Objective: To analyze the infection characteristics of newly reported HIV/AIDS cases in Hangzhou City, so as to provide the reference for effective AIDS intervention. Methods: Newly reported HIV/AIDS cases in Hangzhou City in 2022 were recruited. Demographic information, HIV testing status, infection routes and sexual behaviors were collected using questionnaire surveys. Blood samples were collected before antiviral treatment, and HIV-1 pol gene sequences were detected to construct molecular transmission networks. The characteristics of HIV/AIDS cases, including infection routes, time, and location were analyzed. Factors affecting infection time and location among HIV/AIDS cases were analyzed using a multivariable logistic regression model. Results: A total of 1 007 HIV/AIDS cases were reported in Hangzhou City in 2022, with 907 cases (90.07%) completing questionnaire surveys. Among them, 833 were males (91.84%), and 532 had out-of-province household registrations (58.65%). Ninety-one molecular transmission networks were established, and 276 cases were involved, with homosexual contact as the main infection route (199 cases, 72.10%). There were 311 recently infected cases (35.34%) and 569 previously infected cases (64.66%) among 880 cases whose infection time could be determined. There were 531 locally infected. cases (70.24%) and 225 imported cases (29.76%) among 756 cases whose infection location could be determined. Multivariable logistic regression analysis showed that the HIV/AIDS cases who were identified through voluntary counseling and testing (OR=1.826, 95%CI: 1.055-3.175) and sought sexual partners through homosexual dating apps (OR=2.461, 95%CI: 1.193-5.234) were more likely to be recently infected; the cases who lived in Hangzhou City for more than one year (>1 to 5 years, OR=2.853, 95%CI: 1.552-5.358; >5 years, OR=3.534, 95%CI: 1.382-9.804), sought sexual partners through entertainment venues (OR=3.449, 95%CI: 1.390-8.935), online/social apps (OR=2.416, 95%CI: 1.084-5.488) and homosexual dating apps (OR=3.734, 95%CI: 1.677-8.493) were more likely to be locally infected; student cases were more likely to be infected outside Hangzhou City (OR=0.115, 95%CI: 0.019-0.525). Conclusions The newly reported HIV/AIDS cases in Hangzhou City in 2022 were primarily infected through homosexual contact, previously and locally. Seeking sexual partners through homosexual dating apps is an important influencing factor for recent and local infections, highlighting the need for strengthening traceback investigations of related cases.

Objective:To analyze the survival status and death factors of confirmed HIV-infected patients in Hangzhou to provide a basis for the formulation of AIDS prevention and treatment strategies.Methods:A retrospective cohort study was conducted. The data were from the HIV/AIDS Comprehensive Response Information Management System of the Chinese Disease Control and Prevention Information System.Epidemiological characteristics of HIV-infected patients were comparied in Hangzhou City from 2004 to 2023 by using chi-square Test. The survival rate of HIV-infected patients in Hangzhou was calculated by the life table method, the survival curves of different subgroups were described by the Kaplan-Meier method, and the Cox proportional hazard regression model was used to analyze the influencing factors of death risk. The SPSS 26.0 software was used for statistical analysis.Results:Among the 9 457 subjects, the total follow-up time was 58 004.18 person-years, 494 patients died, fatality rate of all-cause cases was 0.85 per 100 person-years.The average survival time was 18.59 (95% CI:18.40-18.78) years. Malignant neoplasms and pneumocystis pneumonia were the first (14.37%,71/494) and second (10.73%, 53/494) causes of death, respectively. Death within 6 months after diagnosis accounted for 42.51% (210/494), and suicide accounted for 4.25% (21/494). Multivariate Cox regression analysis showed that compared with those who received antiviral treatment (ART) within 3 months of diagnosis, those who received ART outside 3 months and those who did not receive ART had a 1.65 (95% CI:1.25-2.19) and 20.68 (95% CI:15.80-27.06) times risk of death, respectively. The HIV-infected patients with high CD4 +T lymphocytes (CD4) counts for the first time had a lower risk of death. The risk of death of patients with baseline CD4 counts of 200-349 cells/μl, 350-499 cells/μl, and ≥500 cells/μl was 0.38 (95% CI:0.29-0.49), 0.26 (95% CI:0.19-0.36), 0.21 (95% CI:0.14-0.31) times higher than that of baseline CD4 counts <200 cells/μl, respectively. Conclusions:The overall survival of the HIV-infected patients was good in Hangzhou from 2004 to 2023. Early detection of HIV infection and timely mobilization to participate in ART was the key to improving the survival rate of patients. At the same time, given the suicide problem of HIV-infected patients, suicide surveillance and depression and anxiety screening of HIV-infected patients should be further strengthened, and targeted psychological intervention policies should be implemented.

