Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is one of the most important targeted drugs for lung cancer patients carrying EGFR sensitive mutations.However,almost all patients that are effective to this treatment will eventually develop secondary resistance to EGFR-TKI.The most accepted mechanisms of resistance mainly include T790M mutation,MET amplification,PIK3CA mutation,down-regulation of PTEN expression and activation of Fas-transcription factor-κB.Recent years,many new drugs are developed to overcome this resistance.Although most of drugs are in the stages of cell or animal experiment,some new drugs get positive clinical results.

In order to investigate the application of standard score in the examination of eight-year program's clinical practice and to keep consistency of learning level among groups, we translate the original scores into standard scores and discuss the results and how to define the excellent grade so that the scores may have more comparability.

Objective:To investigate the efficacy of personalized family doctor contract services on risk factors of atherosclerotic cardiovascular disease (ASCVD) in high-risk population.Methods:Ten matched-community health centers of Shenzhen Luohu district were divided into intervention group and control group by cluster randomiztion. Subjects with high risks of ASCVD were screened out as intervention group from contracted residents who visited these centers and had complete data of the China-PAR model from August 2018 to April 2019. The control group received conventional general family doctor contract services. The individualized management were given to the intervention group after fully understanding patients′ ideas, concerns, and expectations (ICE). After 2-year intervention, score changes of ASCVD risk factors within and between groups were compared.Results:A total of 571 patients were enrolled, including 288 in the intervention group and 283 in the control group. After 2 years of intervention, 7 and 18 were lost to follow-up in two groups, respectively. Finally, 281 in the intervention group and 265 in the control group were included in the study. At baseline, there was no significant difference in ASCVD scores between the intervention group and the control group [(13.33±3.54) vs. (13.09±3.54) points; t=0.84, P=0.403], and the scores in both groups decreased significantly after the intervention [(10.89±4.01), (11.62±4.11) points], while the intervention group decreased more significantly (both P<0.05). Among the risk factors at baseline, HDL-C and diastolic blood pressure in the intervention group were lower than those in the control group, and there were no significant differences in other factors between the two groups. After the intervention, the levels of total cholesterol, systolic blood pressure and diastolic blood pressure in the two groups decreased significantly, and the number of people taking antihypertensive drugs increased significantly ( P<0.001 and P<0.05); HDL-C decreased in the control group ( P=0.023). After the intervention, compared to control group the intervention group had a higher proportion of patients taking antihypertensive drugs, with lower systolic and diastolic blood pressure ( P<0.05). After the intervention, the increase rate of HDL-C in the intervention group was more than that in the control group, and the decrease rate was less than that in the control group (χ 2=6.65, P=0.036). Conclusion:Family doctor contract services can reduce the risk factors of ASCVD, and personalized family doctor contract services can further improve the effects in the prevention and control of ASCVD. However, the effects might be insignificant and inconsistent for the ASCVD risk factors with deeper management requirements or no specific management measures, which highlights the complexity and diversity of ASCVD prevention and control, calling for multi-level and multi-faceted thinking and exploration.

OBJECTIVETo analyze the characteristics of germline mutations of adenomatous polyposis coli (APC) gene in pedigrees affected with familial adenomatous polyposis (FAP).

METHODSGenomic DNA was extracted from peripheral blood samples from members of the 13 FAP pedigrees. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large fragment deletions of the APC gene. Subsequently, potential mutation was screened from all exons of the APC gene with PCR amplification and direct sequencing.

RESULTSGermline mutations have been identified in 5 FAP pedigrees, which included c.3184_3187delCAAA, c.5432C>T, c.3925_3928delAAAA and c.3925_3929del AAAAG(in two pedigrees). Small deletional mutations were found primarily in the area of AAAAG tandem repeat sequences.

CONCLUSIONC.3925_3929 located in AAAAG tandem repeats is probably the hot spot for APC gene mutations, which are mostly deletional mutations, especially the 5 bp base deletion at codon 1309.

Adenomatous Polyposis Coli ; genetics ; Adenomatous Polyposis Coli Protein ; genetics ; Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Female ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Sequence Deletion

