Objective To compare the clinical outcomes of gefitinib and erlotinib treating non-small-cell lung cancer (NSCLC)with epidermal growth factor receptor (EGFR)mutation in either exon 19 or 21 . Methods A total of 242 patients diagnosed as NSCLC with EGFR mutation in either exon 19 or 21 from May 201 3 to December 2014 in our hospital were chosen in this study.According to age,sex,smoking history,eastern cooperative oncology group performance status and types of EGFR mutation,all the patients were matched to 121 pairs,and randomly divided into group A and B.Patients in group A received gefitinib treatment,and those in group B received erlotinib treatment.Based on the response evaluation criteria in solid tumors (RECIST),overall response rate (ORR),disease control rate (DCR),progression-free survival (PFS)were assessed.To assess the independent risk factors for PFS by univariate and multivariate Cox regression analysis.The subgroup analysis was performed for the 63 NSCLC patients using these two drugs as the first-line treatment.To evaluate the adverse drug reactions and quality of life between A and B groups.Results The median PFS of group A and B were 11 .6 months and 9.5 months,respectively,with no significant difference (HR =0.39,P >0.05).The ORR and DCR in the two groups were 76.9%,74.4% (χ2 =1 .03,P =0.58)and 90.1 %,86.8% (χ2 =1 .46,P =0.31 ). The independent risk factors of poor PFS were ECOG PS≥2 (HR =2.60,95%CI:1 .54 -4.43,P =0.001 )and non-adenocarcinoma (HR =3.61 ,95%CI:1 .54-8.66,P =0.003).For patients receiving these two drugs as the first-line treatment,there was no significant difference between two groups in overall response rates (76.6% vs. 90.2%,χ2 =0.83,P =0.12)and median PFS (11 .6 months vs.14.4 months,HR =0.59,P >0.05).The adverse drug reactions were significant differences in emotion function (F =10.27,P =0.03),diarrhea (F =10.24,P =0.03)and pain (F =9.02,P =0.04).After receiving drug treatment,the quality of life scores were improved,and most of the differences were statistically significant between A and B groups(P <0.05). Conclusion As for NSCLC with EGFR mutation in either exon 1 9 or 21 ,both gefitinib and erlotinib are well tolerated and have similar clinical effectiveness.

The expression of synaptotagmin Ⅱ (Syt2) in RBL-2H3 (RBL) and its role during exocytosis of RBL was investigated. The expression of Syt2 in RBL was detected by western blot and Syt2 gene was amplified by PCR. The anti-sense full length Syt2 cDNA expression vector was constructed with pEGFP-N1 and transfected into RBL by electroporation, and stable transfectants were selected by using G418. To analyze the role of Syt2 during exocytosis of RBL, the release of cathepsin D was assayed by immunoblotting. The results showed that Syt2 was expressed in RBL.The anti-sense expression vector pEGFP-N1-Syt2-AS was constructed and the sequence of insertion was completely consistent with rat Syt2 (accession number in GeneBank: NM012665). The stable transfectants (RBL-Syt2-AS) were obtained. Western blot showed that RBL-Syt2-AS expressed a lower level of Syt2 (8 % and 10 % of control cells), indicating that the expression of Syt2 in RBLSyt2-AS was markedly down-regulated by anti-RNA. Compared with control, the release of cathepsin D by RBL-Syt2-AS was increased. It was concluded that Syt2 expressed in RBL and could inhibit exocytosis of lysosomes in RBL.

OBJECTIVETo establish quality control criteria for medicinal herb Cajanus cajan based on the determination of longistylin A and longistylin C, two bioactive and specific stilbenes of the plant.

METHODLongistylin A and longistylin C were obtained from the leaves of C. cajan by silica gel column chromatography and identified as marker compounds of this plant by spectroscopic analysis. A RP-HPLC method was established to determine the two compounds.

RESULTLongistylin A and longistylin C were well separated on a Thermo BDS Hypersil C18 column (4.6 mm x 250 mm, 5 microm) with a mobile phase methanol-water (8:2), and showed good linearity in the range of 0.00288 - 0.0576 microg and 0.0112 - 0.224 microg, respectively. The average recoveries were 98.9% and 97.2% with RSD of 2.4% and 2.2% for these two compounds, respectively.

CONCLUSIONThe established analysis method is simple and accurate, whicn can be used for quality control of C. cajan.

