Multimodal imaging and photothermal/chemotherapy in vitro study of peptide-mediated network engineering paclitaxel nanoparticles loaded with metal polyphenols / 中华超声影像学杂志

Objective:To prepare a phase-change lipid nanoparticle modified by tumor homing membrane-penetrating peptide (tLyP-1) and carrying paclitaxel (PTX) engineered by metal polyphenol network (TA-Fe 3+ ), and evaluate the therapeutic effects of tumor targeting, ultrasound/photoacoustic imaging and photothermal combined chemotherapy in vitro. Methods:Phase-change lipid nanoparticles (t-P@TFP) with TA-Fe 3+ engineered PTX mediated by tLyP-1 were prepared by solvent replacement method, thin film hydration method and double emulsification method. Its detection and characterization, in vitro targeting ability, photothermal conversion ability, in vitro photoacoustic and ultrasonic imaging ability, CCK-8 method, cell live and death double staining method and flow cytometry method were used to detect the safety of nanoparticles and the killing effects of different nanoparticles on 4T1 cells. Results:t-P@TFP nanoparticles were successfully prepared. Transmission electron microscopy showed that the nanoparticles were spherical with uniform shape and size, with a particle size of (209.8±1.56)nm and a potential of (-25.9±1.36)mV. Laser confocal scanning microscopy showed that t-P@TFP nanoparticles could gather around 4T1 cells in a targeted manner. It had an efficient photothermal conversion effect, and nanoparticles could quickly become microbubbles after being irradiated by near-infrared laser, which enhanced the in vitro ultrasonic imaging effect; The photoacoustic signal of nanoparticles increased with the increase of concentration. CCK-8 method, double staining of living and dead cells and flow cytometry showed that t-P@TFP combined photothermal chemotherapy had the best anti-tumor effect. Conclusions:t-P@TFP nanoparticles are successfully prepared. The nanoparticles have good targeting ability for photoacoustic and ultrasonic imaging and have good photothermal effect, killing breast cancer cells, which is expected to realize the integration of diagnosis and treatment.

Repair cervical esophageal perforation after anterior cervical spine surgery using thyroid and thyroid capsule: a case report and literature review / 中华骨科杂志

According to the literature review, using thyroid and thyroid capsule to repair cervical esophageal perforation after anterior cervical spine surgery was just mentioned, but no literature reported operative process in detail. In this study, a 51-year-old male patient was admitted to the hospital because of cervical spine injury. The patient underwent anterior cervical discectomy with the iliac bone graft and ORION plate fixation. Esophageal perforation occurred after anterior cervical spine surgery. After conservative treatment, esophageal perforation didn't heal. A repairing operation was performed to remove the plate and repair esophageal perforation using sternocleidomastoid flap. After repairing surgery 6 months, perforation didn't heal completely. A second repairing surgery was performed to repair esophageal perforation using thyroid and its capsule. After second repairing surgery, esophageal perforation healed. The present study reviewed the literature about cause, clinical manifestation, diagnosis method and treatment of esophageal perforation. Using thyroid and thyroid capsule to repair cervical esophageal perforation could offer a treatment option in repairing esophageal perforation, especially the esophageal perforation after muscle flap repair still didn't heal.

Effect of ω-3 polyunsaturated fatty acid on oxidative stress production and apoptosis in hippocampus of neonatal rats with brain injury induced by lipopolysaccharide / 新乡医学院学报

