The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of "eat me" signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.
Humans ; Mice ; Animals ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Lung Neoplasms/metabolism* ; Acrylamides/pharmacology* ; ErbB Receptors/metabolism* ; Cell Line, Tumor ; CD47 Antigen/therapeutic use*

Described as a "don't eat me" signal, CD47 becomes a vital immune checkpoint in cancer. Its interaction with signal regulatory protein alpha (SIRPα) prevents macrophage phagocytosis. In recent years, a growing body of evidences have unveiled that CD47-based combination therapy exhibits a superior anti-cancer effect. Latest clinical trials about CD47 have adopted the regimen of collaborating with other therapies or developing CD47-directed bispecific antibodies, indicating the combination strategy as a general trend of the future. In this review, clinical and preclinical cases about the current combination strategies targeting CD47 are collected, their underlying mechanisms of action are discussed, and ideas from future perspectives are shared.

Objective To develop a new mPCR method for rapid diagnosis of six types of encephalitis causing viruses of HS-VI,HSVII,VZV,EBV,EV71 and CMV.Methods Six pairs of specific primers for CMV,EV71,HSV I,VZV,EBV and HSV II were designed.The mPCR detection method was established and the sensitivity was detected.In order to verify the clinical application value of their multiplex PCR system,fifteen cerebrospinal fluid specimens of clinically suspected VE from the First Affiliated Hospital of Soochow University from 2014 to 2015 were examined by the mPCR method.Results The 6 pairs of primers did not interfere with each other,and the sensitivity of the mPCR system was over 103copies/μl.Among 15 cerebrospinal fluid specimens from patients with suspected viral encephalitis,six specimens(6/15,40%)were tested positive by the mPCR.Among them,HSV I was 5 and CMV was 1.Conclusion The mPCR method for detecting six types of en-cephalitis-associated virus at same time was established with high specificity,sensitivity and stability.

Objective To explore the survival time and its influencing factors of patients in Guizhou Province after they received antiretroviral therapy(ART)for treating human immunodeficiency virus (HIV)infection and acquired immunodeficiency syndrome (AIDS).Methods A retrospective cohort analysis was conducted to analyze survival time of AIDS patients who received ART in Guizhou Province in 2005-2016,life table method was used to calculate the survival probability,Cox proportional hazards regression model was used to analyze the influencing factors of survival time.Results A total of 15921 patients were included in the study,the median age at the beginning of therapy was(42.13±14.40)years old,58.61% of patients were married/housemate.The length of ART follow-up was (median[P 25 -P 75 ]:15.96[6.00 - 33.00])months.9.77% of the follow-up cases died,59.29% of the deaths occurred within 12 months of initiation of treatment;survival rates in the first,fifth,and tenth year were 93.00%,82.00%,and 74.00% respectively.Cox proportional hazards regression model analysis showed that fe-male patients were 0.58 times more likely to die than male patients(95% CI :0.49-0.68);the risk of death in-creased with increase of ages;the higher the baseline CD4+ T lymphocyte count,the lower the risk of death;the risk of death in patients without symptoms or signs before therapy was 0.70 times than those with symptoms or signs(95% CI :0.60-0.81).Conclusion The antiviral therapy of AIDS patients in Guizhou Province is generally well,patients with high risk factors for death should be paid high attention,it is suggested that medical level and service quality should be improved when patients are treated.

OBJECTIVETo analyze the cancer incidence and mortality of Henan province in 2009.

METHODSOn basis of the criteria of data quality from the National Central Cancer Registry (NCCR), data from 6 registries in Henan province were evaluated, covering 6 061 564 people, accounting for 6.45% of the total population in Henan in 2009. There were 3 104 991 people of males, and 2 956 573 people of females. The incidence, mortality, 10 most common cancers, constitution and cumulative rate (0-74 years old) were then calculated. The age-standardized rate was calculated and adjusted by the Chinese standard population in 1982 as well as the Segi's world standard population.

