Objective To construct a dynamic prediction model for JC polyomavirus (JCV) reactivation after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 128 recipients who met the inclusion criteria and received kidney transplantation in Nanfang Hospital, Southern Medical University, from June 2021 to December 2024. Dynamic Cox regression and dynamic restricted mean survival time (RMST) regression based on the landmark method were adopted to establish the dynamic prediction models, and Monte Carlo cross-validation was used to evaluate model performance. Results The dynamic models could predict the incidence and onset time of JCV reactivation within the subsequent 3 months according to covariates at each landmark time point from the 1st to the 6th month after transplantation. Remuzzi score, body mass index and warm ischemia time were independent risk factors for JCV reactivation, while a history of urinary BK polyomavirus reactivation served as a protective factor. The median values of the area under the curve, C-index and Brier score of the dynamic Cox model were 0.873, 0.851 and 0.065 respectively, and the C-index of the dynamic RMST model was 0.829, all of which were superior to those of the static model. Conclusions The landmark-based dynamic models exhibit excellent predictive performance, which may integrate baseline data and post-transplant follow-up information to realize dynamic assessment of the risk and time window of JCV reactivation, thereby providing evidence for optimizing post-operative monitoring and individualized intervention strategies.

Chronic obstructive pulmonary disease （COPD） is a respiratory disease characterized by airflow limitation， and its high morbidity and disability rates pose a severe challenge to global public health. Traditional Chinese medicine （TCM） has demonstrated definite efficacy and distinctive characteristics in the treatment of COPD. Based on the understanding of ancient and modern physicians regarding the etiology， pathogenesis， and stage-based syndrome differentiation of COPD， this article systematically elaborates on the etiology， pathogenesis， and clinical principles of syndrome differentiation and treatment of COPD. COPD is characterized by deficiency at root and excess in manifestation， with the coexistence of deficiency and excess. Qi deficiency is the fundamental pathogenesis underlying the occurrence and development of COPD and runs throughout the entire disease course. The disease begins with deficiency of lung qi and gradually affects the spleen and kidney， leading to the internal generation of dampness， phlegm， and blood stasis. Phlegm and blood stasis are not only pathological products but also deep-rooted causes of recurrent disease. Together with qi deficiency， they are mutually causal and form a vicious cycle. During the acute exacerbation stage of COPD， phlegm and blood stasis constitute the predominant underlying pathology and are often induced by invasion of pathogenic factors due to deficiency of healthy Qi. In addition， innovative understandings of the etiology and pathogenesis of COPD have emerged from the perspectives of collateral disease， latent pathogens， smoke toxins， and dysfunction of the Shaoyang pivot. During the stable stage， deficiency of Qi in the lung， spleen， and kidney predominates and is often accompanied by phlegm and blood stasis. In the clinical differentiation and treatment of COPD， treatment should be based on different disease stages and syndrome characteristics. During the acute exacerbation stage， eliminating pathogenic factors is the primary principle， with treatment determined according to syndrome differentiation. For wind-cold attacking the lung， the treatment is to ventilate the lung， disperse cold， and relieve cough. For phlegm-dampness accumulating in the lung， the treatment is to dry dampness， resolve phlegm， and direct qi downward. For phlegm-heat obstructing the lung， the treatment is to clear the lung， resolve phlegm， and relieve asthma. For phlegm and blood stasis obstructing the lung， the treatment is to eliminate phlegm， remove blood stasis， and relieve asthma. During the stable stage， reinforcing healthy Qi is the key principle. For lung-spleen qi deficiency， the treatment is to tonify the lung and strengthen the spleen， resolve phlegm， and direct Qi downward to relieve asthma. For deficiency of both lung and kidney， the treatment is to tonify the lung and benefit the kidney， resolve phlegm， promote Qi reception， and relieve asthma. When accompanied by phlegm and blood stasis， the treatment should focus on tonifying deficiency， resolving phlegm， and removing blood stasis. This article aims to systematically summarize the TCM etiology， pathogenesis， syndrome differentiation and treatment principles of COPD， as well as the current shortcomings in related research， in order to provide a reference for the clinical treatment of COPD with TCM， give full play to the advantages of TCM in the prevention and treatment of COPD， and optimize the whole-course management of COPD.

