Early hyperbaric oxygen therapy inhibits aquaporin 4 and adrenocorticotropic hormone expression in the pituitary gland of rabbits with blast-induced craniocerebral injury

In the present study, rabbits were treated with hyperbaric oxygen for 1 hour after detonator-blastinduced craniocerebral injury. Immunohistochemistry showed significantly reduced aquaporin 4 expression and adrenocorticotropic hormone expression in the pituitary gland of rabbits with craniocerebral injury. Aquaporin 4 expression was positively correlated with adrenocorticotropic hormone expression. These findings indicate that early hyperbaric oxygen therapy may suppress adrenocorticotropic hormone secretion by inhibiting aquaporin 4 expression.

Fat deposition deficiency is critical for the high mortality of pre-weanling newborn piglets

Background: The high mortality of pre-weanling piglets is a dominant challenge which severely restricts the development of pig industry. A number of factors including nutrients imbalance and temperature variation during postnatal period of piglets have been reported to closely associated with the high mortality of postnatal piglets.This study aims to find out the relationship between fat deposition and survival of newborn piglets.Results: There were no differences in organ coefficient and bone density between the surviving and dead piglets(P > 0.05). The body weight and the fat deposition in the dead piglets were lower than the live individuals(P < 0.05).Consistently, the average sizes of white adipocytes in back and abdominal adipose tissues of dead piglets were smaller than the survivals(P < 0.05). The protein expression levels of adipocyte differentiation markers PPARγ and C/EBPα in the back and abdominal adipose tissues were lower in dead piglets compared to live piglets. The mRNA expressions of thermogenic markers PGC1α and PRDM16 in adipose tissues were decreased in the dead piglets(P < 0.05). The microarray of back fat samples from the surviving and dead piglets were conducted; two down-regulated genes namely AAMDC and CASTOR1 were identified from the dead piglets. According to quantitative real-time PCR(RT-PCR) analysis, the mRNA expression of AAMDC decreased, whereas CASTOR1 expression elevated in the dead piglets compared to the surviving piglets(P < 0.05).Conclusions: The fat deposition and adipocyte differentiation in the dead piglets are insufficient compared to the surviving piglets, which may attenuate the thermogenic ability of white adipose tissue(WAT). Our data indicate that fat deposition in newborn piglets is vital to their survival.

Effects of magnesium on the performance of sows and their piglets

The objective of this study was to evaluate the effects of supplemental magnesium （Mg） on the performance of gilts and parity 3 sows and their piglets. Fifty-six grits （Trial 1） and 56 sows （Trial 2） were assigned to one of 4 treatments according to their mating weight, respectively. The treatments comprised corn-soybean meal based gestation and lactation diets （0.21% magnesium） supplemented with 0, 0.015, 0.03, or 0.045% Mg from mating until weaning. The results showed that magnesium supplementation significantly （P 〈 0.05） reduced the weaning to estrus interval in both gilts and sows. There were significant effects （P 〈 0.05） of supplemental magnesium on the total number of piglets born, born alive and weaned in sows. In late gestation and lactation, the digestibility of crude fiber （quadratic effects, P 〈 0.05）, and crude protein （P 〈 0.05）, were significantly influenced by magnesium in gilts and sows, respectively. There were differences among the 4 groups in terms of the apparent digestibility of dry matter and crude fiber in sows （P 〈 0.0S） during both early and late gestation. The apparent digestibility of gross energy was increased for sows in late gestation （P 〈 0.05）, and lactation （quadratic effects, P 〈 0.0S）. At farrowing and weaning, serum prolactin levels and alkaline phosphate activities linearly increased in sows as the Mg supplementation increased （P 〈 0.0.5）. Serum Mg of sows at farrowing and serum urea nitrogen of sows at weaning was significantly influenced by Mg supplementation （P 〈 0.05）. The Mg concentration in sow colostrum and the serum of their piglets were increased by supplemental magnesium （P 〈 0.05）. In addition, growth hormone levels were linearly elevated （P 〈 0.05） in the serum of piglets suckling sows. Our data demonstrated that supplemental magnesium has the potential to improve the reproduction performance of sows, and the suitable supplemental dose ranged from 0.015% to 0.03%.

