Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Preparation of poly(lactide-co-glycolide)microspheres and evaluation of pharmacokinetics and tissue distribution of BDMC-PLGA-MS in rats

The aim of the present study was to develop a novel long-acting Poly(lactic-co-glycolic acid)(PLGA)-based microspheres formulation of Bisdemethoxycurcum(BDMC) by emulsionsolvent evaporation method. Meanwhile, the effects of the volume ratio of the dispersed phase and continuous phase, the concentration of PLGA and PVA, the theoretical drug loading and stirring speed were investigated. The mean diameter of the microspheres was 8.5 μm and the size distribution was narrow. The encapsulation efficiency(EE) and drug loading efficiency(DLE) of BDME loaded PLGA microspheres(BDMC-PLGA-MS) was 94.18% and 8.14%,respectively. In an in vitro study of drug release, it can be concluded that the BDMC-PLGAMS exhibited sustained and long-term release properties for 96 h. Stability studies suggested that the microspheres we prepared had a very good stability. Furthermore, the results of an in vivo study indicated that the BDMC-PLGA-MS had sustained release effect and was mainly distributed in the lung tissue, and less distribution in other tissues, which indicated that microspheres could be an effective parenteral carrier for the delivery of BDMC in lung cancer treatment.

全膝关节置换术治疗膝关节僵硬的疗效分析

目的分析并比较膝关节僵硬患者行全膝关节置换术(total knee arthroplasty,TKA)后的临床疗效。方法分析2012年5月至2017年4月19例(23膝)行TKA治疗的膝关节僵硬患者,其中男7例,女12例;年龄48~79岁,平均(63.63±7.75)岁。4例患者双侧均为僵硬膝,在随访时间内分2次行双膝TKA治疗,间隔时间6~12个月。观察并比较各膝术前、术后半年及术后2年的美国膝关节协会评分(the American knee society score,AKS)及关节活动度(range of motion,ROM)。结果19例患者均获得随访,分两次随访全部膝关节术后半年、术后2年的AKS及ROM。关节活动范围:术前10°~47°,平均(31.17±9.63)°;术后半年55°~115°,平均(93.04±14.83)°;术后2年35°~110°,平均(85.00±19.83)°;患者术前与术后比较差异具有统计学意义(P<0.05),术后半年至术后2年关节活动范围均有所减小(P<0.05)。AKS评分:术前12.00~69.00分,平均(33.17±12.32)分;术后半年53.00~99.00分,平均(74.44±12.72)分;术后2年52.00~96.00分,平均(70.57±13.24)分;术后AKS评分较术前显著提高,差异具有统计学意义(P<0.05),术后半年与术后2年AKS评分差异无统计学意义(P>0.05)。结论人工TKA能显著改善膝关节僵硬患者的运动功能及生活质量。

Unconventional Petroleum Sedimentology:A Key to Understanding Unconventional Hydrocarbon Accumulation

The commercial exploitation of unconventional petroleum resources(e.g.,shale oil/gas and tight oil/gas)has drastically changed the global energy structure within the past two decades.Sweet-spot intervals(areas),the most prolific unconventional hydrocarbon resources,generally consist of extraordinarily high organic matter(EHOM)deposits or closely associated sandstones/carbonate rocks.The formation of sweet-spot intervals(areas)is fundamentally controlled by their depositional and subsequent diagenetic settings,which result from the coupled sedimentation of global or regional geological events,such as tectonic activity,sea level(lake level)fluctuations,climate change,bottom water anoxia,volcanic activity,biotic mass extinction or radiation,and gravity flows during a certain geological period.Black shales with EHOM content and their associated high-quality reservoir rocks deposited by the coupling of major geological events provide not only a prerequisite for massive hydrocarbon generation but also abundant hydrocarbon storage space.The Ordovician-Silurian Wufeng-Longmaxi shale of the Sichuan Basin,Devonian Marcellus shale of the Appalachian Basin,Devonian-Carboniferous Bakken Formation of the Williston Basin,and Triassic Yanchang Formation of the Ordos Basin are four typical unconventional hydrocarbon systems selected as case studies herein.In each case,the formation of sweet-spot intervals for unconventional hydrocarbon resources was controlled by the coupled sedimentation of different global or regional geological events,collectively resulting in a favorable environment for the production,preservation,and accumulation of organic matter,as well as for the generation,migration,accumulation,and exploitation of hydrocarbons.Unconventional petroleum sedimentology,which focuses on coupled sedimentation during dramatic environmental changes driven by major geological events,is key to improve the understanding of the formation and distribution of sweet-spot intervals(areas)in unconventional petroleum systems.

