Objective To construct a regulatory network of competing endogenous RNA(ceRNA)with prognostic value for bladder urothelial carcinoma(BLCA),and analyze the relationship between key messenger RNA(mRNA)and immune function.Methods The UCSC Xena database was used to download mRNA expression data from 404 BLCA patients and 28 normal individuals and key mRNAs were screened by differential analysis.ENCORI database was utilized to search microRNAs(miRNAs)that bind to key mRNAs and all long non-coding RNAs(LncRNAs)that bind to miRNAs.The expression data of miRNA and LncRNA were downloaded from TCGA database,co-expression analysis was performed to identify key mRNA with all miRNAs and miRNA with all LncRNAs,and thus key miRNAs and LncRNAs were screened out.Survival analysis was conducted based on the differences in expression levels of these key mRNAs,miRNAs,and LncRNAs between tumor patients and normal individuals,and finally a ceRNA regulatory network was constructed.The correlation between key mRNAs and immune cells,immune checkpoints(CD274,PDCD1 and CTLA4),and immune cell marker genes(IG)was analyzed using the TIMER 2.0 database.Results A total of 22 key mRNAs were screened,with the most significant difference being proline 3-hydroxylase 4(P3H4).The expression of P3H4 in patients with BLCA was high,and survival time was shorter in patients with high expression.A sum of 33 miRNAs and 14 LncRNAs were screened using the key mRNAs as the central link.Through co-expression analysis and survival analysis,hsa-miR-151a-3p and MIR100 HG were identified as the key miRNA and key LncRNA with prognostic value.The differences in the above analysis results were statistically significant(all P＜0.05).Based on these findings,a ceRNA regulatory network consisting of 1 mRNA,1 miRNA,and 1 LncRNA was constructed.Immunoassay firstly revealed a significant positive correlation between double positive T cells and P3H4 expression in the tumor microenvironment of BLCA.Moreover,there were 3 types of immune cells(tumor-associated neutrophils,and tumor-associated macrophages,dendritic cells),3 immune checkpoints(CD274,PDCD1,CTLA4),and 15 IGs with significant correlation with P3H4.These differences were statistically significant(all P＜0.01).Conclusion This study could help to reveal the progression mechanism of BLCA.The constructed ceRNA network and immune analysis can offer new insights into potential biological targets and immunotherapy directions for the diagnosis,treatment,and prediction of BLCA patients.

Background: Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. Methods: Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. Results: Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. Conclusions Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

Tracing the contacts exposed to high risk behaviors of HIV-infected patients can facilitate the diagnosis and discovery of HIV positive individuals for timely treatment and intervention to reduce secondary transmission, which is of great importance for the control of AIDS epidemic. With the development of HIV gene sequence detection and analysis technology, the application of HIV molecular transmission network in traditional contact tracing based on epidemiological investigation can contribute to the accurate reveal of HIV transmission mode, clarification of HIV transmission characteristics and identification of the population at high risk for HIV infection to provide evidence-based insights for the accurate prevention and control of AIDS. This paper summarized the progress in the research of tracing the contacts exposed to high risk behaviors of HIV-infected patients to provide reference for the AIDS prevention and control in the future.

Objective:To estimate the longitudinal association between serum lipid biomarkers and the development of cardiometabolic multimorbidity (CMM) in middle-aged and old adults (≥45) in China, while examining effect differences among degree of dyslipidemia aggregation and various dyslipidemia combination patterns.Methods:Based on data from the China Health and Retirement Longitudinal Study (2011-2018), logistic regression analysis was used to evaluate the associations of TC, LDL-C, HDL-C, TG (4 forms of dyslipidemias), degree and pattern of dyslipidemia combination with CMM. We also used restricted cubic splines to show the dose-response associations between 4 lipid biomarkers and CMM development.Results:Of the 6 522 participants included, 590 (9.05%) developed CMM. After adjusting for covariates, all 4 forms of dyslipidemias were positively associated with CMM development (high TC: OR=1.33, 95% CI: 1.03-1.71; high LDL-C: OR=1.35, 95% CI: 1.05-1.75; low HDL-C: OR=1.45, 95% CI: 1.19-1.77; high TG: OR=1.50, 95% CI: 1.20-1.88). The U-shaped dose-response relationship between LDL-C and CMM development was observed ( P for non-linear =0.022). The odds of CMM increased with the increase of dyslipidemias forms, which was highest in those with ≥3 forms of dyslipidemias ( OR=2.02, 95% CI: 1.33-3.06). In various dyslipidemia form combinations, the possibility of CMM development was highest in those with high TC, high LDL-C and low HDL-C ( OR=3.54, 95% CI: 1.40-8.67). High TC and high LDL-C were significantly associated with CMM development in people without cardiometabolic diseases. Low HDL-C was positively associated with diabetes and CMM development in participants without cardiometabolic diseases, cardiovascular disease (CVD) followed by diabetes, and diabetes followed by CVD. High TG was positively associated with diabetes and CMM in participants without cardiometabolic diseases, and diabetes followed by CVD. Conclusions:A total of 4 forms of dyslipidemia were all independently associated with CMM development in middle-aged and old adults in China. The dose-response relationship between LDL-C level and CMM development was U-shaped. The aggregation of 4 forms of dyslipidemia were associated with the development of CMM. Low HDL-C and high TG were significantly associated with multiple patterns of cardiometabolic diseases development.

