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.

Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/immunology* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Small Cell Lung Carcinoma/genetics* ; Male ; Middle Aged ; Female

This study was aimed at predicting and analyzing the structural and functional properties of the persistence-associated secretory protein PaaX in Mycobacterium tuberculosis(M.tb),identifying its interacting partners,and elucidating its biological roles.Bioinformatics analysis revealed that PaaX comprises 240 amino acids with a molecular mass of 26.54 kDa(C1158H1866N354O334S14).The protein lacks transmembrane domains but contains a signal peptide.Its secondary structure is dominated by α-helices(53.33%),fol-lowed by random coils(36.25%)and extended strands(10.42%),thereby forming a homotetrameric spatial configuration.Potential PaaX-interacting proteins,including Rv0406c,EchA4,EchA5,HsaE,FadE8,LpqP,and End,were predicted.These candidate genes and the paaX gene were cloned into bacterial two-hybrid vectors and co-transformed into Escherichia coli BTH101 cells.Colony PCR and sequencing confirmed the accuracy of the recombinant constructs.Bacterial two-hybrid assays demonstrated direct interac-tions of PaaX with EchA4,HsaE,FadE8,and LpqP.Moreover,gradient dilution experiments indicated that the strongest binding af-finity occurred between PaaX and EchA4.AlphaFold 3 modeling further validated these interactions,thus providing high-confidence predictions of binding interfaces.Our findings revealed that PaaX,a secreted α-helix-rich protein,engages in specific interactions with key metabolic enzymes(EchA4,HsaE,and FadE8)and a lipoprotein(LpqP),thus suggesting its potential involvement in lipid metabolism,stress adaptation,and host-pathogen interactions.This study provides novel insights into PaaX's contribution to M.tb per-sistence and pathogenicity,and highlights its value as a potential target for tuberculosis diagnostics and therapeutic development.

Objective:To understand the consultation for post-exposure prophylaxis(PEP) services and their related factors among college students who were at high risk for HIV infection in Hangzhou,and to provide a reference basis for formulating an intervention model for college students at high risk of HIV infection.Methods:A cross-sectional survey was conducted between November 2022, and March 2023, in 5 different types of schools in Hangzhou. The subjects should meet the inclusion criteria of age between 18 years and 24 years old self-reported having ever had sex in the past. The sample size was estimated at 864. An online survey was conducted among college students by questionnaire star of an online survey platform to collect their demographic information, sexual behavior characteristics, HIV test status, and consultation for PEP services. The HIV infection risk among participants was evaluated according to their sexual behavior. The consultation for PEP services and the related factors of college students who were at high risk for HIV infection were analyzed.Results:A total of 20 973 college students were surveyed, and 2 291 who have ever had sex were recruited in the study. The proportion assessed as being at high risk for HIV infection was 43.47% (996/2 291), and the proportion of consultation for PEP services was 9.24% (92/996). Multivariate logistic regression analysis showed that among college students who were at high risk for HIV infection, the positive related factors of consultation for PEP services included knowing about PEP services (a OR=17.49, 95% CI: 7.98-38.36) ,having HIV tests (a OR=3.92, 95% CI: 2.08-7.42) and access to condoms on campus (a OR=3.38, 95% CI: 2.02-5.65), and the negative related factor was homosexual orientation (a OR=0.24, 95% CI: 0.06-0.91). Conclusions:Among college students who were at high risk for HIV infection, the proportion of consultation for PEP services was at a lower level. It is necessary to strengthen further the health education of PEP services knowledge among college students, improve the PEP services system, and promote the utilization of PEP services to reduce new HIV infections among college students.

Cardiovascular disease represent a significant global health threat,featured with continuously increased morbidity and mortality rates worldwide in recent years.Consequently,there is an urgent need for the development of safe and effective novel approaches for the prevention and treatment of cardiovascular disease.The advancements in nanotechnology within the medical field,including drug delivery and molecular imaging,have opened innovative avenues for the diagnosis and treatment of diseases.Due to their unique physicochemical and biological properties,metal-based nanoparticles have demonstrated remarkable potential and broad prospects in the diagnosis and treatment of cardiovascular disease.This review summarizes the latest research developments in the application of metal-based nanoparticles in cardiovascular disease and discusses the challenges associated with their clinical application,and presents new insights for the individualized and precise diagnosis and treatment of cardiovascular disease.

Atherosclerosis is a severe disease threatening human health,leading to tremendous consequences such as acute coronary syndrome,myocardial infarction,and stroke.The onset and progression of atherosclerosis are attributed to a chronic inflammatory process,closely associated with the biological activities of various cells.Calpain,a Ca2+-dependent cysteine protease within cells,plays a pivotal role in this context by regulating a plethora of substrates through restricted catalysis of protein hydrolysis,thereby participating in pathological and physiological processes including endothelial damage,inflammatory response,and lipid metabolism.This review summarizes the role of calpain in the development of atherosclerosis and the latest research progress in the application of calpain inhibitors for treatment of atherosclerosis,offering new insights for the clinical realization of personalized and precise treatment of atherosclerosis.

