Epidermal growth factor receptor (EGFR) inhibitors targeted therapy is the forward position means for non-small cell lung cancer.However,acquired resistance to EGFR inhibitors limits the development of targeted drugs.Using existing data on drug resistance in EGFR-mutant lung cancer,this review discusses three basic approaches for overcoming resistance to EGFR-targeted therapies:intensification of EGFR inhibition,combination of EGFR inhibitors with other targeted therapies,and altering clinical management via alternate pathways.

Objective To explore the role of conventional protein kinase C(cPKCs) in delayed hypoxic preconditioning.Methods The biochemistry techniques of SDS-PAGE,Western bolt and Gel Doc imagine were applied to analyze the effect of repetitive hypoxic exposure(H5,H6) on the level of cPKC?,? membrane translocation and protein expression in murine brain.Results We found that cPKC? protein expression was significantly decreased(P

Objective To evaluate the role of spinal sigma-1 receptors in the maintenance of bone cancer pain (BCP) in rats and the relationship with extracellular signal-regulated kinase (ERK).Methods Part Ⅰ Twenty-four female Sprague-Dawley rats,weighing 180-220 g,were randomized into 2 groups using a random number table:sham operation group (S group,n =4) and BCP group (n =20).BCP was induced by inoculating Walker 256 mammary gland carcinoma cells into the medullary cavity of the right tibia.Four rats were sacrificed on day 10 after inoculation in S group or on day 3,5,7,10 and 14 after inoculation in BCP group,and the L4-6 segments of the spinal cord were removed to measure the expression of sigma-1 receptors by Western blot.Part Ⅱ Forty female Sprague-Dawley rats,weighing 180-220 g,were randomized into 4 groups (n =10 each) using a random number table:sham operation group (S group),sigma-1 receptor inhibitor BD1047 group (BD group),BCP group,and BCP + BD1047 group (BCP + BD group).On day 10 to 14 after inoculation,normal saline 20 μl was injected intrathecally once a day in S and BCP groups,or BD1047 120 nmol/20μl was injected intrathecally once a day in BD and BCP + BD groups.Mechanical paw withdrawal threshold (MWT) to yon Frey filament stimulation was measured one day before inoculation,on day 3,5 and 7 after inoculation,and on day 10,12 and 14 after administration.After measurement of MWT on day 14 after inoculation,the rats were sacrificed and the L4-6 segments of the spinal cord were removed to determine the expression of phosphorylated ERK (p-ERK) by Western blot.Results Part Ⅰ Compared with group S,the expression of sigma-1 was significantly up-regulated and peaked on day 10 after operation in group BCP.Part Ⅱ Compared with S group,no significant changes were found in MWT and p-ERK expression at each time point in BD group,and MWT was decreased and p-ERK expression was up-regulated in BCP and BCP + BD groups.Compared with group BCP,after intrathecal injection of BD1047,MWT was significantly increased and the expression of p-ERK was down-regulated in BCP + BD group.Conclusion Spinal sigma-1 receptors are involved in the maintenance of BCP in rats possibly through promoting phosphorylation of ERK.

Objective To study the influences of polysacch arides(PS)from Radix Codonopsis on immune function and hematopoiesis in mice.Methods Several experiments have been condu cted for detecting delayed type hypersensitivity(DTH),hemolysin antibody concentration,endogenous spleen colony,3 H-TdRpermeate nuleated cells in bon e marrow.Results By oral administration,PS from Radix Codonopsis can promote the humoral immunity and PS at a small dosage en-hance the cellular immunity.PS from Radix Codonopsis can also elevate the hemoglobin cont ent of the hemolysis -induced blood -deficiency mice and increase the formation of endogenous spleen c olony,but has less effect on DNA synt hesis in the bone marrowof blood -deficiency mic e caused by 60 Co -?ray.Conclusion PS from Radix Codonopsis can enhance the im-mune function and improve the compen satory hematopoiesis of spleen and t heir mechanisms need to be further studied.

