Artificial tumor microenvironment regulated by first hemorrhage for enhanced tumor targeting and then occlusion for synergistic bioactivation of hypoxia-sensitive platesomes

The unique characteristics of the tumor microenvironment (TME) could be exploited to develop antitumor nanomedicine strategies. However, in many cases, the actual therapeutic effect is far from reaching our expectations due to the notable tumor heterogeneity. Given the amplified characteristics of TME regulated by vascular disrupting agents (VDAs), nanomedicines may achieve unexpected improved efficacy. Herein, we fabricate platelet membrane-fusogenic liposomes (PML/DP&PPa), namely "platesomes", which actively load the hypoxia-activated pro-prodrug DMG-PR104A (DP) and physically encapsulate the photosensitizer pyropheophorbide a (PPa). Considering the different stages of tumor vascular collapse and shutdown induced by a VDA combretastatin-A4 phosphate (CA4P), PML/DP&PPa is injected 3 h after intraperitoneal administration of CA4P. First, CA4P-mediated tumor hemorrhage amplifies the enhanced permeation and retention (EPR) effect, and the platesome-biological targeting further promotes the tumor accumulation of PML/DP&PPa. Besides, CA4P-induced vascular occlusion inhibits oxygen supply, followed by photodynamic therapy-caused acute tumor hypoxia. This prolonged extreme hypoxia contributes to the complete activation of DP and then high inhibitory effect on tumor growth and metastasis. Thus, such a combining strategy of artificially-regulated TME and bio-inspired platesomes pronouncedly improves tumor drug delivery and boosts tumor hypoxia-selective activation, and provides a preferable solution to high-efficiency cancer therapy.

Curative effect of radiofrequency thermocoagulation combined with pulsed radiofrequency in the treatment of lumbar disc herniation and its effects on serum IL-8, CXCL10 contents / 中国基层医药

Objective:To observe the effect of radiofrequency thermocoagulation (RFTC) combined with pulsed radiofrequency (PRF) therapy on lumbar disc herniation (LDH) and the impacts on serum interleukin-8 (IL-8), CXC chemokine ligand 10 (CXCL10).Methods:From July 2014 to May 2017, 60 patients with LDH were randomly divided into two groups according to the random digital table method, with 30 patients in each group.The combination group was given RFTC combined with PRF therapy, while the PRF group was given single foraminal nerve PRF therapy.The visual analogue scale (VAS), the curative effect score of Japanese Orthopaedic Association (JOA) and Oswestry disability index (ODI) were assessed in the two groups before treatment, 7 days after treatment and 3 months after treatment.The serum levels of IL-8, CXCL10 were determined simultaneously.Results:After treatment, the VAS score and ODI in the two groups were decreased(VAS score: t=12.14, 27.85, all P<0.05; ODI: PRF group t=4.932, 7.414, all P<0.05; combination group t=4.235, 9.706, all P<0.05), and the JOA scores increased(PRF group: t=5.329, 7.576, all P<0.05; combination group: t=5.980, 9.526, all P<0.05). There were statistically significant differences in VAS score, JOA score and ODI between the two groups at 3 months after treatment( t=7.329, 5.719, 2.255, all P<0.05), which of the combination group after treatmentwere superior to the PRF group (all P<0.05). The serum levels of IL-8 in the two groups after treatment were decreased (PRF group: t=3.621, 4.631, all P<0.05; combination group: t=3.393, 5.370, all P<0.05), and the CXCL10 levels in the two groups after treatment were increased(PRF group: t=2.251, 3.559, all P<0.05; combination group: t=3.393, 5.370, all P<0.05). There were statistically significant differences in IL-8, CXCL10 levels between the two groups at 3 months after treatment, and the regulation of IL-8 and CXCL10 levels in the combination group was significantly better than those in the PRF group ( t=20258, 2.237, all P<0.05). Conclusion:RFTC combined with PRF is effective in the treatment of LDH, which can significantly relieve the clinical symptoms, reduce the inflammatory response and has a lasting efficacy.

