ObjectiveTo prepare recombinant human basic fibroblast growth factor (rhbFGF) loaded magnesium-poly(D,L-lactide-co-glycolide) (Mg-PLGA) stent and to evaluate its angiogenesis effect in rat model of hindlimb ischemia.MethodsThe stent was prepared with spiral magnesium (Mg) and loaded with therapeutic agent rhbFGF and PLGA matrix.In vitro drug release study was carried out and the effect was evaluated using a standard animal model of rat hindlimb ischemia.A mechanical drill was conducted and the stent was implanted.The concentrations of Mg2+ in the muscle adjacent to the stent,rat plasma,urine and stools of the experimental animals were tested to analyze the degradation and metabolism of metal Mg.Immunohistochemical staining was performed to evaluate the angiogenesis effect of the stent.ResultsThe drug loaded in the stent could release continuously for about 4 weeks.The concentrations of Mg2+ in the rat plasma,urine and stools were within normal range.Immunohistochemical and quantitative analysis showed that the effect of Mg-PLGA-rhbFGF stent on angiogenesis of rat limb ischemia was better than that of the control group.ConclusionRhbFGF loaded MgPLGA stent could promote angiogenesis of rat limb ischemia,and it may provide theoretical basis for the critical patients suffered from lower limb ischemic disease.

Aims Toevaluatethepharmacodynamic efficacy of different types of antiangiogenic agents as HM-3 on a non-small cell lung cancer xenografts tumor model .To explore the interaction between the antian-giogenic agents and the tumor microenvironment,and to offer suggestions for clinical therapy.Methods Thenon-smallcelllungcarcinomaxenograftmodelwas established in Balb/c nude mice.The model mice were treated with Docetaxel(10 mg·kg-1 )as the positive control.The mice were parallelly treated with,HM-3 at the doses of 3 mg · kg-1 and 48 mg · kg-1 and, Avastin(5 mg·kg-1 ).The parameters include tumor volume,tumor weight and immunohistochemical analy-sis.Result Animalexperimentsshowedthatdocetaxel had good anti-tumor activity.Tumor growth inhibition by tumor weight of G2 docetaxel(10 mg·kg-1 )group was 60. 80%.Tumor growth inhibition by tumor weight of G3 HM-3(3 mg·kg-1 )group,G4 HM-3(48 mg· kg-1 )group ,G4 Avastin(5 mg·kg-1 )group,were 43. 60%,-34. 80%,44. 40%,respectively.Con-clusion Theantigiogeniceffectisaffectedbytumor growth stage,tumor microenvironment and their work-ing mechanisms.Angiogenesis inhibitors HM-3 has a certain effect of inhibiting tumor growth,but to little a-vail.HM-3 shows on inhibitory effect in a dose-de-pendent manner at the doses of 0~6 mg·kg-1 .HM-3 at a high dose of 48 mg · kg-1 has no inhibitory but promoting effects on human non-small cell lung carci-noma A549 xenografts in nude mice .Special dose-effect relationship indicates that dosage should be paid attention to in the clinical use of blood vessel inhibi-tors.

