Trend analysis of chronic kidney disease incidence and mortality in Chinese population based on age-period-cohort model / 公共卫生与预防医学

Objective To investigate the changing trend and epidemiological characteristics of the incidence and mortality of chronic kidney disease (CKD) with age, period and birth cohort in Chinese population. Methods Based on the data of incidence and mortality of CKD in Chinese population aged 20-80 years from 1990 to 2019 in GHDx database, joinpoint regression model was used to analyze the incidence and mortality trend of CKD. An age-period-cohort model was constructed to analyze the effects of age, period, and birth cohort on the trend of CKD incidence and mortality. Results Joinpoint regression analysis showed that the standardized incidence rate of chronic kidney disease in Chinese population increased from 146.37/100 000 in 1990 to 161.52/100 000 in 2019, while the standardized mortality rate decreased from 12.98/100 000 in 1990 to 11.23/100 000 in 2019. The APC model analysis showed that the risk of CKD incidence and death in the Chinese population increased with age, while the risk of CKD incidence increased with the increase of period. The risk of death did not change significantly with the increase of period. The cohort born later had a lower risk of CKD incidence and death compared to the cohort born earlier. Conclusion At present, the age effect and period effect of the incidence and death risk of chronic kidney disease in China are dominant. It is important to take effective measures and intervene in a timely manner, especially to strengthen the protection of older high-risk groups born earlier.

Trend and gender difference of mortality rate of senile dementia： based on the method of annual percent change / 上海预防医学

ObjectiveTo investigate the characteristics of gender difference and the trend of the mortality rate of senile dementia in registered population in Shanghai from year 2002 to 2018， and to provide the basis for formulating relative intervention measures before and after senile dementia from an public-health view. MethodsBased on the collected data of death registration， focused on the senile dementia disease codes F03，G30.0，G30.1，G30.8，G30.9 according to The International Classification of Diseases 10th revision （ICD-10）. We analyzed the characteristics of gender difference in the mortality rate of senile dementia in registered population in Shanghai from year 2002 to 2018. According to ASR， we calculated the standardized mortality rate of senile dementia， and used the chi-square test to compare the difference between the gender mortality rates. The trend and the turning point of the mortality rate of senile dementia were determined by linear regression analysis by Join-point. ResultsThe crude mortality rate of senile dementia in the registered population in Shanghai from year 2002 to 2018 was 5.46/105， 3.50/105 in males and 7.43/105 in females. The standardized mortality rate of senile dementia was 2.61/105， 1.67/105 in males and 3.56/105 in females. The trend of the standardized mortality rate of senile dementia in 17 years decreased ［APC=-5.5（-6.5，-4.5）%，P<0.01］. The trend of the standardized mortality rate of senile dementia decreased in both males ［APC=-4.9（-6.2，-3.6）%，P<0.01］ and females ［APC=-5.9（-6.9，-4.9）%，P<0.01］. The trend of the gender difference decreased ［APC=-6.8（-8.2，-5.3）%，P<0.01］. The mortality rate of senile dementia was higher in females than in males ［（χ2=33.63，P<0.01）］. ConclusionThe mortality rate of senile dementia in females is higher than in males in Shanghai， though the trend of the gender difference decreased. This gender difference is worth of attention.

Disease burden of multidrug-resistant tuberculosis in China and regions with different income levels in the world / 公共卫生与预防医学

Objective To analyze the disease burden of multidrug-resistant tuberculosis (MDR-TB) in China and regions with different income levels in the world from 1990 to 2019. Methods Using the Global Burden of Disease Study 2019 (GBD2019) results, the changes of the disease burden of MDR-TB in China and regions with different income levels in the world were described and analyzed using the Joinpoint Regression Program 4.8.0.1 software. Results From 1990 to 2019, the age standardized incidence, mortality and DALY rates in China and other areas with different income levels in the world basically showed a trend of first rising and then decreasing at the turning point of the late 20th century and early 21st century, except for low-income areas where the age standardized incidence rate showed an overall upward trend. In 2019, the incidence rate, mortality and DALY rate of MDR-TB in China were 9 times, 6.67 times and 6.89 times higher than those in high-income areas, respectively. The incidence rate in China was 6 times lower than that in low and middle-income areas, while the mortality and DALY rate in China were 26 times and 32.53 times lower than those in low-income areas, respectively. The age standardized incidence, mortality rate and DALY rate of MDR-TB in men were higher than those in women. Risk factors for the burden of MDR-TB disease included alcohol consumption, smoking, and high fasting blood glucose. Conclusion From 1990 to 2019, there are significant regional and gender differences in the disease burden of multidrug-resistant tuberculosis in China and regions with different income levels in the world. Multidrug-resistant tuberculosis is still a major challenge for tuberculosis control in the world. It is necessary to develop more effective control strategies and health care systems to deal with multidrug-resistant tuberculosis.