Chronic obstructive pulmonary disease （COPD） is a respiratory disease characterized by airflow limitation， and its high morbidity and disability rates pose a severe challenge to global public health. Traditional Chinese medicine （TCM） has demonstrated definite efficacy and distinctive characteristics in the treatment of COPD. Based on the understanding of ancient and modern physicians regarding the etiology， pathogenesis， and stage-based syndrome differentiation of COPD， this article systematically elaborates on the etiology， pathogenesis， and clinical principles of syndrome differentiation and treatment of COPD. COPD is characterized by deficiency at root and excess in manifestation， with the coexistence of deficiency and excess. Qi deficiency is the fundamental pathogenesis underlying the occurrence and development of COPD and runs throughout the entire disease course. The disease begins with deficiency of lung qi and gradually affects the spleen and kidney， leading to the internal generation of dampness， phlegm， and blood stasis. Phlegm and blood stasis are not only pathological products but also deep-rooted causes of recurrent disease. Together with qi deficiency， they are mutually causal and form a vicious cycle. During the acute exacerbation stage of COPD， phlegm and blood stasis constitute the predominant underlying pathology and are often induced by invasion of pathogenic factors due to deficiency of healthy Qi. In addition， innovative understandings of the etiology and pathogenesis of COPD have emerged from the perspectives of collateral disease， latent pathogens， smoke toxins， and dysfunction of the Shaoyang pivot. During the stable stage， deficiency of Qi in the lung， spleen， and kidney predominates and is often accompanied by phlegm and blood stasis. In the clinical differentiation and treatment of COPD， treatment should be based on different disease stages and syndrome characteristics. During the acute exacerbation stage， eliminating pathogenic factors is the primary principle， with treatment determined according to syndrome differentiation. For wind-cold attacking the lung， the treatment is to ventilate the lung， disperse cold， and relieve cough. For phlegm-dampness accumulating in the lung， the treatment is to dry dampness， resolve phlegm， and direct qi downward. For phlegm-heat obstructing the lung， the treatment is to clear the lung， resolve phlegm， and relieve asthma. For phlegm and blood stasis obstructing the lung， the treatment is to eliminate phlegm， remove blood stasis， and relieve asthma. During the stable stage， reinforcing healthy Qi is the key principle. For lung-spleen qi deficiency， the treatment is to tonify the lung and strengthen the spleen， resolve phlegm， and direct Qi downward to relieve asthma. For deficiency of both lung and kidney， the treatment is to tonify the lung and benefit the kidney， resolve phlegm， promote Qi reception， and relieve asthma. When accompanied by phlegm and blood stasis， the treatment should focus on tonifying deficiency， resolving phlegm， and removing blood stasis. This article aims to systematically summarize the TCM etiology， pathogenesis， syndrome differentiation and treatment principles of COPD， as well as the current shortcomings in related research， in order to provide a reference for the clinical treatment of COPD with TCM， give full play to the advantages of TCM in the prevention and treatment of COPD， and optimize the whole-course management of COPD.

