Cell membrane camouflaged nanoparticles have been widely used in the field of drug leads discovery attribute to their unique biointerface targeting function. However, random orientation of cell membrane coating does not guarantee effective and appropriate binding of drugs to specific sites, especially when applied to intracellular regions of transmembrane proteins. Bioorthogonal reactions have been rapidly developed as a specific and reliable method for cell membrane functionalization without disturbing living biosystem. Herein, inside-out cell membrane camouflaged magnetic nanoparticles (IOCMMNPs) were accurately constructed via bioorthogonal reactions to screen small molecule inhibitors targeting intracellular tyrosine kinase domain of vascular endothelial growth factor recptor-2. Azide functionalized cell membrane acted as a platform for specific covalently coupling with alkynyl functionalized magnetic Fe₃O₄ nanoparticles to prepare IOCMMNPs. The inside-out orientation of cell membrane was successfully verified by immunogold staining and sialic acid quantification assay. Ultimately, two compounds, senkyunolide A and ligustilidel, were successfully captured, and their potential antiproliferative activities were further testified by pharmacological experiments. It is anticipated that the proposed inside-out cell membrane coating strategy endows tremendous versatility for engineering cell membrane camouflaged nanoparticles and promotes the development of drug leads discovery platforms.

Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.
Humans ; Atherosclerosis/genetics* ; Autophagy/genetics* ; Cell Cycle Proteins/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; MicroRNAs/metabolism* ; Repressor Proteins/metabolism* ; RNA Splicing Factors ; Serine-Arginine Splicing Factors/genetics* ; RNA, Long Noncoding/metabolism*

AIM: To investigate the distribution characteristics of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and its correlation with blood Hcy in hypertensive patients and to provide reference for the prevention and treatment of H-type hypertension in southern Anhui Province. METHODS: A total of 657 hypertensive patients were treated in our hospital from October 2019 to August 2020 were selected as the research objects. The MTHFR C677T and A1298C loci were genotyped by fluorescence staining in situ hybridization, and the blood Hcy concentration was determined by the enzyme cycle method. The distribution characteristics of MTHFR gene in the Han nationality hypertensive population in southern Anhui Province were analyzed, and compared with the reported MTHFR gene distribution data of hypertensive populations in other regions and ethnic groups. RESULTS: Among the 657 patients, the distributions of CC, CT and TT types at the C677T site of MTHFR gene were 212(32.27%), 321 (48.86%), 124(18.87%), and the distribution of AA, AC, and TT types at the A1298C site were 467 (71.08%), 171(26.03%), 19(2.89%). There was no gender difference in the distribution of the two loci of this gene in the hypertensive population in southern Anhui Province (P > 0.05). The distribution frequency of CC genotype at C677T locus is lower than that in Foshan and Guangxi, but higher than that in Henan, Xinjiang and Inner Mongolia; the frequency of CT genotype is higher than that in Foshan and Guangxi; the frequency of TT genotype is higher than that in Foshan and Guangxi. Guangxi region was lower than Henan region, Xinjiang region and Inner Mongolia region, and the difference was statistically significant (P < 0.05). The mean blood Hcy of 657 patients was (15.8 ± 7.80) μmol/L, of which 510(77.62%) were in line with the diagnosis of H-type hypertension. The level of Hcy in males was significantly higher than that in females, and the difference was statistically significant (P < 0.000 1). Compared with the different genotypes of the C677T locus, the TT type was higher than the CT type and CC type, and the difference was statistically significant (P < 0.05). There was no significant difference in Hcy levels between different genotypes at the A1298C locus (P > 0.05). CONCLUSION: The distribution of MTHFR gene polymorphism in the Han nationality hypertensive population in southern Anhui is significantly different from other regions, and it is also significantly related to the level of Hcy, which has obvious regional characteristics. The genetic detection technology combined with the determination of Hcy concentration can provide a scientific basis for the prevention and treatment of H-type hypertension in southern Anhui Province.