Alterations in APC, BECN1, and TP53 gene expression levels in colon cancer cells caused by monosodium glutamate

Abstract Colorectal cancer (CRC) is a disease with high incidence worldwide. As of 2018, it is the second leading cause of cancer deaths in the world. In Saudi Arabia, the incidence of this disease has been increasing in the younger population. Both genetic and lifestyle factors may have contributed to its increased incidence and pathogenesis. Monosodium glutamate (MSG) is a food flavor enhancer that can be found in many commercial foods, and it can sometimes be used as a substitute to table salt. MSG has been investigated for its possible genotoxicity, yielding controversial results. In the present study, the effect of MSG on cell viability and its effect on expression of APC, BECN1, and TP53 genes in SW620 and SW480 colon cancer cell lines were studied. TP53 is a tumor suppressor gene that functions in modifying DNA errors and/or inducing apoptosis of damaged cells, and both APC and BECN1 genes are involved in CRC and are of importance in cellular growth and metastasis. Cancer cell viability was analyzed using MTT assay, and the results showed a significant increase in the number of viable cells after 24 h of treatment with MSG with different concentrations (0.5, 1.0, 10, 50, and 100mM). Moreover, gene expression results showed a significant increase in the expression levels of APC and BECN1 under specified conditions in both cell lines; conversely, TP53 showed a significant decrease in expression in SW620 cells. Thus, it can be concluded that MSG possibly confers a pro-proliferative effect on CRC cells.

Resumo O câncer colorretal (CCR) é uma doença com alta incidência mundial. Desde 2018, é a segunda principal causa de mortes por câncer no mundo. Na Arábia Saudita, a incidência dessa doença vem aumentando na população mais jovem. Tanto fatores genéticos quanto de estilo de vida podem ter contribuído para o aumento da sua incidência e patogênese. O glutamato monossódico (MSG) é um intensificador de sabor de alimentos que pode ser encontrado em muitos alimentos comerciais e às vezes pode ser usado como um substituto do sal de cozinha. O MSG tem sido investigado por sua possível genotoxicidade, produzindo resultados controversos. Neste estudo, foram estudados o efeito do MSG na viabilidade celular e seu efeito na expressão dos genes APC, BECN1 e TP53 em linhas de células de câncer de cólon SW620 e SW480. TP53 é um gene supressor de tumor que atua modificando erros de DNA e/ou induzindo apoptose de células danificadas, estando os genes APC e BECN1 envolvidos no CRC e sendo importantes no crescimento celular e metástase. A viabilidade das células cancerosas foi analisada por meio do ensaio MTT, e os resultados mostraram um aumento significativo no número de células viáveis após 24 h de tratamento com MSG em diferentes concentrações (0,5; 1,0; 10; 50 e 100mM). Além disso, os resultados da expressão gênica mostraram um aumento significativo nos níveis de expressão de APC e BECN1 sob condições especificadas em ambas as linhagens celulares. Por outro lado, TP53 mostrou uma diminuição significativa na expressão em células SW620. Assim, pode-se concluir que, possivelmente, o MSG confere um efeito pró-proliferativo às células CRC.

Alterations in APC, BECN1, and TP53 gene expression levels in colon cancer cells caused by monosodium glutamate / Alterações nos níveis de expressão gênica APC, BECN1 e TP53 em células de câncer de cólon causadas por glutamato monossódico