Objective:To understand the consultation for post-exposure prophylaxis(PEP) services and their related factors among college students who were at high risk for HIV infection in Hangzhou,and to provide a reference basis for formulating an intervention model for college students at high risk of HIV infection.Methods:A cross-sectional survey was conducted between November 2022, and March 2023, in 5 different types of schools in Hangzhou. The subjects should meet the inclusion criteria of age between 18 years and 24 years old self-reported having ever had sex in the past. The sample size was estimated at 864. An online survey was conducted among college students by questionnaire star of an online survey platform to collect their demographic information, sexual behavior characteristics, HIV test status, and consultation for PEP services. The HIV infection risk among participants was evaluated according to their sexual behavior. The consultation for PEP services and the related factors of college students who were at high risk for HIV infection were analyzed.Results:A total of 20 973 college students were surveyed, and 2 291 who have ever had sex were recruited in the study. The proportion assessed as being at high risk for HIV infection was 43.47% (996/2 291), and the proportion of consultation for PEP services was 9.24% (92/996). Multivariate logistic regression analysis showed that among college students who were at high risk for HIV infection, the positive related factors of consultation for PEP services included knowing about PEP services (a OR=17.49, 95% CI: 7.98-38.36) ,having HIV tests (a OR=3.92, 95% CI: 2.08-7.42) and access to condoms on campus (a OR=3.38, 95% CI: 2.02-5.65), and the negative related factor was homosexual orientation (a OR=0.24, 95% CI: 0.06-0.91). Conclusions:Among college students who were at high risk for HIV infection, the proportion of consultation for PEP services was at a lower level. It is necessary to strengthen further the health education of PEP services knowledge among college students, improve the PEP services system, and promote the utilization of PEP services to reduce new HIV infections among college students.

This study was aimed at predicting and analyzing the structural and functional properties of the persistence-associated secretory protein PaaX in Mycobacterium tuberculosis(M.tb),identifying its interacting partners,and elucidating its biological roles.Bioinformatics analysis revealed that PaaX comprises 240 amino acids with a molecular mass of 26.54 kDa(C1158H1866N354O334S14).The protein lacks transmembrane domains but contains a signal peptide.Its secondary structure is dominated by α-helices(53.33%),fol-lowed by random coils(36.25%)and extended strands(10.42%),thereby forming a homotetrameric spatial configuration.Potential PaaX-interacting proteins,including Rv0406c,EchA4,EchA5,HsaE,FadE8,LpqP,and End,were predicted.These candidate genes and the paaX gene were cloned into bacterial two-hybrid vectors and co-transformed into Escherichia coli BTH101 cells.Colony PCR and sequencing confirmed the accuracy of the recombinant constructs.Bacterial two-hybrid assays demonstrated direct interac-tions of PaaX with EchA4,HsaE,FadE8,and LpqP.Moreover,gradient dilution experiments indicated that the strongest binding af-finity occurred between PaaX and EchA4.AlphaFold 3 modeling further validated these interactions,thus providing high-confidence predictions of binding interfaces.Our findings revealed that PaaX,a secreted α-helix-rich protein,engages in specific interactions with key metabolic enzymes(EchA4,HsaE,and FadE8)and a lipoprotein(LpqP),thus suggesting its potential involvement in lipid metabolism,stress adaptation,and host-pathogen interactions.This study provides novel insights into PaaX's contribution to M.tb per-sistence and pathogenicity,and highlights its value as a potential target for tuberculosis diagnostics and therapeutic development.

Cardiovascular disease represent a significant global health threat,featured with continuously increased morbidity and mortality rates worldwide in recent years.Consequently,there is an urgent need for the development of safe and effective novel approaches for the prevention and treatment of cardiovascular disease.The advancements in nanotechnology within the medical field,including drug delivery and molecular imaging,have opened innovative avenues for the diagnosis and treatment of diseases.Due to their unique physicochemical and biological properties,metal-based nanoparticles have demonstrated remarkable potential and broad prospects in the diagnosis and treatment of cardiovascular disease.This review summarizes the latest research developments in the application of metal-based nanoparticles in cardiovascular disease and discusses the challenges associated with their clinical application,and presents new insights for the individualized and precise diagnosis and treatment of cardiovascular disease.

Atherosclerosis is a severe disease threatening human health,leading to tremendous consequences such as acute coronary syndrome,myocardial infarction,and stroke.The onset and progression of atherosclerosis are attributed to a chronic inflammatory process,closely associated with the biological activities of various cells.Calpain,a Ca2+-dependent cysteine protease within cells,plays a pivotal role in this context by regulating a plethora of substrates through restricted catalysis of protein hydrolysis,thereby participating in pathological and physiological processes including endothelial damage,inflammatory response,and lipid metabolism.This review summarizes the role of calpain in the development of atherosclerosis and the latest research progress in the application of calpain inhibitors for treatment of atherosclerosis,offering new insights for the clinical realization of personalized and precise treatment of atherosclerosis.