ObjectivesTo investigate the molecular epidemiological characteristics of HIV-1 infection among men who had sex with men (MSM) in Taizhou City, Zhejiang Province, and to provide a scientific reference for acquired immune deficiency syndrome prevention and control efforts. MethodsThe research subjects were all newly reported MSM population in Taizhou City from 2020 to 2023. Blood samples without antiviral therapy were collected. The HIV-1 pol gene was amplified and sequenced, and the sequences were submitted to the Stanford University drug resistance database to identify the mutation sites and drug resistance. MEGA 11.0 software was used to analyze the nucleic acid sequences, construct phylogenetic tree, and calculate genetic distance of gene sequences. The molecular transmission network diagram of HIV-1 was constructed using Cytoscape_v3.10.1, and the influencing factors of network entry were analyzed by logistic regression. ResultsA total of 363 newly reported HIV-infected MSM patients were included, with a median age [M (P₂₅, P₇₅)] of 34 (26,47) years old. The majority had an educational level of junior high school or below (55.65%). A total of eight subtypes were found, mainly CRF07_BC and CRF01_AE. The primary drug resistance rate was 10.47% (38/363). The optimal molecular network gene distance was 0.019, with a network access rate of 42.70% (155/363), and a total of 47 molecular clusters were formed. Multivariate logistic analyses showed that compared with the CRF01_AE subtype, the clustering risk of CRF07_BC subtype was higher (OR=1.916, 95%CI: 1.191‒3.109), cases with drug resistance had a higher risk of cluster formation than those without drug resistance (OR=2.011, 95%CI: 1.006‒4.080), and recent infected patients had a lower risk of entering the largest molecular cluster than long-term infected patients (OR=0.376, 95%CI: 0.137‒0.928). ConclusionThe newly diagnosed infections among the MSM population are active in Taizhou City, Zhejiang Province, with a high level of primary drug resistance. Individuals carrying drug-resistant strains are more likely to cluster. Drug resistance monitoring should be strengthened to prevent further spread of drug-resistant strains in the network.

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

OBJECTIVE To investigate the in vitro antitumor activity and in vivo targeting of nanopolymers co-loaded with arse-nic trioxide(ATO),an active ingredient of traditional Chinese medicine arsenic,and photosensitizer(IR780)to activate the patient's own immune system in the treatment of brain glioma in synergistically with chemotherapy and phototherapy.METHODS PLGA/AI containing ATO and IR780 was prepared by volatilization with multiple emulsion solvent.The particle size,potential and polydispersity index(PDI)were determined by dynamic light scatterometer(DLS)at different feed ratios.Transmission electron microscopy(TEM)was used to detect the morphology of PLGA/AI.Fluorescence spectrophotometer was used to investigate the spectroscopic characteris-tics.UV-vis spectrophotometer was used to determine the drug loading and encapsulation rate of IR780.Under laser irradiation,the physiological release of ATO was measured by dialysis bag method.The uptake of PLGA/AI in GL261 cells was photographed by confo-cal microscopy(CLSM).The cell uptake mechanism of PLGA/AI was investigated by flow cytometry(FCM).3D tumor spheroid mod-el was constructed to simulate the deep penetration of PLGA/AI in solid tumors.The synergistic anti-tumor effects of PLGA/AI in vitro were studied by MTT assay and dying staining.DCFH-DA staining and FCM determination of the co-expression of CD80 CD86 co-stimulatory molecules verified the immune activation induced by PLGA/AI in vitro photochemotherapy.The in vivo targeting of PLGA/AI and the tissue distribution of the main organs were investigated by means of in vivo imaging of small animals after tail vein injection.RESULTS The optimal ratio of ATO to IR780 was 1∶10,its particle size was(134.11±2.19)nm,Zeta potential was(-7.02±0.649)mV,PDI was 0.254±0.059,and it was a uniform spherical shape under TEM.The fluorescence spectra showed that IR780 was successfully loaded onto PLGA,and the drug loading and encapsulation rate of IR780 in PLGA/AI were(2.53±0.02)%and(71.26±0.38)%respectively.The results of in vitro release experiments showed that ATO could be released in response to laser light by IR780-mediated photo-dynamics.Cell uptake experiments showed that the nano-polymer could effectively enter tumor cells under clathrin-mediated endocytosis.In vitro investigation of cell viability,ROS detection and dendritic cell maturation experiment showed that it could effectively kill tumor cells by inducing a large amount of ROS to generate and activate immune cells.In vivo targe-ting and biological distribution study confirmed that PLGA/AI could effectively penetrate BBB into tumor sites.CONCLUSION The active ingredients of traditional Chinese medicine arsenic,ATO and IR780,use PLGA as carriers to form nano-polymers through the volatilization of multiple emulsion solvents,which can cross the BBB and effectively accumulate at the tumor site.Based on"strengthe-ning the healthy qi and eliminating pathogenic factors"and combined with chemotherapy and photo-immune activation,it has the po-tential for long-term anti-glioblastoma treatment.

