OBJECTIVE To investigate the effects of quercetin （QUE） on intervertebral disc degeneration in rats with lumbar intervertebral disc herniation （LDH） and explore its mechanism based on the forkhead box protein O3/silent information regulator 1 （FOXO3/Sirt1） pathway. METHODS A rat model of LDH was established. The successfully modeled rats were randomly divided into LDH group （gavaged with and intraperitoneally injected with an equal volume of normal saline）， QUE-L group （gavaged with 50 mg/kg QUE+intraperitoneally injected with an equal volume of normal saline）， QUE-H group （gavaged with 100 mg/kg QUE+ intraperitoneally injected with an equal volume of normal saline）， and QUE-H+EX-527 （a Sirt1 inhibitor） group （gavaged with 100 mg/kg QUE+intraperitoneally injected with 1 mg/kg EX-527）， with 12 rats in each group. Additionally， 12 healthy normal rats were selected as the control group （gavaged with and intraperitoneally injected with an equal volume of normal saline）. All rats were administered the corresponding agents once daily for consecutive 8 weeks. After the final administration， the pain threshold and serum levels of inflammatory factors in rats were measured； pathological damage of lumbar intervertebral disc tissue was observed， the apoptosis of nucleus pulposus cells in lumbar intervertebral disc tissue was assessed， and the expression levels of matrix metalloproteinase-3 （MMP-3）， phospholipase A2 （PLA2）， as well as apoptosis-related proteins and FOXO3/Sirt1 pathway- related proteins in intervertebral disc tissue were determined. RESULTS Compared with LDH group， pathological damage of intervertebral disc tissue were improved significantly in QUE-L group and QUE-H group； paw withdrawal mechanical threshold， paw withdrawal thermal latency， the serum levels of transforming growth factor-β1 and interleukin-10 （IL-10） as well as the expression levels of B-cell lymphoma-2 （Bcl-2）， FOXO3 and Sirt1 were significantly increased or prolonged （P＜0.05）. Serum levels of tumor necrosis factor-α and IL-1β， histopathological score of intervertebral disc tissue， apoptotic rate of nucleus pulposus cells， positive expressions of MMP-3 and PLA2 in intervertebral disc tissue and expression levels of Bcl-2 associated X protein were significantly decreased （P＜0.05）. Compared with the QUE-H group， the QUE-H+EX-527 group presented aggravated pathological damage of intervertebral disc tissue， and the trends of all the above indicators were significantly reversed（P＜0.05）. CONCLUSIONS QUE can ameliorate intervertebral disc degeneration in LDH rats， and its mechanism may be related to the activation of the FOXO3/Sirt1 pathway.

Objective To explore the predictive value of artificial intelligence (AI)-based lung nodule CT quantitative analysis for the invasion degree of lung adenocarcinoma spectrum lesions. Methods According to the invasion degree of lung adenocarcinoma spectrum lesions, patients with surgically and pathologically confirmed lung adenocarcinoma spectrum lesions from January to June 2023 in Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University were retrospectively collected and divided into a non-invasive group and an invasive group, including atypical adenomatous hyperplasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma patients in the non-invasive group, and invasive adenocarcinoma patients in the invasive group. All enrolled patients underwent chest CT before surgery, and then the lung nodules were quantitatively analyzed using an AI-based computer-aided diagnosis system to compare the related quantitative parameters of lung nodules that have been surgically removed and pathologically confirmed as lung adenocarcinoma spectrum lesions between the two groups. The relationship between various CT quantitative features and the invasion degree of lung adenocarcinoma spectrum lesions was analyzed. Results A total of 149 patients (149 lesions) were included, including 42 males and 107 females, aged 29-81 (56.35±10.75) years. There were 72 patients in the non-invasive group and 77 patients in the invasive group. Statistical differences were observed between the two groups in long diameter, short diameter, volume, surface area, mass, maximum cross-sectional area, 3D long diameter, maximum CT value, minimum CT value, average CT value, entropy, kurtosis, skewness, malignancy probability and other indicators (P<0.05). Multivariate binary logistic regression analysis showed that long diameter [OR=1.687, 95%CI (1.364, 2.085), P<0.001], average CT value [OR=1.006, 95%CI (1.002, 1.009), P=0.002], and malignancy probability [OR=1.034, 95%CI (1.005, 1.063), P=0.020] were independent risk factors for the invasion degree of lung adenocarcinoma. The predictive model combining the above parameters demonstrated optimal performance, with an area under the receiver operating characteristic curve of 0.951, sensitivity of 0.818, and specificity of 0.972. Using a Nomogram to quantify the three independent risk factors, the cross-validation was performed to evaluate the stability of the model, and the average C-index of cross-validation was 0.950, with each fold C-index >0.75, indicating that the prediction performance of the model was stable, and the calibration curve and decision curve indicated good predictive performance. Conclusion The visualization prediction model constructed by AI-based quantitative analysis of lung nodules in CT demonstrates significant discriminative effectiveness in the assessment of invasiveness in lung adenocarcinoma spectrum lesions. This visualization prediction model can provide a quantitative decision-making basis for the preoperative identification of the degree of invasiveness in lung adenocarcinoma spectrum lesions.