Objective: To explore the effect of melatonin(MLT) on human umbilical vein endothelial cell(HUVEC) injury induced by high glucose and to explore its probable molecular mechanism. Methods: HUVEC were cultured and divided into three groups: control group, model group and treatment group. The control group(Ctrl group) was treated with DMEM medium at a normal low glucose level(5.5 mmol/L glucose), and the model group(HG group) was treated with DMEM medium at a high glucose level(30 mmol/L glucose). Treatment group(HG+MLT group) was treated with DMEM medium at a high glucose level containing 100 μmol/L melatonin. The method of MTT was used to detect the effects of high glucose and melatonin on HUVEC proliferation. The release of lactate dehydrogenase(LDH) in cell culture supernatant was determined. The production of reactive oxygen species(ROS) was detected by flow cytometry. Hoechst 33342/PI double-staining was used to detect cell apoptosis and necrosis. Western blot was used to detect the effects of high glucose and melatonin on endoplasmic reticulum stress and cell pyroptosis related protein expression in HUVEC. Results: Compared with the control group, cell proliferation level of the model group decreased, LDH releasing in cell culture supernatant increased, ROS production increased, the blue and red fluorescence increased in the double-staining, the expressions of GRP78, ATF4, CHOP, IRE1α, PERK, ATF6α, NLRP3, cleaved caspase-1, IL-1β increased. Compared with model group, cell proliferation level of the treatment group increased, LDH releasing in cell culture supernatant decreased, ROS production decreased, the blue and red fluorescence decreased in the double-staining, the expressions of GRP78, ATF4, CHOP, IRE1α, PERK, ATF6α, NLRP3, cleaved caspase-1, IL-1β decreased. Conclusion MLT can alleviate HUVEC damage induced by high glucose, and the probable mechanism may be related to the regulation of endoplasmic reticulum stress and cell pyroptosis.

Objective:To evaluate 5-years breast cancer-specific survival (CCS) by age, and the relationship of age at diagnosis and the risk of breast cancer mortality.Methods:Medical records of 3 470 resident patients diagnosed with primary, invasive female breast cancer between January 1, 2006 and December 31, 2010 in four hospitals in Beijing were reviewed and collected. All patients were followed up until December 31, 2018 to acquire survival outcome. Five-years breast CCS of the five subgroups was estimated by the life-table method. Cox proportional hazard regression models were used to estimate hazard ratios ( HRs) and 95% confidence intervals (CIs) of different levels of age stratification and breast cancer mortality, and restricted cubic spline (RCS) model was used to detect the dose-response relationship. Results:The median diagnosis age among 3 470 female breast cancer patients was 53.2 years. There were 1 289 patients in the age-group of 45~54 years, with the highest proportion of 37.15%. However, only 126 patients occurred in the age-group of less than 35 years, with the lowest proportion of 3.63%. A total of 528 (15.22%) patients died of breast cancer during the study period. Overall 5-year CCS was 90.72% (95% CI: 89.74%~91.70%), 88.68% (95% CI: 83.09%~94.27%) and 87.05% (95% CI: 84.27%~89.82%) for all of the patients, aged less than 35 years and those aged 65 years and older. Compared with patients with diagnosis age of 45~54 years, the multivariate-adjusted HRs for breast cancer mortality associated with patients in age-group of <35 years and those in the age-group of ≥65 years were 1.72 (95% CI: 1.06~2.81) and 1.89 (95% CI: 1.43~2.49), respectively. In addition, patients aged ≥65 years had significantly higher risk of breast cancer mortality in Luminal subtypes, with HR of 1.70 (95% CI: 1.17~2.46) for Luminal A breast cancer and HR of 3.84 (95% CI: 1.74~8.49) for Luminal B breast cancer. RCS analysis exhibited a non-linear ( "J-shaped" ) relationship between diagnosis age of female breast cancer and the risk of breast cancer mortality (nonlinear P<0.000 1). In addition, patients aged ≥65 years had significantly higher risk of breast cancer mortality in Luminal subtypes, with HR of 1.70 (95% CI: 1.17~2.46) for Luminal A breast cancer and HR of 3.84 (95% CI: 1.74~8.49) for Luminal B breast cancer. RCS analysis exhibited a non-linear ( "J-shaped" ) relationship between diagnosis age of female breast cancer and the risk of breast cancer mortality (nonlinear P<0.000 1). Conclusion:Age at diagnosis is an important prognostic factor for female breast cancer, with worse outcome for both young and old patients.