Colorectal cancer (CRC) is a disease with high incidence worldwide. As of 2018, it is the second leading cause of cancer deaths in the world. In Saudi Arabia, the incidence of this disease has been increasing in the younger population. Both genetic and lifestyle factors may have contributed to its increased incidence and pathogenesis. Monosodium glutamate (MSG) is a food flavor enhancer that can be found in many commercial foods, and it can sometimes be used as a substitute to table salt. MSG has been investigated for its possible genotoxicity, yielding controversial results. In the present study, the effect of MSG on cell viability and its effect on expression of APC, BECN1, and TP53 genes in SW620 and SW480 colon cancer cell lines were studied. TP53 is a tumor suppressor gene that functions in modifying DNA errors and/or inducing apoptosis of damaged cells, and both APC and BECN1 genes are involved in CRC and are of importance in cellular growth and metastasis. Cancer cell viability was analyzed using MTT assay, and the results showed a significant increase in the number of viable cells after 24h of treatment with MSG with different concentrations (0.5, 1.0, 10, 50, and 100mM). Moreover, gene expression results showed a significant increase in the expression levels of APC and BECN1 under specified conditions in both cell lines; conversely, TP53 showed a significant decrease in expression in SW620 cells. Thus, it can be concluded that MSG possibly confers a pro-proliferative effect on CRC cells.

O câncer colorretal (CCR) é uma doença com alta incidência mundial. Desde 2018, é a segunda principal causa de mortes por câncer no mundo. Na Arábia Saudita, a incidência dessa doença vem aumentando na população mais jovem. Tanto fatores genéticos quanto de estilo de vida podem ter contribuído para o aumento da sua incidência e patogênese. O glutamato monossódico (MSG) é um intensificador de sabor de alimentos que pode ser encontrado em muitos alimentos comerciais e às vezes pode ser usado como um substituto do sal de cozinha. O MSG tem sido investigado por sua possível genotoxicidade, produzindo resultados controversos. Neste estudo, foram estudados o efeito do MSG na viabilidade celular e seu efeito na expressão dos genes APC, BECN1 e TP53 em linhas de células de câncer de cólon SW620 e SW480. TP53 é um gene supressor de tumor que atua modificando erros de DNA e/ou induzindo apoptose de células danificadas, estando os genes APC e BECN1 envolvidos no CRC e sendo importantes no crescimento celular e metástase. A viabilidade das células cancerosas foi analisada por meio do ensaio MTT, e os resultados mostraram um aumento significativo no número de células viáveis após 24 h de tratamento com MSG em diferentes concentrações (0,5; 1,0; 10; 50 e 100mM). Além disso, os resultados da expressão gênica mostraram um aumento significativo nos níveis de expressão de APC e BECN1 sob condições especificadas em ambas as linhagens celulares. Por outro lado, TP53 mostrou uma diminuição significativa na expressão em células SW620. Assim, pode-se concluir que, possivelmente, o MSG confere um efeito pró-proliferativo às células CRC.

Alteraciones genéticas en la vía canónica Wnt/β-catenina en cáncer colorrectal

El objetivo de esta revisión es comprender la complejidad de la vía de señalización canónica Wnt/β-catenina (VSC-WβC) en el cáncer colorrectal (CCR): funcionamiento, principales mutaciones y nuevas moléculas terapéuticas en investigación. Se buscaron los artículos médicos más relevantes del tema en PubMed, Scopus y SciELO. VSC-WβC controla importantes fenómenos biológicos celulares; las alteraciones genéticas de esta vía contribuyen significativamente al CCR. La VSC-WβC se activa por la unión del ligando Wnt con el receptor Frizzled y la proteína relacionada al receptor 5 o 6 de la lipoproteína de baja densidad (LRP5/6); este complejo ternario en la membrana extracelular activa a las quinasas que inducen la fosforilación del dominio intracelular de LRP5/6 e inicia la cascada de señalización celular. La VSC-WβC está alterada en más del 90 % de todos los CCR, y es el gen de la poliposis coli adenomatosa, uno de los componentes con mayores transgresiones en este tipo de cáncer. La VSC-WβC es un blanco importante en la investigación de los nuevos tratamientos del cáncer, en los últimos años; varios inhibidores de la vía se han desarrollado para el tratamiento de CCR (anticuerpos monoclonales, proteínas inhibidoras, pequeñas moléculas selectivas y otras familias innovadoras), la mayoría de ellos en etapas preclínicas. En conclusión, el CCR está asociado con mutaciones en VSC-WβC, cuya activación continua otorga a las células cancerosas propiedades de crecimiento autorrenovables y se asocia con la resistencia al tratamiento del CCR. Existe una activa investigación de nuevas moléculas innovadoras que modulan esta vía de señalización; sin embargo, ninguna ha sido aprobada para uso comercial hasta la fecha.

