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.

Gliomas, especially high-grade gliomas such as glioblastoma multiforme (GBM), are primary malignant tumors of the central nervous system, characterized by high proliferative capacity, invasiveness, and therapeutic resistance. The development of GBM relies heavily on continuous metabolic reprogramming to adapt to the unique intracranial microenvironment, with nicotinamide adenine dinucleotide (NAD⁺) metabolic remodeling playing a pivotal role. Dysregulation of NAD⁺ and its associated metabolic pathways sustains increased intracellular NAD⁺ levels, which drive the malignant proliferation and invasive potential of GBM, correlating with worsened patient prognosis. This review systematically summarizes the current research landscape of NAD⁺ metabolic remodeling in GBM, elucidates the mechanisms by which NAD⁺ contributes to GBM pathogenesis and progression, and explores the clinical potential of NAD⁺-targeted diagnostic and therapeutic strategies to provide novel insights and directions for the clinical management of GBM.

Objective To investigate influencing factors for failed cardiopulmonary resuscitation(CPR)in patients with respiratory and cardiac arrest.Methods A retrospective analysis was con-ducted on the clinical data of 204 patients with respiratory and cardiac arrest.All patients underwent CPR treatment and were divided into success group and failure group based on the CPR outcome.A matched case-control study based on matching design was carried out.The success and failure groups were matched at a ratio of 1 to 2 using gender,age,body mass index(BMI),and the presence or absence of hypertension,hyperlipidemia,and diabetes as covariates.Logistic regression analysis was employed to explore the influencing factors for failed CPR in patients with respiratory and cardiac ar-rest.Results Among the 204 patients,65(31.86％)had successful CPR and were included in success group,while 139(68.14％)had failed CPR and were included in failure group.After a rati-o of 1 to 2 matching design,62 patients in the success group and 124 patients in the failure group were finally included in the study.Multivariate logistic regression analysis revealed that cardiovascular disease as the cause of respiratory and cardiac arrest,CPR performed outside the hospital,a long time interval from the onset of the condition to the initiation of CPR,and a large dose of epinephrine were independent risk factors for failed CPR(P＜0.05).In contrast,the combined use of a bag-mask de-vice and endotracheal intubation during respiratory and cardiac arrest,a prolonged duration of CPR,and electrical defibrillation were independent protective factors for successful CPR(P＜0.05).Con-clusion Cardiovascular disease,out-of-hospital CPR,a long time interval from the onset of the condi-tion to the initiation of CPR,and a large dose of epinephrine are risk factors for failed CPR in patients with respiratory and cardiac arrest.The combined use of a bag-mask device and endotracheal intubation during respiratory and cardiac arrest,prolonging the duration of CPR,and electrical defibrillation are protective factors for successful CPR.The matched case-control study method based on a matc-hing design can reduce the interference of confounding factors,ensure the reliability of the results,and provide a reliable basis for the formulation of CPR intervention protocols.

