Objective To investigate the radon activity concentrations in subways of Nanning City and assess the average annual effective doses for subway staff and passengers due to radon exposure. Methods Sixty-three stations across the subway lines 2, 3, and 5 were selected as study sites. Radon activity concentrations were measured using the scintillation counting method with scintillation vials. Results The radon activity concentrations in subway lines 2, 3, and 5 were 7.9-24.4, 12.0-26.2, and 12.6-18.2 Bq/m³, respectively. The average radon activity concentrations for these three lines were (17.4 ± 4.6), (19.1 ± 4.1), and (14.6 ± 1.7) Bq/m³, respectively. Statistical analysis using SPSS 26.0 software revealed a significant difference in radon activity concentrations among these stations (P<0.01). Considering the data in previous research, the average radon activity concentration across all stations in the subway lines of Nanning City was determined to be 17.4 Bq/m³. The estimated average annual effective dose due to radon exposure was 0.131 mSv for subway staff and 0.033 mSv for passengers. Conclusion The radon activity concentrations in the subway lines of Nanning City were significantly lower than the national standard limit (400 Bq/m³). The annual effective doses from radon exposure for both subway staff and passengers were below the limits specified in the Basic Standards for Protection Against Ionizing Radiation and for the Safety of Radiation Sources (GB18871—2002). The health impact of radon and its progeny on subway staff and passengers in the subway lines of Nanning City was extremely low and can be considered negligible.

With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

The advancement of tissue clearing technology has significantly propelled neuroscience research. Nevertheless, the fluorescent proteins used in traditional transgenic mouse strains were not specifically optimized for tissue clearing procedures, resulting in a substantial decrease in fluorescent intensity after clearing. In this study, we developed the Ci1 reporter mouse strain (where Ci stands for the Chinese Institute for Brain Research, CIBR) based on the bright red fluorescent protein mScarlet. The Ci1 reporter exhibits no fluorescence leakage in various organs or tissue types and can be readily crossed with multiple tissue-specific Cre lines. Compared to the Ai14 mouse strain, the Ci1 reporter strain demonstrates lower non-specific leakage, stronger fluorescence intensity in different tissues, and better preservation of fluorescence following tissue clearing treatment. The creation of the Ci1 reporter provides a more effective tool for both neuroscience and other biomedical research applications.
Animals ; Luminescent Proteins/metabolism* ; Mice, Transgenic ; Mice ; Red Fluorescent Protein ; Brain/metabolism* ; Genes, Reporter ; Fluorescence

Paramyxoviruses are important respiratory pathogens with substantial clinical relevance in pediatric infectious diseases. During infection, multiple forms of programmed cell death (PCD) may be induced, and this plays pivotal roles in viral replication, dissemination, and host immune responses, thereby profoundly influencing the viral life cycle and disease progression. On one hand, PCD facilitates the clearance of infected cells, restricts viral spread, and activates host immune defenses, thereby enhancing antiviral immunity. On the other hand, excessive or dysregulated cell death may lead to tissue damage and immune imbalance, creating a microenvironment conducive to viral replication and exacerbating disease severity. For instance, apoptosis-mediated by both extrinsic and intrinsic pathways-contributes to infection control but may also be hijacked by viruses to promote dissemination. Pyroptosis, driven by inflammasome activation, triggers lytic cell death and the release of pro-inflammatory cytokines. Necroptosis, mediated by the RIPK1-RIPK3-MLKL signaling axis, and pyroptosis both amplify innate immune responses but may concurrently induce inflammatory dysregulation. Immunogenic cell death (ICD), characterized by the release of damage-associated molecular patterns and neoantigens, activates antigen-specific immune responses and holds therapeutic potential for antiviral and antitumor interventions. Emerging evidence suggests that ferroptosis, through the modulation of iron metabolism and associated transporters, may also participate in viral replication and infected cell clearance. This review comprehensively summarizes the roles of apoptosis, pyroptosis, necroptosis, ICD, and ferroptosis in paramyxovirus infection, aiming to deepen the understanding of paramyxovirus pathogenesis and to provide insights for developing novel antiviral strategies.
Humans ; Paramyxoviridae Infections/pathology* ; Pyroptosis ; Apoptosis ; Virus Replication ; Necroptosis ; Inflammasomes ; Immunity, Innate ; Immunogenic Cell Death ; Paramyxoviridae/physiology* ; Signal Transduction