Anti-aging effects of moxa cone moxibustion As a free radical scavenger complement

Therapies that complement free radical scavenging are an important approach for treating aging in the brain. In the present study, two formulations of moxa cone moxibustion were applied at acupoints Zusanfi （ST 36） and Xuanzhong （GB 39）, and at acupoints Baihui （DU 20） and Guanyuan （RN 4）, in D-galactose-induced senile mice. The results revealed that moxa cone moxibustion improved total superoxide dismutase and Cu/Zn-superoxide dismutase activity in the homogenates of the cerebral tissue, as well as ameliorating deficits in neuronal morphology and neuronal density in the cerebral cortex and hippocampal CA3. Moxa cone moxibustion also enhanced learning and memory functions of senile mice. Moxa cone moxibustion at Zusanli, Xuanzhong, Baihuiand Guanyuan acupoints can thus be used to complement free radical scavengers, with efficacy that is equal to that of electroacupuncture at Zusanliand Xuanzhong, and superior to that of nimodipine treatment.

Screening and bioinformatics analysis of diabetic peripheral neuropathy-related genes in women

Objective: To obtain the key genes and signal pathways of diabetic peripheral neuropathy (DPN) through bioinformatics analysis of related gene chips in the GEO database. Methods: The DPN-related gene chip was downloaded from the GEO database, and the differential genes (DEGs) between DPN female patients and the normal control group were analyzed and visualized using R language. According to the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), DEGs were annotated, their functions and related pathways were predicted, and a protein interaction network was constructed using the STRING database to screen for core genes. Results: The analysis chip GSE95849 obtained 4746 DEGs of which 2218 genes were up-regulated and 2528 genes were down-regulated. Among them, TFAP2C, ESR1, CX3CR1, and FGL2 are at the core site of protein interaction. Conclusions: Differential genes are mainly involved in the MAPK pathway. They participate in the pathogenesis of DPN through blood glucose homeostasis, inflammatory effects, and neuronal development, providing new ideas for the diagnosis and treatment of DPN.

Theory, Technology and Practice of Unconventional Petroleum Geology

0 INTRODUCTION The breakthroughs in unconventional petroleum have a great impact on world petroleum industry and innovation in petroleum geology(Dou et al,2022;Jia,2017;Zou et al.,2015b,2014a;Yerkin,2012;Pollastro,2007;Schmoker,1995).The exploration and development evolution from conventional petroleum to unconventional petroleum and more and more frequent industrial activities of exploring petroleum inside sources kitchen have deepened theoretical understanding of unconventional petroleum geology and promoted technical research and development(Jia et al.,2021,2017;Jin et al.,2021;Zhao W Z et al.,2020;Ma Y S et al.,2018,2012;Zou et al.,2018b,2016,2009;Dai et al.,2012).We have introduced and extended the theory of continuous hydrocarbon accumulation since 2008 and published several papers/books(in Chinese and English)with respect to unconventional petroleum geology since 2009,basically forming the theoretical framework for this discipline(Yang et al.,2022a,2021a,2019a,,2015a;Zou et al.,2019c,2017b,2014a,,2013a).In this paper,we present the background of unconventional petroleum geology,review the latest theoretical and technological progress in unconventional petroleum geology,introduce relevant thinking and practices in China,and explore the pathway of unconventional petroleum revolution and multi-energy coordinated development in super energy basins,hopefully to promote the unconventional petroleum geology and industry development.