Objective To study the cytotoxicity against brain microvessel endothelial cells and blood compatibility in rats of OX26 conjugated endomorphin (EM) loaded hyperbranched polyglycerols-poly(lactic-co-glycolic acid)(HBPG-PLGA) nanoparticles.Methods Prepared nanoparticles were divided into group B (HBPG-PLGA nanoparticles),group EP (EM-HBPG-PLGA nanoparticles) and group OEP (OX26-EM-HBPG-PLGA nanoparticles).The cytotoxicity against brain microvessel endothelial cells (BMECs) of nanoparticles of different groups were measured by MTT test,haemolysis test,normal haemotological parameter and several primary items of coagulation system were tested after nanoparticles of different groups and different dosages injection on rats.Results ①All the three groups of nanoparticles induced decreased cell viability in a dose dependent manner in MTT test,whereas all groups of nanoparticles showed low cytotoxicity against the BMECs during 30 to 600 μg/ml.②There was no significant difference in haemolysis ratio (P＞0.05) and normal haemotological parameter (P＞0.05).③There was no significant difference between the low dosage of all the three groups of nanoparticles and the control group on the function of coagulation system in rats (P＞0.05).④Compared with C group,high dose groups demonstrated longer prothrombin time (PT),activeated partial thromboplasting time (APTT) and lower fibrinogen (Fbg) (P＜0.05).At the same time,compared with the low dose subgroups,PT and APTT were prolonged,Fbg significantly decreased in the high dose subgroups (P＜0.05 or P＜0.01).Conclusion OX26 coupled with EM-HBPG-PLGA nanoparticles showed low cytotoxicity against BMECs and had no significant effect on the coagulation system in rats with low concentration and low dosage.

Objective To prepare a novel brain active-targeting endomorphin (EM) loaded hyperbranched polyglycerols-poly (lactic-co-glycolic acid) (HBPG-PLGA) nanoparticles (NPs) and study its mechanism of passing across blood brain barrier (BBB) in brain microvascular endothelial cells (BMEC).Methods The OX26 (transferring receptor monoclonal antibody) conjugated EM loaded HBPG-PLGA NPs was constructed according to water-in-oil-in-water emulation solvent evaporation technique as a novel biodegradable brain active-targeting drug delivery system.The properties of the NPs were evaluated by transmission electron microscope (TEM) in vitro.Through flow cytometry and laser scanning confocal microscope,the mechanism of passing across BBB was evaluated.Results The preparation methodology of NPs was optimized and established.The mean diameter was (170±20) nm and Zeta potential was about-27 mV.Core-shell construction was showed on TEM.Cellular uptake study showed that the uptake of NPs was via a caveolae-mediated endocytic pathway,then endomorphin and carrier were divided into two parts in BMEC.Conclusions The OX26 conjugated EM loaded NPs were stable,and demonstrate remarkable effects on crossing BBB.Cellular uptake by BMEC is a very important mechanism of the NPs' brain activating-targeting effect.

Purpose The diagnosis, treatment and prognosis of benign and malignant biliary stricture are significantly different. This study aims to evaluate the quantitative analysis of biliary structures using magnetic resonance cholangiopancreatography (MRCP) combined with dynamic contrast enhanced CT (DCE-CT).Materials and Methods The quantitative parameters of MRCP and DCE-CT imaging data from 27 patients with benign biliary stricture (benign group) and 30 patients with malignant biliary stricture (malignant group) were retrospectively analyzed. The wall thickness, stricture length and diameter, proximal ductal dilatation and degree of enhancement in two groups were compared, and its correlation was analyzed to evaluate the accuracy of MRCP and DCE-CT.Results There were significant differences in wall thickness [(3.2±2.0) mmvs (2.1±0.6) mm], stricture length [(15.8±8.1) mmvs (9.5±6.5) mm] and diameter [0 mmvs (2.0±0.9) mm], proximal ductal dilatation and the degree of enhancement [(12.7±3.6) mmvs (9.3±2.7) mm] between the two groups (t=2.825, 3.270, 4.025,P<0.001;Z=-3.909,P<0.001). Multivariable stepwise regression analysis showed that the wall thickness and diameter, and the CT HU in portal venous and equilibrium phases combined with CT plain scanning were significant predictors of malignant biliary strictures (t=-6.424-2.309,P<0.05). The sensitivity, specificity, inter-modality agreement and Youden index of MRCP and DCE-CT in diagnosing 57 patients with biliary stricture were 96.67%, 100.00%, 98.25% and 0.97, respectively; with statistical significance in predicting benign and malignant biliary stricture (AUC=0.994,P<0.001).Conclusion Using MRCP and DCE-CT, the wall thickness and diameter of the stricture, and the difference in CT HU in portal venous and equilibrium phases combined with CT plain scanning are valuable in differential diagnosis of benign and malignant biliary stricture.

