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Borneol (Bo) and Arg-Gly-Asp (RGD) co-modified docetaxel (DTX) loaded MPEG-PLGA nanoparticles (DTX-Bo-RGD-NPs) were prepared to improve the therapeutic effect of DTX against glioma after intranasal administration. DTX-Bo-RGD-NPs were prepared by emulsification-solvent evaporation method, and their morphology, particle size, zeta potential, drug loading capacity (DLC), stability, and in vitro release properties were investigated. The fluorescence probe coumarin-6 loaded NPs were prepared for investigating the NPs' uptake property on C6 and 16HBE cell models to evaluate in vitro targeting ability. The DiR loaded NPs were prepared for observing the fluorescence intensity at the brain tumor site after intranasal administration through in vivo imaging system in a C6 rat orthotropic model, evaluating the targeting ability in vivo. The anti-tumor effects of DTX-Bo-RGD-NPs were also investigated in such C6 rat orthotropic model in vivo. Animal welfare and experimental procedures are in compliance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine. The results showed that DTX-Bo-RGD-NPs were spherical and uniformly distributed, with a particle size of about 140 nm and a zeta potential of -20 to -30 mV. The drug delivery system showed good stability and sustained release property in vitro, and favorable brain tumor targeting effect in vitro and in vivo. Such novel drug delivery system significantly improved the accumulation of DTX-Bo-RGD-NPs in tumor sites and displayed a higher brain tumor targeting efficiency, providing promising therapeutics of DTX for the treatment of glioma after intranasal administration.
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Objective To summarize the imaging features of multi-slice spiral CT (MSCT) in primary pulmonary lymphoma (PPL),in order to provide effective imaging diagnostic basis for clinical diagnosis.Methods The MSCT findings of 11 patients with PPL in Dalian Municipal Friendship Hospital from January 2010 to March 2019 were retrospectively analyzed.Results Among the 11 patients,pulmonary non-Hodgkin lymphoma was in 9 cases,of which pulmonary mucosa-associated lowgrade marginal zone B-cell lymphoma (MALT lymphoma) was in 7 cases,pulmonary diffuse large B-cell lymphoma (DLBCL) was in 2 cases,and pulmonary Hodgkin lymphoma was in 2 cases.Single lesion was in 2 cases,and multiple lesions was in 9 cases.Nodules and mass type was in 6 cases,solid type in 2 cases,interstitial type in 1 case,and mixed type was in 2 cases.Consolidations with air bronchogram was in 6 cases,ground-glass opacity like nodules in 3 cases,angiogramsign in 4 cases,perilymphatic and/or peribronchovascular spread in 4 cases,and lymphadenopathies were in 2 cases.Conclusions Although the imaging diagnosis of primary lung lymphoma is difficult,MSCT has certain characteristics,and improving the identification of corresponding signs has certain guiding significance for clinical practice.
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Many clinicians have the following 4 misconceptions about the incidence and epedemil trend of gallbladder cancer.(1) The incidence of gallbladder cancer and extrahepatic bile duct carcinoma is considered as the incidence of gallbladder cancer.(2) The gallbladder cancer is the common malignant tumor of the digestive system.(3) The gallbladder cancer is the most common malignant tumor of biliary tract system.(4) The incidence of gallbladder cancer is increasing year by year.Based on the latest annual report of the 2016 Chinese Cancer Registry Annual Report,published by the National Cancer Center (NCCR),combined with previous annual reports and the data of the incidence of gallbladder and extrahepatic bile duct cancer in the related articles,supplemented by clinical data,the author points out that the incidence of gallbladder cancer in China is about 1.00-1.30 per 100 000.It is pointed out that gallbladder cancer is not the most common cancer in the digestive and biliary systems.The incidence of gallbladder cancer has not been significantly increased in recent years,and its 5-year relative survival rate has been reduced by 0.9％ since 2003.Although the incidence of gallbladder cancer is low,the malignant degree is high and the prognosis is poor.It highlights the lack of effective treatment for the disease,and further hints that we should strengthen the necessity of early diagnosis and treatment of gallbladder cancer.