Objective To evaluate the regulatory effect of Diwu Yanggan(DWYG)Decoction on lysoglycerophospholipids(Lyso-GPLs)in circulating exosomes in a mouse model of nonalcoholic fatty liver disease(NAFLD).Methods Circulating exosomes isolated from mouse serum by size exclusion chromatography were morphologically characterized using transmission electron microscope and examined for surface markers CD9,CD63 and TSG101 using Western blotting.Twenty-four male Kunming mice were randomized into 3 groups for normal feeding(control,n=8)or high-fat diet feeding for 1 week to induce NAFLD,after which the latter mice were given DWYG decoction(treatment group,n=8)or normal saline(model group,n=8)by gavage for 4 weeks.After the last treatment,blood samples were collected from the mice for testing serum TC,HDL-C,LDL-C,ALT and AST levels and isolating circulating exosomes.Using multivariate statistical analysis based on targeted metabolomics strategy,the potential biomarkers for Lyso-GPLs in the exosomes were screened.Results The isolated exosomes about 100 nm in size had a typical saucer-like structure with distinct double-layer membranes and a mean particle size of 137.5 nm and expressed the specific surface marker proteins CD9,CD63 and TSG101.The mouse models of NAFLD had significantly increased serum levels of TC,HDL-C,LDL-C and AST and lowered serum ALT level.A total of 43 Lyso-GPLs with significant reduction after DWYG Decoction treatment were identified in NAFLD mice.Conclusion DWYG Decoction can regulate Lyso-GPLs in circulating exosomes in NAFLD mice,which provides a new clue for studying the therapeutic mechanism of DWYG Decoction for liver disease.

Objective To evaluate the regulatory effect of Diwu Yanggan(DWYG)Decoction on lysoglycerophospholipids(Lyso-GPLs)in circulating exosomes in a mouse model of nonalcoholic fatty liver disease(NAFLD).Methods Circulating exosomes isolated from mouse serum by size exclusion chromatography were morphologically characterized using transmission electron microscope and examined for surface markers CD9,CD63 and TSG101 using Western blotting.Twenty-four male Kunming mice were randomized into 3 groups for normal feeding(control,n=8)or high-fat diet feeding for 1 week to induce NAFLD,after which the latter mice were given DWYG decoction(treatment group,n=8)or normal saline(model group,n=8)by gavage for 4 weeks.After the last treatment,blood samples were collected from the mice for testing serum TC,HDL-C,LDL-C,ALT and AST levels and isolating circulating exosomes.Using multivariate statistical analysis based on targeted metabolomics strategy,the potential biomarkers for Lyso-GPLs in the exosomes were screened.Results The isolated exosomes about 100 nm in size had a typical saucer-like structure with distinct double-layer membranes and a mean particle size of 137.5 nm and expressed the specific surface marker proteins CD9,CD63 and TSG101.The mouse models of NAFLD had significantly increased serum levels of TC,HDL-C,LDL-C and AST and lowered serum ALT level.A total of 43 Lyso-GPLs with significant reduction after DWYG Decoction treatment were identified in NAFLD mice.Conclusion DWYG Decoction can regulate Lyso-GPLs in circulating exosomes in NAFLD mice,which provides a new clue for studying the therapeutic mechanism of DWYG Decoction for liver disease.