A new triterpenoid saponin and fourteen known triterpenoids were isolated from the methanol extract of the stems and leaves of Callicarpa integerrima Champ, which is used in Chinese folk medicine for stopping bleeding, expelling the wind, dissipating stagnation, and treating scrofula, by using various chromatographies, such as silica gel, Sephadex LH-20 and RP-C18 column chromatography. Their structures were identified as a new compound 2alpha, 3beta, 19alpha, 23-tetrahydroxy-olean-12-en-28-oic acid-28-O-beta-D-glucopyranosyl-(1 --> 4)-beta-D-glucopyranoside (1), together with fourteen known compounds: oleanolic acid (2), 3-acetyl oleanolic acid (3), 3beta-O-acetyl ursolic acid (4), 2alpha-hydroxy-ursolic acid (5), 2alpha, 3beta, 19alpha, 23-tetrahydroxy-urs-12-en-28-oic acid (6), alpha-amyrin-3-O-beta-D-glucopyranoside (7), pomolic acid (8), betulinic acid (9), ursolic acid (10), 2alpha, 3beta, 19alpha, 23-tetrahydroxy-olean-12-en-28-oic acid (arjungenin) (11), 2alpha-hydroxy-oleanolic acid (12), hederagenin (13), 2alpha, 19alpha-dihydroxy-ursolic acid (14) and pruvuloside A (15), by the spectroscopic techniques of NMR, HMBC, IR and MS, separately. All these compounds were obtained from this plant for the first time, and compounds 3, 4 and 15 were isolated from genus Callicarpa L. for the first time.

The study is to develop an HPLC method for simultaneous determination of rhamnazin (1), rhamnocitrin (2), rhamnetin (3), rhamnazin-3-O-beta-D-glucopyranoside (4), rhamnazin-3-O-beta-D-xylopyranosyl-(1-->4)-beta-D-glucopyranoside (5), rhamnazin-3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranoside (6), and rhamnocitrin-3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranoside (7) in Nervilia fordii. The separation was performed on a Kromasil C18 column (250 mm x 4.6 mm, 5 microm) with 0.4% phosphoric acid-acetonitrile as the mobile phase in a gradient elution at a flow rate of 1.0 mL x min(-1). The detect wavelength was set at 256 nm, and the column temperature was set at 40 degrees C. There were good linear relationships between the logarithm values of concentrations and those of the peak areas of seven flavonoids (1-7) in the range of 0.55-70.00 microg x mL(-1) (r = 0.9997), 0.86-110.00 microg x mL(-1) (r = 0.9997), 0.39-50.00 microg x mL(-1) (r = 0.999 7), 0.55-70.00 microg x mL(-1) (r = 0.999 5), 1.33-170.00 microg x mL(-1) (r = 0.9998), 1.33-170.00 microg x mL(-1) (r = 0.9998), 0.16-20.00 microg x mL(-1) (r = 0.9995), respectively. The recoveries of the seven flavonoids were between 97.19%-99.45%, the relative standard deviations (RSDs) were between 0.91%-2.69%. The established method is rapid, accurate with high repeatability, which could provide scientific evidence for the quality control of Nervilia fordii.

Objective To establish a method for the determination of chimoni and forsythiaside in Kangbingdu Oral Liquid(KOL) and to develop a new quality standard for KOL. Methods A RP-HPLC method was adopted for the determination of chimonin and forsythiaside of KOL. The chromatographic conditions were as follows:Kromasil RP-C18(250 mm? 4.6 mm,5 ? m) column was used,a mixture of acetonitrile -0.1 % acetic acid(15 ∶ 85,v/v) served as mobile phase,the flow rate was 0.80 mL? min-1,and detective wavelengths of time process were 0→ 25 min:258 nm,and 25→ 30 min:277 nm. Theoretical plate number of chimoni was over 6000 and that of forsythiaside was over 5000. Results The chimonin showed a good linearity in the range of 48.8ng～ 1525 ng(r=0.999 4),and the linear range of forsythiaside was in the ranged of 56ng～ 1750 ng(r=0.999 5).The mean recovery of chimonin and forsythiaside was 97.65 % and 99.21 % respectively. The content of chimonin in the 10 batches of samples was in the range of 14.40～ 20.41 ? g? mL-1,and that of forsythiaside was in the range of 28.70～ 36.01 ? g? mL-1. Conclusion The developed method has been proven to be simple,stable and reproducible,and can be applied for quality control of the Kangbingdu Oral Liquid.

