Hepatitis B vaccine by intradermal route in non responder patients:An update

Vaccination is the main prophylactic measure to reduce the mortality caused by hepatitis B virus (HBV) infection in healthy subjects since the immune response to hepatitis B recombinant vaccination occurs in over 90% of general population. Individuals who develop an anti-HBs titer less than 10 mIU/mL after primary vaccination cycle are defined “no responders”. Many factors could cause a non response to the HBV vaccination, such as administration of the vaccine in buttocks, impaired vaccine storage conditions, drug abuse, smoking, infections and obesity. Moreover there are some diseases, like chronic kidney disease, human immunodeficiency virus infection, chronic liver disease, celiac disease, thalassaemia, type I diabetes mellitus, down’s syndrome and other forms of mental retardation that are characterized by a poorer response to HBV vaccination than healthy subjects. To date it is still unclear how to treat this group of patients at high risk of hepatitis B infection. Recent studies seem to indicate that the administration of HBV recombinant vaccine by the intradermal route is very effective and could represent a more useful strategy than intramuscular route. This review focuses on the use of anti hepatitis B vaccine by intradermal route as alternative to conventional intramuscular vaccine in all non responder patients. A comprehensive review of the literature using PubMed database, with appropriate terms, was undertaken for articles in English published since 1983. The literature search was undertaken in September 2013.

Clinical characteristics of null responders to Peg-IFNα2b/ ribavirin therapy for chronic hepatitis C

AIM: To predict which chronic hepatitis C patients are likely to be late-responders, we herein investigated the clinical characteristics of null-responders at 36 wk with hepatitis C virus (HCV) genotype Ib and a high viral load during the course of pegylated interferon (Peg-IFN)/ ribavirin ther apy. METHODS: One hundred forty-two patients with genotype Ib HCV and a high viral load were included in this study. Peg-IFNα2b (1.5 μg/kg once a week) and ribavirin (600-1000 mg per day according to body weight) were administered for 48 wk. We def ined nullresponders as the cases that never cleared serum HCV RNA as determined using RT-PCR until 36 wk. Other patients were def ined as responders. We compared the clinical characteristics (age, gender, body mass index, previous treatment) and HCV RNA titer during the therapy between null-responders and responders.RESULTS: The HCV RNA clearance rate was 17.9% (24/134), 46.3% (62/134), 60.6% (86/142), 86.6% (123/142), and 88.0% (125/142) at 4, 8, 12, 24, and 36 wk, respectively. There were 17 patients (12.0%) who were still null-responders at 36 wk. There were no differences in the clinical characteristics between the responders and null-responders except for the titer and decline rates of HCV RNA at 1 wk and 4 wk. The HCV RNA titers at 1 wk and after 4 wk of treatment were significantly higher in the null-responders in comp arison to the responders (P <0.01). The serum HCV RNA titers of the responders decreased by 1.3 log after 1 wk of treatment, and 1.6 log after 4 wk of treatm ent, respectively. On the other hand, the titers of the null responders decreased by only 0.5 log after 1 wk, and 0.7 log after 4 wk of treatment, respectively. The decrease rates of HCV RNA after 1 and 4 wk of treatm ent were signif icantly worse for null responders than for the responders (P <0.01). CONCLUSION: The HCV RNA titer at 1 wk and 4 wk after initiating treatment may be useful for predicting null-responders to Peg-IFNα2b/ribavirin therapy. However, further investigation is needed to determine the optimal time at which the decision to discontinue the Peg-IFNα2b/ribavirin therapy for null-responders can be made.

Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet

BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Cumulative Live Birth Rate after Three Ovarian Stimulation IVF Cycles for Poor Ovarian Responders According to the Bologna Criteria

Summary： This study explored the cumulative live birth rate after three ovarian stimulation in vitro fer- tilization （IVF） cycles for poor ovarian responders according to the Bologna criteria. In this retrospec- tive cohort study, 479 poor ovarian responders according to the Bologna criteria in the first ovarian stimulation IVF cycle between July 2006 and January 2012 in our IVF centre were included. The cu- mulative live birth rate was calculated by optimistic and pessimistic methods. The cumulative live birth rate after three ovarian stimulation IVF cycles for poor ovarian responders according to the Bologna criteria was 12.7%-20.5%. The three-cycle cumulative live birth rate was 18.5%--24.5%, 13.2%-27.4% and 8.6%-14.9% for poor responders aged ≤35 years, 36-39 years and 〉40 years, re- spectively. In conclusion, poor responders according to the Bologna criteria can receive an acceptable cumulative live birth, rate after three ovarian stimulation IVF cycles, especially poor responders aged 〈40 years.

Ribavirin monotherapy increases sustained response rate in relapsers of end treatment virologic responders

AIM: To assess the efficacy of ribavirin monotherapy in patients with biochemical relapse after combination therapy.METHODS: Twenty-four weeks of ribavirin monotherapy was given to biochemical relapsers of end treatment biochemical responders within 6 mo after combination therapy, including non-responders with HCV-RNA level ≤0.2 Meq/mL and end treatment virologic responders (ETVRs) with or without reappearance of HCV-RNA.RESULTS: Sixty-two chronic HCV-infected patients completed 24 wk of interferon-α plus ribavirin combination therapy. Fifty patients (80%) achieved end treatment biochemical response including 16 non-responders and 34 of 36 ETVRs. Twenty-six patients (41.9%) were nonresponders. Ribavirin monotherapy was given to 20biochemical relapsers including 12 non-responders with HCV-RNA levels ≤0.2 Meq/mL, four of eight HCV-RNA reappearing ETVRs, and four HCV-RNA negative ETVRs.After 24 wk of ribavirin monotherapy, one of 12 nonresponders, two of four HCV-RNA reappearing ETVRs and all four RNA-negative biochemical relapsers of ETVRs showed sustained virologic response. Two of 12monotherapy treated non-responders showed persistent normalization of liver function test. In total, 50% (31/62)of patients achieved sustained virologic response.CONCLUSION: Resumption of ribavirin monotherapy in ETVRs at signs of viral rebound and recurrent biochemical abnormalities rather than continuation of monotherapy appears to be the key to success of ribavirin monotherapy after interferon-related combination therapy.

Aromatase Inhibitors for IVF Poor Responders

Objective To evaluate whether letrozole enhanced follicular recruitment, embryo numbers, and pregnancy rates in poor responders undergoing IVF. Methods We reviewed all IVF cycles between January 2002 and September 2003 using letrozole at Stanford University Medical Center. The entry criteria were the requirement of at least 450 IU/d of injectable gonadotropins in a prior failed cycle, which was used as a control. Results A total of 27 charts were reviewed revealing information on 54 cycles. The number of oocytes retrieved, fertilization, embryo quality and embryos transferred yielded no statistical significance, although there appeared to be a trend toward higher numbers of each in the letrozole group. The clinical pregnancy rate was 9/27 （33.3%, P〈0.001） with a viable pregnancy rate of 7/27 （25.9%, P=0. 002） in the Ietrozole cycle. Conclusion Our study is one of the first to evaluate letrozole with in vitro fertilization. Although this study showed no difference in number of oocytes or embryos, 25.9% of these ＂poor responding＂ patients achieved a pregnancy after a failed cycle at our center.