ObjectiveTo investigate the improvement effect of Qibai Pingfei capsules on pulmonary vascular remodeling in rats at different stages of chronic obstructive pulmonary disease （COPD） and to analyze its possible mechanism of action. MethodsMale Sprague-Dawley （SD） rats were randomly divided into a normal group， an early COPD model group， an advanced COPD model group， an early-intervention high-dose group， a late-intervention high-dose group， an early-intervention low-dose group， a late-intervention low-dose group， an early-intervention pyrrolidine dithiocarbamate （PDTC） group， and a late-intervention PDTC group， with 15 rats in each group. A rat model of early COPD was constructed by using cigarette smoke combined with airway infusion using lipopolysaccharide（LPS）， and a rat model of advanced COPD was constructed by using airway infusion with LPS， cigarette smoke， and hypoxia. All groups except the normal group were given LPS airway drops on days 1 and 14 of the experiment， smoked for 1 h per day， and administered the drug once a day for 40 weeks from day 15 onward. In the high- and low-dose groups， rats were given 1 g·kg^-1 and 250 mg·kg^-1 Qibai Pingfei capsules， respectively by gavage， and in PDTC groups， rats were given 100 mg·kg^-1 of PDTC by intraperitoneal injection. The advanced COPD model group underwent 6 h of hypoxia per day in weeks 5-6. Lung function and mean pulmonary artery pressure were tested in rats. Morphologic changes in lung tissues were detected by hematoxylin-eosin（HE）staining. Collagen deposition in lung tissues was examined by Masson staining， and the levels of inflammatory factors including interleukin-1β（IL-1β）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α）in lung tissues were detected by enzyme-linked immunosorbent assay （ELISA）. The number of inflammatory cells in the alveolar lavage fluid of rats in each group was detected by Giemsa staining， and the protein expression of Toll-like receptor 4（TLR4）， myeloid differentiation factor 88（MyD88）， nuclear factor-κB（NF-κB）， TNF-α， vascular endothelial-cadherin（VE-cadherin）， α-smooth muscle actin（α-SMA）， and platelet endothelial cell adhesion molecule-1（CD31） was detected by Western blot in the lung tissues of rats. ResultsCompared with the normal group， the model group showed significantly decreased forced expiratory volume in 0.3 s （FEV_0.3）， forced vital capacity （FVC）， and FEV_0.3/FVC ratio related to lung function （P<0.05）， thickening of pulmonary vasculature， increased collagen deposition in the lungs， and enhanced mean pulmonary arterial pressure and expression levels of IL-6， IL-1β， and TNF-α （P<0.05）. Additionally， the model group also exhibited increased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， significantly higher protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05）， and significantly lower protein expression of VE-cadherin and CD31 （P<0.05）. Lung function was significantly improved in the Qibai Pingfei capsules groups compared with the model group （P<0.05）， with mean pulmonary arterial pressure reduced and pulmonary vascular thickening and collagen deposition in the lungs ameliorated. The Qibai Pingfei capsules groups also showed reduced expression levels of IL-6， IL-1β， and TNF-α （P<0.05） and decreased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， as well as reduced protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05） and elevated protein expression of VE-cadherin and CD31 （P<0.05） in rat lung tissues. ConclusionQibai Pingfei capsules inhibits inflammatory response and endothelial-to-mesenchymal transition probably by regulating the TLR4/NF-κB signaling pathway， thus improving pulmonary vascular remodeling in COPD model rats and showing therapeutic effects in the early stage of COPD.

BACKGROUND:Autologous or artificial bone grafts have been widely used to repair maxillofacial bone defects clinically,but these methods still suffer from insufficient osteogenesis.Bone marrow mesenchymal stem cells play a key role in the bone formation.Notably,ectoderm-derived jaw bone marrow mesenchymal stem cells have stronger proliferation and osteogenic differentiation capacity compared with mesoderm-derived iliac bone marrow mesenchymal stem cells,elucidating the key mechanisms involved.It is expected to provide a new strategy for the repair of craniomaxillofacial bone defects.OBJECTIVE:To compare the biological differences between human jaw bone marrow mesenchymal stem cells and iliac bone marrow mesenchymal stem cells and identify the key regulatory genes.METHODS:(1)Jaw bone and iliac bone were collected from three patients with alveolar cleft.Primary bone marrow mesenchymal stem cells were isolated and cultured.Cell proliferation ability was detected by colony formation assay.Cell senescence was detected by β-galactosidase staining assay.Senescence and osteogenesis-related protein expression levels were detected by western blot assay.Osteogenic ability was detected by alizarin red staining after osteogenic induction solution treatment.(2)Jaw bone marrow mesenchymal stem cells and iliac bone marrow mesenchymal stem cells were subjected to transcriptome and differential gene expression analysis to find the 20 genes with the largest differential expression and identify the key regulatory factors.(3)The gene in iliac bone marrow mesenchymal stem cells were knocked down to comparatively analyze the changes in self-renewal,anti-aging and osteogenic capacity of iliac bone marrow mesenchymal stem cells.(4)The gene-edited iliac bone marrow mesenchymal stem cells were loaded into β-tricalcium phosphate scaffolds and implant into nude mice for 8 weeks.The scaffolds were stained with Masson staining and immunofluorescence staining to observe the difference in osteogenic capacity.RESULTS AND CONCLUSION:(1)Jaw bone marrow mesenchymal stem cells have stronger proliferation,anti-aging and osteogenic differentiation abilities compared to iliac bone marrow mesenchymal stem cells.(2)By transcriptome analysis,we identified HOXA10 as a highly up-regulated core transcription factor in iliac bone marrow mesenchymal stem cells.(3)After knocking down HOXA10 in iliac bone marrow mesenchymal stem cells,we observed a significant increase in proliferation,anti-aging,and osteogenic differentiation abilities.(4)After HOXA10 knocked-down iliac bone marrow mesenchymal stem cells/β-tricalcium phosphate was implanted subcutaneously on the back of nude mice,and their bone formation ability was stronger.(5)The above results suggest that HOXA10 is a key regulatory gene that determines the proliferative,anti-aging and osteogenic differentiation abilities of bone marrow mesenchymal stem cells.HOXA10 gene-modified iliac bone marrow mesenchymal stem cell transplantation can be used as a potential application strategy for repairing maxillofacial bone defects.