海陆过渡相页岩气储层特征与主控因素——以鄂尔多斯盆地大宁—吉县区块二叠系山西组为例

鄂尔多斯盆地东缘大宁—吉县地区二叠系山西组山_(2)段为海陆过渡相沉积,其中山_(2)^(3)亚段具有页岩厚度大、夹层少而薄的特点,是目前中国海陆过渡相页岩气勘探开发的重点目标层段,但其储层特征等相关研究相对较少,特别是优质储层发育的主控因素有待进一步明确。综合利用有机地球化学分析、矿物成分分析以及储层微观刻画等技术手段,对大宁—吉县区块山_(2)^(3)亚段的储层特征进行系统研究并探讨优质储层发育的主控因素。研究结果表明:山西组山_(2)^(3)亚段上部潟湖相(底部)页岩层段具有高TOC含量、高脆性矿物含量、高BET和高BJH的特征,是最优质的页岩气储集层段;山_(2)^(3)亚段页岩孔隙构成以黏土矿物晶间孔为主体,占总孔隙体积的76.9%,有机质孔占18.7%;扫描电镜观察显示不同矿物组分的孔隙大小分布特征不同,其中有机质孔和方解石溶蚀孔以中孔为主,黏土矿物与石英则主要发育中孔与宏孔,黄铁矿与长石孔径范围分布广,且分布较为均匀。单因素分析显示黏土矿物含量是影响山_(2)^(3)亚段海陆过渡相页岩孔隙发育的第一控制要素,有机质含量对页岩孔隙发育存在着一定影响,有机质类型则对页岩孔隙发育的影响不明显。

鄂尔多斯盆地东缘二叠系山_(2)^(3)亚段海陆过渡相页岩岩相类型与储层发育特征

中国海陆过渡相页岩气的开发正处于起步阶段,而开展页岩岩相划分及储层特征的研究则有利于页岩气的进一步勘探开发。通过薄片鉴定、X-射线全岩衍射、扫描电镜等一系列方法对鄂尔多斯盆地东缘山_(2)^(3)亚段海陆过渡相页岩进行精细研究。结合矿物成分、TOC含量将山_(2)^(3)亚段页岩划分为8种不同的岩相,其中主要发育4种岩相:富有机质黏土质硅质页岩(Ⅰ_(2));富有机质含钙黏土质硅质页岩(Ⅰ_(3));富有机质含钙硅质黏土页岩(Ⅱ_(3));富有机质含钙含硅黏土页岩(Ⅱ_(4))。不同岩相储层品质具有较大差异,富有机质含钙硅质黏土页岩(Ⅱ_(3))TOC含量最高,孔隙之间连通性好,孔比表面积最大,相对应赋存的吸附气含量也较高,发育有良好的纹层状构造,易于压裂形成渗流通道,为最优页岩相;富有机质黏土质硅质页岩(Ⅰ_(2))发育层状构造,易于压裂,孔体积最大,相对应的游离气的聚集含量就越高,为次优页岩相;富有机质含钙黏土质硅质页岩(Ⅰ_(3))及富有机质含钙含硅黏土页岩(Ⅱ_(4))纹层发育情况一般,储层发育程度均低于另外2种岩相,为中等页岩相,不利于勘探开发。

Controlling Factors on Organic Matter Accumulation of Marine Shale across the Ordovician–Silurian Transition in South China: Constraints from Trace-Element Geochemistry

In recent years,significant progress in shale gas exploration has been achieved in the Upper Ordovician(Wufeng Formation)–Lower Silurian(Longmaxi Formation)shales in the Upper Yangtze area,South China.Although many studies have been carried out on the Upper Ordovician–Lower Silurian shales,the controlling factors causing organic matter accumulation of these shales remain controversial.This study uses trace-element geochemistry and sedimentological methods to evaluate terrigenous input,redox conditions and primary productivity to explore the mechanisms of organic matter accumulation.The variation of terrigenous fraction elements(Al,Th and Sc)concentrations reflect a mixed influence of sea-level change and weathering.The sea-level of the Upper Yangtze Sea went through two cycles of transgression to regression during the Ordovician–Silurian transition.The Linxiang Formation,Kuanyinchiao Bed and the upper part of Longmaxi Formation developed during the periods of regression,whereas the Wufeng Formation and the lower part of the Longmaxi Formation developed during the periods of transgression.The paleo-productivity indexes of TOC content,ratios of Ba/Al and P/Al,and redox conditions proxies of Mo concentration,ratios of U/Th and V/Cr generally display similar variation patterns with respect to the sea-level changes.High TOC contents and Ba/Al and P/Al ratios indicate the paleo-productivity was high on the sea surface,as shown by relatively good positive correlations between Th vs.TOC,and Sc vs.TOC.This indicates that the paleo-productivity was controlled by the nutrients input through weathering.The good positive correlations between redox conditions indexes(U/Th and V/Cr ratios)with TOC content reflects reductive preservation conditions(anoxic to euxinic),thus implying they were an important controlling factor for organic matter accumulation.Nevertheless,redox conditions were closely associated with sea level change and organic matter decomposition.Therefore,the sea-level change and weathering were the primary controlling factors for organic matter enrichment across the Ordovician to Silurian transition.