The goal of this study is to better understand the complexity of the canonical Wnt/β-catenin (C-WNT) signaling pathway in colorectal cancer (CRC): how it works, its key mutations and the novel therapeutic compounds under development. PubMed, Scopus and SciELO were used to find the most relevant medical literature on the issue. The C-WNT signaling pathway regulates essential cellular biological processes: genetic changes in this pathway are significant contributors to CRC. The Wnt ligand binding to the Frizzled receptor and low-density lipoprotein receptor-related protein 5 or 6 (LRP5/6) stimulates the C-WNT signaling pathway; this extracellular membrane ternary complex activates kinases that promote phosphorylation of the intracellular domain of LRP5/6 and starts the cell signaling cascade. The C-WNT signaling pathway is changed in more than 90 % of all CRCs, with the adenomatous polyposis coli gene showing the great majority of mutations in this type of cancer. In recent years, the C-WNT signaling pathway has been an important target for researching new cancer treatments; various inhibitors of the pathway (monoclonal antibodies, inhibitory proteins, selective small compounds and other novel families) have been developed for the treatment of CRC, being the majority of them still in preclinical phases. In conclusion, CRC is related to mutations in the C-WNT signaling pathway, whose persistent activation provides cancer cells with self-renewing growth capabilities and is linked to treatment resistance in CRC. There is active research on novel and innovative compounds that affect this signaling pathway; however, none has received commercial approval so far.

An analysis of invitations for article submission received via emails

Predatory journals charge publication fees from authors and publish without an adequate peer review, and often do not provide editorial and/or publishing services. Our objective was to evaluate e-mail solicitations received by authors in a defined time period to identify attributes of these solicitations as a metric to identify legitimacy of the journal. All e-mails seeking article submission received between January 1 and September 30, 2019, were evaluated. Each e-mail along with its respective webpage was evaluated for the journal’s and publisher’s names, mention of peer review, any assurance of publication, a mention of article processing charges (APC), composite invites [in the e-mail] and mention of peer review, the presence and functionality of archives, presence of manuscript management tab, mention of APC [on the webpage]. Descriptive statistics were used for the analysis. Of the 135 e-mails screened, 100 were finally included in the analysis. We found that 72% of the journals and/ or publishers were included in Beall’s list. According to our criteria, a total of 85% of the solicitations were from journals that we identified as “presumed predatory”. Our study has identified assurance of publication, rapid turnaround time, ambiguous information in the email and webpage, false claims of indexing as some descriptors which may help young authors and researchers assess a journal’s legitimacy.

Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

Analysis of mortality of chronic obstructive pulmonary disease among residents in Baoshan District of Shanghai from 2010 to 2019 / 上海预防医学

Objective To analyze the changes of mortality and potential years of life lost （PYLL） due to chronic obstructive pulmonary disease （COPD） among residents in Baoshan District， Shanghai from 2010 to 2019 and provide strategies and basis for COPD prevention and treatment in the future. Methods Based on the cause-of-death surveillance system in Baoshan District of Shanghai from 2010 to 2019， Microsoft Excel 2010， SPSS 22.0 and Joinpoint Trend Analysis Software were used to sort out and analyze the data over the years and calculate the crude mortality， standardized mortality， age-specific mortality， PYLL， annual percent change （APC）， etc. Results From 2010 to 2019， the average annual mortality of COPD was 48.08/100 000， and the standardized mortality rate was 39.95/100 000， accounting for 5.82% of the total deaths in the same period， and COPD ranked as the third leading cause of death in Baoshan District. During the 10 years， the crude and standardized mortality of male COPD patients were generally higher than those of female patients （ P <0.01）. However， the crude mortality and standardized mortality of COPD showed a decreasing trend with the increase of years （ P <0.001）， and an increasing trend with the increase of age， of which the proportion of patients aged 75 and above was the highest， accounting for 85.71% of all age groups. The PYLL caused by COPD deaths was 2 352.5 years， including 1 977.5 years for men and 375.0 years for women. The number of years of life lost per 10 000 people due to COPD in males （4.18 years） was much longer than that in females （0.82 years）. Conclusion From 2010 to 2019， the standardized mortality of chronic obstructive pulmonary disease among residents in Baoshan District， Shanghai has shown a significant decline. However， due to the heavy burden brought by COPD， which has an especially profound impact on the health of elderly and male residents， COPD should be regarded as one of the key diseases in the prevention and control of chronic diseases in public health services， and effective preventive measures should be taken.