Objective To evaluate the therapeutic effect of poloxamer hydrogel loaded with exosomes derived from human dental pulp stem cells genetically modified with human hepatocyte growth factor against radiation skin injuries.Methods Human dental pulp stem cells derived exosomes(DPSC-Exo)and hepatocyte growth factor modified DPSC-Exo(HGF-DPSC-Exo)were extracted via ultracentrifugation separation,identified in terms of particle size and morphology,and analyzed separately by means of nanoparticle tracking analysis and scanning electron microscopy(SEM),while exosome marker proteins were determined by Western blot.Then,the effect of exosomes on radiation-damaged skin cells was assessed.The poloxamer hydrogel was prepared and its safety was evaluated with CCK-8.A mouse model of injury combined with radiation injury was established,and the therapeutic effect of hydrogel loaded with exosomes was determined based on wound size,HE and Masson staining.Furthermore,the underlining therapeutic mechanism was explored with Tunnel assay,malondialdehyde content and peroxidase activity.Results The diameter exosomes ranged from 30 to 150 nm and their morphology was a disc-shaped vesicle under SEM.Moreover,CD9,CD63 and TSG101 were expressed.The results of cellular experiments showed that exosomes significantly promoted the proliferation and migration of radiation-damaged skin keratinocytes and fibroblasts,and reduced their apoptosis.HGF modification enhanced the healing effect of exosomes.Poloxamer hydrogel showed good temperature-sensitive properties and biocompatibility.The results of animal experiments showed that exosomes significantly accelerated the healing of radiation-combined injuries in mice,inhibited inflammatory infiltration and mitigated collagen deposition in the wound.Interestingly,the healing effect in the group treated with hydrogel loaded with exosomes was the best.The underlining mechanism was possibly related to promotion of cell proliferation and inhibition of apoptosis and oxidative stress.Conclusion A novel poloxamer hydrogel loaded HGF-DPSC-Exo has been prepared and its therapeutic effect against radiation combined injury has been proved,thus providing a new strategy for the treatment of radiation skin injury in clinic.

With the rapidly increase of HIV infections in the elderly in China, new challenges have emerged in HIV/AIDS prevention and control. Low awareness of HIV and common unprotected casual sex and commercial sex has made older people at higher risk for HIV infection. In addition, HIV-infected and higher risk elderly people have limited awareness of HIV-related knowledge and access to testing services due to low educational level and socioeconomic status. Furthermore, HIV-infected elderly people usually have elevated risk of death because of late detection and comorbidities of chronic diseases. More research should be made to further understand the behavioural characteristics and social, cultural and psychological determinants of the elderly, development and adoption of HIV prevention service strategy catering for the elderly's need, and strengthening whole-process comprehensive health management of elderly infected people.