MAGED4B belongs to the melanoma-associated antigen family; originally found in melanoma, it is expressed in various types of cancer, and is especially enriched in glioblastoma. However, the functional role and molecular mechanisms of MAGED4B in glioma are still unclear. In this study, we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue, and the level was positively correlated with glioma grade, tumor diameter, Ki-67 level, and patient age. The patients with higher levels had a worse prognosis than those with lower MAGED4B levels. In glioma cells, MAGED4B overexpression promoted proliferation, invasion, and migration, as well as decreasing apoptosis and the chemosensitivity to cisplatin and temozolomide. On the contrary, MAGED4B knockdown in glioma cells inhibited proliferation, invasion, and migration, as well as increasing apoptosis and the chemosensitivity to cisplatin and temozolomide. MAGED4B knockdown also inhibited the growth of gliomas implanted into the rat brain. The interaction between MAGED4B and tripartite motif-containing 27 (TRIM27) in glioma cells was detected by co-immunoprecipitation assay, which showed that MAGED4B was co-localized with TRIM27. In addition, MAGED4B overexpression down-regulated the TRIM27 protein level, and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine (MG132), an inhibitor of the proteasome. On the contrary, MAGED4B knockdown up-regulated the TRIM27 level. Furthermore, MAGED4B overexpression increased TRIM27 ubiquitination in the presence of MG132. Accordingly, MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7 (USP7) involved in the tumor necrosis factor-alpha (TNF-α)-induced apoptotic pathway. These findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-interacting serine/threonine-protein kinase 1 (RIP1)-dependent TNF-α-induced apoptotic pathway, which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.
Humans ; Tumor Necrosis Factor-alpha ; DNA-Binding Proteins/metabolism* ; Ubiquitin-Specific Peptidase 7 ; Cisplatin ; Temozolomide ; Transcription Factors ; Glioma ; Cell Proliferation ; Melanoma ; Cell Line, Tumor ; Apoptosis ; Nuclear Proteins/genetics*

Objective : To investigate the quality of life among people living with HIV/AIDS in Hangzhou City and analyze the influencing factors, so as to provide insights into the control of AIDS. Methods : From 1 January 2014 to 30 June 2018, the demographic characteristics, medical expenditures and disease status were collected from HIV/AIDS patients living in Hangzhou City, and the quality of life was assessed using the simplified Chinese version of Medical Outcomes Study-HIV Health Survey ( MOS-HIV ). Factors affecting the quality of life were identified among HIV/AIDS patients using multivariable linear regression analysis. Results : A total of 2 808 HIV/AIDS patients were surveyed, including 1 684 cases with HIV infections and 1 124 cases with AIDS. The participants included 2 510 men ( 89.39% ) and 298 women ( 10.61% ), and were predominantly at ages of 25 to 39 years ( 1 531 cases, 54.52% ). The physical and mental health scores were 53.87±6.96 and 46.03±9.09, respectively. Multivariable linear regression analysis identified age, average monthly income, self-paid medical expenses during the past year, and the latest CD4+T cell count as factors affecting physical and mental health ( P<0.05 ). Conclusions The quality of life is low among people living with HIV/AIDS in Hangzhou City, and is associated with age, income, medical expenditures and CD4+T cell count.

Objective : To investigate the HIV-1 molecular transmission network among school students with newly confirmed HIV/AIDS in Hangzhou City from 2020 to 2021, so as to provide insights into AIDS control in school. Methods : School students with newly confirmed HIV/AIDS in Hangzhou City from 2020 to 2021 were sampled, and participants' demographics and epidemiological survey data were retrieved from the HIV/AIDS Control Information System of Chinese Disease Prevention and Control Information System. The HIV-1 pol gene was amplified in participants' blood samples using reverse transcription (RT) and nested PCR assays, and the HIV subtypes were characterized through multiple sequence alignments. The gene sequences were aligned among newly confirmed HIV/AIDS patients in Hangzhou City during the same study period. The genetic distance was estimated using the software MEGA 11, and the molecular transmission network was created using the software Cytoscape 3.9.1 to analyze the characteristics of clustered cases in the network. Results: A total of 99 school students were newly confirmed with HIV/AIDS in Hangzhou City from 2020 to 2021, including 98 men (98.98%), and 94 men who had sex with men (94.94%). The HIV-1 pol gene sequence was successfully amplified from 87 cases, and four HIV-1 subtypes were characterized, including CRF07_BC (49 cases, 56.32%), CRF01_AE (27 cases, 31.03%), CRF55_01B (6 cases, 6.90%) and CRF67_01B (5 cases, 5.75%). There were 30 molecular clusters in 50 MSM, with 2 to 16 cases in each cluster, and 27 molecular clusters associated with non-student cases, and clustered cases were all MSM. Infection route, location of schools and current address of non-student cases were identified as factors affecting case clustering, and the residence of schools was an important area of activity among clustered HIV/AIDS cases. Conclusions CRF07_BC and CRF01_AE were predominant HIV-1 subtypes among school students with newly confirmed HIV/AIDS in Hangzhou City from 2020 to 2021, and the transmission of HIV/AIDS strongly correlated with non-student cases, with men-men sexual behaviors as the predominant transmission route. The interventions for of MSM is recommended to be reinforced to block the transmission of HIV/AIDS from community to schools.