Objective To investigate the effects of ω-3 polyunsaturated fatty acid(PUFA)on oxidative stress produc-tion and apoptosis in hippocampus of neonatal rats with brain injury induced by lipopolysaccharide(LPS). Methods Forty-eight neonatal Sprague Dawley rats(3 days)were randomly divided into control group,LPS group,ω-3 PUFA group and ω-6 PUFA group,with 12 rats in each group. The rats in the LPS group,ω-3 PUFA group and ω-6 PUFA group were given 0. 6 mg·kg - 1 LPS via intraperitoneal injection,then equal volume of saline,ω-3 PUFA and ω-6 PUFA was immediately given via intraperitoneal injection respectively;while the rats in the control group were all given equal volume of saline. The rats in each group were sacrificed at 24 hours after intraperitoneal injection with saline or fat emulsions to obtain the hippocampus. The levels of superoxide dismutase(SOD)and malondialdehyde(MDA),reduced glutathion(GSH),oxidized glutathione(GSSG) were detected and GSSG/ GSH was calculated. The apoptotic index was measured by terminal deoxynucleotidyl transferase-me-diated dUTP nick end labeling. Results Compared with the control group,the levels of SOD and GSH in hippocampus of rats in the LPS group,ω-6 PUFA group and ω-3 PUFA group were significantly decreased(P < 0. 05),and the levels of MDA, GSSG and the ratio of GSSG/ GSH were significantly increased(P < 0. 05). Compared with the LPS group,the levels of SOD and GSH in hippocampus of rats in ω-6 PUFA group were significantly decreased(P < 0. 05),the levels of MDA,GSSG and the ratio of GSSG/ GSH were significantly increased(P < 0. 05);the levels of SOD and GSH in hippocampus of rats in ω-3 PU-FA group were significantly increased(P < 0. 05),the levels of MDA,GSSG and the ratio of GSSG/ GSH were significantly de-creased(P < 0. 05). Compared with the ω-6 PUFA group,the levels of SOD and GSH in hippocampus of rats in ω-3 PUFA group were significantly decreased(P < 0. 05),the levels of MDA,GSSG and the ratio of GSSG/ GSH were significantly in-creased(P < 0. 05). The apoptotic index in the LPS group,ω-6 PUFA group and ω-3 PUFA group was higher than that in the control group(P < 0. 05). The apoptotic index in the ω-6 PUFA group was higher than that in the LPS group(P < 0. 05). The apoptotic index in the ω-3 PUFA group was lower than that in the LPS group and ω-6 PUFA group(P < 0. 05). Conclusion ω-3 PUFA can alleviate the oxidative stress,and decrease the apoptosis of hippocampus in neonatal rats with brain injury in-duced by LPS. So it has a neuroprotective effect in brain injury induced by LPS.

Effect of tumor-associated macrophages on gastric cancer stem cell in omental milky spots and lymph node micrometastasis.

We observed whether the effect of tumor-associated macrophages on gastric cancer stem cell in omental milky spots and lymph nodes micrometastasis and research its possible mechanism. Macrophage THP-1 cells and Human gastric adenocarcinoma SGC-7901 cells were collectively cultivated in vivo. We found macrophage could suppress the proliferation and accelerated cell death of MFC cell. Meanwhile, these effects may be concerned with many signaling pathways, and we detected MCP-1 and COX-2 miRNA expressions, PGE-2 release levels, IL-4 and IL-10 activities, and TGF-ß, IFN-γ, VEGF, MMP-2 and MMP-9 protein expressions in collectively cultivated cell. We found that MCP-1 and COX-2 miRNA expressions, and PGE-2 release levels were suppressed, IL-4 activity was inhibited and IL-10 activity was activated in collectively cultivated cell. Meanwhile, TGF-ß, MMP-2 and MMP-9 protein expressions were inhibited and IFN-γ and VEGF protein expressions were activated in collectively cultivated cell. Taken together, these results suggest that the effect of tumor-associated macrophages on gastric cancer stem cell in omental milky spots and lymph nodes micrometastasis via COX-2/PGE-2/TGF-ß/VEGF signal pathways.

Application of PPARαtransgenic mice in the evaluation of drug toxicity / 中国实验动物学报

Objective To explore whether PPARαtransgenic mice are more sensitive animal models in the evalua-tion of toxicity of PPARαagonists.Methods Twenty-eight 8-week old PPARαtransgenic mice (Tg) and 28 C57BL/6J mice (WT) with half males and half females were randomly divided into high dose group (400 mg/kg of clofibrate), low dose group (30 mg/kg of clofibrate) and solvent control group (10%sodium carboxymethyl cellulose ).The time of gavage administration lasted 28 days.The blood biochemistry , organ coefficient and pathological changes of the heart , liver, kid-neyweretestedafterthedrugadministration.Thegrowthofmicewasalsorecorded.Results ①Bloodbiochemistry:Com-pared with the WT male administration group , in the Tg male administration group , the levels of blood creatinine ( CREA) and aspartate aminotransferase (AST) were markedly increased (P<0.01, P<0.05).② Organ coefficient: Compared with the Tg control group, the kidney coefficients of Tg administration group were significantly increased (P<0.01,P<0.05).③Histopathology:Compared with the WT administration group , the pathological damages of liver and kidney were more serious in the Tg administration group .Conclusions Compared with C57BL/6J mouse, PPARαtransgenic mice are more sensitive in evaluation of hepatotoxicity and nephrotoxicity of PPARαagonists .It is a new animal model .

[Clinical analysis of 29 cases with neuroendocrine neoplasm in the digestive system].