Apoptosis-related protein expression in rabbits with blast brain injury following early hyperbaric oxygen therapy

We treated detonator-explosion-induced craniocerebral injury in rabbits with hyperbaric oxygen 1 24 hours post-injury. Expression of the apoptosis-regulating protein cytochrome c, the pro-apoptotic protein Bax and the apoptosis marker caspase-3 in the tissues surrounding the area of injury was significantly reduced, while that of the anti-apoptotic protein Bcl-2 was significantly increased. Our findings indicate that the curative effects of early hyperbaric oxygen on cortical cell apoptosis is associated with suppression of cytochrome c release from mitochondria. This mechanism underlies the observed reduction in Bax expression and upregulation of Bcl-2 expression.

Expression and function of WNT4 involved in larvae development and limb regeneration in Portunus trituberculatus

The wingless-related integration site(WNT)proteins are a family of secreted glycoproteins that are evolutionarily conserved and are believed to be involved in evolution in vertebrates and invertebrates.WNT signaling pathways may be associated with limb regeneration and development in crustaceans.However,the detail mechanisms remain unclear.Therefore,the distribution of WNT4 in the hepatopancreas,muscle,hemocyte,ganglion,heart,eyestalk,gill tissue,and diff erent larvae development stages of the swimming crab(Portunus trituberculatus)were characterized using immunofl uorescence,real-time PCR,and Western blotting.Signifi cant PtWNT4 expression was detected in heart and eyestalk.In addition,PtWNT4 was expressed in all larval stages of P.trituberculatus with a dynamic expression pattern,especially in the eyestalk and other organs in the carapace area.The injection of WNT4 dsRNA into regenerative limbs signifi cantly decreased PtWNT4 mRNA levels in the eyestalk,heart,and muscle,resulting in 1.9-fold,2.2-fold,and 2.7-fold decreases compared with those detected in the group injected with crab saline(P<0.05),respectively,indicating successful gene silencing.Overall,expression analysis on the WNT4 using RNAi provides an insight to its functional mechanism during limb regeneration in P.trituberculatus.The results not only demonstrated the requirement for WNT4 in limb regeneration of Crustaceans,but also suggested its ability to promote larval development at specifi c stages.

Music stimulus has a positive eff ect on survival and development of the larvae in swimming crab Portunus trituberculatus

The sound stimulus has a signifi cant impact on marine animals.However,many studies have focused on the negative impacts of sound on marine vertebrates.The positive impacts of sound on marine animals,especially on marine invertebrates,were rarely studied.In the present study,we evaluated the eff ects of music on the survival and development of an economically important marine invertebrate,swimming crab Portunus trituberculatus.Three pieces of classical music and a control group,i.e.,Eine Kleine Nachtmusik by Mozart(EK),Bach-Violin Concerto No.1(BV),Anonymous Romanza by Anonymous(AR),and environmental sound(EN)were used.The sound pressure received were 163-dB root mean square(RMS)re 1μPa for EK,166-dB RMS re 1μPa for BV,165-dB RMS re 1μPa for AR,44-dB RMS re 1μPa for EN,respectively.The larvae were subject to 3-h classical music transmission every day during the entire larval development period.The result showed that BV and AR signifi cantly elevated the cumulative survival rate of the larva from 3.42%±1.77%(EN)to 10.65%±1.69%(BV)and 7.12%±1.37%(AR)respectively(P<0.05).Though music did not aff ect the cumulative development time of larvae from ZoeaⅠto ZoeaⅣ,it signifi cantly increased the molting rate of megalopa from 24.00%±11.78%(EN)to 44.00%±13.06%(AR)and 46.67%±10.50%(BV)(P<0.05).Musical exposure during critical growth intervals may contribute to the survival and development of larval crustaceans.From an application point of view,music intervention is much economically feasible.The observed music eff ects imply that music could further enhance growth,welfare,and production.

3种中分子量蛋白对镍钛和不锈钢弓丝抗腐蚀能力的影响

目的探索不同类型的蛋白对合金抗腐蚀能力的影响及其机制,以期为镍钛和不锈钢弓丝在临床上的安全应用及表面改性提供参考。方法采用动电位极化法测试纤维蛋白原、IgG或黏蛋白对镍钛和不锈钢弓丝抗电化学腐蚀能力的影响,并用循环极化法检测三种蛋白处理后表面钝化膜的修复能力。电感耦合等离子体发射光谱法(inductively coupled plasma optical emission spectrometer, ICP-OES)测定腐蚀产物的类型,并对腐蚀后表面形貌进行扫描电镜和原子显微镜分析。结果添加纤维蛋白原、IgG或黏蛋白对同一合金的抗腐蚀能力影响不同。添加蛋白能够降低不锈钢合金的抗腐蚀能力,可减缓镍钛合金的腐蚀进程。添加黏蛋白能够提高镍钛合金抗腐蚀性和表面钝化膜的修复能力。与黏蛋白及IgG相比,纤维蛋白原能够降低镍钛和不锈钢合金的抗点蚀能力。结论不同类型的蛋白能与弓丝发生作用,在表面形成不同的沉积形貌,并参与合金的腐蚀过程。