The Challenge of Improving IVF Results in Normogonadotrophic (Unexpected) Young Poor Ovarian Responders: The Predictive Value of a Flexible Treatment Protocol Based on the “Biophysical Profile of the Uterus”

Objective: To study whether the unexpected poor ovarian responders optimization of uterine receptivity with a flexible controlled ovarian hyper stimulation protocol based on the Biophysical Profile of the Uterus, has an impact on their reproductive performance. Design: Observational Prospective study. Setting(s): i) General hospital-IVF and Infertility Centre;ii) University hospital. Patient(s): 44 normogonadotrophic young women (26 - 38 yrs) with previous “unexpected” poor ovarian response underwent IVF/ICSI treatment on a protocol based on the Biophysical Profile of their uterus (Group A). The same patients were used as controls in a preceded IVF cycle on the conventional stimulation protocol. Intervention(s): None. Main outcome measure(s): Pregnancy, miscarriage and home take baby rates, amount and duration of gonadotropins required, number and quality of embryos resulted, Biophysical Profile of the Uterus score. Result(s). Treatment in Group A in comparison to Group B resulted in significantly larger number of eggs retrieved per patient, and improved fertilization rates and higher number of embryos/ET (p = 0.011, 0.010 and 0.034 respectively). Group A also demonstrated a trend for higher rates of clinical pregnancy (29.5% v.s. 15.9%), viable stage pregnancies ≥ 24 weeks (33.3% v.s. 20%) and home take babies (26.6% v.s. 16%). The amount of gonadotropins used per patient (IU) was similar in the two groups (p = 0.264). Cancellation, implantation and miscarriage rates as well as embryos quality, although superior in the treatment Group A, showed no significant difference. The number of pregnancies achieved in Group A, were directly related with the score in the Biophysical Profile of the Uterus 12 point scale. Conclusion(s): Unexpected Poor Ovarian Responders on the flexible IVF/ICSI protocol (Group A), adjusting the management according to the Biophysical Profile of their uterus (duration of stimulation, day of HCG and day of embryo transfer), had a significantly better performance in comparison to the Group B managed on the conventional protocol in this difficult to manage and so far, rather understudied population.

GnRH Antagonist Protocol: Is It Effective for Expected Poor Ovarian Responders with Tubal Factor Undergoing IVF?

Background: This study aimed to determine if the gonadotropin releasing hormone (GnRH) antagonist protocol is optimal for expected poor ovarian responders with tubal factor undergoing in vitro fertilization-embryo transfer (IVF-ET). Methods: A total of 341 IVF-ET cycles were retrospectively identified. The following inclusion criteria were applied: age ≥ 40 years and patients with tubal factors. The cycles were divided into two groups: a GnRH antagonist group (157 cycles) and a GnRH agonist group (184 cycles). Results: The duration of stimulation and the total doses of gonadotropin in the GnRH agonist group were significantly more than those in the GnRH antagonist group (P < 0.05). There were significant differences in LH and P values on the hCG measurement days between the two groups (0.91 ± 1.17 vs. 4.82 ± 4.69 U/L and 0.69 ± 0.42 vs. 1.03 ± 0.50 ng/mL, P < 0.05). The implantation rate of the GnRH antagonist group was 12.24%, which was slightly higher than that of the GnRH agonist group (10.10%, P = 0.437). The clinical pregnancy rate of the two groups showed no statistical differences (23.36% vs. 23.03%, P = 1.000). Conclusion: For expected poor ovarian responders, the GnRH antagonist protocol was, to some extent, superior to the GnRH agonist protocol in terms of the implantation and clinical pregnancy rates.