Objective:To understand the epidemiological characteristics and changing trends of HIV-infected patients aged ≥60 years reported in recent years in China and provide reference for the development of HIV prevention and control strategies for the elderly.Methods:The data of newly reported HIV-infected patients aged ≥60 years between 2015 and 2022 were obtained from China Information System for Disease Control and Prevention. The differences in epidemiological characteristics of HIV infections among groups were compared by using t test and Kruskal-Wallis H nonparametric test in software SPSS 24.0. Software Joinpoint 4.9.0 was used to calculate annual percent change (APC) and trend analysis was conducted by using Joinpoint regression model. Software Excel 2019 was used for graph drawing. Results:The number of reported HIV-infected patients aged ≥60 years in China increased from 17 451 in 2015 to 27 004 in 2022, with newly diagnosed rate rising from 9.0/100 000 to 10.2/100 000. The newly diagnosed rate in men was higher than that in women. Trend analysis demonstrated that the newly diagnosed rate in both elderly men and women peaked in 2019 (APC for men=13.5%, P=0.003; APC for women=15.0%, P=0.002), and showed a downward trend after 2019 (APC for men=-12.4%, P=0.006; APC for women=-13.0%, P=0.007). Among the elderly infected men, those infected by heterosexual and homosexual transmission accounted for 93.5% (160 747/171 924) and 5.1% (8 781/171 924), respectively. Among the elderly infected women, those infected by heterosexual transmission accounted for 98.4% (48 899/49 697). The infected elder people diagnosed by medical institutions accounted for 71.5% (158 394/221 621), whose baseline CD4 +T lymphocytes level was lower than that in those diagnosed by other ways ( H=1 079.82, P<0.001). Conclusions:The poor risk awareness and high-risk sexual behavior made the elderly at higher risk for HIV infection. More efforts should be made to improve active surveillance, timely detection and origin-tracing for infected elderly for the accurate and effective prevention and control of HIV infection.

Objective:To analyze the basic characteristics and change trend of mortality in HIV-infected patients aged ≥60 years in China from 2013 to 2021.Methods:The data of HIV-infected patients aged ≥60 years at diagnosis were collected from China Information System for Disease Control and Prevention to calculate the mortality density. The trajectory model was fitted using the Proc traj process in software SAS 9.4 to explore trajectory of AIDS-related mortality density and non-AIDS-related mortality density under different combinations of region, gender and age.Results:Between 2013 and 2021, a total of 244 770 HIV-infected patients were reported with 40 079 AIDS-related deaths and 50 245 non-AIDS-related deaths. The AIDS-related mortality density was 6.32 per 100 person-years, and the non-AIDS-related mortality density was 7.92 per 100 person-years, both of which showed decreasing trends over the years, and the mortality density in men was higher than that in women. Two developmental trajectories could be categorized for different trends of AIDS-related mortality density: the lower mortality density group accounted for 80.95% and showed a slow decreasing trend; the higher mortality density group accounted for 19.05% and showed a three-curve developmental trend. There were three developmental trajectories of non-AIDS-related mortality density trends: the lower mortality density group accounted for 59.52% and the medium mortality density group accounted for 28.57%, with a flat overall trend in these two groups; the higher mortality density group accounted for 11.91% with a three-curve trend.Conclusions:The mortality in HIV-infected patients aged ≥60 years in China is still high. Further attention should be paid to the early detection, diagnosis and treatment of HIV infection to effectively reduce the density of AIDS-related deaths. At the same time, attention should be paid to non-AIDS-related deaths in the elderly, and comprehensive interventions should be taken. It is necessary to conduct targeted HIV/AIDS prevention and control based on actual situation in different areas and populations

