Research progress on the nucleoside/nucleotide-loaded nanomedicines / 浙江大学学报·医学版

Nucleoside drugs play an essential role in treating major diseases such as tumor and viral infections, and have been widely applied in clinics. However, the effectiveness and application of nucleoside drugs are significantly limited by their intrinsic properties such as low bioavailability, lack of targeting ability, and inability to enter the cells. Nanocarriers can improve the physiological properties of nucleoside drugs by improving drug delivery efficiency and availability, maintaining drug efficacy and system stability, adjusting the binding ability of the carrier and drug molecules, as well as modifying specific molecules to achieve active targeting. Starting from the design strategy of nucleoside drug nanodelivery systems, the design and therapeutic effect of these nanomedicines are described in this review, and the future development directions of nucleoside/nucleotide-loaded nanomedicines are also discussed.

A case with α-thalassemia caused by novel start codon variant in conjunct with right deletion variant of α2-globin gene / 中华医学遗传学杂志

OBJECTIVE@#The explore the genetic basis for a patient with microcytic hypochromic anemia and iron deficiency anemia.@*METHODS@#Common deletions and variants of the globin genes were detected by Gap-PCR and next generation sequencing (NGS). Suspected mutations were verified by Sanger sequencing.@*RESULTS@#Gap-PCR and NGS showed that the proband has carried a αα/-α @*CONCLUSION@#Patients with α HBA2 c.2T>A(p.Met1Lys) α/-α

Analysis of correlation between expression of vascular endothelial growth factor, MMP-2 and MMP-9 and clinical prognosis of patients with hepatocellular carcinoma / 中国基层医药

Objective:To investigate the correlation between the expression of vascular endothelial growth factor (VEGF), MMP-2, MMP-9 and the clinicopathology and prognosis of patients with hepatocellular carcinoma (HCC), and to provide evidence for the occurrence and development of HCC.Methods:From April 2015 to March 2016, 95 HCC tissues were resected in Yiwu Central Hospital.Forty-fivenormal liver tissues which were resected due to liver trauma were selected as control group.Immunohistochemical staining was used to detect the expression of VEGF, MMP-2 and MMP-9 in HCC and normal liver tissues, and the correlation between the expression of VEGF, MMP-2, MMP-9 and clinical pathology and prognosis was analyzed.Results:The positive expression rates of VEGF, MMP-2 and MMP-9 in the HCC tissues were significantly higher than those in the normal liver tissues (81.05%, 75.79%, 84.21% vs.42.22%, 33.33%, 48.89%)(χ 2=21.364, 23.397, 19.265, all P<0.05). The positive expression rates of VEGF, MMP-2 and MMP-9 in HCC were significantly increased in patients with poor differentiation, TNM stage Ⅲ-Ⅳ and vascular invasion (all P<0.05). The survival of patients with negative expression of VEGF, MMP-2 and MMP-9 in HCC tissues was significantly better than that of patients with positive expression (log χ 2=3.271, 2.975, 3.065, all P<0.05). Conclusion:The high expression of VEGF, MMP-2 and MMP-9 plays an important role in the growth, invasion and metastasis of HCC tissues.Therefore, VEGF, MMP-2 and MMP-9 can be used as biological indicators of the progression of HCC.

Effect of high-throughput sequencing for the prevention and control of thalassemia / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of next generation sequencing (NGS) for the prevention and control of thalassemia.@*METHODS@#NGS was used to sequence 3083 clinical blood samples suspected for thalassemia during initial screening. Retrospective analysis was conducted on blood samples detected with rare genotypes of thalassemia and abnormal hemoglobin.@*RESULTS@#NGS analysis of the 3083 samples has found 1089 subjects with thalassemia genotypes (alpha-thelassemia genotype: 26.01%, beta-thalassemia genotype: 6.71%, and alpha-compound-beta genotype: 2.59%), which yielded a positive detection rate of 35.32%. Rare alpha-thalassemia genotypes including HBA2 c.123delG, HBA1 c.354_355insATC and Fusion gene, and rare beta-thalassemia genotypes including HBB c.-100G>A and HBB c.316-90A>G, were discovered. In addition, 19 patients were found to have abnormal hemoglobin, mainly including Hb Hamilton, Hb Hekinan II, Hb Shizuoka, Hb Owari, Hb New York, Hb J-Bangkok and Hb Port Phillip.@*CONCLUSION@#NGS can play a crucial role for improving of the prevention and control of thalassemia and formulating a screening system with better efficacy.

