ObjectiveTo investigate the T lymphocyte subset levels and viral loads in newly human immunodeficiency virus (HIV) antibody-confirmed positive cases in Suzhou (2021‒2024), and to analyze potential influencing factors by integrating their demographic characteristics, immune status, and viral replication patterns, thereby providing evidence for HIV/acquired immune deficiency syndrome (AIDS) prevention and control. MethodsPeripheral whole blood samples were collected from newly confirmed HIV-positive cases in Suzhou from 2021 to 2024. T lymphocyte subset analysis and viral load testing were performed, and influencing factors were identified in combination with demographic characteristics. Logistic regression models were employed to identify factors associated with CD4⁺T lymphocyte counts ≤350 cells·μL^-1, and Spearman’s rank correlation test was used to analyze the correlation between logarithmic value of viral load and CD4⁺/CD8⁺ ratio. ResultsAmong the 3 022 confirmed HIV-positive samples, the median CD4⁺T lymphocyte count was 298.00 cells·μL^-1, with 882 cases (29.19%) showing CD4⁺ T lymphocyte counts <200 cells·μL^-1. The median CD8⁺T lymphocyte count was 1 011.00 cells·μL^-1. The median CD4⁺/CD8⁺ ratio was 0.28, with 32.46% of cases exhibiting CD4⁺/CD8⁺ ratios <0.20, and there were statistically significant differences in CD4⁺/CD8⁺ ratio among different genders, age groups, marital status, and sample sources (all P<0.05). Multivariate logistic regression analyses indicated that individuals aged ≥20 years, those who were divorced or widowed, and cases identified through medical institutions had a significantly higher proportion of CD4⁺T lymphocyte counts ≤350 cells·µL⁻¹ compared to those aged <20 years, unmarried individuals, and cases sourced from voluntary counseling and testing (VCT) clinics, respectively. The mean logarithmic value of viral load was (4.29±1.15) copies·mL^-1. The logarithmic value of viral load demonstrated a significantly negative correlation with both CD4⁺/CD8⁺ ratio (r=-0.43, P<0.001) and CD4⁺T lymphocyte count (r=-0.37, P<0.001). ConclusionA substantial proportion of newly diagnosed HIV/AIDS cases in Suzhou are late presenters with high viral load levels. Targeted interventions should prioritize high-risk populations through enhanced active surveillance and the implementation of combined T lymphocyte subsets analysis and viral load testing, which can enable earlier case-finding and timely antiretroviral therapy initiation.

Although global brain science research has progressed rapidly in recent decades, several fundamental questions in neuroscience remain unresolved. In particular, the physical mechanism underlying neural signal transmission remains controversial, and the carriers responsible for neural information storage and retrieval have not yet been fully clarified. These unresolved issues motivate us to re-examine the processes of neural information generation, transmission, integration, storage, and retrieval from multiple perspectives. A key observation is that neural electromagnetic activities are closely associated with time. Their duration, temporal structure, and dynamic evolution play crucial roles in neural information processing. In this work, we analyze neural electromagnetic activities from the perspective of temporal scales (referred to here as the “time course”). By reviewing and integrating findings from previous studies, we examine the characteristic time requirements and dynamic features of neural processes occurring at different stages of information processing. These stages include neural signal generation, signal transmission along axons, synaptic integration, synaptic plasticity, and memory formation and retrieval. Based on this temporal analysis, we outline a framework describing neural electromagnetic activities across a wide range of time scales, spanning from microseconds to minutes, hours, or even longer periods associated with long-term memory, which suggests that neural information processing involves multiple physical processes operating at different time levels. Rapid electromagnetic events may occur on microsecond scales, whereas electrophysiological phenomena such as action potentials typically last on the order of milliseconds. Longer time scales are associated with synaptic plasticity and memory-related processes. From this perspective, we propose that the physical carrier of neural information may be transient electromagnetic pulses with durations on the microsecond scale. In this framework, action potentials can be interpreted as the macroscopic electrophysiological manifestation of underlying electromagnetic processes triggered by ionic currents across neuronal membranes. Rather than being the fundamental neural signal itself, the action potential may represent a measurable membrane-level response associated with the successful activation of these electromagnetic events. Moreover, we discuss a possible mechanism for long-term memory storage. Considering the apparent temporal contradiction between the millisecond-scale excitation of neurons and the long-term persistence of memories, we believe that long-term memory information may be stored within neural network topologies formed by electrical synapse coupling. Such structures, referred to as electrically coupled memory networks (ECMNs), may enable neurons within the same network to respond rapidly and synchronously to stimuli, thereby facilitating efficient memory retrieval. Overall, this study emphasizes the importance of considering the temporal organization of neural electromagnetic activities when interpreting neural signaling mechanisms. It may provide new insights into the physical nature of neural information carriers and the mechanisms of memory storage and retrieval. Furthermore, highlighting the potential role of electromagnetic interactions in neural activity may contribute to the development of new theoretical frameworks and experimental approaches in neuroscience. Such perspectives may also offer valuable references for future research on neural coding, brain function mechanisms, and neuromodulation technologies.