RESULTSThere were 12 091 new diagnosed cancer and 8040 death cases registered in Henan province in 2009. The rate of pathological diagnosis was 68.2% (8246/12 901) and only 1.75% (2116/12 901) had death certificates. The ratio of mortality and incidence was 0.66 (8040/12 091). The incidence rate was 199.47/100 000 (12 091/6 061 564) in total, and it was 216.36/100 000(6718/3 104 991) in males and 181.73/100 000(5373/2 956 573) among females. The standardized incidence by Chinese population was 126.50/100 000 and it was 166.08/100 000 by world's population. The cumulative rate was 19.95% between 0 and 74 years old. The incidence was the highest in Linzhou city, whose standardized incidence was 156.87/100 000 by Chinese population and the incidence was the lowest in Shenqiu city, whose standardized incidence was 104.82/100 000 by Chinese population. The morphology verified cases accounted for 68.2% (8246/12 091), death certification cases only accounted for 1.75% (2116/12 091), and mortality to incidence ratio was 0.66 (8040/12 091). The crude incidence in cancer registration areas of Henan province was 199.47/10 000 (12 091/6 061 564), 216.36/10 000(6718/3 104 991) for males, 181.73/10 000 (5373/2 956 573) for females, age-standardized incidence rates by Chinese standard population and by world standard population were 126.50/10 000 and 166.08/10 000 with cumulative incidence rate (0-74 age years old) of 19.95%. The crude mortality in cancer registration areas of Henan province was 132.64/100 000 (8040/6 061 564), separately 160.58/100 000 (4986/3 104 991) for males and 103.30/10 000 (3054/2 956 573) for females. The age-standardized mortality rates by Chinese standard population and by world's standard population were 78.41/10 000 and 107.49/10 000. The cumulative mortality rate (0-74 age years old) was 12.18%. The mortality rate was the highest in Linzhou city, whose standardized rate was 93.35/100 000 by Chinese population, and the lowest mortality rate was in Yuzhou city, whose standardized rate was 67.95/100 000. The most common cancers were lung cancer, esophageal cancer, gastric cancer, liver cancer, breast cancer, rectum cancer, brain nervous system cancer, colon cancer, cervical cancer and uterus cancer, all of which accounted for 82.23% (9943/12 091) of the registered cancers.Lung cancer, esophageal cancer, gastric cancer, liver cancer, breast cancer, rectum cancer, brain nervous system cancer, pancreas cancer, colon cancer and gallbladder carcinoma were the major causes for the death, accounting for 86.30% (6938/8040) of all cancer deaths.

CONCLUSIONBoth incidence and mortality of cancer in Henan province were lower than the level in China, prevention and control should be implemented based on practical situation.

Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Neoplasms ; epidemiology ; mortality ; Registries ; Sex Distribution ; Survival Rate ; Young Adult

OBJECTIVETo describe the temporal trends in the mortality rate of gastric cancer during the period of 1988 and 2010, and to predict the gastric cancer mortality between 2016 - 2020.

METHODSThe data of gastric cancer mortality in Linzhou city between 1988 and 2010 was extracted from the cancer registry, including a total of 11 714 cases, covering 22 447 073 person-years. The mortality rate of gastric cancer of each 5-year period was calculated by sub-site and gender. Age-standardized rate (ASR) was calculated using the Chinese standard population in 1982. Intrinsic estimator (IE) model was used to fit the mortality trend by sub-site and gender, and to predict the mortality of gastric cancer in Linzhou city between 2016 and 2020.

RESULTSFrom 1988 to 2010, the gastric cancer mortality in Linzhou city was 52.18/100 000 (11 714/22 447 073) with the ASR at 49.23/100 000; the mortality in male was 67.02/100 000 (7678/11 455 512) with ASR at 68.68/100 000 while the mortality in female was 36.72/100 000 (4036/10 991 561) with ASR at 32.12/100 000. The mortality of cardia carcinoma was 27.87/100 000 (6257/22 447 073) with the ASR at 26.37/100 000; while the mortality of non-cardia carcinoma was 24.31/100 000 (5457/22 447 073) with the ASR at 22.86/100 000. The ASR of gastric cancer during 1988 - 1990 was 63.37/100 000 (1653 cases) and decreased by 28.34%, to 45.41/100 000 (2622 cases) during 2006 - 2010. The IE model showed that the birth cohort effect decreased greatly. The mortality risk of cardia carcinoma in population born after 1950s, decreased significantly; and the mortality risk of non-cardia carcinoma in population born in 20 century continually decreased. The death of gastric cancer among the population over 30 years old was predicted to be 3626 cases, increasing by 40.60% compared with the number between 2006 and 2010 (2579 cases). Among them, the mortality of cardia carcinoma increased by 51.89% (predicted number between 2016 and 2020 was 2456 cases, and 1617 cases between 2006 and 2010), and the mortality of non-cardia carcinoma increased by 21.62% (predicted number between 2016 and 2020 was 1170 cases, and 962 cases between 2006 and 2010).

CONCLUSIONThe mortality rate of gastric cancer in Linzhou city showed a decreasing trend during the period of 1988-2010, being mainly attributed to the cohort effect. However, the mortality will still increase in the future, between 2016 and 2020.

Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Female ; Forecasting ; Humans ; Male ; Middle Aged ; Registries ; Stomach Neoplasms ; epidemiology ; mortality

OBJECTIVETo analyze the trends in mortality of esophageal cancer and explore the effects of age, period and cohort on esophageal cancer mortality rate in Linzhou city in 1986 - 2010, and predict the mortality of esophageal cancer in 2016 - 2020.