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

Objectives:This study aimed to observe the disintegration of clopidogrel and ticagrelor in vitro solution with different pH levels and in human digestive tract.Methods:(1)In vitro study:0.9% normal saline was mixed with hydrochloric acid and sodium bicarbonate respectively to mimic fasting gastric fluid,postprandial gastric fluid,gastric fluid after taking acid-inhibiting agent,acid-free gastric fluid and small intestine fluid.The disintegration of clopidogrel and ticagrelor in different pH solutions was observed.(2)In vivo study:12 patients who were admitted to the Department of Geriatric,Peking University First Hospital from 2022.11 to 2023.6 were included and underwent magnetic controlled capsule endoscopy.We observed the disintegration of clopidogrel(n=6)and ticagrelor(n=6)in the digestive tract.Results:(1)In vitro study:clopidogrel began to disintegrate earlier than ticagrelor([21.67±7.53]s vs.[40.00±6.33]s,P=0.001),but clopidogrel disintegrated more slowly than ticagrelor([23.00±9.38]min vs.[8.33±1.97]min,P=0.011).Clopidogrel disintegrated faster in alkaline solution than in acidic and neutral solution([11.50±4.95]min vs.[28.75±2.50]min,P=0.004),and the disintegration rate of ticagrelor in alkaline solutions is comparable to that in acidic and neutral solutions([7.00±1.41]min vs.[9.00±2.00]min,P=0.285).(2)In vivo study:In the study population,the morphology of clopidogrel and ticagrelor began to change after passing through the esophagus,of which 3 cases(clopidogrel 1 case,ticagrelor 2 cases)were in powder state when passing through the cardia,and the remaining 9 cases were basically intact when entering the stomach and completely disintegrated in the stomach.The complete disintegration time of Clopidogrel varied significantly among individuals,ranging from 8 to 33 min,with an average of(18.80±10.38)min,while the complete disintegration time of ticagrelor ranged from 3 to 6 min,with an average of(4.25±1.26)min.Clopidogrel disintegrated slower than ticagrelor(P=0.034).Conclusions:In vitro study,clopidogrel disintegrated more slowly than ticagrelor in solutions at different pH levels.Compared with clopidogrel,the disintegration rate of ticagrelor was less affected by pH.After oral administration of clopidogrel and ticagrelor,clopidogrel disintegrated more slowly than ticagrelor.The difference of complete disintegration time between individuals of ticagrelor was smaller and the disintegration rate was faster.

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.

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.

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.

Objectives:This study aimed to observe the disintegration of clopidogrel and ticagrelor in vitro solution with different pH levels and in human digestive tract.Methods:(1)In vitro study:0.9% normal saline was mixed with hydrochloric acid and sodium bicarbonate respectively to mimic fasting gastric fluid,postprandial gastric fluid,gastric fluid after taking acid-inhibiting agent,acid-free gastric fluid and small intestine fluid.The disintegration of clopidogrel and ticagrelor in different pH solutions was observed.(2)In vivo study:12 patients who were admitted to the Department of Geriatric,Peking University First Hospital from 2022.11 to 2023.6 were included and underwent magnetic controlled capsule endoscopy.We observed the disintegration of clopidogrel(n=6)and ticagrelor(n=6)in the digestive tract.Results:(1)In vitro study:clopidogrel began to disintegrate earlier than ticagrelor([21.67±7.53]s vs.[40.00±6.33]s,P=0.001),but clopidogrel disintegrated more slowly than ticagrelor([23.00±9.38]min vs.[8.33±1.97]min,P=0.011).Clopidogrel disintegrated faster in alkaline solution than in acidic and neutral solution([11.50±4.95]min vs.[28.75±2.50]min,P=0.004),and the disintegration rate of ticagrelor in alkaline solutions is comparable to that in acidic and neutral solutions([7.00±1.41]min vs.[9.00±2.00]min,P=0.285).(2)In vivo study:In the study population,the morphology of clopidogrel and ticagrelor began to change after passing through the esophagus,of which 3 cases(clopidogrel 1 case,ticagrelor 2 cases)were in powder state when passing through the cardia,and the remaining 9 cases were basically intact when entering the stomach and completely disintegrated in the stomach.The complete disintegration time of Clopidogrel varied significantly among individuals,ranging from 8 to 33 min,with an average of(18.80±10.38)min,while the complete disintegration time of ticagrelor ranged from 3 to 6 min,with an average of(4.25±1.26)min.Clopidogrel disintegrated slower than ticagrelor(P=0.034).Conclusions:In vitro study,clopidogrel disintegrated more slowly than ticagrelor in solutions at different pH levels.Compared with clopidogrel,the disintegration rate of ticagrelor was less affected by pH.After oral administration of clopidogrel and ticagrelor,clopidogrel disintegrated more slowly than ticagrelor.The difference of complete disintegration time between individuals of ticagrelor was smaller and the disintegration rate was faster.

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.