ObjectiveTo evaluate the clinical efficacy and safety of Tengshen Granules in the treatment of grade 1 hypertension with the syndrome of severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency. MethodsA total of 120 patients with grade 1 hypertension presenting with severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency were enrolled in a randomized， double-blind， placebo-controlled， parallel-group clinical trial. Patients were randomly assigned to the observation group （Tengshen granules） and the control group （placebo）， with 60 cases in each group. On the basis of lifestyle intervention， treatment was administered for 8 weeks followed by a 2-month follow-up. During the study period， traditional Chinese medicine （TCM） syndrome scores， blood pressure， antihypertensive efficacy， blood pressure control rate， and other indicators were recorded and analyzed， and safety was evaluated. ResultsA total of 114 patients completed the trial， including 57 in the control group and 57 in the observation group. Compared with baseline， TCM syndrome scores， systolic blood pressure， and diastolic blood pressure in the observation group were significantly reduced after treatment （P<0.01）. Compared with the control group after treatment， systolic blood pressure in the observation group was lower from week 4 of medication （P<0.05）， and this difference persisted until 2 months after drug discontinuation. For diastolic blood pressure， the observation group was superior to the control group at week 8 （P<0.01）， with no statistically significant differences at other time points. Regarding syndrome improvement， the TCM syndrome scores for severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency showed significant improvement at weeks 6 and 8 of treatment， with the observation group superior to the control group （P<0.05）. During the 1-month follow-up after drug discontinuation， the syndrome scores in the observation group remained lower than those in the control group （P<0.01）. The total effective rate of antihypertensive efficacy in the observation group was higher than that in the control group （χ²=11.389， P<0.05）. In addition， the level of urinary microalbumin in the observation group was lower after treatment than before treatment （P<0.05）. ConclusionTengshen granules demonstrate significant clinical efficacy and good safety in the treatment of grade 1 hypertension with severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency. They can effectively reduce blood pressure and improve related TCM syndrome manifestations.