Objective To explore the safety and feasibility of 5G remote robot-assisted thoracoscopic anatomic lobectomy and segmentectomy. Methods A retrospective analysis was conducted on patients who underwent 5G remote robot-assisted thoracoscopic anatomic lobectomy or segmentectomy between July and September 2024. The surgeries were performed collaboratively by Shanghai Chest Hospital, Affiliated Hospital of Yangzhou University, and The First Affiliated Hospital of Nanchang University. Perioperative outcomes were recorded and analyzed. Results Ten patients were included, comprising 4 anatomic lobectomies and 6 segmentectomies. The median age was 61.0 (56.0, 72.0) years. The median intraoperative bi-directional network latency was 52.5 (39.0, 54.0) ms. There were no instances of network interruption, robot-related adverse events, or conversions to open thoracotomy. The median postoperative chest tube drainage volume was 500.0 (375.0, 600.0) mL, and the median hospital stay was 5.5 (4.0, 6.0) days. No complications of Clavien-Dindo grade Ⅱor higher occurred. All patients were recurrence-free and alive during the 6-month postoperative follow-up period. Conclusion 5G remote robot-assisted thoracoscopic surgery demonstrates high safety and operational stability. This technology shows promising potential for clinical application and is worthy of further development and utilization.

ObjectiveTo genotype the specimens from hand-foot-and-mouth disease (HFMD) cases in Dehong Prefecture, Yunnan Province in 2023 by gene sequencing, and to analyze the genetic characteristics of Coxsackievirus A4 (CVA4), CVA6, CVA10, CVA16 and enterovirus A71 (EV-A71), so as to clarify the serotypes of enteroviruses causing endemic HFMD and the genotype composition of CVA4, CVA6, CVA10, CVA16 and EV-A71 prevalent in HFMD, and to provide baseline genotype data for monitoring the dynamic changes of the five virus genotypes. MethodsStool specimens from HFMD cases in Dehong Prefecture in 2023 that tested positive for EV-A71, CVA16 and other enteroviruses by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) were first subjected to gene sequencing and typing of the VP4/VP2 junction region to determine the viral types. Subsequently, the complete VP1 gene of each virus was amplified in two segments using group-specific VP1 gene primers corresponding to enterovirus groups (i.e., enterovirus group A, B, and C) and sequenced (group A virus: primers 486/488 and 487/489, group B virus: primers 490/492 and 491/493, group C virus: primers 494/496 and 495/497). The representative reference sequences of VP1 genes for CVA4, CVA6, CVA10, CVA16 and EV-A71 were downloaded from the literature, and the VP1 gene phylogenetic tree was constructed using MEGA 6.0 software for genetic characterization. ResultsA total of 256 stool specimens were collected from HFMD cases in Dehong Prefecture in 2023, of which 94 tested positive for nucleic acid by RT-qPCR, yielding a positive rate of 36.72%. Of the 94 positive specimens, 83 were identified as group A viruses, and were classified into 5 serotypes (17 strains of CVA4, 3 of CVA6, 6 of CVA10, 49 of CVA16, and 8 of EV-A71). Nine strains were group B viruses, comprising 2 serotypes: 2 strains of echovirus type 3 (E3) and 7 strains of Coxsackievirus B type 5 (CVB5). The remaining 2 strains were group C viruses, both identified as poliovirus type 3 (PV3). Genetic analyses of the VP1 region showed that all 17 CVA4 strains