Logistic Regression Analysis the Risk Factors of Peripherally Inserted Central Catheter Related Blood Stream Infection of Tumor Patients

Objective: Our object is to study risk factors of tumor patients’ PICC catheter-related blood stream infection. Method: a retrospective analysis of data of 586 PICC catheterized patients was implemented, a univariate analysis of general data and catheterizing data of tumor patients was then carried out, and data of single factors with statistical significance were incorporated into multi-factor Logistic regression model for analysis. Results: PICC catheter-related blood stream infection occurred to 16 patients, and occurrence rate was 2.73%. Multi-factor Logistic regression analysis results showed that number of puncturing times, positioning method and maintenance frequency were risk factors for tumor patients’ peripherally inserted central catheter catheter-related blood stream infection, and odds risk values were respectively 8.762, 9.253 and 10.324. Conclusion: for tumor patients implanted with peripherally inserted central catheters, using ECG positioning during strict sterile operation and catheterizing process to avoid repeated puncturing and increasing maintenance frequency could effectively reduce occurrence of PICC catheter-related blood stream infection.

Meta-Analysis of Atrial Electro-Gram Applied to PICC Catheter Tip Positioning

Objective: Assess the location effect of the atrial electrogram in the PICC catheter tip. Method: Make online research in the CNKI, CBM, Wanfang, VIP, Database, Cochrane Library, JBI Library, PubMed, Ovid, Springer, Web of science, MEDLINE database to collect the randomized controlled trial data of using the atrial electrogram to locate the PICC catheter tip. When making the online research, only the data to November 20, 2016 can be searched out. Two researchers independently select the literature and information, make quality assessment, and then use the RevMan 5.2 software to make Meta analysis. Result: 16 random tests are done. The Meta analysis results show that compared with the traditional X ray chest radiograph location method, the atrial electrogram can increase the accuracy rate of the location of the catheter tip [RR = 1.13, 95%CI (1.07, 1.19), P &minus;12.56, 95%CI (&minus;18.56, &minus;6.57), P Conclusion: The atrial electrogram can increase the accuracy rate of the location of the catheter tip, decrease the incidence rate of related complications and save the catheter placing time. Therefore, it is worthy of clinical application.

无模板插层-剥离勃姆石合成具有优异稳定性的多孔硅掺杂氧化铝二维纳米片

高比表面积和大孔容的多孔氧化铝已被广泛应用在各种领域,但不使用有机模板合成多孔氧化铝仍面临巨大挑战.在此,我们报道了基于插层-剥离策略的多孔氧化铝合成方法,利用硅物种削弱勃姆石(氧化铝前体)的层间作用力,从而在不使用有机模板的情况下将勃姆石剥离成二维纳米片.该合成过程可放大到3 L,并获得厚度为2 nm的二维纳米片.此外,这些二维纳米片可组装成比表面为542 m^(2)g^(-1)和孔容为2.43 cm^(3)g^(-1)的勃姆石.在不同温度下对二维纳米片进行热/水热处理得到的多孔氧化铝其孔结构优于多数有机模板法合成的氧化铝,并表现出优异的吸附性能.本研究为合成二维勃姆石纳米片和多孔氧化铝材料提供了一种新策略.