Cajanus ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Diethylstilbestrol ; analysis ; isolation & purification ; Drugs, Chinese Herbal ; analysis ; isolation & purification ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry

OBJECTIVETo observe the synergistic effects of paclitaxel and gemcitabine on prostate cancer cell line PC-3 in vitro.

METHODSCell morphology, MTU, flow cytometer and immunocytochemical method were used to observe the effects of 10(-6), 10(-7), 10(-8) mol/L paclitaxel and 10(-7), 10(-8), 10(-9) mol/L gemcitabine on prostate cancer cell line PC-3 by single or synergistic administration for 48 hours in vitro.

RESULTSGemcitabine above 10(-8) mol/L enhanced the growth suppression [suppression ratio > or = (50.8 +/- 4.2)%, P < 0.05] and apoptosis [apoptosis ratio > or = (22.9 +/- 2.3)%, P < 0.05] and down-regulation of the expression of cyclin D1 [expression ratio < or = (9.6 +/- 1.6)%, P < 0.01] induced by paclitaxel above 10(-7) mol/L in PC-3 cells. Gemcitabine changed the ratio of G2/M cell arrest induced by paclitaxel from (70.3 +/- 9.7)% to (38.2 +/- 4.2)%, and reversed the G2/M arrest partially (P < 0.01).

CONCLUSIONPaclitaxel and gemcitabine can enhance the growth suppression and apoptosis induced by paclitaxel in a synergistic way. They show great potential in the treatment of androgen-independent carcinoma of the prostate.

Antimetabolites, Antineoplastic ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Dose-Response Relationship, Drug ; Down-Regulation ; Drug Synergism ; Flow Cytometry ; Humans ; Male ; Paclitaxel ; pharmacology ; Prostatic Neoplasms ; pathology

Although methyltransferase has been recognized as a major element that governs the epigenetic regulation of the genome during temozolomide (TMZ) chemotherapy in glioblastoma multiforme (GBM) patients, its regulatory effect on glioblastoma chemoresistance has not been well defined. This study investigated whether DNA methyltransferase (DNMT) expression was associated with TMZ sensitivity in glioma cells and elucidated the underlying mechanism. DNMT expression was analyzed by western blotting. miR-20a promoter methylation was evaluated by methylation-specific PCR. Cell viability and apoptosis were assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and TdT-mediated dUTP-biotin nick end labeling assays, respectively. The results showed that compared with parental U251 cells, DNMT1 expression was downregulated, miR-20a promoter methylation was attenuated and miR-20a levels were elevated in TMZ-resistant U251 cells. Methyltransferase inhibition by 5-aza-2\'-deoxycytidine treatment reduced TMZ sensitivity in U251 cells. In U251/TM cells, DNMT1 expression was negatively correlated with miR-20a expression and positively correlated with TMZ sensitivity and leucine-rich repeats and immunoglobulin-like domains 1 expression; these effects were reversed by changes in miR-20a expression. DNMT1 overexpression induced an increase in U251/TM cell apoptosis that was inhibited by the miR-20a mimic, whereas DNMT1 silencing attenuated U251/TM cell apoptosis in a manner that was abrogated by miR-20a inhibitor treatment. Tumor growth of the U251/TM xenograft was inhibited by pcDNA-DNMT1 pretreatment and boosted by DNMT1-small hairpin RNA pretreatment. In summary, DNMT1 mediated chemosensitivity by reducing methylation of the microRNA-20a promoter in glioma cells.
Animals ; Antineoplastic Agents, Alkylating/*pharmacology/therapeutic use ; Apoptosis/drug effects ; Brain/drug effects/metabolism/pathology ; Brain Neoplasms/drug therapy/*genetics/pathology ; DNA (Cytosine-5-)-Methyltransferase/antagonists & inhibitors/*genetics/metabolism ; DNA Methylation ; Dacarbazine/*analogs & derivatives/pharmacology/therapeutic use ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; Glioma/drug therapy/*genetics/pathology ; Humans ; Mice, Inbred C57BL ; MicroRNAs/*genetics ; Promoter Regions, Genetic