Objective To study the difference between intensity-modulated radiation therapy (IMRT) and three dimensional conformal radiation therapy (3D-CRT) for pelvic radiation of post-operative treatment with gynecologic malignant tumor. Methods A prospective investigation study was conducted on 183 patients of post-operative patients with whole pelvic radiation therapy of cervical cancer or endometrial cancer in Zhejiang Cancer Hospital [IMRT group (n=85) and 3D-CRT group (n=98)] from Oct. 2015 to Oct. 2016. The two groups received same dose (45 Gy in 25 fractions). Comparison of two groups with radiation dosimetry:the score according to the Radiation Therapy Oncology Group (RTOG) acute radiation injury grading standards before and after radiotherapy reaction, the score from functional assessment of cancer therapy scale-cervix (FACT-Cx) scale and expanded prostate cancer index composite for clinical practice (EPIC-CP) scale were also analyzed. Results (1) There were no significant effect with age, culture level, family economic condition and ratio of radiochemotherapy between two groups (all P>0.05). (2) Dosimetric comparison for IMRT vs 3D-CRT:the average dose of planning target volume (PTV) decreased(46.1 ± 0.4) vs(46.4 ± 0.5)Gy, V45 dose percentage increased(95.2 ± 1.0)%vs (93.3 ± 2.0)%, intestinal bag dose of V40 decreased(24.4 ± 6.8)%vs (36.5 ± 15.9)%, rectal V40 dose percentage decreased(73.9 ± 12.3)%vs (85.4 ± 8.4)%, and lower rectal V45 dose percentage(32.8 ± 13.4)%vs (71.5 ± 13.7)%, bladder V40 dose percentage decreased(55.5 ± 13.0)% vs (84.4 ± 13.0)%. Bone marrow V20 lower:(67.9 ± 5.4)% vs (79.5 ± 6.6)%, V10 lower:(82.1 ± 6.0)% vs (86.3 ± 6.6)%; there were significant differences (all P<0.05). There was no significant difference between the dose of V45 in the intestinal pouch and bladder (P>0.05). (3) Acute radiation injury classification for IMRT vs 3D-CRT:big or small intestine:Ⅱ-Ⅲreaction [13%(11/85) vs 24% (24/98); χ2=3.925, P=0.048], there was significant difference. Bladder: Ⅲ reaction [19% (16/85) vs 26% (25/98); χ2=1.171, P=0.279], there was no significant difference. Radiochemotherapy of bone marrow suppression:Ⅲ-Ⅳreaction (14/20), the incidence rate [26%(14/54) vs 31%(20/65);χ2=0.339, P=0.562], the difference was not statistically significant. (4) Quality of life scale by FACT-Cx scale in IMRT vs 3D-CRT:there were no significant difference before radiotherapy (82 ± 16 vs 85 ± 16;t=1.279, P=0.203), while there was significant difference after radiotherapy (76 ± 14 vs 71 ± 18;t=-2.160, P=0.032). EPIC-CP scale score:before radiotherapy they were (16±7 vs 15±6;t=-0.174, P=0.862) ,but after radiotherapy (18±7 vs 22± 7; t=3.158, P=0.002), there was significant difference between them. Before and after radiotherapy, the increased EPIC-CP scale of the IMRT group vs 3D-CRT group were 3 ± 4 and 6 ± 4, the 3D-CRT group was significantly higher, the difference was statistically significant (t=5.500, P=0.000). Conclusion IMRT has shown that there are a significant benefit for the post-operative patients with cervical cancer and endometrial cancer compared to 3D-CRT.