METHODSAll of the esophageal cancer-attributed deaths in 1986 - 2010 were drawn from the database in Center of Cancer and Vita Statistics in Henan Province. The numbers of the death cases and population were tabulated into 5-year age groups and 5-year period groups for each sex and linked each other. The age-adjusted mortality rates were calculated by direct standardization to the Chinese population structure in 1982. Intrinsic estimator model (IE model)was used to perform the age-period-cohort analysis and estimate the corresponding parameters. Age effect, period effect and cohort effect on esophageal cancer mortality rate was plotted separately. The mortality of esophageal cancer during 2016 - 2020 was predicted according to the parameters by that model.

RESULTSA total of 15432 cases died from esophageal cancer in Linzhou city in1986 - 2010. The overall crude mortality rate was 63.89 per 100, 000. Among men, the age-adjusted mortality rate was 109.66 per 100, 000 during 1986-1990 and decreased to 60.59 per 100, 000 during 2006 - 2010. For women, the age-adjusted mortality rate decreased from 74.72 per 100, 000 to 39.05 per 100, 000 at the same two calendar periods. The IE model showed that age effect was remarkable, the period effect was stable and the cohort effect decreased greatly. The predicted mortality of over 30-years old population during 2016 - 2020 is 1501 for men and 1083 for women. Compared with 2006 - 2010 period the mortality will be decreased by 6.71% and 11.08%, respectively.

CONCLUSIONSThe mortality rate of esophageal cancer in Linzhou city shows a decreasing trend during the period of 1986 - 2010. This trend is mainly attributed to the cohort effect. The predicted mortality in the future will decrease continually.

Adult ; Age Distribution ; Aged ; Aged, 80 and over ; China ; epidemiology ; Cohort Studies ; Esophageal Neoplasms ; mortality ; Female ; Humans ; Male ; Middle Aged ; Mortality ; trends

OBJECTIVETo analyze the level of mortality of brain tumor and its changes at different periods in China.

METHODSDeath records for tumor of brain and central nervous system, which the code of international classification of diseases-10 (ICD-10) were C70-C72, were extracted from the database of the Third National Retrospective Sampling Survey of Death Causes in China during 2004 to 2005. The corresponding population data was linked to the data of death records, that the total population was 142 660 482 person years (72 970 241 person years in male, 69 690 241 person years in female). Then crude death rate, age-specific death rate, the constitute proportion to all death caused by tumor and the age-standardized death rate were calculated by taking reference of Chinese standard population or the world standard population. The indexes of mortality were compared with that of previous retrospective surveys of death causes at 1973 - 1975 and 1990 - 1992.

RESULTSThe result showed that during 2004 to 2005, the number died from brain tumor was 4463 and the crude death rate in China was 3.13/100 000, which accounted for 2.30% of the all number died from tumor (193 841 cases). The age-standardized death rate by Chinese standard population was 2.37/100 000 and the age-standardized death rate by the world standard population was 2.90/100 000. Of which, there were 2556 death cases for males with crude death rate of 3.50/100 000. While for females, the crude death rate was 2.74/100 000 (1907 death cases). Age-standardized death rates by Chinese standard population in male and female were 2.71/100 000 and 2.03/100 000 respectively. The age-standardized death rate by world standard population was 3.31/100 000 for male and for female that was 2.48/100 000. The age-specific death rate of brain tumor in China was increasing as age growing. The crude death rates were 3.78/100 000 (1809/47 899 806), 2.80/100 000 (2654/94 760 676), and the age-standardized death rates by Chinese standard population were 2.71/100 000 and 2.20/100 000 for urban and rural area respectively, and the crude death rates of brain tumor in east, middle and west region were 3.60/100 000 (1894/52 556 694), 3.14/100 000 (1565/49 781 225), 2.49/100 000 (1004/40 322 563). The age-standardized death rates by Chinese population were 2.57/100 000, 2.43/100 000 and 2.02/100 000. Compared to the data in the first survey during 1973 to 1975, in which the crude death rate was 1.13/100 000 and age-standardized death rate by Chinese standard population was 1.10/100 000, the crude death rate and age-standardized death rate by Chinese standard population were increased by 176.99% and 115.45% respectively. While compared with the second survey during 1990 to 1992, that crude death rate was 1.89/100 000 and age-standardized death rate by Chinese standard population was 1.74/100 000, the rising percent of the rates were 65.61% and 36.21% respectively.