Microbial-driven ectopic uranium extraction with net electrical energy production

The extraction of uranium (U) from U-bearing wastewater is of paramount importance for mitigating negative environmental impacts and recovering U resources. Microbial reduction of soluble hexavalent uranium (U(VI)) to insoluble tetravalent uranium (U(IV)) holds immense potential for this purpose, but its practical application has been impeded by the challenges associated with managing U-bacterial mixtures and the biotoxicity of U. To address these challenges, we present a novel spontaneous microbial electrochemical (SMEC) method that spatially decoupled the microbial oxidation reaction and the U(VI) reduction reaction. Our results demonstrated stable and efficient U extraction with net electrical energy production, which was achieved with both synthetic and real wastewater. U(VI) removal occurred via diffusion-controlled U(VI)-to-U(IV) reduction-precipitation at the cathode, and the UIVO_(2) deposited on the surface of the cathode contributed to the stability and durability of the abiotic U(VI) reduction. Metagenomic sequencing revealed the formation of efficient electroactive communities on the anodic biofilm and enrichment of the key functional genes and metabolic pathways involved in electron transfer, energy metabolism, the TCA cycle, and acetate metabolism, which indicated the ectopic reduction of U(VI) at the cathode. Our study represents a significant advancement in the cost-effective recovery of U from U(VI)-bearing wastewater and may open a new avenue for sustainable uranium extraction.

Correlation of gut microorganisms and non-volatile flavor substances provides new insights for breeding Scylla paramamosain

The farming of Scylla paramamosain with specific flavors has a higher commercial value,and the flavors are related to the integrated farming environment and non-volatile flavor substances,while the survival environment is one of the important ways to source gut microorganisms in the organism.In this study,the levels of dominant taxa in the gut flora of S.paramamosain from Mong Cai,Vietnam(VN),Taishan City,Guangdong Province(TS)of China,and Ninghai County,Ningbo City(NB)Zhejiang Province of China converged with those of S.paramamosain from Sanmen County,Ningbo City(CK 1,CK 2,and CK 3)at 28 d of domestication.The top 15 genera with the highest abundance of VN,TS,and NB gut flora were the same as CK 1,CK 2,and CK 3,but with different percentages,and gradually converged to CK 1,CK 2,and CK 3,respectively,at 28 d of domestication.Correlation between intestinal flora and non-volatile flavor substances in the hepatopancreas at the percentage level of relative abundance of bacterial genera found that above 28 d of domestication,Muribaculaceae,Psychrilyobacter,Clostridia_vadinBB 60_group,Halarcobacter Carboxylicivirga,Sediminispirochaeta may be the most important genera affecting flavor amino acids of VN.Sediminispirochaeta,Carboxylicivirga,Halarcobacter,Photobacterium,ZOR 0006,Psychrilyobacter,and Pseudomonas may be the most important genera affecting flavor amino acids of NB.Sediminispirochaeta,Carboxylicivirga,Halarcobacter,Photobacterium,ZOR 0006,Vibrio,and Sphingomonas may be the most important genera affecting flavor amino acids of TS.These results show that the intestinal flora structure of crabs from different areas were domesticated in the same area for at least 28 d before they converged to that of the domesticated crab,and the most important genera affecting the flavor amino acids of TS,VN,and NB were also identified.The results of this study provide a reference and basis for the technique of directional cultivation of the flavor quality of the crab.

日粮添加褐藻糖胶对断奶仔猪抗炎能力和肠道微生物多样性的影响

【目的】本试验旨在研究日粮添加海带提取物褐藻糖胶对断奶仔猪生长性能、营养物质消化率、机体免疫力和肠道微生物多样性的影响。【方法】试验选用36头初始体重为(7.43±0.12) kg的健康仔猪,按照随机区组设计分为3组,每组12头。日粮处理组分别为不含抗生素的基础日粮组、抗生素组和褐藻糖胶组;试验期为28d。评价褐藻糖胶对仔猪生长性能和营养物质消化率的影响;通过比色法和酶联免疫吸附法检测血清中与免疫相关的指标;通过16S rRNA扩增子高通量测序检测试验第0、14和28天肠道微生物多样性。【结果】日粮添加褐藻糖胶可降低试验0–14 d仔猪耗料增重比(P<0.05),但对试验全期仔猪平均日增重和平均日采量无显著影响(P>0.05)。与对照组相比,饲喂褐藻糖胶日粮后,仔猪的中性洗涤纤维和酸性洗涤纤维表观消化率显著提高(P<0.05);仔猪饲喂抗生素和褐藻糖胶日粮后,血清IL-22含量显著降低。试验第14天,抗生素组和褐藻糖胶处理组中Bacteroidetes数量呈上升趋势(P=0.07);试验第28天,抗生素组和褐藻糖胶处理组Actinobacteria丰度显著高于对照组(P<0.05),且褐藻糖胶处理组Bacteroides属的菌群丰度显著高于对照组和抗生素组。【结论】日粮添加褐藻糖胶提高了断奶仔猪纤维养分消化率和拟杆菌属的丰富度和多样性,并且降低了促炎性细胞因子IL-22含量,这有助于缓解仔猪的断奶应激反应,建立稳定健康肠道菌群。

