10.888, P=0.001) and prolonged the life span about 14 days compared to the untreated SOD1-G93A littermates((202.19±4.09) days vs (188.32±3.51) days, x~2=3.917, P=0.04).The loss of motor neurons in untreated mice was earlier and more severe than in hMSCs transplanted mice.At 20 weeks, the number of motor neurons in transplanted mice was significantly higher than those in untreated mice.Human specific nuclear antigen in brain and spinal cord was detected in transplanted SOD1-G93A mice.Conclusion hMSCs can be implanted for a long-term into central nervous system by intracardiac transplantation and the transplantation can prolong life span, and delay the onset of the disease and motor neuron loss in SOD1-G93A mice.
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The abnormality of serine/threonine kinase Aurora-A is seen in many types of cancers. Although in physiological context it has been shown to play a vital role in cellular mitosis, how this oncogene contributes to tumorigenesis remains unclear. Here we demonstrate that Aurora-A overexpression enhances both the expression level and transcriptional activity of c-Myc. The inhibition of c-Myc expression by RNA interference significantly impaired the oncogenic potential of Aurora-A, resulting in attenuated cellular proliferation and transformation rates as well as fewer centrosomal aberrations. Furthermore, downregulation of c-Myc effectively overcame Aurora-A-induced resistance to cisplatin in esophageal cancer cells. Taken together, our results suggest an important role for c-Myc in mediating the oncogenic activity of Aurora-A, which may in turn allow for future targeting of c-Myc as a potential therapeutic strategy for tumors with Aurora-A overexpression.
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Humans , Cell Line, Transformed , Cell Proliferation/drug effects , Cell Transformation, Neoplastic/drug effects , Cisplatin/pharmacology , Down-Regulation , Gene Expression Regulation, Neoplastic/drug effects , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins c-myc/genetics , RNA, Small Interfering/genetics , Transcriptional Activation , Transgenes/geneticsABSTRACT
AIM:To observe the effects of supraoptic ADH neurons and central diabetes insipidus(CDI)in Wistar rats at different times after hypophysectomy.METHODS:Hypophysectomy was undergone by stereotaxic instrument.Water intake,urine output and urine specific gravity(SG)were observed each day.The survival rate of supraoptic ADH neurons was determined by immunofluorescence after hypophysectomy at different times.RESULTS:The rats manifested triphasic CDI after hypophysectomy.The average water intake in experiment group was 73.9 mL vs 30.9 mL in control group(P0.05),but the cellular body hypertrophy appeared.The survival rate at 10th day was 72%(P0.05),but they were all less than the 10th day(P