Lipid peroxidation and anti-lipid peroxidation and the skin pigment in skin of C57BL/6 mice exposed to arsenic / 中华地方病学杂志

Objective To study the effect of lipid peroxidation and anti-lipid peroxidation and the pigment in skin of C57BL/6 mice exposed to arsenic.Methods Forty male C57BL/6 mice were divided into four groups via the random number table method,ten mice in each group,and the mice were fed ad libitum drinking water containing arsenic at 0,1,5 and 25 mg/L concentrations for a period of 6 weeks,respectively.Twelve days before the end of the experiment,procedure of depilation was performed to induce anagen of hair cycle.On the 30th day of experiment,the activity of superoxide dismutase (SOD) was determined by nitrite method,the activity of glutathione peroxidase (GSH-Px) was determined by dithiobisobenzoic acid method,the content of malondialdehyde (MDA) in skin of C57BL/6 mice was determined by thiobarbituric acid method.Melanin was measured by NaOH dissolution method.Results No significant difference was found in body weight and water intaken between groups (F =0.119,0.363,P ＞ 0.05).The activity of SOD [(16.00 ± 5.05),(13.96 ± 2.02),(10.46 ± 3.14) U/mg prot] in 1,5 and 25 mg/L arsenic groups were all significantly lower than that in control group [(20.36 ± 4.82) U/mg prot,P ＜ 0.05].GSH-Px activity in 1,5 and 25 mg/L arsenic groups [(98.14 ± 23.92),(87.18 ± 10.87),(53.56 ± 19.97) U/mg prot] were all significantly lower than that in control group [(119.34 ± 33.14) U/mg prot,P ＜ 0.05].While MDA levels in 5 and 25 mg/L arsenic groups [(9.09 ± 2.04),(11.48 ± 2.21) nmol/mg prot] were significantly higher than that of control group [(6.19 ± 0.56) nmol/mg prot,P ＜ 0.05] and that of 1 mg/L arsenic group [(6.52 ± 1.67) nmol/mg prot,P ＜ 0.05).No significant difference was found in melanin levels (P ＞ 0.05).Conclusions Lipid peroxidation and the decreasing of antioxidation may be one of the mechanisms of arsenic-induced skin damage.Arsenic-induced skin melanin content change is not found.

Comparative Study of Conventional Vascular Ultrasound and Superb Micro Vascular Imaging for Diagnosing Carotid Artery Stenosis in Relevant Patients / 中国循环杂志

Objective: To assess the values of conventional vascular ultrasound (US) and superb micro vascular imaging (SMI) for diagnosing carotid artery stenosis in relevant patients. Methods: A total of 37 patients of extra cranial carotid stenosis (with 70 blood vessels) treated in our hospital from 2014-08 to 2015-03 were retrospectively studied. Digital subtraction angiography (DAS) examination was used as golden standard, the diagnostic efifcacies for carotid artery stenosis by US and by SMI were compared. Results: The accuracy, sensitivity and specificity for diagnosing carotid stenosis by US were 81.42%, 83.33% and 80.95%; by SMI were 91.43%, 92.16% and 89.47% respectively. Conclusion: US and SMI showed good agreement for diagnosing carotid artery stenosis, while SMI was superior to US for accurately assess the degree of carotid stenosis, it might be used as a more reliable method for evaluating carotid plaque and stenosis in relevant patients.

Studies on the therapy of endometriosis by antiangiogenesis with endostatin gene / 解放军医学杂志

Objective To study the inhibitory effect of recombinant adenoviruses carrying the mouse endostatin gene on the therapy of endometriosis in nude mice.Methods Animal endometriosis models were established by inoculating human endometrial fragments.Mice were randomly divided into three groups(10 each):PBS control group,Ad-lacZ group and Ad-mEndo therapy group when ectopic lesion diameter reached 5-10mm.The ectopic lesion size was measured every day.The expression of endostatin in ectopic lesion was detected by immunohistochemical stainining.The microvessel density(MVD) of ectopic lesion was traced by CD34 immunohistological labeling.Meanwhile,the contents of steroid hormone and histological changes in mice uterus and ovary were detected.Results The titer of the recombinant adenovirus was about 5.0?109pfu/ml.The endostatin gene was transferred into mice successfully and expressed effectively.The lesion volume was significantly less in Ad-mEndo group(34.3?11.2mm3) than that in Ad-lacZ group(93.3?10.7mm3) and PBS group(90.4?18.7mm3,P

Laparoscopic Treatment for Interstitial Tubal Pregnancy:a Simple,Quick,and Safe Method / 中国微创外科杂志