Short‐term effect of the prone masturbation training on premature ejaculation

Background:Whether conventional behavioral therapies for premature ejaculation can significantly improve the intravaginal ejaculatory latency time is still controversial.Prone masturbation is rare and observed in some patients with delayed ejaculation.Therefore,we tried to verify whether the regular prone masturbation training method had a therapeutic effect on premature ejaculation.Methods:From July to December 2018,a total of 21 patients met the enrollment criteria and volunteered to participate.Participants were diagnosed with premature ejaculation with an intravaginal ejaculatory latency time of less than 3min and a Premature Ejaculation Diagnostic Tool score greater than 9.Participants performed 12‐week prone masturbation training.Results:Ten patients completed the entire treatment regimen.The mean age of the 10 participants was 30.4±6.1 years,the mean frequency of sexual intercourse was 1.9±0.83 times a week,and the median duration of premature ejaculation was 1.5 years.After 3 months of prone masturbation training,the median self‐reported intravaginal ejaculatory latency time significantly increased from 60 to 105 s(p=0.011),and the mean Premature Ejaculation Diagnostic Tool scores decreased from15.0±3.7 to 12.7±3.7 points(p=0.119).Conclusions:The regular prone masturbation training method,as a novel behavioral therapy,probably has a therapeutic effect on premature ejaculation.

中国城镇儿童不同Tanner分期身高体重现况调查

目的了解我国城镇3~18岁儿童不同Tanner分期身高、体重的情况,为建立各青春发育期身高、体重的标准化参照值提供依据。方法于2017年1月至2019年12月应用分层随机整群抽样的方法,对中国12个省、自治区、直辖市218185名健康儿童体格发育情况进行横断面调查。调查指标包括体重、身高、腰围、臀围和第二性征。采用基于GAMLSS软件构建各年龄组男、女童的身高、体重百分位数参照值及生长曲线,采用Wilcoxon秩和检验比较各Tanner分期儿童与同年龄同性别不分发育分期组所有儿童的身高、体重第50百分位值。结果绘制出3~18岁儿童男、女各自年龄的身高、体重第3、50、97百分位曲线。绘制出儿童男、女各青春发育期年龄的身高、体重第3、50、97百分位曲线。9岁及以上Tanner 1期男童和7岁及以上Tanner 1期女童身高及体重低于同年龄同性别所有儿童(均P<0.01),男女童身高差值范围分别为-4.0~-0.6、-4.4~-0.5 cm,体重差值范围分别为-4.8~-0.4、-4.0~-0.3 kg。Tanner 2期与3期儿童年龄的身高及年龄的体重呈先高后低趋势,两组曲线呈交叉走势。16岁及以下Tanner 4期男童和14岁以下Tanner 4期女童年龄的身高、体重高于同龄同性别所有儿童(均P<0.01),身高差值范围男女童分别为0.2~10.0、0.2~9.4 cm,体重差值范围分别为0.7~10.9、1.0~11.2 g,曲线各年龄组两组间差异随年龄逐渐缩小。结论建立了我国城镇3~18岁不同性别儿童各青春发育期年龄的身高、体重百分位曲线,可供临床进行青春期体格发育评估使用。

Enhanced efficiency of cadmium removal by Boehmeria nivea(L.) Gaud. in the presence of exogenous citric and oxalic acids

Boehmeria nivea（L.） Gaud. is a potential candidate for the remediation of Cd contaminated sites. The present investigation aims to explore Cd tolerance threshold and to quickly identify the role of exogenous organic acids in Cd uptake and abiotic metal stress damage.Elevated Cd levels（0–10 mg/L） resulted in an obvious rise in Cd accumulation, ranging from268.0 to 374.4 in root and 25.2 to 41.2 mg/kg dry weight in shoot, respectively. Citric acid at1.5 mmol/L significantly facilitated Cd uptake by 26.7% in root and by 1-fold in shoot,respectively. Cd translocation efficiency from root to shoot was improved by a maximum of66.4% under 3 mmol/L of oxalic acid. Citric acid exhibited more prominent mitigating effect than oxalic acid due to its stronger ligand affinity for chelating with metal and avoiding the toxicity injury of free Cd ions more efficiently. The present work provides a potential strategy for efficient Cd remediation with B. nivea.