Objective·To explore the effects and potential mechanisms of emodin on Alzheimer's disease(AD).Methods·Wild-type C57BL/6J mice and 3×Tg-AD mice were divided into 6 groups:Control group(C57BL/6J mice),AD group(3×Tg-AD mice),Emodin 25 mg/kg group(3×Tg-AD mice+Emodin 25 mg/kg),Emodin 50 mg/kg group(3×Tg-AD mice+Emodin 50 mg/kg),Emodin 100 mg/kg group(3×Tg-AD mice+Emodin 100 mg/kg)and Donepezil group(3×Tg-AD mice+Donepezil 3 mg/kg).The Morris water maze test was used to evaluate the learning and memory abilities of mice.The expression of glial fibrillary acidic protein(GFAP),glucose-regulated protein 78kDa(GRP78),and inositol-requiring enzyme 1α(IRE1α)was detected by immunohistochemistry.The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in brain tissue were measured by enzyme-linked immunosorbent assay(ELISA).Western blotting was used to detect the expression of NF-κB p65,p-NF-κB p65,p38,and p-p38 proteins.Results·Compared with the control group,mice in the AD group showed impaired cognition,increased GFAP expression,elevated levels of TNF-α,IL-1β and IL-6,and increased expression of GRP78 and IRE1α,along with enhanced phosphorylation of NF-κB p65 and p38.Compared with the AD group,emodin improved cognitive impairment of AD mice,inhibited astrocyte overactivation and neuroinflammation,and decreased the expression of GRP78,IRE1α,phosphorylated NF-κB p65,and phosphorylated p38 in brain tissue.Conclusion·Emodin can effectively improve cognitive impairment in AD mice,which may be related to the inhibition of endoplasmic reticulum stress-mediated neuroinflammation in astrocytes.

Objective To investigate the effects of a continuous-dose administration versus different dosage regimens of polyethylene glycol electrolyte solution(PEG)taken in two doses with a 12-hour interval on bowel cleansing efficacy,with the goal of optimizing bowel preparation protocols and improving patient tolerability.Methods 232 patients who underwent painless colonoscopy and used PEG as a bowel cleanser from June 2024 to September 2024 were selected as study subjects.Participants were divided into three groups:the control group(3.00 L PEG continuous dose),experimental group A(0.75 L+2.25 L PEG),and experimental group B(1.50 L+1.50 L PEG).All patients underwent painless colonoscopy within 4～6 h after completing PEG intake.The interval between the two doses of PEG in group A and group B was 12 h.The bowel cleansing efficacy was assessed by using the Boston bowel preparation scale(BBPS),and the rates of colon polyp detection,adverse reactions,sleep duration,and tolerability were recorded.Results There were no significant statistical differences in BBPS scores and colon polyp detection rates among the three groups(P>0.05).Experimental group B experienced the least adverse reactions,followed by experimental group A,while the control group reported the most significant adverse reactions(P<0.05).The timing of PEG administration did not have a significant impact on sleep duration among the three groups(P>0.05).Patients in experimental group B showed good tolerability to PEG and were willing to accept this bowel preparation regimen,followed by group A,while the control group exhibited the poorest tolerability,with significant statistical differences among the three groups(P<0.05).Conclusion The continuous administration and divided administration of PEG have no significant impact on the effectiveness of intestinal cleansing and the detection rate of colonic polyps.However,the divided PEG regimen with a 12 h interval results in fewer adverse reactions and better tolerance,especially the optimal regimen of taking 1.50 L PEG in two doses with a 12 h interval.