Objective To evaluate the efficacy of laparoscopic treatment for interstitial tubal pregnancy. Methods A total of 12 cases of interstitial tubal pregnancy underwent laparoscopy in our hospital from 1993 April to June 2007. Among the patients,9 received tubal ligation using lasso (1-0 suture were used during the surgery and the fetal tissues were removed at the same time),1 underwent salpingotomy to remove the fetus,1 were treated by salpingectomy using stapling device,and 1 received injection of MTX (40 mg). Results The procedure was completed within 30-120 minutes. The intraoperative blood loss was ≤20 ml in all of the cases,except one who received salpingectomy (200 ml). In 10 patients,the level of blood hCG decreased to a normal range in 2 weeks,while the other two cases recovered in 4 and 8 weeks respectively postoperation. Conclusion Laparoscopic treatment is safe and effective for interstitial tubal pregnancy.

Exploring the Anatomical Relationship between the Umbilicus and Major Retroperitoneal Vessels during Laparoscopy / 中国微创外科杂志

Objective To study the anatomical relationship between the umbilicus and the retroperitoneal major vessels. Methods A total of 80 female patients undergoing laparoscopy in our department were enrolled in this study. The patients were divided into 4 groups according to their body mass index (BMI):low-weight group,normal-weight group,overweight group,and obese group. During the operation,the surgeons palpated the abdominal aorta,right common iliac artery,and left common iliac artery with hand to determine their relationship to the umbilicus. The abdominal aortic bifurcation was used as a reference point to determine its position in relation to the umbilicus. Results (1) The bifurcation was above the level of the umbilicus in 17 (21.2%) cases,at the umbilicus level in 29 (36.3%) cases,and below that in 34 (42.5%) cases. Among the four groups,the position of the bifurcation was significantly different (?2=16.769,P=0.010). In the overweight and obese groups,most of the patients had the umbilicus located under the level of the aortic bifurcation [65.0% (13/20) and 75.0% (6/8) respectively],while in the normal-weight group,47.6% (20/42) of the cases had the umbilicus above the aortic bifurcation(P

Long-term Follow-up for Patients with Stage Ⅰ Endometrial Cancer after Laparoscopic Surgery / 中国微创外科杂志

Objective To compare the long-term prognosis of patients with stage Ⅰ endometrial cancer (EMC) after laparoscopic surgery or open laparotomy. Methods Totally 83 patients with stage Ⅰ EMC who underwent laparoscopic surgery or open laparotomy between 1993 and 2008 were enrolled in this study. The clinical data were analyzed retrospectively to compare the survival time during long-term follow-up between the two groups. Results The total survival rate was 95.2% (79/83) in the 83 cases. The median survival time was 77,51,and 31 months respectively in stages Ⅰa,Ⅰb,and Ⅰc EMC patients. No significant difference was found in the survival rate between open and laparoscopy groups [94.2% (49/52) vs 96.8% (30/31),Z=0.028,P=0.978]. For the stage Ⅰa,stages Ⅰb and Ⅰc,and G2 and G3 patients,the median survival time was similar between the open and laparoscopy groups (80 month vs 63 months,P=0.483; 49 months vs 48 months,P=0.781; and 51 months vs 49 months,P=0.635). However,in the G1 patients,significantly difference was detected in the median survival time between the two groups (77 vs 51 months,P=0.037). Conclusion Laparoscopic surgery should be used as a routine surgical approach for patients with stage Ⅰ EMC considering its minimal invasiveness and promising prognosis.

Effect of Different Types of Pneumoperitoneum on the Ultrastructure of the Extraperitoneal Muscular Tissues in Rat / 中国微创外科杂志

Objective To investigate the influence of different types of pneumoperitoneum on the ultrastructure of the extraperitoneal muscular tissues in rats. Methods By using pulse-mode or constant-pressure mode insufflators,we established CO2 pneumoperitoneum in 80 rats (40 for each) with the pressure set at 15 mmHg. At 60,90,120 and 180 minutes after the insufflation,the muscular tissues below the peritoneum of the rats (10 rats at each time point) were obtained to observe the ultrastructural change under a transmission electron microscope (TEM). Ten rats that received anesthesia only were set as a control. Results In both the groups,vacuolar degeneration was found in the myocytes below the peritoneum after 60 minutes of pneumoperitoneum,and became more and more marked with time. Moreover,the phenomenon was more significant in the pulse-mode insufflator group,in which,we observed widened gaps and vacuoles among the myocytes at 180 minutes after the insufflation,while in the other group,such changes were not apparently detected. Conclusions CO2 pneumoperitoneum may injure the muscular tissues below the peritoneum in rats. Constant-pressure mode insufflator is helpful to decrease such an injury.