Preliminary Results of DHEA in Poor Responders in IVF

Objective: Dehydroepiandrosterone (DHEA) has been previously reported to improve ovarian response in IVF for poor responders. Its effect remains uncertain. The purpose of this study was to evaluate the effect of DHEA given during two years in our unit, in order to build hypothesis for a future randomized controlled trial. Design: Cohort of exposed and non-exposed DHEA study. Patient(s): 224 patients with AMH under 1.6 ng/ml undergoing IVF with a short antagonist protocol adding FSH and LH rec were enrolled for 327 IVF cycles. 176 patients had been treated with DHEA before IVF, and 151 had not. Intervention(s): None. Main Outcome Measure(s): Cancellation cycle rate, amount of gonadotrophins used, estradiol level on day six of stimulation, number of oocytes retrieved, metaphase II oocytes, blastocysts and frozen embryos, clinical pregnancy rate and miscarriage rate. Results: The cancellation rate was significantly higher in the group without DHEA (29.8% versus 13.1%, p = 0.002). The amount of gonadotrophins used for stimulation, the estradiol level on day six of stimulation, the number of oocytes retrieved, metaphase II oocytes, blastocysts, frozen embryos and miscarriage rate were not different in both groups. The clinical pregnancy rate per included patient in the DHEA group was 17.1% versus 8.6% in the non-treated group (p = 0.02). Conclusion: DHEA appears to improve clinical pregnancy rate by decreasing the cancellation rate.

Retinoic acid receptor responder 2 and lipid metabolic reprogramming:A new insight into brain metastasis

The brain is one of the most common metastatic sites for carcinoma,especially for breast cancer,the second leading cause of brain metastases(BrM)after lung cancer[1].During organ‐tropic metastases,cancer cells have to survive and expand in target organs through a process involving a complex interplay between invading cells and the microenvironment.

Elective single blastocyst transfer is more suitable for normal responders than for high responders

Background Embryo quality and receptivity of the endometrium are two factors that determine the results of in vitro fertilization/intra-cytoplasmic sperm injection-embryo transfer （IVF/ICSI-ET）. There is no consensus of the optimal transfer strategy for normal responders or high responders. The current study aimed to find the optimal transfer strategy for different subgroups of patients. Methods From April 2010 to December 2010, patients who meet the following criteria were included in this study; primary infertility, female age 〈35 years, FSH level on female cycle day 2-3 〈12 mlU/ml, at least six good quality embryos available on day three.The clinical outcomes using different transfer strategies between normal responders and high responders were reviewed and compared. Results For the normal responders, the clinical pregnancy rate of day three double-embryo transfer （DET） was comparable to that of day five elective single blastocyst transfer （eSBT）, 64.04% vs. 60.33% （P〉0.05）. For the high responders, the clinical pregnancy rate of day five eSBT was significantly lower than that of day three DET, 43.35% vs. 57.21% （P〈0.05）. For the high responders, the rates of clinical pregnancy and implantation in frozen-thawed embryo transfer （FET） cycles were notably higher than in eSBT cycles （64.56% vs. 43.35% and 62.11% vs. 43.35% respectively） （P〈0.05）. Conclusions For normal responders, eSBT might be an applicabte strategy to reduce multiple pregnancy rates while maintaining acceptable overall pregnancy rates. And in order to reduce multiple pregnancies and increase the chance of pregnancy of high responders, FET may be a preferable strategy.

Psychological Outcomes in Disaster Responders: A Systematic Review and Meta-Analysis on the Effect of Social Support

Disaster response work is associated with various psychological outcomes. In post-disaster conditions,social support is generally observed to impact mental health, particularly for survivors. This review was conducted to survey the extent of social support effectiveness on disaster responder groups. Published quantitative social support studies on police, emergency medical responders,rescue and recovery workers, firefighters, and military responders were searched in various academic databases using keyword searches, a reference list search, and a citation search that resulted in 24 studies with 90 effect sizes being included in the final data base. Articles were coded and effect sizes were averaged using the Hedges–Vevea Random Effects model. Nineteen categories of psychological outcomes(for example, anxiety, depression,posttraumatic stress symptoms, and psychological distress)and eight classifications of support were coded. Social support was found to be associated with anxiety, burnout,depression, job control, job satisfaction, psychological distress, turnover intentions, and work engagement, with mean effect sizes from-0.36 to 0.57. Most studies measured perceived social support and negative outcomes.Social support correlated with outcomes in police responders and rescue and recovery workers. This review discusses the breadth of effect of social support, as well as other elements, such as temporal factors, that may affect the effectiveness of social support in disaster responders.