Objective To provide experimental evidence for selecting acupuncture timing in clinical practice,the optimal time for enhancing the brain effects of electroacupuncture at the Hegu acupoint(LI4)by observing brain imaging data,hemodynamic changes and differences in brain functional connectivity across the twelve traditional Chinese time periods were determined.Methods Thirty-six C57BL/6 mice were randomly divided into 12 groups corresponding to each of the twelve time periods(Zi,Chou,Yin,Mao,Chen,Si,Wu,Wei,Shen,You,Xu,Hai),with 3 mice per group.Each mouse received electroacupuncture stimulation using the same protocol.Brain imaging data and dynamic hemodynamic changes were collected using functional ultrasound imaging(FUS)ultrasound imaging technology every 0.4 s over a total duration of 420 s,covering pre-acupuncture(resting state),during acupuncture(task state),and post-acupuncture(post-task state)phases.The hippocampal region(HIP)was used as the observation point to analyze changes in functional connectivity between HIP and other brain regions before and after acupuncture.Results Compared to other time periods,the Mao group exhibited the largest whole-brain activation area and the highest average activation signal intensity.The hemodynamic signal increase in the hippocampal region was more pronounced,and the post-acupuncture blood flow signal intensity remained significantly higher than the pre-acupuncture resting state.Functional connectivity data revealed that,using 0.2 as the standard value,the Mao group showed the greatest number of altered brain regions before and after acupuncture.Notably,only in the Mao group was there a significant enhancement in connectivity between the bilateral hippocampal regions.Conclusion The immediate effects of electroacupuncture at the Hegu acupoint(LI4)and brain functional connectivity vary significantly across different time periods,aligning with the traditional Chinese medicine theory of meridian qi and blood flow.Mao time is identified as the optimal period.

OBJECTIVES: This study aims to compare the effects of two orthodontic treatment modalities for skeletal class Ⅲ malocclusion on specific changes in airway volume, morphology, palatal angle, mandibular rotation, and bone displacement. Results provide scientific evidence for the selection of orthodontic treatment plans and reduce the risk of developing obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Thirty-six patients diagnosed with skeletal class Ⅲ malocclusion at the Department of Orthodontics, the Affiliated Stomatological Hospital of Nanjing Medical University from September 2018 to December 2023 were divided into two groups: orthodontic-orthognathic treatment group (18 patients) and camouflage orthodontic treatment group (18 patients). Changes in airway volume, cross-sectional area, palatal angle, mandibular, and tongue positions were observed through pre- and post-operative cone beam computed tomography and 3D cephalometric measurements. RESULTS: In the camouflage orthodontic treatment group, nasopharyngeal volume and oropharyngeal volume statistically increased after treatment (P<0.05). In the orthodontic-orthognathic treatment group, changes in nasopharyngeal volume, nasopharyngeal airway, distance from posterior tongue to pharyngeal wall, palatal angle, mandibular rotation, and hyoid bone displacement were statistically significant after surgery (P<0.05). In the comparison between the two groups after treatment, changes in the distance from posterior tongue to pharyngeal wall, palatal angle, and distance from hyoid bone to sella turcica point were statistically significant (P<0.05). CONCLUSIONS Patients in the orthodontic-orthognathic treatment group showed significantly greater changes in oropharyngeal cross-sectional area, palate angle, and tongue position compared with patients in the camouflage orthodontic treatment group. As individuals susceptible to OSAHS often exhibit mandibular retrusion and decreased minimum airway cross-sectional area, special attention should be paid to airway morphology changes when adopting orthodontic-orthognathic treatment to avoid adverse consequences.
Humans ; Hyoid Bone/diagnostic imaging* ; Malocclusion, Angle Class III/therapy* ; Male ; Female ; Cone-Beam Computed Tomography ; Cephalometry ; Orthodontics, Corrective/methods* ; Adult ; Mandible ; Pharynx/diagnostic imaging* ; Sleep Apnea, Obstructive/etiology* ; Orthognathic Surgical Procedures

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.