[Purpose]To analyze the disease burden of malignant tumors and its changing trends in Chinese and global non-smoking female population from 1990 to 2021.[Methods]Data of mortality and disability-adjusted life year(DALY)due to malignant tumors for Chinese and global non-smoking female malignant tumors from 1990 to 2021 were extracted from the Global Burden of Disease Study 2021(GBD 2021),and the average annual percentage change(AAPC)were calculated using Joinpoint regression model.[Results]From 1990 to 2021,the number of deaths for malignant tu-mors in Chinese non-smoking female population increased from 13.7 1×104 to 26.8 1×104,with a higher increased trend compared with the global(China:AAPC=2.19％,95％CI:2.06％～2.33％;Global:AAPC=1.92％,95％CI:1.80％～2.04％,P=0.003);the age-standardized mortality rate decreased from 32.42/105 to 24.58/105,with a higher decreased trend compared with the global(China:AAPC=-0.88％,95％CI:-1.00％～-0.76％;Global:AAPC=-0.59％,95％CI:-0.68％～-0.51％,P＜0.001).From 1990 to 2021,the DALY for malignant tumors in Chinese non-smoking female population increased from 412.96×104 to 691.20×104 person-years,with a similar changing trend compared with the global(China:AAPC=1.68％,95％CI:1.56％～1.81％,Global:AAPC=1.63％,95％CI:1.52％～1.75％,P=0.536);the age-standardized DALY rate in Chinese non-smoking female population decreased from 889.58/105 to 642.65/105,with a higher decreased trend compared with the global(China:AAPC=-1.04％,95％CI:-1.15％～-0.92％;Global:AAPC=-0.69％,95％CI:-0.78％～-0.61％,P＜0.001).The top five malignant tumors of high age-standardized mor-tality rate in Chinese non-smoking female population in 2021 were tracheal,bronchus and lung cancer,colon and rectum cancer,cervical cancer,breast cancer,and liver cancer.The top five malignant tumors of high age-standardized mortality rate globally in 2021 were cervical cancer,colon and rectum cancer,breast cancer,tracheal,bronchus and lung cancer,and pancreatic cancer.The age-standardized mortality rate and DALY rate of breast cancer,liver cancer,pan-creatic cancer and corpus cancer showed overall upward trends(all P＜0.05).[Conclusion]From 1990 to 2021,the number of deaths and DALY of malignant tumors in Chinese and global non-smoking female population showed overall increased trends,and age-standardized mortality rate and DALY rate showed overall decreased trends.In future,more targeted cancer prevention measures are needed to reduce the disease burden of malignant tumors in non-smoking female population.

Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.

[Purpose]To analyze the disease burden of malignant tumors and its changing trends in Chinese and global non-smoking female population from 1990 to 2021.[Methods]Data of mortality and disability-adjusted life year(DALY)due to malignant tumors for Chinese and global non-smoking female malignant tumors from 1990 to 2021 were extracted from the Global Burden of Disease Study 2021(GBD 2021),and the average annual percentage change(AAPC)were calculated using Joinpoint regression model.[Results]From 1990 to 2021,the number of deaths for malignant tu-mors in Chinese non-smoking female population increased from 13.7 1×104 to 26.8 1×104,with a higher increased trend compared with the global(China:AAPC=2.19％,95％CI:2.06％～2.33％;Global:AAPC=1.92％,95％CI:1.80％～2.04％,P=0.003);the age-standardized mortality rate decreased from 32.42/105 to 24.58/105,with a higher decreased trend compared with the global(China:AAPC=-0.88％,95％CI:-1.00％～-0.76％;Global:AAPC=-0.59％,95％CI:-0.68％～-0.51％,P＜0.001).From 1990 to 2021,the DALY for malignant tumors in Chinese non-smoking female population increased from 412.96×104 to 691.20×104 person-years,with a similar changing trend compared with the global(China:AAPC=1.68％,95％CI:1.56％～1.81％,Global:AAPC=1.63％,95％CI:1.52％～1.75％,P=0.536);the age-standardized DALY rate in Chinese non-smoking female population decreased from 889.58/105 to 642.65/105,with a higher decreased trend compared with the global(China:AAPC=-1.04％,95％CI:-1.15％～-0.92％;Global:AAPC=-0.69％,95％CI:-0.78％～-0.61％,P＜0.001).The top five malignant tumors of high age-standardized mor-tality rate in Chinese non-smoking female population in 2021 were tracheal,bronchus and lung cancer,colon and rectum cancer,cervical cancer,breast cancer,and liver cancer.The top five malignant tumors of high age-standardized mortality rate globally in 2021 were cervical cancer,colon and rectum cancer,breast cancer,tracheal,bronchus and lung cancer,and pancreatic cancer.The age-standardized mortality rate and DALY rate of breast cancer,liver cancer,pan-creatic cancer and corpus cancer showed overall upward trends(all P＜0.05).[Conclusion]From 1990 to 2021,the number of deaths and DALY of malignant tumors in Chinese and global non-smoking female population showed overall increased trends,and age-standardized mortality rate and DALY rate showed overall decreased trends.In future,more targeted cancer prevention measures are needed to reduce the disease burden of malignant tumors in non-smoking female population.

Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.

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*

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.

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.