OBJECTIVE: To investigate the diagnosis and treatment of neuroendocrine neoplasm (NEN) in the digestive system. METHODS: Clinical data of 29 patients with NEN from January 2000 to December 2012 in The First Affiliated Hospital of Dalian Medical University were analyzed retrospectively and the prognosis was evaluated according to the new WHO classification. RESULTS: There were 19 males and 10 females and the average age was 46.5 years. All the patients had no clinical manifestations of carcinoid syndrome, and they all received surgical treatment. Two cases were gastric neuroendocrine carcinoma(NEC), who received radical total gastrectomy and distal gastric resection respectively. Three cases had neoplasm in the duodenum, including 2 NEC and 1 neuroendocrine tumor(NET), and they all underwent Whipple's procedure. Two cases were small intestine NEC, who received partial small intestine resection. Three cases had neoplasm in the appendix, including 1 NEC treated with right hemicolectomy and 2 NET with appendectomy. One case was ascending colon NEC, who received right hemicolectomy. Eighteen cases had neoplasm in the rectum, including 4 NEC treated with low anterior resection and abdominoperineal resection respectively, and 14 cases of NET underwent low anterior resection, local resection, and endoscopic resection respectively. The 1- and 3- year survival rates of 13 NEC cases were 38.4% and 7.7% respectively. The 5-year survival rate of 16 NET cases was 81.3%. CONCLUSIONS: NEN of digestive system is located mainly in the rectum and the clinical symptom is unspecific. Radical resection of NEN is the preferred treatment. The prognosis of NEC is poor, and that of NET is better.

Clinical analysis of 29 cases with neuroendocrine neoplasm in the digestive system / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the diagnosis and treatment of neuroendocrine neoplasm (NEN) in the digestive system.</p><p><b>METHODS</b>Clinical data of 29 patients with NEN from January 2000 to December 2012 in The First Affiliated Hospital of Dalian Medical University were analyzed retrospectively and the prognosis was evaluated according to the new WHO classification.</p><p><b>RESULTS</b>There were 19 males and 10 females and the average age was 46.5 years. All the patients had no clinical manifestations of carcinoid syndrome, and they all received surgical treatment. Two cases were gastric neuroendocrine carcinoma(NEC), who received radical total gastrectomy and distal gastric resection respectively. Three cases had neoplasm in the duodenum, including 2 NEC and 1 neuroendocrine tumor(NET), and they all underwent Whipple's procedure. Two cases were small intestine NEC, who received partial small intestine resection. Three cases had neoplasm in the appendix, including 1 NEC treated with right hemicolectomy and 2 NET with appendectomy. One case was ascending colon NEC, who received right hemicolectomy. Eighteen cases had neoplasm in the rectum, including 4 NEC treated with low anterior resection and abdominoperineal resection respectively, and 14 cases of NET underwent low anterior resection, local resection, and endoscopic resection respectively. The 1- and 3- year survival rates of 13 NEC cases were 38.4% and 7.7% respectively. The 5-year survival rate of 16 NET cases was 81.3%.</p><p><b>CONCLUSIONS</b>NEN of digestive system is located mainly in the rectum and the clinical symptom is unspecific. Radical resection of NEN is the preferred treatment. The prognosis of NEC is poor, and that of NET is better.</p>

Identification of mutation c.632G>A (p.G211D) in the ATP2A2 gene and genotype-phenotype correlation in a large Chinese family with Darier's disease.

Darier's disease (DD, MIM 124200) is an autosomal dominant inherited skin disease. Mutations in the ATP2A2 gene, which encoded the sarcoplasmic/endoplasmic reticulum Ca(2+) -ATPase isoform 2 (SERCA2), are responsible for this skin disorder. Here we report the clinical, genetic, and molecular characterization of a large Chinese family with DD. We identified mutation c.632G>A (p.G211D) in the ATP2A2 gene in this family. Genotype-phenotype correlation in available family members provided helpful genetic counseling information for mutation carriers.

Generation of trans-arachidonic acid under nitrative stress is associated with upregulation of thromponsdin-1 in diabetic rats.