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Objective To explore the effect of resolvin D2 ( RvD2) on radicular pain induced by interver-tebral disc herniation. Methods Thirty-six male Sprague-Dawley rats were randomly divided into a sham opera-tion group, a model group and an RvD2 group, each of 12. Non-compressive lumbar disc herniation was induced in the rats in the model and RvD2 groups using the autologous nucleus pulposus filling method. Those in the sham group had the surgical site exposed without any other treatment. After the modeling, 10μl of phosphate-buffered sa-line solution was administered intrathecally to the rats in the sham and model groups for 3 days, while the rats in the RvD2 group received 10 ng/10 μl of RvD2 intrathecally as well. Paw withdrawal thresholds (50％PWT) were ob-served 1 day before modeling and 7 days afterward for the rats of all three groups. On the 7th day after modeling, the L4 to L6 spinal dorsal horns on the surgery side were resected to detect the protein expression of phosphorylated protein kinase B ( p-AKT) , protein kinase B ( t-AKT) , phosphorylated glycogen synthase kinase 3β( p-GSK-3β) and glycogen synthase kinase 3β( GSK-3β) using western blotting. The protein levels of tumor necrosis factor alpha ( TNF-α) , interleukin-6 ( IL-6) , transforming growth factor-β1 ( TGF-β1) and interleukin-10 ( IL-10) were de-termined using enzyme-linked immunosorbent assays. Results On the 1st and 7th day after modeling, significant differences were observed between the model and sham groups in terms of the 50％PWT. From the 3rd day the aver-age 50％PWT in the RvD2 group was significantly higher than that of the model group at the same time points. On the 7th day after the modeling the average p-AKT and p-GSK-3βprotein levels of the model and RvD2 groups were significantly different from that of the sham group, and the model group′s average was also of significantly different from that of the RvD2 group. The average protein levels of the pro-inflammatory cytokines TNF-αand IL-6, as well as of the anti-inflammatory factors TGF-β1 and IL-10 in the dorsal horns of the model group and the RvD2 group were also significantly different on the 7th day, and both were significantly different from the sham group′s average. Conclusion RvD2 can alleviate radicular pain in rats with non-compressive disc herniation. The mechanisms might involve inhibition of GSK-3β activity, down-regulation of pro-inflammatory factors and up-regulation of anti-inflammatory factors.
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Objective To evaluate the effect of exogenous resolvin D2 on radicular pain in a rat model of non-compressive lumbar intervertebral disc herniation.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 8 weeks,weighing 230-270 g,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),radicular pain induced by non-compressive lumbar intervertebral disc herniation group (group P) and exogenous resolvin D2 group (group R).The right L5 dorsal root ganglions were covered by autologous nucleus pulposus tissues to establish the model of non-compressive lumbar disc herniation in P and R groups.The corresponding surgical site was only exposed in group S.The corresponding drugs were intrathecally injected within 3 days after establishing the model,phosphate buffer solution 10 μl was injected in group P,1 ng/μl resolvin D2 solution 10 μl was injected in group R,and normal saline 10 μl was given for pipe washing after administration in the three groups.The mechanical paw withdrawal threshold (MWT) was measured on 1 day before establishing the model and 1-7 days after establishing the model.The spinal dorsal horns of lumbar enlargement segments were removed on day 7 after establishing the model for determination of the expression of glial fibrillary acidic protein (GFAP) (by Western blot) and co-expression of G-protein-coupled receptor 18 with GFAP (by double-label immunofluorescence).Results Compared with group S,the MWT was significantly decreased at 1-7 days after establishing the model,and the expression of GFAP was up-regulated in group P (P＜0.05).Compared with group P,the MWT was significantly increased at 3-7 days after establishing the model,and the expression of GFAP was down-regulated in group R (P＜0.05).G-protein-coupled receptor 18 was co-expressed with GFAP.Conclusion Exogenous resolvin D2 can reduce radicular pain in a rat model of non-compressive lumbar intervertebral disc herniation,and the mechanism is related to inhibiting activation of astrocytes in the spinal dorsal horns.
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AIM To establish an HPLC method for the simultaneous content determination of saikosaponin a,saikosaponin c,saikosaponin d,rutin,quercetin,isorhmnetin and kaempferol in the aerial and underground parts of “Zhongchai No.2” (Bupleurum chinense DC.from Sichuan Province).METHODS The analysis of “Zhongchai No.2” methanol extract was performed on a 30 ℃ thermostatic Hypersil GOLD column (250 mm × 4.6mm,5.0 μm),with the mobile phase comprising of acetonitrile-0.1％ phosphoric acid flowing at 0.8 mL/min in a gradient elution manner,and the detection wavelength was set at 210 nm.RESULTS Seven constituents showed good linear relationships within their own ranges (r≥0.999 1),whose average recoveries were 96.30％-102.7％ with the RSDs of 0.95％-3.8％.There were a lot of flavonoids in the aerial parts of samples,while a large number of saponins existed in the underground parts,but almost no flavonoids were found.CONCLUSION The aerial parts (stems and leaves) of “Zhongchai No.2” also have medicinal value,to which we should pay attention.