Objective To investigate the effects of Jiuwei Jianbu Drink on oxidative stress and inflammatory injury in rats with knee osteoarthritis via the high mobility group box-1 protein(HMGB1)/receptor for advanced glycation endproducts(RAGE)/phosphatidyli-nositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods A total of 60 rats were randomly divided into six groups according to the random number table method:blank control group,model group,positive drug group,and Jiuwei Jianbu Drink low-,medium-,and high-dose groups,with 10 rats in each group.Except for the blank control group,knee osteoarthritis models were estab-lished in the other groups,which were then subjected to corresponding treatments.Knee joint diameter and mechanical pain and thermal pain threshold changes were observed.Hematoxylin-eosin staining and safranin O/fast green staining were used to assess pathological changes in cartilage tissue.Oxidative stress markers and inflammatory factor levels in knee joint cartilage tissue of each group were meas-ured.Western blot was used to detect the expression of proteins related to the HMGB1/RAGE/PI3 K/Akt signaling pathway in knee joint tissues.Results Compared with the blank control group,the model group exhibited increased knee joint diameter and decreased mechan-ical pain and thermal pain threshold.Jiuwei Jianbu Drink at all doses groups and the positive control group significantly improved these in-dicators in a dose-dependent manner(P＜0.05).Additionally,the Mankin score and Osteoarthritis Research Society International(OARSI)score in the model group were significantly higher than those in the blank control group,while Jiuwei Jianbu Drink intervention significantly reduced the OARSI score,with the best effect observed in the high-dose group(P＜0.05).Compared with the blank con-trol group,the model group showed increased levels of nitric oxide(NO)and malondialdehyde(MDA),decreased levels of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px),and significantly elevated levels of tumor necrosis factor-alpha(TNF-α)and interleukin-1β(IL-1β).Compared with the model group,Jiuwei Jianbu Drink significantly inhibited oxidative stress and inflam-matory responses,especially at high doses(P＜0.05).Moreover,the expression of HMGB1,RAGE,p-PI3K/PI3K,and p-Akt/Akt in the model group was higher than that in the blank control group,while Jiuwei Jianbu Drink intervention dose-dependently downregulat-ed the expression of these proteins(P＜0.05).Conclusion Jiuwei Jianbu Drink alleviates oxidative stress and inflammatory injury in rats with knee osteoarthritis by inhibiting the HMGB1/RAGE/PI3K/Akt signaling pathway,thereby improving cartilage pathological chan-ges and demonstrating potential therapeutic value.

Objective Based on the phosphatidylinositol kinase(PI3K)/protein kinase B(AKT)pathway and M2 polarization of macrophages,the effects of polydatin on malignant phenotype of osteosarcoma cells were investigated.Methods The macrophages were divided into M0 group,M2 group,polydatin group,and polydatin+PI3K pathway agonist 740Y-P group.The expression of arginase-1(Arg-1)and CD206 mRNAs and proteins in macrophages were detected by RT-qPCR and Western blot.Western blot was used to detect p-PI3K/PI3K and p-AKT/AKT protein expression in macrophages.The osteosarcoma cells MG-63 were divided into control group,control group(RPMI-1640 medium culture),CM-M0 group(M0 group M0 macrophage supernatant is collected for osteosarcoma cells),CM-M2 group(M2 group M2 macrophage supernatant is collected for osteosarcoma cells),CM-polydatin group(M2 macrophage supernatant in the polydatin group was collected on osteosarcoma cells),and CM-polydatin+740Y-P group(M2 macrophage supernatant was collected on osteosarcoma cells in the CM-polydatin+740Y-P group).Edu staining assay was used to detect the proliferation of MG-63 cells.Scratches and Transwell assays were used to detect the migration and invasion of MG-63 cells.Results Compared with the M0 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the M2 group significantly(P<0.05).Compared with the M2 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT decreased in the polydatin group significantly(P<0.05).Compared with the polydatin group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the polydatin+740Y-P group significantly(P<0.05).Compared with the CM-M0 group,the proportion of Edu-positive cells in the CM-M2 group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Compared with the CM-M2 group,the proportion of Edu-positive cells in the CM-polydatin group decreased significantly(P<0.05),and MG-63 cell migration and invasion rates decreased significantly(P<0.05).Compared with the CM-polydatin group,the proportion of Edu-positive cells in the CM-polydatin+740Y-P group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Conclusion Polygonum cuspidatum can inhibit the proliferation,migration and invasion of osteosarcoma cells by inhibiting the M2 polarization of macrophages,and its mechanism may be related to the inhibition of PI3K/AKT signaling pathway.