Objective To evaluate the clinical application of implantation of totally implantable venous access port (TIVAP) via the internal jugular vein (IJV) guided by ultrasonography in infants.Methods The clinical data of 446 sick infants,who received TIVAP at the Affiliated Shanghai Children's Medical Center,School of Medicine,Shanghai Jiaotong University,China (single center) during the period from January 2009 to July 2016,were retrospectively analyzed.The time spent on surgery,the success rate of first puncturing of IJV and the incidence of puncture-related complications were recorded,and the results were compared between traditional IJV blind puncture group and ultrasound-guided IJV puncture group.Results Of the 446 sick infants,traditional IJV blind puncture was employed in 265 and ultrasound-guided IJV puncture was adopted in 181.In traditional IJV blind puncture group,the mean time spent on surgery was 7.6 min,the success rate of first puncturing of IJV was 75.85％ (201/265),and the incidence of puncturerelated complications was 5.66％ (15/265).In ultrasound-guided IJV puncture group,the mean time spent on surgery was 4.2 min,the success rate of first puncturing of IJV was 97.24％(176/181),and the incidence of puncture-related complications was 1.70％ (3/181).Conclusion For the performance of TIVAP implantation in sick infants,the use of ultrasound-guided IJV puncture technique can shorten the operation time,improve the success rate of first puncturing,and reduce the incidence of puncture-related complications.Therefore,ultrasound-guided IJV puncture is a safe,effective,simple and feasible technique.This technique is worthy of clinical promotion.

Interferon ( IFN) kills tumor through:direct tumor killing, stimulating immune response to tumor cells by activating the immune system and inhibiting tumor angiogenesis.However, its clinical application has been restrained by the deficiencies such as short half-life and severe side effects.IFN-antibody fusion can bring IFN to the vicinity of tumors using tumor specific antibody, while reducing the concentration of IFN in the rest parts of the body.Thus, system toxicity caused by IFN can be significantly lessened.We herein summarized the research and development of preclinical antibody-interferon conjugates and provide new thought on the development of IFN or antibody based fusion proteins.

Objective To evaluate thetherapeutic effect of sodium deoxyribonucleotide injection at Zusanli point for chemotherapy-induced leukopenia in patients with lung cancer.MethodsA total of 116 chemotherapy-induced leukopenia patients with lung cancer were randomly divided into a therapy group and a control group, 60 in the treatment group and 56 in the control group. The patients in the treatment group were treated with sodium deoxyribonucleotide injection atZusnlipoint, and those in the control group were treated with vein injection of sodium deoxyribonucleotide.Results The total effective rate in the treatment group was significant higher than that in the control group (91.7%vs.76.8%;χ2=4.890,P=0.032). The effective rates on days 3,5,7 and 10 in the treatment group were also significant higher than those in the control group (on day 3: 51.7%vs. 32.1%,χ2=4.530,P=0.036; on day 5: 76.7%vs. 53.6%,χ2=6.840,P=0.018; on day 7: 85.0%vs. 67.9%,χ2=4.770,P=0.026; on day 10: 78.3%vs. 53.6%,χ2=7.960,P=0.011).Conclusion Sodium deoxyribonucleotide injection atZusanlipoint has definite efficacy for chemotherapy-induced leukopenia in patients with lung cancer.