Clomiphene Citrate or Medroxyprogesterone Acetate with Human Menopausal Gonadotropin in Poor Responders during In vitro Fertilization/Intracytoplasmic Sperm Injection Treatments Combined with Embryo Cryopreservation?

Objective:This study aimed to compare the efficacy of clomiphene citrate(CC)with human menopausal gonadotropin(hMG)and that of medroxyprogesterone acetate(MPA)with hMG in poor responders defined according to the Bologna criteria.Methods:The data of patients with poor ovarian response(POR)according to the Bologna criteria from September 2016 to November 2017 were retrospectively reviewed.All participants received either CC+hMG or the progesterone-primed ovarian stimulation protocol(PPOS)protocol.Results:A total of 340 patients and 563 in vitro fertilization cycles were analyzed in this study.The incidence of spontaneous luteinizing hormone(LH)surge and the mean LH level on trigger day were significantly lower in the PPOS group than in the CC+HMG group(0.04%vs.3.49%and 4.26±3.59 vs.9.38±6.92 mIU/mL,respectively,P<0.05);however,the incidence of premature ovulation was similar between the two groups.The number of viable embryos harvested was not statistically different between the two groups(1.7±1.1 vs.1.5±0.8,P=0.06).The mean dose and duration of hMG were significantly higher in the PPOS group than in the CC+hMG group(908.7±556.6 vs.177.9±214.5 IU and 6.0±3.4 vs.1.2±1.5 days,respectively,P<0.05).However,the number of oocytes retrieved,number of metaphase II oocytes,and fertilization rate were comparable between the two groups.Conclusions:The CC with low-dose gonadotropin strategy was superior to the MPA with hMG protocol for POR.

Predictive factors for clinical pregnancies of poor responders diagnosed according to the Bologna criteria in ovarian stimulation in vitro fertilization(IVF)

Objective To explore the predictive factors for clinical pregnancies of poor responders diagnosed according to the Bologna criteria in ovarian stimulation in vitro fertilization （IVF） .Methods The present study included 392 poor responders diagnosed according to the Bologna criteria （392 first poor response cycles and 247 subsequent conventional stimulation cycles） in our IVF center. Binary Logistic regression analysis was used to study the association between possible predictive factors and clinical pregnancy of poor responders in ovarian stimulation IVF.Results The significant predictive factors for clinical pregnancies of poor responders in ovarian stimulation IVF were female age, number of embryos transferred and ovarian stimulation protocol. Female age had the best predictive value for clinical pregnancy of poor ovarian responders.Conclusion Poor responders should be encouraged to attempt Jurther ovarian stimulation IVF treatment as soon as possible because the pregnancy rate decreases with advancing female age. Growth hormone supplementation, intracytoplasmic sperm injection （ICSI） procedure or assisted hatching seem not be able to prominently improve the pregnancy outcomes of poor responders diagnosed according to the Bologna criteria in ovarian stimulation IVF.

Hsa-miR-483-5p/mRNA network that regulates chemotherapy resistance in locally advanced rectal cancer identified through plasma exosome transcriptomics

BACKGROUND Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy(nCRT)for rectal cancer.However,the underlying mechanisms remain elusive.AIM To detect the differential expression profiles of plasma exosomal microRNAs(miRNAs)in poor and good responders and explore the potential mechanisms of chemoresistance.METHODS In this study,the profiles of plasma exosomal miRNAs were compared in two dimensions according to treatment responses(poor/good responders)and treatment courses(pre/post-nCRT)using RNA sequencing.RESULTS Exosome hsa-miR-483-5p was up-regulated in good responders post-nCRT.Bioinformatics analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways,such as the MAPK signaling pathway,EGFR tyrosine kinase inhibitor resistance,Toll-like receptor signaling pathway,VEGF signaling pathway,and mTOR signaling pathway.Further analysis indicated that MAPK3,RAX2,and RNF165 were associated with inferior recurrence-free survival in patients with rectal cancer,and the profiles of MAPK3,TSPYL5,and ZNF-417 were correlated with tumor stage.In addition,the expression profiles of MAPK3,RNF165,and ZNF417 were negatively correlated with inhibitory concentration 50 values.Accordingly,an hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 network was constructed.CONCLUSION This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs.However,further research is required within the framework of our established miRNA-mRNA network.