The atmospheric particulate matter(PM) is widely regarded as one of major environmentally and unfriendly ambient air pollution, and therein PM2.5 (diameter≤2.5 μm) is most closely related to human health.Because of its smaller diameter with longer suspension duration, PM can absorb many pathogenic microorganisms, and easily enter into the deep of airway and then deposit on the bronchus and alveoli, and it brings damage to the lung tissues and the surfactant proteins.PM can give rise to oxidative stress, inflammation response, cells and DNA damage.Now, this review focuses on the characterization and composition of PM, as well as the impact of PM2.5 on the lung, surfactant proteins and human health, which helps to call for more people to pay attention to this environmental issue in order to better mitigate and prevent the damage caused by PM.

OBJECTIVEThe aim of this study was to clarify whether the fusion of bone marrow mesenchymal stem cells (MSCs) with tumor cells can promote tumor angiogensis.

METHODSHuman glioma stem/progenitor cells (GSPCs) (SU3 cells) were transfected with red fluorescent protein (RFP) gene. Bone marrow mesenchymal stem cells (MSCs) were harvested from nude mice with whole-body green fluorescent protein (GFP) gene expression. Then the two kinds of cells were co-cultured in vitro. At the same time SU3-RFP was transplanted into the brain of GFP-expressing nude mice to establish xenograft tumors. The co-cultured cells, GFP/RFP double positive (yellow) cells and blood vessels obtained from the xenograft tumors were observed under fluorescent microscope and laser scanning confocal microscope.

RESULTSAfter five passages in vitro, MSCs maintained the proliferative activity and highly expressed CD105. CD105 was also expressed in the femurs of GFP-expressing nude mice, tumor cells, blood vessels of SU3 xenograft tumors, and clinical malignant gliomas. When MSCs were co-cultured with SU3-RFP, the ratio of yellow cells co-expressing RFP and GFP was significantly increased after extended time and continuous passages. According to the flow cytometry, yellow cells co-expressing RFP and GFP were 83.7% of the cultured cells. In tissue slices of the xenograft tumors, bundles of yellow vessel-like structure and cross-sectioned yellow vascular wall structures including vascular wall stroma cells were observed with RFP and GFP expression, and were identified as de novo formed vessels derived from fusion of MSCs with SU3-RFP cells.

CONCLUSIONCell fusion occurs between tumor cells and host MSCs and it promotes tumor angiogenesis.

Animals ; Bone Marrow Cells ; physiology ; Cell Communication ; Cell Fusion ; Cells, Cultured ; Glioma ; Green Fluorescent Proteins ; Humans ; Luminescent Proteins ; Mesenchymal Stromal Cells ; Mice ; Mice, Nude ; Microscopy, Fluorescence ; Neoplasms ; Neovascularization, Pathologic ; Stem Cells ; Transfection ; Transplantation, Heterologous

Objective To establish a new congenic inbred mouse strain carrying and expressing EGFP and Foxn1nugene for cancer research including human glioma as well .Methods According to criterion of GB14923-2010, the male Foxn1nu nude mice backcross the female C57BL/6-Tg (CAG-EGFP) transgenic mice for 10 times, Then identify the phenotype using the methods and equipment as below: fluorescent flashlight and matching glasses; multifunction vivo imager; fluorescence microscopy.Results The congenic inbred mouse strain named Foxn1nu.B6-CAG-EGFP/SU ( Soochow University ) .All the 14 biochemical loci are homozygous and same with Balb/c mouse in addition to the Pep3 loci (“b” type instead of “a” type).Peripheral blood lymphocyte count shows the lymphocytes occupy 15%of nucleated cells;T lymphocytes occupy 0.3%, meet the requirement of inbred strain of EGFP nude mice .Conclusions Established a new congenic inbred strain -Foxn1nu.B6-CAG-EGFP/SU which both express EGFP stably, and own immunodeficiency with lack of T lymphocytes .The phenotype “b” of biochemical loci “Pep3” is the unique characteristic that distinguish SU to Foxn1nu.