Objective:To evaluate 5-years breast cancer-specific survival (CCS) by age, and the relationship of age at diagnosis and the risk of breast cancer mortality.Methods:Medical records of 3 470 resident patients diagnosed with primary, invasive female breast cancer between January 1, 2006 and December 31, 2010 in four hospitals in Beijing were reviewed and collected. All patients were followed up until December 31, 2018 to acquire survival outcome. Five-years breast CCS of the five subgroups was estimated by the life-table method. Cox proportional hazard regression models were used to estimate hazard ratios ( HRs) and 95% confidence intervals (CIs) of different levels of age stratification and breast cancer mortality, and restricted cubic spline (RCS) model was used to detect the dose-response relationship. Results:The median diagnosis age among 3 470 female breast cancer patients was 53.2 years. There were 1 289 patients in the age-group of 45~54 years, with the highest proportion of 37.15%. However, only 126 patients occurred in the age-group of less than 35 years, with the lowest proportion of 3.63%. A total of 528 (15.22%) patients died of breast cancer during the study period. Overall 5-year CCS was 90.72% (95% CI: 89.74%~91.70%), 88.68% (95% CI: 83.09%~94.27%) and 87.05% (95% CI: 84.27%~89.82%) for all of the patients, aged less than 35 years and those aged 65 years and older. Compared with patients with diagnosis age of 45~54 years, the multivariate-adjusted HRs for breast cancer mortality associated with patients in age-group of <35 years and those in the age-group of ≥65 years were 1.72 (95% CI: 1.06~2.81) and 1.89 (95% CI: 1.43~2.49), respectively. In addition, patients aged ≥65 years had significantly higher risk of breast cancer mortality in Luminal subtypes, with HR of 1.70 (95% CI: 1.17~2.46) for Luminal A breast cancer and HR of 3.84 (95% CI: 1.74~8.49) for Luminal B breast cancer. RCS analysis exhibited a non-linear ( "J-shaped" ) relationship between diagnosis age of female breast cancer and the risk of breast cancer mortality (nonlinear P<0.000 1). In addition, patients aged ≥65 years had significantly higher risk of breast cancer mortality in Luminal subtypes, with HR of 1.70 (95% CI: 1.17~2.46) for Luminal A breast cancer and HR of 3.84 (95% CI: 1.74~8.49) for Luminal B breast cancer. RCS analysis exhibited a non-linear ( "J-shaped" ) relationship between diagnosis age of female breast cancer and the risk of breast cancer mortality (nonlinear P<0.000 1). Conclusion:Age at diagnosis is an important prognostic factor for female breast cancer, with worse outcome for both young and old patients.

Objective: To understand the consciousness of the cancer early treatment and its demographic and socioeconomic factors. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China (CanSPUC) from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The questionnaire collected personal information, the consciousness of the cancer early treatment and relevant factors. The Chi square test was used to compare the difference between the consciousness of the cancer early treatment and relevant factors among the four groups. The logistic regression model was used to analyze the influencing factors related to the consciousness of the cancer early treatment. Results: With the assumption of being diagnosed as precancer or cancer, 89.97% of community residents, 91.84% of cancer risk assessment/screening population, 93.00% of cancer patients and 91.52% of occupational population would accept active treatments (P<0.001). If the immediate family members were diagnosed as precancer or cancer, people who would encourage their family members to receive early treatment in the four groups accounted for 91.96%, 91.94%, 92.44% and 91.55%, respectively (P<0.001). The company employees, annual household income with 40 000 yuan and more and other three groups had a relatively better consciousness of the cancer early treatment (P<0.05). Male, widowed, unemployed and from the central and western regions had a relatively worse consciousness of the cancer early treatment (P<0.05). Conclusion Residents in urban China participants had a good consciousness of the cancer early treatment. The marital status, occupation, annual household income and residential regions were major factors related to the consciousness of the cancer early treatment.

With the increasing number of immunocompromised hosts, the epidemiological characteristics of fungal infections have undergone enormous changes worldwide, including in China. In this paper, we reviewed the existing data on mycosis across China to summarize available epidemiological profiles. We found that the general incidence of superficial fungal infections in China has been stable, but the incidence of tinea capitis has decreased and the transmission route has changed. By contrast, the overall incidence of invasive fungal infections has continued to rise. The occurrence of candidemia caused by Candida species other than C. albicans and including some uncommon Candida species has increased recently in China. Infections caused by Aspergillus have also propagated in recent years, particularly with the emergence of azole-resistant Aspergillus fumigatus. An increasing trend of cryptococcosis has been noted in China, with Cryptococcus neoformans var. grubii ST 5 genotype isolates as the predominant pathogen. Retrospective studies have suggested that the epidemiological characteristics of Pneumocystis pneumonia in China may be similar to those in other developing countries. Endemic fungal infections, such as sporotrichosis in Northeastern China, must arouse research, diagnostic, and treatment vigilance. Currently, the epidemiological data on mycosis in China are variable and fragmentary. Thus, a nationwide epidemiological research on fungal infections in China is an important need for improving the country's health.
Animals ; China ; epidemiology ; Fungi ; genetics ; pathogenicity ; Genotype ; Humans ; Incidence ; Mycoses ; epidemiology ; transmission