were identified as subgenotype C2, all 3 CVA6 strains as subgenotype D3a, all 6 CVA10 strains as genotype C. Among the 49 CVA16 strains, 46 were identified as subgenotype B1a and 3 as subgenotype B1b, and all 8 EV-A71 strains were identified as subgenotype C4a. ConclusionIn 2023, group A viruses dominated the pathogenic spectrum of HFMD in Dehong Prefecture. Among them, CVA16 had the highest positivity rate. Genetic characteristic analyses showed that CVA4, CVA6, CVA10 and EV-A71 were each composed of a single genotype (subgenotype), while CVA16 was composed of two subgenotypes (B1a and B1b), with B1a being the predominant one. It is recommended that molecular epidemiological surveillance of HFMD pathogens, particularly group A viruses, be continuously strengthened in Dehong Prefecture.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

OBJECTIVE To investigate the effect and mechanism of Jingangteng capsules in the treatment of non-alcoholic fatty liver disease （NAFLD）. METHODS Thirty-two SD rats were randomly divided into normal group and modeling group. The modeling group was fed a high-fat diet to establish a NAFLD model. The successfully modeled rats were then randomly divided into model group， atorvastatin group[positive control， 2 mg/（kg·d）]， and Jingangteng capsules low- and high-dose groups [0.63 and 2.52 mg/（kg·d）]， with 6 rats in each group. The pathological changes of the liver were observed by hematoxylin-eosin staining and oil red O staining. Enzyme-linked immunosorbent assay was performed to determine the serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine transaminase （ALT）， aspartate transaminase （AST）， tumour necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， IL-18. 16S rDNA amplicon sequencing and metabolomics techniques were applied to explore the effects of Jingangteng capsules on gut microbiota and metabolisms in NAFLD rats. Based on the E-mail：591146765@qq.com metabolomics results， Western blot analysis was performed to detect proteins related to the nuclear factor kappa-B （NF-κB）/NOD-like receptor family protein 3 （NLRP3） signaling pathway in the livers of NAFLD rats. RESULTS The experimental results showed that Jingangteng capsules could significantly reduce the serum levels of TG， TC， LDL-C， AST， ALT， TNF-α， IL-1β， IL-6， IL-18， while increased the level of HDL-C， and alleviated the hepatic cellular steatosis and inflammatory infiltration in NAFLD rats. They could regulate the gut microbiota disorders in NAFLD rats， significantly increased the relative abundance of Romboutsia and Oscillospira， and significantly decreased the relative abundance of Blautia （P＜0.05）. They also regulated metabolic disorders primarily by affecting secondary bile acid biosynthesis， fatty acid degradation， O-antigen nucleotide sugar biosynthesis， etc. Results of Western blot assay showed that they significantly reduced the phosphorylation levels of NF-κB p65 and NF-κB inhibitor α， and the protein expression levels of NLRP3， caspase-1 and ASC （P＜0.05 or P＜0.01）. CONCLUSIONS Jingangteng capsules could improve inflammation， lipid accumulation and liver injury in NAFLD rats， regulate the disorders of gut microbiota and metabolisms， and inhibit NF-κB/NLRP3 signaling pathway. Their therapeutic effects against NAFLD are mediated through the inhibition of the NF-κB/NLRP3 signaling pathway.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔ_pMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.