Analysis of mortality of chronic obstructive pulmonary disease among residents in Baoshan District of Shanghai from 2010 to 2019 / 上海预防医学

Objective To analyze the changes of mortality and potential years of life lost （PYLL） due to chronic obstructive pulmonary disease （COPD） among residents in Baoshan District， Shanghai from 2010 to 2019 and provide strategies and basis for COPD prevention and treatment in the future. Methods Based on the cause-of-death surveillance system in Baoshan District of Shanghai from 2010 to 2019， Microsoft Excel 2010， SPSS 22.0 and Joinpoint Trend Analysis Software were used to sort out and analyze the data over the years and calculate the crude mortality， standardized mortality， age-specific mortality， PYLL， annual percent change （APC）， etc. Results From 2010 to 2019， the average annual mortality of COPD was 48.08/100 000， and the standardized mortality rate was 39.95/100 000， accounting for 5.82% of the total deaths in the same period， and COPD ranked as the third leading cause of death in Baoshan District. During the 10 years， the crude and standardized mortality of male COPD patients were generally higher than those of female patients （ P <0.01）. However， the crude mortality and standardized mortality of COPD showed a decreasing trend with the increase of years （ P <0.001）， and an increasing trend with the increase of age， of which the proportion of patients aged 75 and above was the highest， accounting for 85.71% of all age groups. The PYLL caused by COPD deaths was 2 352.5 years， including 1 977.5 years for men and 375.0 years for women. The number of years of life lost per 10 000 people due to COPD in males （4.18 years） was much longer than that in females （0.82 years）. Conclusion From 2010 to 2019， the standardized mortality of chronic obstructive pulmonary disease among residents in Baoshan District， Shanghai has shown a significant decline. However， due to the heavy burden brought by COPD， which has an especially profound impact on the health of elderly and male residents， COPD should be regarded as one of the key diseases in the prevention and control of chronic diseases in public health services， and effective preventive measures should be taken.

The association between postmenopausal osteoporosis and APC gene polymorphism was analyzed based on quantitative CT measurement of lumbar vertebral bone density / 中华内分泌外科杂志

Objective:To investigate the relation of two SNPs of adenomatous polyposis coli (APC) gene E1317Q (RS1801166, G > C) and D1822V (RS45952, A > T) polymorphism with osteoporosis and bone metabolism in postmenopausal women.Methods:A total of 374 postmenopausal women who underwent routine physical examination in the Second Affiliated Hospital of Zhejiang University School of Medicine from Mar. 2019 to Mar. 2021 were selected as subjects, and divided into normal bone mass group (103 cases) , osteoparrosia group (114 cases) and osteoporosis group (157 cases) . Bone mineral density was measured by a 128-slice spiral CT machine manufactured by Siemens. Clinical and bone metabolic indicators were recorded. Two SNPs were genotyped by capillary electrophoresis and fragment analysis (SNaPshot) . The relative expression level of APC gene mRNA was measured in quantitative real-time fluorescence quantitative polymerase chain reaction system.Results:There were significant differences in genotype and allele frequency distribution of APC rs1801166 and RS45952 among the three groups (all P<0.05) . For rs1801166 site, paircomparison results showed that the genotype distribution of the osteoporosis group was significantly different from that of the normal bone mass group and the decreased bone mass group ( P<0.05) . Allele frequency was significantly different between the two groups ( P<0.05) . For rs45952 site, pairwise comparison showed that the genotype distribution and allele frequency were significantly different between the osteoporosis group and the normal bone mass group ( P<0.05) . There were statistically significant differences in serum calcium, serum phosphorus, alkaline phosphatase, 25-hydroxyvitamin and bone mineral density between wild type and mutant type at rs1801166 (all P<0.05) . There were statistically significant differences in serum calcium, alkaline phosphatase, 25-hydroxyvitamin and bone mineral density between wild type and mutant at RS45952 site (all P<0.05) . There was statistical significance in the mRNA relative expression of APC gene in the normal bone mass group, the bone mass reduction group and the osteoporosis group ( P<0.05) . The mRNA relative expression level of APC gene in wild type at rs1801166 and RS45952 sites was significantly higher than that in mutant type (all P<0.05) . Conclusion:APC gene polymorphism is significantly correlated with osteoporosis and bone metabolism in postmenopausal women, and may affect the expression level of APC gene.