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Objective To investigate the risk factors of pneumorrhagia and pneumothorax occurring after CT-guided cutting needle biopsy for pulmonary solid nodules.Methods The clinical data and imaging materials of 320 patients with pulmonary solid nodule (≤3 cm),who received 16 G semi-automatic cutting needle biopsy,were retrospectively analyzed.Both univariate and multivariate logistic regression analysis methods were used to evaluate the risk factors of pneumorrhagia and pneumothorax.Results The incidence of needle track hemorrhage was 33.1％ and the incidence of pneumothorax was 18.1％,the diagnostic accuracy for benign and malignant nodules was 99.6％.Needle track length was an independent risk factor for pneumorrhagia;every increase of 3 cm in needle track length,the risk of pneumorrhagia would increase 3.881 times,besides,the risk of pneumorrhagia had a parallel relationship with the time used for puncturing (P=0.061) as well as with the number of pleural puncturing (P=0.062).The age,lesion's location and needle-pleural angle were independent risk factors for pneumothorax.Each increase of 10 years in age,the risk of pneumothorax would increase 2.102 times.The pneumothorax risk of pulmonary lesion located at upper lung lobe was strikingly lower than that of pulmonary lesion located at lower lung lobe.Each increase of 20 degrees in needle-pleural angle,the risk of pneumothorax would increase 2.413 times.Emphysema was excluded from the equation because it had only a minute difference (P=0.086).Based on the pneumorrhagia and pneumothorax probability values,ROC curves of pneumorrhagia and pneumothorax were drawn,and AUC values of pneumorrhagia and pneumothorax were 0.753 and 0.725 respectively.Conclusion The occurrences of pneumorrhagia and pneumothorax after CT-guided cutting needle biopsy for pulmonary solid nodules are affected by many factors.Careful preoperative evaluation and skilled intraoperative manipulation can effectively reduce the incidence of pneumorrhagia and pneumothorax.
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In order to prevent the canceration of gallbladder polyps or avoid the misdiagnosis of gallbladder cancer,the mainstream practice is cholecystectomy for polyps larger than 1 cm,while gallbladder polyps larger than 0.5 cm as an indication of gallbladder preserving surgery.The reasons for this result is that we put the diameter of more than 1 cm of gallbladder polyps as high risk factors for prediction of gallbladder carcinoma,and we ignored the characteristics of gallbladder polyps that most of them are not gallbladder cancer or are not cancerous even larger than 1 cm.We analysed the high risk factors for gallbladder cancer on the basis of variety of clinical data,and we believe that the most valuable indicator of gallbladder cancer are the growth time of gallbladder polyps,the age of the patients,the combination of gallstones,the single polyps,and the sex.Polyps diameter greater than 1 cm are not a high risk factor for gallbladder cancer.We can use these five high risk factors to manage gallbladder polyps and reduce unnecessary cholecystectomy and gallbladder preserving surgery.
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Objective To investigate the expression and role of β-catenin in small-for-size liver grafts during early stage of liver regeneration after liver transplantation in rats.Method The livers of male Sprague-Dawley rats were reduced to 30％ or 50％ of their original sizes and transplanted.The experiment was divided into 3 groups:small-for-size graft group (SSG),half-size graft group (HSG) and sham-operated group.Liver samples were harvested at various time points after transplantation (n =6 per time point) for Western blotting and immunohistochemistry.Six rats in each group were sacrificed at 3rd day after liver transplantation for estimating liver regeneration rate.Result Liver regeneration rate in SSG group was lower than that in HSG group.The expression of β-catenin was down-regulated in liver graft of both groups after being stored in cold Ringer solution for 2 h.The expression of β-catenin was significant up-regulated in HSG group from 5 min to 12 h after operation,while the down-regulated expression of β-catenin was persisted in SSG group at 5 min after operation,and mildly increased expression of β-catenin occurred at 2 h and 6 h,which was significantly lower than that in HSG group at the corresponding time points.The expression of active-β-catenin was low in each group before transplantation.Significant expression of active-β-catenin was found at 5 min in HSG group and persisted until 12 h after operation,mildly increased expression of active-β-catenin in SSG group was only found at 2 h,which was lower than that in HSG group at the same time points.Immunohistochemical staining revealed that β-catenin was mainly expressed on the hepatocyte membrane and in cytoplasm in the sham-operative group,many hepatocytes exhibited nuclear localization of β-catenin in HSG group from 5 min to 24 h,while only some hepatocytes exhibited nuclear localization of β-catenin in SSG group.The expression of Cyclin D1 in SSG group was significantly lower than that in HSG group,which was similar to the expression of C-Myc.Conclusion Attenuated activation of Wnt/β-catenin signaling and down-regulated expression of target genes during early regeneration of small-for-size liver grafts may be involved in the inhibition of liver regeneration of small for size liver grafts.