Objective To characterize the disease ofneurogenic pulmonary edema (NPE),and to investigate the optimal fluid therapeutic strategy as well as to assess the role of extravascular lung water index (EVLWI) in management of fluid resuscitation.Methods Data of seven patients with NPE,admitted to our intensive care unit (ICU) from September 2012 to January 2014,were collected and analyzed retrospectively.The continuous cardiac output pulse indication (PICCO) monitoring was implemented as soon as the patients were admitted.Conservative fluid therapeutic strategy was adopted,targeting at decreasing EVLWI as the primary goal and maintaining normal blood volume or mean aortic pressure more than or equal to 65 mmHg as the secondary goal.The hemodynamic parameters and input and output volume of fluid,pulmonary vascular permeability index (PVPI),global end-diastolic volume index (GEDVI),extravascular lung water index (EVLW1),oxygenation index (PaO2/FiO2) and lactic acid (Lac) level,and the chest Ⅹ ray and cranial CT images were recorded and analyzed.The starting point of the record was defined as the time of NPE occurring,and the ending point as time of discharging from ICU or rectification of hypotension or pulmonary edema.Results In a lot of cases,NPE was secondary to severe traumatic brain injury or acute cerebrovascular diseases,concomitant with severe hypotensive shock and pulmonary capillary leakage with a mean PVPI value of 3.3±1.7.The mean fluid input in 7 patients was (2099±1146) mL/d,and the net fluid balance was achieved in a median of-250 mL/d.The mean value of GEDVI was maintained at a level of (727±149) mL/m2.The mean value of EVLWI declined gradually firom (18.0±7.0) mL/kg at the startting point to (10±4.3) mL/kg at the ending point of record,and 5 patients showed significant improvement in lung effusion and brain edema as being illustrated in the chest Ⅹ ray or CT images,1 died and the other abandoned therapy; the mean length of ICU stay was 9 days.Pearson correlation analysis showed that EVLWI was correlated with PaO2/FiO2 and PVPI (r=-0.570 and 0.760,respectively,P＜0.05).Conclusion Successful management of NPE relies on an elaborate balance of both improvement of cranial perfusion and prevention of pulmonary edema exacerbation; PICCO monitoring is a useful tool in assessment of the blood volume status,and targeting at the decreasing EVLWI as a goal of fluid resuscitation is of benefit to patients with NPE.

Objective To evaluate the efficacy and safety of tigecycline combined with cefoperazone-sulbactam sodium in the treatment of multi-/extensively-drug resistant Acinetobacter baumannii(MDRAB/XDRAB)associated central nervous system(CNS)infection,and to provide clinical evidence for antibiotic treatment of MDRAB/XDRAB-related intracranial disease.Methods The Wanfang Data Knowledge Service Platform,Chinese Biomedical Literature Database,VIP Chinese Science and Technology Journal Full-text Database,China National Knowledge Infrastructure(CNKI),Pubmed,Embase database,and Cochrane Library were searched to extract the literature of randomized controlled studies on tigecycline and cefoperazone sulbactam in the treatment of MDRAB/XDRAB CNS infection until September 1st,2022.The included studies were assessed for quality using the Cochrane Collaboration Risk of Bias assessment tool,and valid data were extracted and meta-analyzed using RevMan5.4 software.Results A total of 184 articles were screened and 4 Chinese RCTs were finally included,with a sample size of 267 cases.Meta-analysis showed that the overall efficacy of combination therapy for MDRAB/XDRAB CNS infection was better than monotherapy[OR = 4.30,95%CI =(1.93,9.58),P＜0.01].Combination therapy had a better bacterial clearance[OR=4.20,95%CI=(2.08,8.48),P＜0.01].And combination therapy resulted in a lower incidence of adverse effects[OR= 0.19,95%CI =(0.05,0.67),P＜0.05].There was no apparent difference in cure rate between combination therapy and monotherapy(P＞0.05).Conclusion Current evidence suggests that tigecycline combined with cefoperazone-sulbactam sodium may have better clinical efficacy and safety than monotherapy for MDRAB/XDRAB CNS infections.Limited by the number and quality of included studies,needs to be verified by more and higher-quality studies.

Objective:To explore the mediating role of mentoring function between proactive personality and transition shock in new nurses, with the aim of providing reference and basis for managers to develop effective intervention measures for new nurses during their transformational period.Methods:Convenience sampling method was used to select 280 new nurses from the Second Affiliated Hospital of Zhejiang University School of Medicine, and a cross-sectional survey was conducted by applying the General Information Questionnaire, Transition Shock Scale, Proactive Personality Scale, and Mentoring Function Scale. The mediating role of mentoring function between new nurses′ proactive personality and transition shock was evaluated by constructing structural equation modelling.Results:265 valid questionnaires were ultimately collected. Among 265 nurses, there were 25 males and 240 females, with an age of (22.88 ± 2.12) years. The score of transition shock, proactive personality, and mentoring function of new nurses were (83.45 ± 18.95), (58.66 ± 9.96) and (81.72 ± 14.46) respectively; transition shock was negatively correlated with proactive personality and mentoring function ( r=-0.379, -0.340, both P<0.01), and proactive personality was positively correlated with mentoring function ( r=0.452, P<0.01); the mediating effect of mentoring function between proactive personality and transition shock was significant (95% CI -0.085 - -0.015, P<0.01), accounting for 29.14% of the total effect. Conclusions:New nurses' transition shock is at a moderately high level, and proactive personality can affect transition shock directly or indirectly through mentoring function. Managers can mitigate new nurses′ transition shock by improving the quality of mentoring.