Purpose To investigate the expression of LAMB3 and ITGB4 in esophageal squamous cell carcinoma(ESCC)and analyze their associations with clinicopathological features.Methods Bioinformatics was used to assess the expression of LAMB3 and ITGB4 in pan-cancer and ESCC.Immunohistochemistry was performed to evaluate their expression and distribution in ESCC tissues,and correlations clinicopathological features were analyzed.Follow-up data were collected to construct Kaplan-Meier survival curves,and Cox regression analysis was proformed to determine their prognostic significance.Results Bioinformatics analysis showed that LAMB3 and ITGB4 were highly expressed in ES-CC tissues(P＜0.001).Immunohistochemistry confirmed that both proteins were localized in the cytoplasm and membrane of tumor cells.High LAMB3 expression was significantly associated with poor differentiation(P＜0.001),lymph node metastasis(P=0.015),and T staging(P＜0.001).High ITGB4 expression was significantly correlated with poor differentiation(P=0.004)and advanced T staging(P=0.004).Cox regression analysis identified high ex-pression of LAMB3 and ITGB4 as independent prognostic factors for overall survival[HR=4.97(95％CI:2.73-9.02);HR=2.33(95％CI:1.36-3.99)].Conclusion LAMB3 and ITGB4 are highly expressed in ESCC.High LAMB3 expression is associated with tumor differentiation,lymph node metastasis,and T staging,while high ITGB4 expression is correlated with tumor differentiation and T staging.Patients with high expression of LAMB3 or ITGB4 have poorer overall survival,suggesting that these proteins may serve as prognostic biomarkers for unfavorable outcome in ESCC.

Objective:To explore the effectiveness of generative artificial intelligence (GAI) -empowered interprofessional collaborative learning model in nursing psychology practical teaching for undergraduate nursing students.Methods:From November to December 2024, 109 second-year nursing students from the Xiangya School of Nursing, Central South University were selected as research subjects using convenience sampling. Two classes were randomly divided into an experimental group (55 students) and a control group (54 students) using a random draw method. Control group received a traditional teaching model based primarily on case discussion and scenario simulation teaching, while experimental group used the GAI-empowered interprofessional collaborative learning model on the basis of control group. The teaching effectiveness was evaluated using the Psychological Nursing Practice Competency Assessment Scale, Caring Ability Inventory (CAI), Readiness for Interprofessional Learning Scale (RIPLS), and Satisfaction Survey Questionnaire.Results:After teaching, experimental group's practical course assessment scores, CAI total scores, and scores in each dimension were all higher than those of control group, with statistically significant differences ( P<0.01). The RIPLS score of nursing students in experimental group after teaching was higher than that before teaching, and the difference was statistically significant ( P<0.01). 90.9% of nursing students supported the introduction of GAI into the classroom, and 90.9% of nursing students recognized the auxiliary role of GAI in achieving learning objectives, and the teaching satisfaction was 96.4%. Conclusions:This study validates the effectiveness of GAI-empowered interprofessional collaborative learning model in nursing psychology practical teaching for undergraduate nursing students, providing new ideas for nursing education reform.

In October 2024, a 36-year-old female patient with botulinum toxin type A intoxication for 15d was admitted to the Department of Neurology of Northern Jiangsu People’s Hospital. Although type A botulinum antitoxin (BAT) therapy remained effective, the patient developed a serum sickness-like reaction (SSLR) on day 4 of treatment after receiving eight consecutive desensitizing intramuscular injections of BAT. After stopping the injection of the drug and giving intravenous dexamethasone, the patient’s symptoms improved. On the 6th day after stopping the injection of botulinum antitoxin type A, the patient was followed up in the outpatient clinic and the skin symptoms had almost disappeared. This article analyzed the patient’s medical records and explored the association between BAT and SSLR, suggesting that medical personnel should be alert to the risk of adverse reactions when applying antitoxin therapy, and that they should identify and intervene in a timely manner in order to ensure the safety of the medication and therapeutic efficacy of the patients.

Ferroptosis is an iron-dependent cell death modality triggered by the accumulation of lipid peroxides and is closely linked to tumor pathogenesis. Ferritinophagy refers to the selective autophagic degradation of ferritin, releasing intracellular stored iron to maintain iron metabolic homeostasis. This process is also significantly associated with tumor-targeted interventions. This review systematically elucidates the mechanisms of ferroptosis and ferritinophagy, their roles in tumor progression, and the therapeutic potential of pharmacologically induced ferritinophagy in anticancer strategies.