RARRES2's impact on lipid metabolism in triplenegative breast cancer:a pathway to brain metastasis

Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical Research investigated the role of retinoic acid receptor responder 2(RARRES2)in regulating lipid metabolism in BCBrM,highlighting the clinical relevance of alterations in lipid metabolites,such as phosphatidylcholine(PC)and triacylglycerols(TAGs),by RARRES2 through the modulation of phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway.This commentary aims to elaborate on the key findings and their relevance to the field.

The role of tazarotene-induced gene 1 in carcinogenesis:is it a tumor suppressor gene or an oncogene?

Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.

RITSD Analysis of the Agronomic Traits of Somaclonal in Rice

[Objective]The aim was to study the sensitive response characteristics of the main agronomic traits of somaclonal and the variation of sensitive response of the lines of somaclonal to sowing date. [Method]The RITSD changing of agronomic traits was studied by using 24 rice somaclonal and its donor parent under two sowing dates. [Result]The average values of RITSD were higher （over one） for the traits of pant height （PH）,density of spikelets （DS）,filled spikelets per panicle （FSP）,spikelets per panicle （SP） and grain weight per plant （GWP）,but lower for days of sowing to heading （DSH）,effective panicles （EP）,panicle length （PL）,seed setting rate （SS） and 1 000-grain weight （1 000-GW）. These showed that PH,DS,FSP,SP and GWP were easily affected by sowing date and tended to higher with the later sowing; the RITSD of somaclonal changed with the agronomic traits. The frequency of RITSD＇ variation of DSH and PH was higher than that of PL. The RITSD＇ value of EP,PL,DS,FSP,SP and SS became higher,and higher or lower for DSH and GWP in different somaclonal; compared with the donor,20 of 24 was significantly different,and the frequency of RITSD variation was over 83. 3%,however,RITSD of the most lines （75%） changed only for 1-2 characters; cluster analysis showed that the RITSD of agronomic traits belonged to different combinations of somaclonal in rice. [Conclusion]the study had provided a theoretical basis for the screening and using of the somaclonal.

Personalized targeted therapy for esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial.

What are the ten new commandments in severe polytrauma management？

This review aims to provide a concise overview of the trauma management evolution in the past decade. 1） Trauma care priorities have incorporated staff protection against infection and early decision making in addition to the conventional ABCDE. 2） Five stratified levels for DAM have replaced the non-specific conventional Plans A ＆ B. 3） CT scanning can be the tunnel to death for the hemodynamically unstable patient. 4） DPL has virtually been replaced by the FAST USG. 5） Direct whole-body MDCT provides rapid imaging diagnosis ＆ expedites the definitive treatment but carries high radiation hazards. 6） The dynamic shock assessment by fluid resuscitation response provides more outcome-specific evaluation than the static blood volume loss model. 7） DCR comprising of permissive hypotension, hemostatic resuscitation ＆ DCS aims to overcome the lethal triad of trauma. Early transfusion of blood components of FFP ＆ platelet concentrates improves the outcome in massive blood transfusion. 8） DCS aims to rectify the deranged physiology and not to fully restore the damaged anatomy. 9） A pre-defined protocol for major pelvic fracture can be life-saving and the novel Pre-PPP （pre-peritoneal pelvic packing） may further reduce mortality coupled with the necessary TCAE. 10） Injury prevention is equally important if not more than the trauma resuscitation ＆ operation.