Objective: To evaluate the incidence and mortality status of thyroid cancer in China, 2013. Methods: Incidence and mortality data of thyroid cancer were derived from 255 population-based cancer registries in China. Age-specific and age standardized incidence and mortality rates of thyroid cancer in different areas (urban and rural) with different gender were calculated based on the stratification of area (urban and rural), gender, age and tumor position. Chinese census in 2000 and the world Segi′s population were used for age-standardized incidence/mortality rates. The incident cases and deaths were estimated using age-specific rates and national population data in 2013. Results: The estimates of new cancer incident cases and deaths were 143.9 thousand and 6 500, respectively. The crude incidence rate was 10.58/100 000 (Male 5.12/100 000, Female 16.32/100 000). Age-standardized incidence rates by Chinese standard population (ASIRC, 2000) and by world standard population (ASIRW) were 8.82/100 000 and 7.67/100 000, respectively. Male to female ratio was 1∶3.2. The crude incidence rate in urban and rural areas were 15.03/100 000 and 5.41/100 000, respectively. After adjustment by China standard population, the rate in urban areas was 2.57 times higher than that of rural areas. The crude mortality rate of thyroid cancer was 0.48/100 000 (Male 0.33/100 000, Female 0.63/100 000). Age-standardized mortality rates by Chinese standard population (ASIRC, 2000) and by world standard population (ASIRW) were 0.33/100 000 and 0.32/100 000, respectively. The crude mortality rate in urban and rural areas were 0.57/100 000 and 0.38/100 000, respectively. After adjustment by China standard population, the rate in urban areas was 1.41 times higher than that of rural areas. The cumulative incidence and mortality rates (0-74 years old) were 0.74% and 0.03%, respectively. According to the data from 255 cancer registries, papillary carcinoma is the main pathology type, which accounted for 89.9% of all malignant tumors. Conclusions The disease burden of thyroid cancer in urban areas is higher than that in rural areas. Females have the higher incidence rate than that of males. The reasons related to the higher incidence rate of thyroid cancer should be further investigated to provide evidence for appropriate cancer control strategies and policies to be made in China.

BACKGROUND:The auditory ossicle chain reconstruction is stil an important method to treat conductive deafness. Although a great variety of materials have been applied, the blood supply of otosteon after the implantation is ignored. Moreover, there is no real bone formed.
OBJECTIVE:To observe the angiogenesis of vascular endothelial growth factor and col agen I modifiedβ-tricalcium phosphate porous scaffold which is implanted into the otocyst of guinea pig.
METHODS:Total y 60 guinea pigs were randomly divided into experimental group (vascular endothelial growth factor and col agen I modifiedβ-tricalcium phosphate porous scaffold), col agen I control group (col agen I modifiedβ-tricalcium phosphate porous scaffold) and blank control group (β-tricalcium phosphate porous scaffold). The guinea pigs were executed under anesthesia at weeks 1, 2, 3, 4 respectively. The surface of scaffolds was observed by scanning electron microscopy. The angiogenesis of scaffolds were observed by hematoxylin-eosin staining and CD34 immunohistochemistry staining, and then the microvascular density was counted. The osteogenesis of the scaffolds was observed by toluidine blue staining.
RESULTS AND CONCLUSION:Endothelial cel proliferation and lumen formation could be observed after 1 week in the experimental group, and the angiogenesis reach the peak after 3 weeks with traffic branches formedbetween micropores. In the other two groups, the lumen formed at 2 weeks but no traffic branches were visible. The sprouting of new blood vessels in the pores were observed more in the experimental group than the other two groups (P<0.05). The adherence and proliferation of cel s could be examined in the surface and pores of the scaffold by scanning electron microscope. After 4 weeks, the osteogenesis could be observed by toluidine blue staining, especial y in the experimental group. These findings suggest that the vascular endothelial growth factor and col agen I modifiedβ-tricalcium phosphate porous scaffold can realize an effective vascularization in the environment of guinea pigs’ middle ear. What’s more, the scaffold also can promote bone formation.