Effects of butylphthalide soft capsules on cognitive function and daily living ability in patients with Parkinson's disease dementia / 中国基层医药

Objective To investigate the effects of butylphthalide soft capsules on cognitive function and daily living ability in patients with Parkinson's disease dementia(PDD). Methods From January 2016 to January 2017, 90 patients with PDD in the First People's Hospital of Wenling were divided into control group and study group by random number table method,with 45 cases in each group. The patients in the two groups were treated with conventional symptomatic treatment, and the control group was treated with donepezil, the study group was treated with butylphthalide soft capsules on this basis. The treatment time was 12 weeks. The clinical efficacies of the two groups were compared. Before treatment and 12 weeks after treatment,the cognitive functions of patients were assessed by Montreal cognitive assessment scale (MoCA) and mini - mental state examination (MMSE),and the daily living abilities of patients were assessed by Barthel index scale. Results The total effective rate of the study group was 93. 33％ ,which was higher than 75. 56％ of the control group (χ2 = 5. 414,P < 0. 05). 12 weeks after treatment,the scores of MoCA and MMSE scales in the two groups were (20. 54 ±2. 53)points,(18. 95 ± 2. 63)points,(23. 53 ± 2. 87)points,(22. 53 ± 2. 62)points,respectively,which were significantly higher than those before treatment[(16. 78 ±2. 34)points,(16. 03 ± 2. 24)points,(16. 23 ± 2. 78)points,(15. 23 ± 2. 34)points](t = 2. 863,2. 735,3. 062,3. 178,all P < 0. 05),and the scores of MoCA and MMSE scales in the study group were higher than those in the control group (t = 2. 798, 2. 753,all P < 0. 05). 12 weeks after treatment,the Barthel scores of the two groups were (64. 43 ± 5. 89) points, (76. 33 ± 5. 23 ) points, respectively, which were significantly higher than those before treatment [( 59. 34 ± 4. 83)points,(58. 26 ± 6. 65)points](t = 2. 916,3. 203,all P < 0. 05),and the Barthel score in the study group was higher than that in the control group (t = 2. 835,P < 0. 05). The incidence rate of adverse reaction in the control group was 6. 67％ ,which in the study group was 8. 89％ ,there was no statistically significant difference between the two groups (χ2 = 0. 155,P > 0. 05). Conclusion Butylphthalide soft capsules can significantly improve the cognitive function and daily living ability of patients with PDD,which is suitable for clinical application and promotion.

Effects on cervical spondylosis of vertebral artery type and the concentrations of plasma NPY and UII in the patients treated with the modified acupuncture at unilateral/bilateral Renying (ST 9) / 中国针灸

<p><b>OBJECTIVE</b>To observe the differences in the clinical therapeutic effects on cervical spondylosis of vertebral artery type (CSA) between the modified acupuncture and the routine acupuncture at unilateral/bilateral Renying (ST 9) as well as the impacts on the concentrations of plasma neuropeptide Y (NPY) and urotensinⅡ(UⅡ) in the patients.</p><p><b>METHODS</b>A total of 160 patients were divided into a modified bilateral acupuncture group, a modified unilateral acupuncture group, a routine bilateral acupuncture group and a routine unilateral acupuncture group, 40 cases in each one according to the random number table. In the modified bilateral acupuncture group, the modified acupuncture was applied bilaterally to Renying (ST 9). In the modified unilateral acupuncture group, the modified acupuncture was applied unilaterally to Renying (ST 9). In the routine bilateral acupuncture group, the routine acupuncture was applied bilaterally to Renying (ST 9). In the routine unilateral acupuncture group, the routine acupuncture was applied unilaterally to Renying (ST 9). The treatment was given once every day, continuously for 6 days as one course. Two courses of treatment were required at the interval of 1 day. In each group, before and after treatment, we observed the peak systolic blood flow velocity (Vs) of the vertebral artery (VA) and the basilar artery (BA), cervical vertigo symptoms and functional assessment scales (ESCV) and the concentration of plasma NPY and UⅡ. The clinical therapeutic effects were compared among the groups.</p><p><b>RESULTS</b>After treatment, the clinical therapeutic effect in the modified bilateral acupuncture group was 90.0% (36/40), which was better than 80.0% (32/40) in the modified unilateral acupuncture group, 77.5% (35/40) in the routine bilateral acupuncture group and 65.0% (26/40) in the routine unilateral acupuncture group (all <0.05). After treatment, Vs of VA and BA was improved remarkably in every group (all <0.01), and the result in the modified bilateral acupuncture group was higher than those in the other groups (all <0.01). After treatment, ESCV scores were all increased remarkably in every group (all <0.01). ESCV score and improvement index in the modified bilateral acupuncture group were all higher than those in the other groups (<0.05, <0.01). After treatment, the concentrations of plasma NPY and UⅡ were all reduced remarkably in every group (all <0.01) and the differences were significant among the groups (all <0.01).</p><p><b>CONCLUSION</b>The modified bilateral acupuncture at Renying (ST 9) effectively regulates the blood supply of the vertebral basilar artery and improves the cerebral circulation. The effects are superior to those of the unilateral acupuncture at Renying (ST 9).</p>