A case of a young male patient,who came to the Second Xiangya Hospital,Central South University because of snoring for 10 years and nocturnal gatism for half month,was analyzed retrospectively.He was diagnosed as obstructive sleep apnea hypopnea syndrome (OSAHS) finally.The patient had been diagnosed and treated as stroke in the local hospital,while urinary and anal incontinence were not relieved.It was a dilemma for him to be properly diagnosed and treated.Polysomnography in our hospital revealed apnea hypopnea index (AHI) at 44.7 events/h,oxygen desaturation index (ODI) at 70.8 events/h and the longest apnea time at 185 seconds while the lowest blood oxygen saturation reduced to 31％.In addition,413 events of apnea accounted for 61.2％ of the sleep time and the minimal heart rate was 23 times/min.The patient was diagnosed as severe OSAHS with hypoxia metabolic brain disease,moderate pulmonary arterial hypertension,secondary polycythemia and obesity hypoventilation syndrome finally.He received the treatment of positive airway pressure non-invasive ventilator with an average pressure at 11.7 cmH2O with reduced AHI and increased blood oxygen saturation.The urinary and anal incontinence disappeared during the first night of treatment and it has been totally resolved so far.We considered that gatism was secondary to OSAHS with severe hypoxia resulted from attenuated regulation of primary defecation in the night.Physicians should pay attention to OSAHS when accepting obese patients with nocturnal incontinence,obvious daytime sleepiness and night snoring.Urinary and anal incontinence could be completely disappeared under therapy of positive airway pressure.

Objective:To investigate clinical and histopathological features of congenital melanocytic nevi (CMN) complicated by proliferative nodules (PN) .Methods:Ten patients with clinically and pathologically confirmed CMN complicated by PN were collected from Department of Dermatology, the Fourth Military Medical University from 2015 to 2019, and their clinical and pathological data were analyzed retrospectively.Results:The 10 patients were aged from 2 to 45 years, with an average age of 15 years. Nine patients developed PN in infancy, and 1 in adulthood. The skin lesions were located on the extremities in 4 cases, on the head and face in 3 cases, and on the trunk in 2 cases, and the trunk and extremities were both involved in 1 case. Skin lesions clinically manifested as 1 or more nodules arising in black patches or plaques. Six patients presented with multiple PN, 4 with solitary PN, with the diameter of a single nodule being 0.2-1.5 cm, and only 1 case presented with ulcers. Histopathological examination showed mature melanocytes in the PN, with few mitotic figures, no obvious cytological atypia, and no necrosis. Immunohistochemical study showed that nevus cells diffusely expressed Melan-A, but did not express or partially expressed HMB45, and the Ki67 proliferation index was below 5%.Conclusion:CMN complicated by PN can occur on the extremities, head, face, and trunk, clinically manifesting as solitary or multiple nodules on pre-existing CMN; histopathologically, mature melanocytes can be observed in PN, immunohistochemical staining for HMB45 and Ki67 can facilitate the diagnosis, and its prognosis needs long-term follow-up.