Objective:To understand the epidemiological characteristics of HIV-infected farmers aged ≥60 years in China and provide evidence for the development of AIDS prevention and control policies for elderly farmers.Methods:Data of newly HIV-infected farmers aged ≥60 years reported between 2018 and 2022 were obtained from China Information System for Disease Control and Prevention. The differences in epidemiological characteristics of HIV infection between farmers and other populations were compared using χ2 test. Based on 6 representative indicators, 31 provinces were divided into three sub-epidemic areas of A, B, and C by using sample system clustering method in SPSS 24.0 software. Results:From 2018 to 2022, a total of 113 311 HIV infection cases in farmers aged ≥60 years were reported, accounting for 71.8% of the reported cases in this age group nationwide (113 311/157 792). In the 113 311 HIV infection cases, 86 517 (76.4%) were men, 80 176 (70.8%) were diagnosed by medical institutions, 80 667 (71.2%) were distributed in the western region and 92 191 (81.4%) had education level of primary school or below [higher than the proportion in other populations (49.8%, 22 165/44 481)]. In 113 311 HIV infection cases, 96.7%(109 562/113 311) were infected through heterosexual transmission, in whom 50.4% (55 184/109 562) had commercial heterosexual behavior, 9.1%(9 958/109 562) had fixed sexual partners, 40.5%(44 420/109 562) had other heterosexual behaviors. The clustering analysis indicated that in region A (Guangxi, Chongqing, Guizhou, Sichuan, Yunnan and Xinjiang), the proportions of people living with HIV (30.2/10 000), HIV-infected farmers aged ≥60 years in rural population (22.8/10 000), counties reported HIV-infected elderly farmers (93.4%), the population had HIV test (44.2%), were all higher than those in region B and C. Compared with region B and C, The net income of farmers (10 000 yuan) was lower in region A, and the proportion of commercial heterosexual behavior in male farmers in region A (41.0%) was slightly lower than that in region B (46.1%), but higher than that in region C (15.2%).Conclusions:HIV infections in farmers aged ≥60 years were mainly caused by heterosexual behaviors, such as commercial heterosexual sex, in China from 2018 to 2022. The low awareness of self-protection against AIDS and high-risk sexual behaviors are closely associated with HIV infection in elderly farmers. Attention should be paid to the behavior intervention and health education about AIDS prevention in elderly farmers and the prevention and intervention in rural female sex workers and HIV positive spouses should be strengthened.

Background The use of heating and ventilation air conditioning (HVAC) in public places is conducive to improving indoor air quality and increasing the users comfort level. However, HVAC may also become potential carriers of indoor airborne microbial contamination. Objective To understand the characteristics of microbial pollution and distribution of related pathogenic microorganisms in HVAC of star-rated hotels, and to provide a basis for effective control of such pollution. Methods According to the requirements of the Hygienic specification of central air conditioning ventilation system in public buildings (WS 394-2012), two sets of HVAC in two star-rated hotels (A and B, inaugurated in 2002 and 1998, respectively) in the central area of Shanghai were randomly selected on September 9, 2020 for the hygienic evaluation of microorganisms in the air supply and respirable particulate matter (PM₁₀) in the air supply, dust accumulation and microorganisms on the inner surface of the ducts, as well as Legionella pneumophila in cooling water and condensate water. At the same time, 3 samples from the inner surface of ducts, 1 sample from the surface of the filter, 1 sample from the condensate, and 1 sample from the cooling water were collected from each set of HVAC, a total of 12 sample from 2 sets of HVAC, for Illumina HiSeq metagenomic sequencing，and the samples are divided into 3 groups according to their types: duct group, filter group, and water sample group. The α-diversity indices (Shannon index, Simpson index, Chao1 index, ACE index, and goods_coverage index) were calculated to reflect the microbial community composition; and the β-diversity of the three groups were studied by principal component analysis to determine the similarity of the microbial communities. Results The maximum total number of bacteria and fungi in the air supply of the HVAC were 1158 CFU·m⁻³ and 344 CFU·m⁻³ for Hotel A respectively; and 2000 CFU·m⁻³ and 532 CFU·m⁻³ for Botel B respectively. β-hemolytic streptococci were negative in all samples; the respirable particulate matter, microorganisms and dust accumulation on the inner surface of air ducts, Legionella pneumophila IN cooling water and condensate samples all met the standards. The results of Illumina HiSeq sequencing showed that a total of 17322 microorganisms were reported in the 12 samples, with bacterial microbiota accounting for 97.31% of the classified genes and the remaining 2.69% were from fungi, viruses, and parasites. At the species level, Staphylococcus epidermidis, Pseudomonas, Alternaria, and Malassezia were the dominant microbial taxa measured in this survey. The results of α-diversity analysis showed that the values of Shannon index, Simpson index, and Chao1 index for the three groups of samples were duct > filter > water sample. The goods coverage indices of all sample groups s were close to 1. The principal component analysis showed that the contributions of two principal components were 19.27% and 14.25%, respectively, in which the samples of the filter and duct groups were better clustered into one category. Conclusion The overall hygiene conditions of the two hotels are good, except for the serious microbial contamination in the air supply of HVAC. Metagenomic sequencing reveals complex microbial communities of HVAC, including bacteria, fungi, viruses, and parasites. The species composition vary by sample groups, particularly the species compositions of the samples from filters and ducts are close and dominated by pathogenic microorganisms of human origin, suggesting that the potential biosafety hazards of HVAC should not be ignored.