Study on the association of USP8 gene polymorphisms with male infertility in ethnic Han Chinese from Sichuan / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of single nucleotide polymorphisms (SNPs) of ubiquitin-specific protease 8 gene (USP8) with male infertility among ethnic Han Chinese from Sichuan.</p><p><b>METHODS</b>A total of 316 infertile males were recruited (case group), which included 72 severe oligozoospermic (SO) cases and 244 non-obstructive azoospermic (NOA) cases. The control group consisted of 149 fertile males. The genotypes of 4 SNPs (rs2241769, rs11857513, rs7174015 and rs3743044) were determined with a Sequenom MassArray technique. The frequencies of genotype, allele and haploptye were analyzed.</p><p><b>RESULTS</b>No significant difference was detected in the allelic or genotypic frequencies of the 4 SNPs between the two groups (P>0.05). Based on linkage disequilibrium analysis and haplotype construction, the frequency distribution of haplotype CAAG showed a significant difference between non-obstructive azoospermic patients and the controls (P=0.021).</p><p><b>CONCLUSION</b>The 4 SNPs (rs2241769, rs11857513, rs7174015 and rs3743044) of USP8 gene may not be associated with male infertility in ethnic Hans from Sichuan. While the haplotype CAAG may be a down-regulating factor for the risk of NOA.</p>

3D-TOF MRA screening of intracranial aneurysms in the population of Wenling community ZHANG / 介入放射学杂志

Objective To evaluate the application of three dimensional time-of-flight (3D-TOF) MRA in screening intracranial aneurysms in the population of Wenling community. Methods A total of 2 124 patients with suspicious intracranial aneurysm in Wenling community, who received 3D-TOF MRA and three dimensional digital subtraction angiography(3D-DSA) during the period from September 2011 to August 2012, were enrolled in this study. The epidemic data of intracranial aneurysm in Wenling community were analyzed, the effectiveness of 3D-TOF MRA in detecting intracranial aneurysm was assessed, and the consistency between 3D-TOF MRA and 3D-DSA (regarded as the golden standard) in detecting intracranial aneurysm was statistically analyzed. Results The results of 3D-TOF MRA showed that the morbidity of intracranial aneurysm in the population of Wenling community was 6.87% (146/2 124), among which the morbidities in males and females were 48.63% (n=71) and 51.37% (n=75) respectively; the mean age of patients was (41.2±11.6) years old. The accompanying diseases included hypertension, diabetes mellitus, arteriosclerosis and cerebrovascular lesions. 3D-TOF MRA examination revealed 149 intracranial aneurysms, among which misdiagnosis was made in 5 patients and missed diagnosis in 2 patients. The sensitivity, specificity and accuracy of 3D-TOF MRA in diagnosing intracranial aneurysm were 98.63% (144/146), 99.72%(1 773/1 778) and 99.67%(2 117/2 124) respectively. No statistically significant difference in measuring the longitudinal diameter and neck width of intracranial aneurysms existed between 3D-TOF MRA and 3D-DSA examinations (P>0.05). Conclusion In detecting intracranial aneurysm, 3D-TOF MRA carries higher sensitivity, specificity and accuracy, and its non-invasive advantage is more suitable for the screening of intracranial aneurysms.

Association of single nucleotide polymorphisms in H2BFWT with male infertility in southwest China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of single nucleotide polymorphisms (SNPs) in exons of H2BFWT gene with male infertility in southwest China.</p><p><b>METHODS</b>Three hundred and twelve infertile men and 211 fertile men were recruited. PCR was employed to amplify the target fragments of H2BFWT, and PCR products were sequenced. Prevalence of SNPs in the two groups was analyzed by statistical method.</p><p><b>RESULTS</b>The detected SNPs have mainly distributed in the first exon of the H2BFWT gene. The ratios of 368G/A (rs553509) and -9C/T (rs7885967) were significantly higher in infertile group than fertile group. Additionally, a context-dependent effect was observed between 368G/A and -9C/T which the allele 368G combined with allele -9T will considerably increase the risk of male infertility.</p><p><b>CONCLUSION</b>The present study has revealed that the SNPs in H2BFWT are associated with male infertility, and may increase the susceptibility of male infertility in southwest China.</p>