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Objective To explore the impacts of over-expression of microRNA-7 (miRNA-7) on the sensitivity of cis-platin in esophageal carcinoma cell line TE-1, and the possible mechanism thereof. Methods Lipofectmin 2000 method was used to transient transfect with miRNA-7 mimic into esophageal cancer cell line TE-1, which was taken as transfection group, mimic negative control was taken as transfection conrtol group. The expressions of miRNA-7 and epidermal growth factor receptor (EGFR) mRNA were detected by RT-PCR in the above two groups and normal control group. The total EGFR and EGFR in cytoplasmic and nucleus were detected with Western blot assay in transfection group and transfection control group. CCK-8 was used to detect IC50 of cisplatin in transfection group and transfection control group. The expression of EGFR was observed with immunofluorescence confocal microscope in two groups. Results The miRNA-7 expression was signifi-cantly increased in transfection group than that of transfection conrtol group and control group. The expression of EGFR mRNA was significantly reduced in transfection group (P<0.001). The total EGFR was significantly decreased in transfec-tion group than that of transfection conrtol group. The level of nuclear EGFR was significantly increased ( P<0.01),and cyto-plasm EGFR expression was significantly decreased in transfection group than that of transfection control group ( P<0.05). CCK-8 results showed that after the over expression of miRNA-7 in TE-1, the IC50 of cisplatin (48 h) increased in transfec-tion group than that of control group (P<0.01). Immunofluorescence results showed that EGFG in nuclear was higher in transfection group than that of transfection control group but its expressions reduced in cell membrane and cytoplasm. Con-clusion The over-expressed miRNA-7 in esophageal cancer cells TE-1 can reduce cisplatin sensitivity by the increased EGFR in nuclear translocation.
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Objective To investigate the expressions of tyrosine kinase receptor (Trk)B and brain-derived neurotrophic factor (BDNF) protein in human gastric careinoma and compare them with those in epithelial cells of normal mucous, in order to evaluate their clinicopathological significance. Method The expressions of TrkB and BDNF protein in tumor tissues, matched with para-tumor mueosal tissues from 64 cases with gastric carcinoma and normal mucous of 20 cases were observed immunohistochemically and related to some of the clinicopathological parameters. Results The positive rates of TrkB and BDNF protein in tumor tissues were 60.9% and 59.4% respectively, but there was negative in matched para-tumor mueosal tissues and normal mucosal tissues. TrkB and BDNF protein expressions were related to invasive depth,lymph node metastasis and TNM stage of cancer, but not to sex, age and degrees of cancerous differentiation.The positive rates of TrkB and BDNF protein in cases with serosal infiltration, lymph node metastasis and TNM stage Ⅲ - Ⅳ were significantly higher than those in cases without serosal infiltration, lymph node metas-tasis, and TNM stage Ⅰ - Ⅱ (P< 0.01 ). In group with metastasis the positive rates of TrkB and BDNF protein were lower in metastatic foci (76.5%, 26/34, 70.6%, 24134) than those in primary tumor (85.3%, 29134,82.4%, 28/34 ), but statistically there was no significant difference between them (P > 0.05 ). Conclusions The expressions of TrkB and BDNF protein are closely relatedto tumorigenesis and progression of gastric carcinoma. The increased expression of TrkB and BDNF may promote the occurrance of local invasion and metastasis of gastric carcinoma.
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Objective To evaluate the damage caused by high intensity ultrasound(HIU)on tumor micro- vessels.Methods Rabbit models of the VX_2 tumor were set up.The target hepatic carcinomas were treated with HIU,and the results were observed using hematoxylin-eosin(HE)staining,vascular endothelial cell biotinylated-ulex europaeus agglutininiⅠ(UEAI)immunohistochemical staining,tumor micro-vessel counts,and electron microscopy. Results Histological examination through HE staining indicated that HIU induced carcinoma vascularities with whole tumor tissue coagulative necrosis.The UEAI immunohistochemical staining of the target lesions treated by HIU was ne- gative,and complete tumor micro-vessel uhrastructure damage was observed under the electron microscope.Conclu- sion HIU can damage tumor micro-vessels thoroughly,in such way that it may inhibit tumor growth and metastasis.
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Based on the well-known Pennes' bioheat equation, we analyzed theoretically the temperature rise in tissue during high intensity focused ultrasound(HIFU) irradiation, and measured the focal temperature rise induced by HIFU in the treatment of freshly excised cow liver with different acoustic intensity and exposure time. The results showed that a threshold exposure time always existed under a certain acoustic intensity. Temperature rise was slow when exposure time exceeded the threshold exposure time. The greater the acoustic intensity was, the earlier the threshold time appeared. The focal temperature rise and the relative cumulative thermal dose (RCTD) increased with the increase of acoustic intensity and exposure time. For a certain therapeutic dose, the effects of acoustic intensity on focal temperature rise were more distinct than the effects of exposure time on focal temperature rise. Therefore, the optimal HIFU therapeutic dose should meet the need, i.e. moderate acoustic intensity, and the exposure time be the threshold exposure time under this acoustic intensity.