Cancer is a group of heterogeneous disease caused by diverse genomic alterations in oncogenes and tumor suppressor genes .Despite recent advances in high-throughput sequencing technologies and development of targeted therapies, novel cancer drug development is limited due to the high attrition rate from clinical studies .Patient-derived xenografts ( PDX) models are generated by implanting sectioned patient tumor fragments into immunodeficient mice .PDX models retain many of the key characteristics of patients ' tumors including histology , genomic signature , cellular heterogeneity , and drug responsiveness .These models cannot only serve as a platform for co-clinical trials by enabling the integration of clinical data , genomic profiles , and drug responsiveness data to determine precisely targeted therapies , but also be applied to the development of biomarkers for drug responsiveness and personalized drug selection .This review summarizes our current knowledge of this field , including methodologic aspects , applications in drug development , challenges and limitations , and utilization for precision cancer medicine .

Objective Acute bilirubin encephalopathy in neonates is the most serious complication of neonatal hyperbilirubinemia, is one of the main causes of neonatal death and disability. Clinical early diagnosis, early treatment can improve the prognosis in children. Methods Brainstem auditory evoked potential (BAEF) was detected on two patients (40 patients with ABE, 40 cases of normal controls, all full-term) in the state of sleep in children and analysis the difference between the two groups ,all testing was completed by experienced Department of ENT full-time technician in charge,SPSS15.0 statistical analysis software was took for data analysis (using rank sum test method). Results There was significant difference between the two groups of neonatal latency of wave I, latency of waveⅤ, interpeak time , acute bilirubinⅠ-Ⅴencephalopathy group was significantly longer than that of the control group. Conclusions The BAEF detection is the sensitive index of brainstem damage , can objectively and sensitively reflect the function of the central nervous system , can reflect the functional status of cochlear and brainstem structures , often brainstem was slightly damaged but no clinical symptoms and signs , BAEP has changed significantly , so the conventional BAEP examination performed on patients with hyperbilirubinemia help to find bilirubin brain damage as early as possible,and prevent the occurrence of bilirubin encephalopathy.

OBJECTIVETo observe the effect of Huannao Yicong capsule (HYC) on senile mild cognitive impairment.

METHODSSixty-two patients were randomly divided into two groups, the 31 patients in the treated group were treated with HYC 3 capsules, 3 times daily, and the 31 in the control group with Hydergin 3 tablets, 3 times daily. Treatment for two successive months was a therapeutic course. The changes of cognitive effect index (CEI), integral of measuring scale (CCSE, FQA and MMSE), TCM Syndrome scoring, quality of life (QOL), cerebral arterial blood flow (CBF) and hemorrheologic parameters in the two groups were observed.

RESULTSThe total effective rate of treatment in improving cognition in the 30 patients of the treated group (with one case lost) was 83.33%, while that in the 29 patients of the control group (with two cases lost) was 48.28%, the difference between them was significant (u = 2.36, P < 0.05). Intent-to-treat analysis, namely, the case lost in the treated marked as ineffective and those in the control group as effective, showed the total effective rate in the two groups was 80.65% and 51.61% respectively, which also showed significant difference (u = 2.02, P < 0.05). In the treated group after treatment, the integrals of CCSE, FAQ and MMSE significantly increased (P < 0.05 or P < 0.01), the TCM Syndrome scoring decreased (P < 0.01), the scoring of QOL significantly improved, the mean BBF increased (P < 0.05 or P < 0.01), and the cerebral arterial resistance index improved significantly. All these improvements in the treated group were significantly higher than those in the control group respectively (P < 0.05). Besides, the hemorrheologic parameters in the treated group were improved, most of them were better than those in the control group (P < 0.05 or P < 0.01).

CONCLUSIONHYC has good therapeutic effect on senile mild cognitive impairment, it is safe without any adverse reaction.

Aged ; Aged, 80 and over ; Capsules ; Cognition ; drug effects ; Dementia ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Intelligence Tests ; Male ; Middle Aged ; Phytotherapy ; Quality of Life