Targeting RAS phosphorylation in cancer therapy: Mechanisms and modulators

RAS, a member of the small GTPase family, functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state. RAS gain-of-function mutations are one of the leading causes in human oncogenesis, accounting for ∼19% of the global cancer burden. As a well-recognized target in malignancy, RAS has been intensively studied in the past decades. Despite the sustained efforts, many failures occurred in the earlier exploration and resulted in an 'undruggable' feature of RAS proteins. Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins. Therefore, the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties. A better understanding of RAS phosphorylation can contribute to future therapeutic strategies. In this review, we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways. Importantly, the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.

Natural compounds in the regulation of proteostatic pathways: An invincible artillery against stress, ageing, and diseases

Cells have different sets of molecules for performing an array of physiological functions. Nucleic acids have stored and carried the information throughout evolution, whereas proteins have been attributed to performing most of the cellular functions. To perform these functions, proteins need to have a unique conformation and a definite lifespan. These attributes are achieved by a highly coordinated protein quality control (PQC) system comprising chaperones to fold the proteins in a proper three-dimensional structure, ubiquitin-proteasome system for selective degradation of proteins, and autophagy for bulk clearance of cell debris. Many kinds of stresses and perturbations may lead to the weakening of these protective cellular machinery, leading to the unfolding and aggregation of cellular proteins and the occurrence of numerous pathological conditions. However, modulating the expression and functional efficiency of molecular chaperones, E3 ubiquitin ligases, and autophagic proteins may diminish cellular proteotoxic load and mitigate various pathological effects. Natural medicine and small molecule-based therapies have been well-documented for their effectiveness in modulating these pathways and reestablishing the lost proteostasis inside the cells to combat disease conditions. The present article summarizes various similar reports and highlights the importance of the molecules obtained from natural sources in disease therapeutics.

Familial Adenomatous Polyposis Coli in East Africa: A Case Report and Review of the Literature

Introduction: Familial adenomatous polyposis (FAP) is a rare diagnosis in East Africa. The author reports a case of a 21 year old gentleman presenting with occasional passage of blood stained stool, and found to have familial adenomatous polyposis coli. This is followed by a literature review on the pathogenesis, clinical features and treatment options of FAP in East Africa.Presentation of Case: This patient presented with a strong family history of familial adenomatous polyposis, blood stained stool and a rectal mass. A total proctocolectomy and ileoanal anastomosis was carried out. The postoperative course of this patient was uneventful.Discussion: The typical gross pathological and histological features of familial adenomatous polyposis and rectal adenocarcinoma were seen on the resected colorectal specimen. In addition this study reviews the literature regarding the clinical presentation, pathological characteristics and treatment options of familial adenomatous polyposis coli.Conclusion: FAP should always be considered in a young patient presenting with a strong family history of CRC. Colonoscopy should be performed on these patients with early symptoms and those patients with a strong family history of FAP. In East Africa, the creation of a permanent stoma is unacceptable and therefore a proctocolectomy and Brooke ileostomy will not be a desirable option in a young patient in this part of the world

Epigenetic strategies synergize with PD-L1/PD-1 targeted cancer immunotherapies to enhance antitumor responses

Immunotherapy strategies targeting the programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) pathway in clinical treatments have achieved remarkable success in treating multiple types of cancer. However, owing to the heterogeneity of tumors and individual immune systems, PD-L1/PD-1 blockade still shows slow response rates in controlling malignancies in many patients. Accumulating evidence has shown that an effective response to anti-PD-L1/anti-PD-1 therapy requires establishing an integrated immune cycle. Damage in any step of the immune cycle is one of the most important causes of immunotherapy failure. Impairments in the immune cycle can be restored by epigenetic modification, including reprogramming the environment of tumor-associated immunity, eliciting an immune response by increasing the presentation of tumor antigens, and by regulating T cell trafficking and reactivation. Thus, a rational combination of PD-L1/PD-1 blockade and epigenetic agents may offer great potential to retrain the immune system and to improve clinical outcomes of checkpoint blockade therapy.