Background and purpose: Long non-coding RNA small nucleolar RNA host gene 5 (lncRNA SNHG5) plays a cancer-promoting role in many cancers, however its effect on colorectal cancer (CRC) and its regulatory mechanism are not clear. This study aimed to explore the mechanism of lncRNA SNHG5/miR-26a-5p/metadherin (MTDH) signal axis promoting metastasis of CRC. Methods: The data of The Cancer Genome Atlas (TCGA) database was analyzed, the abnormal expression of lncRNA in CRC was explored and analyzed the survival. Samples of CRC, paracancerous tissues and complete clinical data of patients who underwent surgical resection from October 2020 to October 2021 were collected. The expression levels of SNHG5 and miR-26a-5p in lncRNA were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR), and the expression level of MTDH was detected by immunohistochemistry. The relationship between the relative expression level of lncRNA SNHG5 in CRC and clinicopathological features and survival time was analyzed. The effects of lncRNA SNHG5 on the proliferation, migration and invasion of CRC cells were detected by cell counting kit-8 (CCK-8), clone formation, scratching assays, transwell test and in vivo xenotransplantation. The relationship between CRC cell metastasis, the expression level of epithelial-mesenchymal transition related molecules and lncRNA SNHG5 expression level by Western blot and immunohistochemical detection were explored. The physical interaction between SNHG5 and miR-26a-5p, MTDH and miR-26a-5p was studied by RNA pull-down test, double luciferase reporter gene detection and RNA co-immunoprecipitation. The functional relationship among the three was verified by CCK-8, EdU and transwell experiments. The effect of SNHG5, miR-26a-5p and MTDH expression on migration and invasion related molecules was analyzed by Western blot. Results: The results of TCGA database analysis showed that lncRNA SNHG5 was significantly upregulated in CRC. The results of RTFQ-PCR and immunohistochemistry showed that the levels of lncRNA SNHG5 and MTDH in CRC tissues were significantly upregulated (P＜0.05), the level of miR-26a-5p was decreased (P＜0.05), and the level of MTDH in samples with high expression of SNHG5 was also increased. The expression of lncRNA SNHG5 in CRC tissues with serosa and extraserosal invasion, distant metastasis, lymph node metastasis and TNM stage Ⅲ was significantly higher compared with subserosal invasion, no distant metastasis and lymph node metastasis and TNM stage Ⅰ-Ⅱ (P＜0.05). The results of survival analysis showed that the high expression of lncRNA SNHG5 was significantly correlated with overall survival rate (P＜0.05). Overexpression of lncRNA SNHG5 could enhance the proliferation, clone formation, migration and invasion of CRC cells, promote the growth and lung metastasis of transplanted tumor, increase the relative expression level of Ki-67 proliferation index and vimentin (P＜0.05), and decrease the relative expression level of E-cadherin (P＜0.05). However, the development of CRC cells was inhibited after inhibition of lncRNA SNHG5 expression. RNA pull-down test, double luciferase reporter gene detection and RNA co-immunoprecipitation confirmed the physical interaction between SNHG5 and miR-26a-5p, MTDH and miR-26a-5p. Upregulation of miR-26a-5p or downregulation of MTDH expression in lncRNA SNHG5 overexpressed cells partially reversed the effects of lncRNA SNHG5 on proliferation, migration, invasion and expression of related molecules in CRC cells. Conclusion: LncRNA SNHG5 is upregulated in CRC tissues and cells, and its high expression is related to tumor progression and poor survival. It can be used as a molecular sponge of miR-26a-5p to regulate the expression of MTDH to promote the proliferation and metastasis of SW620 cells.

Objective To evaluate the diagnostic value of ultrasound-guided fine needle aspiration cytology(US-FNAC)in the assessment of radiologically detected ovarian neoplasms and retroperitoneal metastatic lymph nodes. Methods FNAC was performed under ultrasound guidance on 126 patients suspected of ovarian neoplasms and retroperitoneal metastatic lymph nodes. Cytologic examination was performed after staining smears with the haematoxylin and eosin method. Clinical data were retrieved from the medical records and all cytological specimens were reviewed. In these cases, the cytologic findings were correlated with histology of the primary tumor and were compared with surgical pathology. Results Satisfactory sampling was obtained in 86.2% of punctures, and cytological diagnosis was made in 85.7% cases. The size of the lymph nodes punctured was less than 20 mm in 93.5% cases, with the sensitivity of 81.6%、86.2%, specificity of 95.8%、100.0%, positive predictive value of 98.3%、100.0%, negative predictive value of 63.9%、33.3%, and accuracy of 85.3%、87.1%. Seven patients presented slight abdominal discomfort, and relieved without clinical treatment. Conclusions The fine needle aspiration technique has excellent positive predictive value and low morbidity. US-FNAC, as the valuable investigation, is not only useful in the diagnosis of ovarian masses and lymph nodes but can also help in choosing appropriate management. From our experience, US-FNAC can be added in follow-up of selected patients in whom the cytological identification of such masses and nodes is significant for the patient′s treatment.