BACKGROUND:Gait dysfunction is one of the significant reasons for patient dissatisfaction following total knee arthroplasty.Clinical studies have identified a relationship between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction,but the exact nature of this correlation is not yet fully understood.OBJECTIVE:To investigate the correlation between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction in total knee arthroplasty.METHODS:A retrospective analysis was conducted on longitudinal data from 70 patients who underwent unilateral primary total knee arthroplasty.Preoperative measurements included peak torque of the extensor and flexor muscles,peak torque/body weight,and total work.Six months postoperatively,the Timed Up and Go Test and gait speed were measured.Ridge regression analysis was used to identify factors influencing postoperative gait function.RESULTS AND CONCLUSION:(1)Preoperative peak torque,peak torque/body weight,and total work of the extensor muscles,as well as the peak torque and total work of the flexor muscles,showed a very strong positive correlation with postoperative gait speed(P＜0.001).The preoperative flexor muscle peak torque/body weight had a strong positive correlation with postoperative gait speed(P＜0.001).Preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work showed a very strong negative correlation with results from postoperative Timed Up and Go Test(P＜0.001).(2)Ridge regression analysis indicated a 94.2％likelihood that preoperative extensor muscle peak torque,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a positive impact on gait speed after total knee arthroplasty(P＜0.001).The preoperative flexor muscle peak torque/body weight had a negative impact on postoperative gait speed(P＜0.001).There was an 87.7％likelihood that preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a negative impact on postoperative Timed Up and Go Test(P＜0.05),while the flexor muscle peak torque/body weight had no impact on the Timed Up and Go Test(P＞0.05).(3)It is indicated that the strength of the quadriceps and hamstring muscles prior to total knee arthroplasty correlates with postoperative gait speed and Timed Up and Go Test,and can predict the outcomes of postoperative gait function.Enhancing preoperative knee muscle exercises may be a way to reduce the incidence of gait dysfunction following total knee arthroplasty.

Objective:To mine the risk signals of adverse events (AEs) in mavacamten treatment for hypertrophic cardiomyopathy, and provide reference for safe use of the drug in clinic.Methods:AE reports on mavacamten from June 2022 to June 2024 were collected by searching US Food and Drug Administration Adverse Event Reporting System (FAERS) database. AEs were classified and standardized according to the system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities version 26.1. Reporting odds ratio (ROR) method and comprehensive standard method of the UK Medicines and Healthcare Products Regulatory Agency (MHRA) were used to mine the AE risk signals. An AE that simultaneously met the criteria of ≥3 reports, lower limit of the 95% confidence interval ( CI) of ROR>1, PRR ≥2, and χ2 ≥4 was defined as a risk signal. Descriptive statistical analysis on signals was performed. Results:A total of 1 041 AE reports were collected, involving 47 PTs and 12 SOCs. The top 10 risk signals based on the number of AE reports were dyspnea, dizziness, fatigue, atrial fibrillation, cardiac failure, palpitation, nasopharyngitis, chest pain, COVID-19, and weight increased. Except dizziness and heart failure, above AEs were not recorded in the label. The top 10 risks in signal intensity were acquired left ventricle outflow tract obstruction, transvalvular pressure gradient increased, cardiovascular symptom, echocardiogram abnormal, hypervolaemia, left ventricular failure, ejection fraction decreased, coronavirus infection, brain fog, and atrial fibrillation. Except cardiovascular symptom, left ventricular failure, and ejection fraction decreased, above AEs were not recorded in the label.Conclusions:The AE risk signals of mavacamten in the treatment for hypertrophic cardiomyopathy recorded in the label are mainly heart failure and ejection fraction decreased. Clinicians and pharmacists should also be vigilant against risk signals not recorded in the lakel, such as atrial fibrillation, fatigue, nasopharyngitis, coronavirus infection, and brain fog, etc.