预测结直肠癌远处转移的临床预测模型:结合术前CEA、CA19-9及临床病理因素

目的探讨术前肿瘤标志物CEA、CA19-9联合检测相关临床病理因素在结直肠癌远处转移中的预测价值。方法回顾性分析了接受R0根治术的2 758例结直肠癌患者临床资料,包括年龄、性别、肿瘤分化程度、肿瘤直径、肿瘤位置、CEA、CA19-9、肿瘤组织学类型、远处转移等临床资料,通过对可能反映结直肠癌患者出现远处转移的因素进行单因素及多因素分析,进而选择合适的变量构建列线图,并通过校准曲线来验证列线图的识别性。绘制受试者工作特征曲线(ROC)检验列线图对于伴随远处转移的结直肠癌患者的预测性能。结果单因素及多因素分析结果表示,术前CEA、CA19-9、肿瘤部位、肿瘤分化程度是反映结直肠癌患者出现远处转移的重要因素(P<0.05)。上述变量构建列线图,该预测模型的ROC值为0.771(95%置信区间:0.730~0.813)。结论术前CEA、CA19-9联合临床病理信息构建的预测模型是无创预测结直肠癌患者发生远处转移的有效方法。

Evolution of tumor microenvironment in colorectal liver metastases under treatment stress

Dear editor,The tumor microenvironment(TME)heavily impacts disease biology and may influence responses to systemic treatments,and thereby,affects patients’prognosis.In our previous study,we found that immune features could predict prognosis and guide the therapy choices for stage I-III colon cancer[1,2].Increasing evidence shows that therapyinduced TME changes can promote tumor progression,metastasis,and the development of resistance[3,4].However,the TME dynamics in colorectal liver metastases(CRLM)under treatment are still incompletely clear.

Trilineage Sequencing Reveals Complex TCRβTranscriptomes in Neutrophils and Monocytes Alongside T Cells

Recent findings indicate the presence of T cell receptor(TCR)-based combinatorial immune receptors beyond T cells in neutrophils and monocytes/macrophages.In this study,using a semiquantitative trilineage immune repertoire sequencing approach as well as under rigorous bioinformatic conditions,we identify highly complex TCRβtranscriptomes in human circulating monocytes and neutrophils that separately encode repertoire diversities one and two orders of magnitude smaller than that of T cells.Intraindividual transcriptomic analyses reveal that neutrophils,monocytes,and T cells express distinct TCRβrepertoires with less than 0.1%overall trilineage repertoire sharing.Interindividual comparison shows that in all three leukocyte lineages,the vast majority of the expressed TCRβvariants are private.We also find that differentiation of monocytes into macrophages induces dramatic individual-specific repertoire shifts,revealing a surprising degree of immune repertoire plasticity in the monocyte lineage.These results uncover the remarkable complexity of the two phagocyte-based flexible immune systems which until now has been hidden in the shadow of T cells.

New insights into the role of intra-tumor genetic heterogeneity in carcinogenesis: identification of complex single gene variance within tumors

Aim:Present cancer hypotheses are almost all based on the concept that accumulation of specific driver gene mutations cause carcinogenesis.The discovery of intra-tumor genetic heterogeneity(ITGH),has resulted in this hypothesis being modified by assuming that most of these ITGH mutations are in passenger genes.In addition,accumulating ITGH data on driver gene mutations have revealed considerable genotype/phenotype disconnects.This study proposes to investigate this disconnect by examining the nature and degree of ITGH in breast tumors.Methods:ITGH was examined in tumors using next generation sequencing of up to 68,000 reads and analysis tools that allowed for identification of distinct minority variants within single genes,i.e.,complex single gene variance(CSGV).Results:CSGV was identified in the androgen receptor genes in all breast tumors examined.Conclusion:Evidence of CSGV suggests that a selection-as opposed to a mutation-centric hypothesis could better explain carcinogenesis.Our hypothesis proposes that tumors develop by the selection of preexisting de novo mutations rather than just the accumulation of de novo mutations.Thus,the role of selection pressures,such as changes in tissue microenvironments will likely be critical to our understanding of tumor resistance as well as the development of more effective treatment protocols.