BACKGROUND: Trans-arachidonic acids (TAAs), newly discovered markers of nitrative stress and the major products of nitrogen dioxide (NO2(·))-mediated isomerization of arachidonic acid (AA), represent a new mechanism of NO2(·)-induced toxicity. It has been reported that TAAs were generated in oxygen-induced microvascular degeneration model and TAAs were also generated in a diabetic retinopathy (DR) model. In this study, we examined high glucose-induced nitrative stress damage and TAAs levels and explored the possible mechanisms for DR caused by reactive nitrogen species. METHODS: Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) at 60 mg/kg. Bovine retinal capillary endothelial cells (BRECs) were selectively cultured and incubated with normal or high glucose. The serum TAAs and AA in diabetic rats were measured by the gas chromatography and mass spectrometry (GC/MS) method. The ratio of peak area of TAAs to AA with selected ion of 79 was estimated by a group t-test. Thrombospondin-1 (TSP-1) in the rat retinas and BRECs extracts were examined by Western blotting. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) protein was examined by Western blotting in BRECs incubated with high glucose. RESULTS: The TAAs to AA ratio (TAAs/AA) was significantly increased in the serum at 8, 12 and 16 weeks after STZ injection (P < 0.05), with no noticeable change found at 2 or 4 weeks (P > 0.05). Expression of TSP-1 in the retina of diabetic rats was progressively elevated according to the duration of diabetes. TSP-1 expression was increased in BRECs incubated with high glucose at 48 hours. Moreover, high glucose also increased ERK1/2 expression, which peaked at 30 minutes and then decreased in the following 48 hours. CONCLUSION: An elevation of TAAs/AA is associated with high glucose-induced nitrative stress, which probably involves upregulation of TSP-1 through activating ERK1/2.

Preliminary study on the quick detection of Acquired Immune Deficiency Syndrome by saliva analysis using surface enhanced Raman spectroscopic technique.

45 saliva samples of AIDS patients and 55 saliva samples in normal population were detected by the Surface-enhanced Raman spectroscopy (SERS) system. And the spectrum data were analyzed using the Support Vector Machine (SVM) algorithm, one of the data mining technologies. Statistical analysis showed that two groups were distinguished effectively. This study provided a new research direction of the quick non-invasive testing for AIDS.

The complete sequence analysis of Enterovirus 71 strain from the fatal case of the hand, foot and mouth disease during an epidemic of Guangdong province in 2008 / 中华微生物学和免疫学杂志

Objective To understand the genetic characteristics of Enterovirus 71 ( EVT1 ) circu-lating strains of Guangdong province in 2008. Methods We isolated an EV71 strain from the fatal case of the hand, foot and mouth disease during an epidemic of Guangdong in 2008. Its complete genome was se-quenced and analyzed comparatively. Results The results showed that the full length of EV71 GDFS-3 ge-nome( not including poly A tail ) is 7405 bp. No insertion or deletion is detected in the coding region. There are several insertions and deletions in 5'and 3'UTR. Phylogenetic analysis of GDFS-3 and reference strains showed GDFS-3 strain shares the highest nueleotide homology with TW984 strain(96.0% ) but low homology with SIN5865, MS and BrCr( about 81.0% ). GDFS-3 strain also shares the highest amino acid homology with TW984 strain(99.0% ). It clustered with reference strains of CA subgenotype in the phylogenetie tree. The nucleotide identity with CA reference strains is 91.0% -95.0%. Conclusion The phylogenetic analysis based on the entire genome demonstrates that GDFS-3 strain has the nearest genetic relationship with TW984 strains ( isolated in 2004). GDFS-3 may belong to the same subgenogroup ( CA ) with Taiwan predominant strains. Otherwise,Some mutations in 5'UTR of EV71 may play the very important role in heightened viru-lence.

Tuning the acyclic ether moiety of anticancer agent AA005 with conformationally constrained fragments.

A new series of anticancer annonaceous acetogenin mimetics were designed, synthesized, and evaluated based on our previously developed compound AA005, in which a variety of conformationally constrained fragments were introduced. Parallel syntheses of all new compounds were accomplished by replacement of the acyclic bis-ether functionality of AA005 with certain conformationally constrained fragments. Slight effects to the anticancer activity were exerted by altering stereochemistries in the middle modification region. Similar to AA005, most newly synthesized mimetics were found to exhibit potent activities against breast cancer cells, and showed satisfactory selectivities between cancerous and non-cancerous cells. An N,N'-dimethyl bis-amide compound 67 exhibits 30 times more potency against MDA-MB-468 cells than its parent molecule AA005. This study indicates that the introduction of appropriate conformational constraints is a useful optimizing tool for this class of anticancer agents. Successes in the bis-amide analogues of AA005 make this unique class of anticancer agents much simpler and more flexible for future further developments.

STUDIES ON THE TECHNIQUE OF FERMENTATION TO A NEW GENRE OF INSECTICIDE——SPINOSAD / 微生物学通报

the mutative strain, after excerpted the optima formula of medium for seeds and fermentation with the method of orthogonal design, were mutagenesised by UV, 60 Co and so on. The production of mutant was enhanced to 150% of the original one.