Objective To investigate the clinicopathologic features of Chinese patients with early gastric cancer (EGC) according to the World Health Organization(WHO) diagnostic criteria,and to explore the risk factors of lymph node metastasis (LNM) in EGC.Methods From 2002 to 2017,at the Second Affiliated Hospital of Nantong University,and from 2014 to 2017,at the People's Hospital of Qidong City,the People's Hospital of Haimen City and the People's Hospital of Rugao City,315 EGC patients with complete clinicopathological data were enrolled.The clinicopathologic features were analyzed including gender,age,tumor location,tumor size,macroscopic type,histological type (WHO),differentiation degree,depth of tumor invasion,Lauren subtype,infiltration pattern,ulceration,lymphoid follicles,lymphovascular invasion and perineural invasion.Chi-square test and Fisher's exact test were performed for univariate analysis and the logistic regression was used for multivariate analysis.Results The ratio of EGC was 10.0％ (315/3 140) of patients with gastric cancer and received surgery during the same period.Among the 315 EGC,the ratio of well-differentiated tubular adenocarcinoma was 11.7％ (37/315),which was lower than 24.8％(2 752/11 104) in Japan and 19.9％(41/206) in South Korea,and the differences were statistically significant (x2 =28.208,P＜0.01;x2 =6.51 0,P =0.011),however there was no statistically significant difference when compared with Western countries (11.9 ％,8/67;x2 =0.002,P=0.964).Among the 276 patients who underwent radical gastrectomy,49 (17.8 ％) patients had with LNM.The results of univariate analysis showed that tumor size,macroscopic type,differentiation degree,depth of invasion,infiltration pattern,ulceration and lymphovascular invasion were related with LNM(x2=9.327,6.038,6.381,34.983,19.309,52.297 and 5.058;all P＜0.05).The results of multivariate analysis revealed that lymphovascular invasion and ulceration were the independent risk factors of LNM (odd ratio (OR)=7.028 and 2.566,both P＜0.05).Conclusions There is obvious difference in pathological diagnostic standard of well-differentiated tubular adenocarcinoma between China,Japan and South Korea,which may influence the therapeutic strategy of EGC.Lymphovascular invasion and ulceration are independent risk factors of LNM in EGC.

Objective:Laboratory evaluation of the relationship between cerebrospinal fluid and plasma indicators and intrathecal immunoglobulin G(IgG) synthesis in patients with neurological diseases, and establishment of a new diagnostic method for intrathecal IgG synthesis.Methods:This study retrospectively analyzed the content of IgG in cerebrospinal fluid samples and blood albumin in blood samples, and other test results of 410 patients with neurological diseases who visited Beijing Tiantan Hospital from 2019 to 2022. According to the results of oligoclonal bands in cerebrospinal fluid, patients were divided into intrathecal IgG synthesis group and non-intrathecal IgG synthesis group. The Mann Whitney U test was used for inter group comparison, and a bilateral test with P<0.05 indicates a statistically significant difference. Include indicators with differences between groups in logistic regression analysis, construct a predictive model, and compare it with the established quantitative formula IgG index. Results:There were significant differences in 10 indicators, including cerebrospinal fluid leukocyte count and 24-hour intrathecal IgG synthesis rate, between the intrathecal IgG synthesis group and the non-intrathecal IgG synthesis group, with P<0.05. The area under the curve (AUC) of intrathecal IgG synthesis was higher than the IgG index (AUC=0.920, 0.809, Z=31.178, P<0.001), the sensitivity was higher than the IgG index (0.825, 0.618), and the specificity was lower than the IgG index (0.876, 0.908). Conclusion:The combination of 10 indicators such as cerebrospinal fluid white blood cell count and 24-hour intrathecal IgG synthesis rate can improve the diagnostic efficacy and sensitivity of intrathecal IgG synthesis.

Currently, titanium alloys are widely used in the field of stomatology; however, owing to long-term exposure to a complex microbial environment, dental plaques easily form on the surface of the materials, affecting the use efficiency and the service life of the materials. The antibacterial titanium alloy is a new kind of titanium alloy with antimicrobials added through surface modification or overall modification. Based on the location of antibacterial agents in titanium alloy materials, antibacterial titanium alloys can be divided into coating and alloy types. The antibacterial effect of coated antibacterial titanium alloy is good, but the disadvantage is that most of the coatings are not wear-resistant. The widely-used antibacterial agent of the alloy type is metal elements, which can be evenly distributed in the alloy, and the antibacterial properties are stable and long-lasting. Based on whether antibacterial agents can be released, antibacterial titanium alloys can be further divided into active antibacterial and passive antibacterial types. Active antibacterial type titanium alloys can release loaded antibacterial agents, and the antibacterial effect is more obvious, but the release duration of antibacterial agents is relatively short. Passive antibacterial titanium alloys exhibit an antibacterial effect by contact sterilization or inhibition of bacterial adhesion instead of releasing antibacterial agents. The antibacterial titanium alloy can inhibit the adhesion of bacteria on the surface of the material and prolong the service life of oral orthodontic appliances, implants and titanium plates. Moreover, the mechanical properties of the titanium alloy after antibacterial modification are not significantly affected, and the addition of antibacterial agents such as hydroxyapatite can increase the osteogenic function of the material. Therefore, the alloy has good application prospects in the fields of dental implant, orthodontic treatment and oral and maxillofacial surgery. However, most of the current studies on antibacterial titanium alloys are in vitro experiments, and their long-term clinical effects and antibacterial mechanisms are still unclear and need further study.