Objective To investigate the anatomic characteristics of the nasolabial fold and to give an accurate description and definition of it in order to to provide theoretical basis for plastic, cosmetic and maxillofacial surgery. Methods Ten (20 sides) adult fresh bodies with vascular perfusion of formalin fixed after morphological observation under a 10 × magnifying len. Results Nasolabial fold was a border between fat-rich zone and non-fat zone in the midfacial region. The nasolabial fold derived from nasal alar skin point in the transverse portion of nasalis, and ended at the outer skin point of zygomaticus major muscle in the mouth. From the anatomy point of view, the nasolabial fold was divided into three segments: the upper, the middle and the under. The upper segment ( Ⅰ ) was the transverse portion of nasalis, (20. 38± 0. 74) mm in length; the middle section ( Ⅱ ): levator labii superioris,(17.13 ± 0.57) mm in length; the under segment (Ⅲ ): modiolus, (20. 81 ±0. 70) mm in length. The nasolabial fold was a connecting region where seven mimetic muscles inserted into the skin point. Superficial musculoapneurotic system (SMAS) and the nasolabial fold were composed of seven mimetic muscles belonging to the same layer. Conclusions The nasolabial fold is a region where the seven mimetic muscles insert into the skin point for connection, and regardless of age, it is an eternal existence. The nasolabial fold is different from the nasolabial wrinkle formed with facial aging and the nasolabial ridges formed by facial mimetic muscles changes.

Objective To investigate the evolution of surgical treatment and it's influence on prognosis in reptured liver cystic echinococcosis.Method Clinical data of 110 surgically treated cases of reptured liver cystic echinococcosis from January 1990 to December 2008 were retrospectively analysed,and these cases were divided into three groups by different surgical approach;Group A(22 cases):removal of internal capsule,with formaldehyde or hydrogen peroxide regional anthelminthic,with residual cavity side edge of lock stitching or greater omentum filling or drainage after residual cavity closure;Group B (65 cases):Removal of intemal capsule,with hypertonic saline regional anthelminthic,with external capsule extrahepatic partial resection,with residual cavity bile leakage sutured,and with residual cavity open drainage,Group C(23 cases):the total or subtotal external capsule stripping operation,with hypertonic saline regional anthelminthic and drainage.Result The rate of overall postoperative complications of residual cavity was 40.9%、16.9%、0.0%(P<0.05)respectively and the recurrence rate was 18.2%、4.6%、0.0%(P<0.05)respectively;drainage time needed was the longest in group A,and shortest in group C,whereas the operation time was the longest in group C and it costed higher blood loss.Intraabdominal implantation of the hydatid significantly decreased with hypertonic saline treatment.Conclusion Total or near total removal of the external capsule of the hydatic cyst and hypertonic saline treatment with postoperative external drainage is the therapy of choice for reptured liver cystic echinococcosis.

N6-methyladenosine (m 6A), one of the most common types of eukaryotic mRNA methylation modification, is widely distributed in the nervous system and participates in important regulatory mechanisms for controlling gene expression. With the participation of related methylation-modifying enzymes and proteins, m 6A plays an important role in the growth and development of the nervous system, related functions, and the occurrence and development of diseases in the nervous system by affecting the "life cycle" of mRNA. This article briefly reviews the research progress on the role of mRNA m 6A methylation modification in neurological diseases and nervous system growth and development.

The most effective sequence of small interfering RNA (siRNA) silencing STAT3 of psoriatic keratinocytes (KCs) was screened out,and the effects of the most effective siRNA combined with ultrasonic irradiation and SonoVue microbubbles on the expression of STAT3 of KCs and the dose-and time-response were investigated.Three chemically-synthetic siRNAs targeting STAT3 carried by Lipofectamine 3000 were transfected into KCs,and the effects on STAT3 expression were detected,then the most effective siRNA was selected for the subsequent experiments.The negative controls of siRNA (siRNA-NC) labeled with Cy3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles were transfected into KCs,then the optimal parameters of ultrasonic irradiation were determined.The most effective siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation at the optimal parameters and SonoVue microbubbles was transfected into KCs,and the dose-and time-response of RNA interference was determined.The effect of RNA interference by the most effective siRNA at the optimal time and dose carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (LUS group) was compared with that only carried by Lipofectamine 3000 (L group).The results showed that siRNA-3 achieved the highest silencing efficacy.0.5 W/cm2 and 30 s were selected as the parameters of ultrasonic irradiation.The siRNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue mierobubbles could effectively knock down the STAT3 expression at mRNA and protein levels in dose-and time-dependent manners determined at 100 nmol/L with maximum downregulation on mRNA at 48 h,and on protein at 72 h after transfection.The LUS group achieved the highest silencing efficacy.It was concluded that siRNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles could effectively knock down the STAT3 expression in psoriatic KCs,and the optimized transfection condition and the sequence of siRNA-3 could serve for further research on gene therapy of psoriasis.