APC model analysis of lung cancer death trend in residents of Macheng City, Hubei Province, 1984-2018 / 公共卫生与预防医学

Objective To study the trends of lung cancer mortality among adult residents in Macheng City, Hubei Province from 1984 to 2018． Methods Mortality data was extracted from Macheng City disease surveillance points (DSPs) system and China Demographic Yearbook. The age-period-cohort (APC) model and Intrinsic Estimator algorithm were used to estimate the age effect, period effect and cohort effect of lung cancer mortality. Results The age effect coefficient of lung cancer mortality increased with age from 20 to 74 years old. The mortality risk of the 70-74 group was 42.62 times that of the 20-24 group. The period effect coefficient of lung cancer mortality also continued to rise with time. The cohort effect coefficient was parabolic, and residents born in 1939-1943 had the highest coefficient (1.298 4). Conclusion The risk of lung cancer death of adult residents in Macheng City significantly increased with the year and the rapid development of socio-economics.

Trends in prostate cancer mortality in Chinese men from 1990 to 2017: an APC model analysis / 公共卫生与预防医学

Objective To explore the prevalence trend of male prostate cancer mortality in China during the 25 years from 1992 to 2017. Methods The age-period-cohort (APC) model and the Intrinsic Estimator (IE) algorithm were used to estimate the age effect, period effect and cohort effect of prostate cancer mortality risk in Chinese men. Results The overall mortality rate of prostate cancer in Chinese men was on the rise from 1992 to 2017, with the crude mortality rate rising from 3.39‰ to 7.17‰. The results of the APC model analysis showed that the age effect of prostate cancer mortality increased with age in Chinese men after the age of 40. The period effect was generally on the rise. The cohort effect indicated that men born in China after 1980 experienced a declining risk of prostate cancer death. Conclusions The period effect of prostate cancer mortality risk was dominant in Chinese men. Changes in lifestyle and sexual attitudes, population aging, smoking, environmental pollution and other factors may be the main reasons for the increase in the period effect. The attention should be paid to improve these aspects in the prevention and treatment of prostate cancer, and at the same time the awareness rate of PSA screening should be strengthened. Comprehensive prevention with health education can help reduce overall prostate cancer mortality in men.

Trends of upper gastrointestinal cancer mortality from 1983 to 2015 in Cixian County, Hebei Province / 中国肿瘤临床

Objective: To analyze the mortality of upper gastrointestinal cancer in Cixian County, Hebei Province, China, over the past 33 years, and provide evidence for the prevention and treatment of such cancer. Methods: According to the cancer registration regulations, changes in the mortality of upper gastrointestinal cancer were collected, sorted and evaluated, and the trends in the mortality of upper gastrointestinal cancer were analyzed using the cancer registration data accumulated by the Cixian cancer Registration Office between January 1, 1983, and December 31, 2015. The percentage changes in crude mortality, standardized mortality in China, and the standardized worldwide mortality were calculated. The annual percent change of mortality was estimated using a linear regression model of the adjustment rate. Results: Over the 33-year period in Cixian County, the average crude mortality of upper gastrointestinal cancer was 119.31/100,000, including 149.21/100,000 for males and 88.40/100,000 for females. The standardized mortality rate in China was 160.85/100,000, including 227.00/100,000 males and 108.07/100,000 females. The worldwide standardized mortality rate was 162.39/100,000, including 228.52/100,000 males and 109.30/100,000 females. Conclusions: The mortality of upper gastrointestinal cancer displayed a decreasing trend, but it still had the highest mortality rate of malignant tumors in Cixian County. Age-specific mortalities were increasing along with the rise of age.

Adapting liposomes for oral drug delivery

Liposomes mimic natural cell membranes and have long been investigated as drug carriers due to excellent entrapment capacity, biocompatibility and safety. Despite the success of parenteral liposomes, oral delivery of liposomes is impeded by various barriers such as instability in the gastrointestinal tract, difficulties in crossing biomembranes, and mass production problems. By modulating the compositions of the lipid bilayers and adding polymers or ligands, both the stability and permeability of liposomes can be greatly improved for oral drug delivery. This review provides an overview of the challenges and current approaches toward the oral delivery of liposomes.

MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate

Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1 PBD was confirmed using fluorescence polarization and microscale thermophoresis. This compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cells revealed that MCC1019 induced cell growth inhibition through inactivation of AKT signaling pathway, it also induced prolonged mitotic arrest-a phenomenon known as mitotic catastrophe, which is followed by immediate cell death apoptosis and necroptosis. MCC1019 significantly inhibited tumor growth in a murine lung cancer model without affecting body weight or vital organ size, and reduced the growth of metastatic lesions in the lung. We propose MCC1019 as promising anti-cancer drug candidate.