Objective To explore the good death status of terminally ill cancer patients from the nurses' perspective and identify associated factors. Methods A cross-sectional survey was conducted among the nurses in charge of the patients within 3 months after their death to evaluate the status quo of patients with end-stage cancer from the perspective of nurses, using anonymous questionnaire. Using convenient sampling method, 101 competent nurses from 209 patients with end-stage tumors who died in a hospital from October 2017 to January 2018 were selected. The nurses were investigated with nurses' general information questionnaire, patient information questionnaire and Good Death Inventory (GDI). Single factor analysis, Pearson correlation and multivariate linear regression analysis were used to analyze the influencing factors of good death in patients with end-stage cancer. Results The total score of GDI was (243.00±39.21). Among GDI, the three lowest scores were independence (7.43±4.25), physical and psychological comfort (8.17±4.82), and religious and spiritual comfort (8.53±4.72);while the three highest scores were being respected as an individual (18.32±2.76), good relationship with medical staff (18.23±2.59), and natural death (17.97±3.42). There were significant differences in patients' death status among different departments, medical payment methods, professional training experience of competent nurses and treatment methods within 3 months before death (t=17.351, 2.158, -2.679, -2.993;P＜0.05). Pearson correlation analysis showed that nurse working life was positively correlated with the total score of GDI (r=0.953, P＜0.01). Regression analysis showed that the factors influencing the good death of patients with end-stage cancer were the department of oncology medicine, the way of treatment and the professional training experience of nurses (P＜0.05). Conclusions The overall status of good death of terminally ill cancer patients is poor. To strengthen the palliative care training about the knowledge and skills helps to improve the nursing quality of end-of-life care and achieve the goal of good death.

Objective To investigate the antimicrobial resistance profile of the clinical isolates collected from selected hospitals across China. Methods Twenty-nine general hospitals and five children's hospitals were involved in this program. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems. Results were interpreted according to CLSI 2017 breakpoints. Results A total of 190 610 clinical isolates were collected from January to December 2017, of which gram negative organisms accounted for 70.8％ (134 951/190 610) and gram positive cocci 29.2％ (55 649/190 610). The prevalence of methicillin-resistant strains was 35.3％ in S. aureus (MRSA) and 80.3％ in coagulase negative Staphylococcus (MRCNS) on average. MR strains showed much higher resistance rates to most of the other antimicrobial agents than MS strains. However, 91.6％ of MRSA strains were still susceptible to trimethoprim-sulfamethoxazole, while 86.2％ of MRCNS strains were susceptible to rifampin. No staphylococcal strains were found resistant to vancomycin. E. faecalis strains showed much lower resistance rates to most of the drugs tested (except chloramphenicol) than E. faecium. Vancomycin-resistant Enterococcus (VRE) was identified in both E. faecalis and E. faecium. The identified VRE strains were mainly vanA, vanB or vanM type based on phenotype or genotype. The proportion of PSSP or PRSP strains in the non-meningitis S.pneumoniae strains isolated from children decreased but the proportion of PISP strains increased when compared to the data of 2016. Enterobacteriaceae strains were still highly susceptible to carbapenems. Overall, less than 10％ of these strains (excluding Klebsiella spp.) were resistant to carbapenems. The prevalence of imipenem-resistant K. pneumoniae increased from 3.0％ in 2005 to 20.9％ in 2017, and meropenem-resistant K. pneumoniae increased from 2.9％ in 2005 to 24.0％ in 2017, more than 8-fold increase. About 66.7％ and 69.3％ of Acinetobacter (A. baumannii accounts for 91.5％) strains were resistant to imipenem and meropenem, respectively. Compared with the data of year 2016, P. aeruginosa strains showed decreasing resistance rate to carbapenems. Conclusions Bacterial resistance is still on the rise. It is necessary to strengthen hospital infection control and stewardship of antimicrobial agents. The communication between laboratorians and clinicians should be further improved in addition to surveillance of bacterial resistance.