To investigate the protective effect of preconditioning with hyperoside ( Hyp) against myocardial ischemia-reperfusion injury (MIRI) in rats and the role of PI3K/Akt signaling pathway. MIRI was established by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 120 min in rats. Male SD rats were randomly divided into five groups: sham group,model group (MIRI),Hyp preconditioning group(Hyp), Hyp preconditioning + LY294002 (a PI3K/Akt signaling pathway inhibitor) group (Hyp + LY), and LY294002 group (LY). At the end of reperfusion, hemodynamic parameters were recorded as left ventricular systolic pressure (LVSP) , left ventricular end-diastolic pressure ( LVEDP) and maximal rate of increase and decrease of left ventricular pressure (± dP/dt(max)). Myocardial infaret size, the oxidative stress markers, myocardial enzymes indicators and inflammatory factors were also analyzed. The expressions of Akt, p-Akt, Bax and Bcl-2 proteins was detected by using Western blot method. The results showed that Hyp preconditioning remarkably improved cardiac constriction and relaxation function, reduced myocardial infarct size and enhanced the activities of oxidative stress markers about correlated to MIRI, such as superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px) and decreased the contents of malondialdehyde (MDA) as compared with MIRI group. Simultaneouly, the levels of myocardial enzymes, i. e. creatine kinase ( CK) and creatine kinase MB isoenzyme (CK-MB), and inflammatory factors, for instance tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were decreased. Hyp pretreatment apparently restrained myocardial apoptosis as evidenced by decreasing the level of Bax expression, increasing the levels of phosphorylation of Akt and Bcl-2 expression. These effects were inhibited by LY294002, a blocker of PI3K/Akt signaling pathway. These findings indicated that the cardioprotection of Hyp preconditioning against MIRI may be related to activating PI3K/Akt signaling pathway, upregulating the expression of BCL-2 protein and down-regulating the expression of Bax protein.
Animals ; Creatine Kinase ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Heart ; drug effects ; Humans ; Interleukin-6 ; genetics ; metabolism ; Ischemic Preconditioning, Myocardial ; Male ; Malondialdehyde ; metabolism ; Myocardial Reperfusion Injury ; drug therapy ; enzymology ; genetics ; prevention & control ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Quercetin ; administration & dosage ; analogs & derivatives ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; genetics ; metabolism

To investigate the effects and potential mechanisms of hyperoside (Hyp) on the vascular endothelium function in middle cerebral artery (MCA) ex vivo in rats. Isolated arterial segments from MCAs of rats were used for surveying vasomotoricity in a pressurized chamber. Transmembrane potential was recorded by using glass microelectrodes to evaluate hyperpolarization. Hyp (1 x 10(-6)-1 x 10(-4) mol . L-1) was utilized to observe the effect on 1 x 10(-7) mol . L-1 U46619-preconstricted MCA in rats. The results showed that 1 x 10(-6)-1 x 10(-4) mol . L-1 Hyp significantly induced concentration-dependent vasodilatation and hyperpolarization, leading to the maximal diastolic ratio of (73. 2 ± 6. 1)% and maximal changes in membrane potentials of (-13. 2 ± 2. 2) mV. Hyp still elicited vasorelaxation and hyperpolarization by removal of endothelium in MCA of rat, which was notably attenuated as compared with vascular endothelium-intact group (P <0. 01). In the MCAs preconstricted by U46619 (1 x 10(-7) mol . L-1), Hyp (1 x 10(-6)-1 x 10(-4) mol . L-1) produced concentration-dependent vasorelaxation and hyperpolarizition that were partially attenuated by 3 x 10(-5) mol . L-1 L-NAME(a NOS inhibitor) plus 1 x 10(-5) mol . L-1 PGI2 ,(a synthetase inhibitor). The residual effects were further decreased by 1 x 10(-3) mol . L-1 TEA (an inhibitor of Ca2+-activated potassium channel) or 1 x 10(-5) mol . L-1 PPG (a blocker of endogenous H2S synthese-CSE). Similarly, 1 x 10(-5)-1 x 10(-3) mol . L-1 NaHS (a donor of exogenous H2S) or 1 x 10(-5)-1 x 10(-3) mol . L-1 L-Cys (the substrate of endogenous H2S synthesis) obviously evoked dose-dependent vasodilatation and hyperpolarization of MCA in rats. These findings indicated that Hyp may induce endothelium-dependent and endothelium-independent responses. And the endothelium-dependent vasodilatation may be related to the increases of endogenous H2S that has been promoted Hyp in the endotheliocyte of MCAs, and activated Kca and opening of Kca channels, resulting in the hyperpolarization of vascular smooth muscle cell membrane and subsequent reduction of Ca2+ influx and vasodilation.
Animals ; Endothelium, Vascular ; drug effects ; Enzyme Inhibitors ; pharmacology ; Female ; Male ; Middle Cerebral Artery ; Muscle, Smooth, Vascular ; drug effects ; Nitric Oxide ; metabolism ; Potassium Channels ; metabolism ; Quercetin ; analogs & derivatives ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sulfides ; metabolism ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology

Humans ; Supranuclear Palsy, Progressive ; Acupuncture Therapy