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.

Objective:To explore the effects of different feeding patterns on weight gain and feeding intolerance in hospitalized premature infants.Methods:The retrospective cohort study design was adopted. From April 2019 to October 2020, 155 premature infants admitted to the Neonatal Intensive Care Unit of China-Japan Friendship Hospital were selected as the study subject by convenience sampling. Premature infants were divided into a mixed feeding group ( n=47) and a formula milk feeding group ( n=108) based on their feeding patterns. The observation indicators included weight gain, feeding intolerance, infectious diseases, nutrition and other related indicators. Results:The weight change value and the weight change rate during hospitalization in the mixed feeding group were higher than those in the formula milk feeding group, with statistically significant differences ( P<0.05) . In terms of the total milk volume on the day of discharge, the mixed feeding group were higher than the formula milk feeding group, and the differences were statistically significant ( P<0.05) . During hospitalization, the number of new infectious diseases in the mixed feeding group was less than that in the formula milk feeding group, with a statistically significant difference ( P<0.05) . There was no statistically significant difference in the incidence of feeding intolerance between the two groups of premature infants ( P>0.05) , The incidence of vomiting in the formula milk feeding group was lower than that in the mixed feeding group, with a statistically significant difference ( P<0.05) . Conclusions:Mixed feeding is more conducive to promoting the weight gain of premature infants during hospitalization and reducing the occurrence of infectious diseases than formula milk feeding. The impact of two feeding patterns on feeding intolerance in hospitalized premature infants needs further comparative analysis.

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.

Objective:To provide supports for the cancer prevention and control strategies in China by comparing the disease burden, epidemic trends, 5-year relative survival rate and major determinants of common cancers between China and the United States.Methods:A descriptive secondary analysis was conducted using data extracted from the GLOBOCAN database, the Surveillance, Epidemiology, and End Results database, Global Burden of disease 2019 database, and previous studies. The main indicators included the cases of malignant tumors in different sites, the cases of deaths, the age-standardized incidence (world standard incidence) and mortality (world standard mortality), the 5-year relative survival rate, and population attributable fraction (PAF).Results:In 2022, an estimated 4.825 million new cases and 2.574 million deaths of malignant neoplasms in China. The world standard incidence rate (201.6/100 000) in China was lower than that in the United States (367.0/100 000), and the world standard mortality rate (96.5/100 000) was higher than that in the United States (82.3/100 000). Lung cancer ranked first in the disease burden of malignant tumors in China, the new cases and deaths accounted for 22.0% and 28.5% of all malignant tumors, respectively. The top three malignant tumors in China were breast cancer (11.5%), prostate cancer (9.7%) and lung cancer (9.5%), which were also among the top five causes of death. However, the second to fifth leading causes of death from malignant tumors in China were digestive system tumors (liver cancer 12.3%, stomach cancer 10.1%, colorectal cancer 9.3%, and esophageal cancer 7.3%). From 2000 to 2018, the world standard incidence of malignant tumors showed an increasing trend and the world standard mortality of malignant tumors showed a decreasing trend in China, while the world standard incidence and mortality of malignant tumors in the United States showed a significant decreasing trend after 2000. The incidence of breast cancer, colorectal cancer and thyroid cancer increased rapidly in China, while the incidence and mortality of stomach cancer, liver cancer and esophageal cancer decreased, but they still had a heavy disease burden. From 2003 to 2015, the overall 5-year relative survival rate of malignant tumors increased from 30.9% to 40.5% in China. However, with the exception of esophageal cancer, the 5-year relative survival rates of other major malignant tumors were lower than those in the United States. In 2019, the PAF of malignant tumors death attributable to potential modifiable risk factors was 48.3% in China, which was similar to the United States (49.8%). Of these, smoking was the most important attributable risk factor, and the PAF was more than 30% both in China and the United States. In addition, about 18.8% of malignant tumors were caused by preventable chronic infections, such as hepatitis B virus and Helicobacter pylori, while less than 4% of malignant tumors in the United States were caused by infection.Conclusions:China has made great progress in the prevention and treatment of malignant tumors, but it still faces a serious disease burden. The cancer spectrum is changing from developing countries to developed countries. We should pay attention to modifiable factors, take comprehensive measures, and prevent cancer scientifically.

Objective:To provide supports for the cancer prevention and control strategies in China by comparing the disease burden, epidemic trends, 5-year relative survival rate and major determinants of common cancers between China and the United States.Methods:A descriptive secondary analysis was conducted using data extracted from the GLOBOCAN database, the Surveillance, Epidemiology, and End Results database, Global Burden of disease 2019 database, and previous studies. The main indicators included the cases of malignant tumors in different sites, the cases of deaths, the age-standardized incidence (world standard incidence) and mortality (world standard mortality), the 5-year relative survival rate, and population attributable fraction (PAF).Results:In 2022, an estimated 4.825 million new cases and 2.574 million deaths of malignant neoplasms in China. The world standard incidence rate (201.6/100 000) in China was lower than that in the United States (367.0/100 000), and the world standard mortality rate (96.5/100 000) was higher than that in the United States (82.3/100 000). Lung cancer ranked first in the disease burden of malignant tumors in China, the new cases and deaths accounted for 22.0% and 28.5% of all malignant tumors, respectively. The top three malignant tumors in China were breast cancer (11.5%), prostate cancer (9.7%) and lung cancer (9.5%), which were also among the top five causes of death. However, the second to fifth leading causes of death from malignant tumors in China were digestive system tumors (liver cancer 12.3%, stomach cancer 10.1%, colorectal cancer 9.3%, and esophageal cancer 7.3%). From 2000 to 2018, the world standard incidence of malignant tumors showed an increasing trend and the world standard mortality of malignant tumors showed a decreasing trend in China, while the world standard incidence and mortality of malignant tumors in the United States showed a significant decreasing trend after 2000. The incidence of breast cancer, colorectal cancer and thyroid cancer increased rapidly in China, while the incidence and mortality of stomach cancer, liver cancer and esophageal cancer decreased, but they still had a heavy disease burden. From 2003 to 2015, the overall 5-year relative survival rate of malignant tumors increased from 30.9% to 40.5% in China. However, with the exception of esophageal cancer, the 5-year relative survival rates of other major malignant tumors were lower than those in the United States. In 2019, the PAF of malignant tumors death attributable to potential modifiable risk factors was 48.3% in China, which was similar to the United States (49.8%). Of these, smoking was the most important attributable risk factor, and the PAF was more than 30% both in China and the United States. In addition, about 18.8% of malignant tumors were caused by preventable chronic infections, such as hepatitis B virus and Helicobacter pylori, while less than 4% of malignant tumors in the United States were caused by infection.Conclusions:China has made great progress in the prevention and treatment of malignant tumors, but it still faces a serious disease burden. The cancer spectrum is changing from developing countries to developed countries. We should pay attention to modifiable factors, take comprehensive measures, and prevent cancer scientifically.

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.