CONCLUSIONThe level of mortality of brain tumor has been changing with an increasing trend from the period of 1973 - 1975 to the period of 2004 - 2005. The rate in male was higher than that of female with great diversity in different areas in China.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Brain Neoplasms ; epidemiology ; mortality ; Cause of Death ; Child ; Child, Preschool ; China ; epidemiology ; Death Certificates ; Female ; Health Surveys ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Young Adult

Objective To observe the change of the salivary occult blood after periodontal mechanical therapy,and to assess the correlations between salivary occult blood and the level of volatile sulphur compounds (VSC) in oral cavity,periodontal clinical parameters,respectively.Methods Fifty patients with gingivititis,mild or moderate periodontitis were included.The level of VSC were measured by Halimeter(R) and salivary occult blood was tested by Periosereen(R) before periodontal examination.Then full mouth plaque index (PLI),probing depth (PD),bleeding index (BI) were charted.Attachment loss (AL) of the Ramfj(o)rd teeth were recorded lastly.Intensive periodontal mechanical therapy was conducted including oral hygiene instruction,scaling and root planing(SRP).Four weeks after SRP,the same examinations were repeated.Results Salivary occult blood was significantly correlated with BI (r = 0.294) and PLI (r =0.308) before periodontal therapy (P < 0.01),and also significantly correlated with VSC level (r = 0.386),PLI (r = 0.456),BI (r = 0.352),AL(r = 0.325) after therapy (P < 0.05).The improvement of VSC level [211.0(111.0-389.5)×10-9 vs 100.0(46.3～165.3)× 10-9],the clinical periodontal parameters including PLI[(1.3 ±1.0) vs (0.4±0.6)],PD[(3.7±l.5)mmvs (2.7±0.9)mm],BI[(1.8±1.2)vs (0.4±0.7) ]and AL[(1.0± 1.1)mm vs (0.1±0.5) mm after the treatment was statistically singnificant(P <0.001).However,standing on the viewpoint of salivary occult blood changes from positive before therapy to negative after therapy,only 80% (40/50) individuals were totally cured.VSC level in oral cavity and periodontal clinical parameters significantly decreased (P < 0.001) following the trends from strong positive,weak positive,to negative results of salivary occult blood test .Condnsions Salivary occult blood was correlated with VSC level in oral cavity of periodontal treated patients.It may be an objective parameter to evaluate the gingival inflammation and the efficacy of the periodontal therapy at individual level.

OBJECTIVETo analyze the survival level and variation of esophageal cancer in Linzhou city of Henan province from 1988 to 2004, and evaluate the effects of diagnosis and treatments on esophageal cancer in this area.

METHODSAll incidence and death records for esophageal cancer during 1988 to 2004 were collected from Linzhou Tumor Registry. Cases with duplicate information or death certificate only were excluded. A total of 12,160 cases of esophageal cancer were collected, of which, 6914 cases were male, and 5246 cases were female. The sex-specific and age-specific probabilities of survival in 1992, 1997 and 2002 were calculated and linked to the data of incidence and death on esophageal cancer in this area. Five-year observed survival rate and five-year relative survival rate during 1990 to 1994, 1995 to 1999, 2000 to 2004 were calculated respectively using period survival analysis and cohort survival analysis and Z test.

RESULTSThe 5-year relative survival rates among the three-episode were 28.24%, 35.24% and 40.76% respectively during 1988 to 2004. This showed an increasing trend by periods (Z values were 3.94 and 3.07, P < 0.05). The 5-year observed survival rates in men among the three-episode were 13.67%, 18.08% and 22.46% respectively, the 5-year relative survival rates were 29.94%, 36.96% and 38.40%. The 5-year observed survival rates in women among the three-episode were 15.56%, 19.29% and 28.01% respectively, the 5-year relative survival rates were 26.78%, 33.12% and 43.70%. During the two former periods, there was no significant difference in the 5-year observed survival rate and relative survival rate between men and women (Z values of observed survival rate were 1.48 and 0.88, P > 0.05. Z values of relative survival rate were 1.27 and 1.50, P > 0.05). In the third period, the 5-year observed survival rate and relative survival rate in women was higher than that in men (observed survival rate Z = 3.56, P < 0.05; relative survival rate Z = 2.09, P < 0.05). The relative survival rate that calculated using period method (respectively 35.24% and 40.76%) was higher than that using cohort method (respectively 28.77% and 33.35%) from 1995 to 1999, and from 2000 to 2004.

CONCLUSIONThe survival rate on esophageal cancer in Linzhou city was increasing in the three different periods. This indicated a rising status in the secondary prevention and clinical diagnosis and treatments on esophageal cancer.

China ; epidemiology ; Esophageal Neoplasms ; epidemiology ; mortality ; Female ; Humans ; Life Tables ; Male ; Survival Analysis