Objective:To investigate the implementation of boxed warning of drug labels in US Food and Drug Administration (FDA) from 2019 to 2024, and compared it with the relevant situations in China, in order to provide reference for the revision of drug labels and safe drug use.Methods:Data on boxed warning revisions in the US FDA "Drugs Safety Related Labeling Changes" Database from January 1, 2019 to December 31, 2024 were retrieved, and the revised contents were classified. The drug labels for newly marketed drugs in the United States during the same period were collected, the boxed warnings were recorded and summarized, and compared with the warning statements in drug labels of relevant drugs approved in China.Results:From 2019 to 2024, FDA revised boxed warnings in 209 drug labels. Among them, 22 items (10.53%) were newly added, 63 items (30.14%) were major updates, 115 items (55.02%) were minor updates, and 9 items (4.31%) were removed. A total of 293 new drugs were approved in the United States from 2019 to 2024, of which 69 (23.55%) had boxed warnings when they were approved, and 4 (1.37%) were added boxed warnings when they were revised in the labels. Up to December 31, 2024, 92 of the 293 new drugs had been approved in China. Compared with the labeling in the United States, some drugs lacked warning statements section in China, including zolpidem tartrate, dexzopiclone, zaleplon, montelukast sodium, denosumab, terlipressin, etc.Conclusions:The warning statements in some Chinese drug labels are inconsistent with the boxed warnings in the American drug labels. It is suggested that the revision of the boxed warning by US FDA should be regarded as one of the new sources of safety information to assess the risks of related drugs and determine whether it is necessary to revise the relevant drug labels in China.

Objective Based on the phosphatidylinositol kinase(PI3K)/protein kinase B(AKT)pathway and M2 polarization of macrophages,the effects of polydatin on malignant phenotype of osteosarcoma cells were investigated.Methods The macrophages were divided into M0 group,M2 group,polydatin group,and polydatin+PI3K pathway agonist 740Y-P group.The expression of arginase-1(Arg-1)and CD206 mRNAs and proteins in macrophages were detected by RT-qPCR and Western blot.Western blot was used to detect p-PI3K/PI3K and p-AKT/AKT protein expression in macrophages.The osteosarcoma cells MG-63 were divided into control group,control group(RPMI-1640 medium culture),CM-M0 group(M0 group M0 macrophage supernatant is collected for osteosarcoma cells),CM-M2 group(M2 group M2 macrophage supernatant is collected for osteosarcoma cells),CM-polydatin group(M2 macrophage supernatant in the polydatin group was collected on osteosarcoma cells),and CM-polydatin+740Y-P group(M2 macrophage supernatant was collected on osteosarcoma cells in the CM-polydatin+740Y-P group).Edu staining assay was used to detect the proliferation of MG-63 cells.Scratches and Transwell assays were used to detect the migration and invasion of MG-63 cells.Results Compared with the M0 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the M2 group significantly(P<0.05).Compared with the M2 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT decreased in the polydatin group significantly(P<0.05).Compared with the polydatin group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the polydatin+740Y-P group significantly(P<0.05).Compared with the CM-M0 group,the proportion of Edu-positive cells in the CM-M2 group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Compared with the CM-M2 group,the proportion of Edu-positive cells in the CM-polydatin group decreased significantly(P<0.05),and MG-63 cell migration and invasion rates decreased significantly(P<0.05).Compared with the CM-polydatin group,the proportion of Edu-positive cells in the CM-polydatin+740Y-P group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Conclusion Polygonum cuspidatum can inhibit the proliferation,migration and invasion of osteosarcoma cells by inhibiting the M2 polarization of macrophages,and its mechanism may be related to the inhibition of PI3K/AKT signaling pathway.