ObjectiveTo evaluate the clinical efficacy and safety of Tengshen Granules in the treatment of grade 1 hypertension with the syndrome of severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency. MethodsA total of 120 patients with grade 1 hypertension presenting with severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency were enrolled in a randomized， double-blind， placebo-controlled， parallel-group clinical trial. Patients were randomly assigned to the observation group （Tengshen granules） and the control group （placebo）， with 60 cases in each group. On the basis of lifestyle intervention， treatment was administered for 8 weeks followed by a 2-month follow-up. During the study period， traditional Chinese medicine （TCM） syndrome scores， blood pressure， antihypertensive efficacy， blood pressure control rate， and other indicators were recorded and analyzed， and safety was evaluated. ResultsA total of 114 patients completed the trial， including 57 in the control group and 57 in the observation group. Compared with baseline， TCM syndrome scores， systolic blood pressure， and diastolic blood pressure in the observation group were significantly reduced after treatment （P<0.01）. Compared with the control group after treatment， systolic blood pressure in the observation group was lower from week 4 of medication （P<0.05）， and this difference persisted until 2 months after drug discontinuation. For diastolic blood pressure， the observation group was superior to the control group at week 8 （P<0.01）， with no statistically significant differences at other time points. Regarding syndrome improvement， the TCM syndrome scores for severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency showed significant improvement at weeks 6 and 8 of treatment， with the observation group superior to the control group （P<0.05）. During the 1-month follow-up after drug discontinuation， the syndrome scores in the observation group remained lower than those in the control group （P<0.01）. The total effective rate of antihypertensive efficacy in the observation group was higher than that in the control group （χ²=11.389， P<0.05）. In addition， the level of urinary microalbumin in the observation group was lower after treatment than before treatment （P<0.05）. ConclusionTengshen granules demonstrate significant clinical efficacy and good safety in the treatment of grade 1 hypertension with severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency. They can effectively reduce blood pressure and improve related TCM syndrome manifestations.

Objective To explore the predictive value of the classification of carotid plaque reporting and data system (Plaque-RADS) and ultrasound features for the severity of coronary artery stenosis. Methods This was a single-center prospective observational study. Patients with suspected coronary artery disease or at high cardiovascular risk, who were hospitalized in the Department of Cardiology of Zhongshan Hospital, Fudan University from July 2023 to June 2024, were consecutively enrolled and divided into mild-to-moderate stenosis group and severe stenosis group according to the degree of coronary artery stenosis. Clinical parameters, carotid ultrasound features, and Plaque-RADS classification were compared between the two groups. A multivariate logistic regression model was constructed, and its predictive performance was assessed using receiver operating characteristic curve. Results A total of 271 patients were included, with age of (65.49±9.44) years. The proportion of males, patients with diabetes and hyperlipidemia, and smokers was significantly higher in the severe stenosis group, accompanied by greater plaque thickness as well as lower maximum elasticity (E_max) and mean elasticity (E_mean; P＜0.05). Statistically significant differences were also observed between the two groups in target plaque location, Plaque-RADS classification, and plaque stability distribution (P＜0.05). Specifically, type Ⅱ plaques predominated in the mild-to-moderate stenosis group, whereas the severe stenosis group had a higher proportion of type Ⅲ plaques and vulnerable plaques. Multivariate logistic regression analysis demonstrated that male, diabetes, and type Ⅲ–Ⅳ plaques were risk factors for severe coronary artery stenosis, while E_max served as a protective factor. The predictive model constructed by the above indicators exhibited favorable predictive performance (AUC＝0.838). Conclusions The combination of Plaque-RADS classification, E_max, sex, and comorbid diabetes has certain predictive value for the severity of coronary artery stenosis.

This study employs ultra-performance liquid chromatography(UPLC) to analyze the differences in alkaloid content of Commelina communis from various geographical origins, exploring its feasibility as a quality evaluation indicator. A total of 57 batches of C. communis samples from 23 provinces, autonomous regions, and municipalities in China were selected. The MicroPulite HSS T3(2.1 mm×50 mm, 1.8 μm)column was used with a mobile phase of acetonitrile-0.2% phosphoric acid aqueous solution(20∶80), detection wavelength at 254 nm, and a flow rate of 0.3 mL·min~(-1) to measure the content of 1-deoxynojirimycin(DNJ) and deoxymannojirimycin(DMJ). The MicroPulite XP tC_(18)(2.1 mm×100 mm, 1.7 μm)column was employed with a mobile phase of acetonitrile-0.2% phosphoric acid aqueous solution(4∶96), detection wavelength at 254 nm, and a flow rate of 0.4 mL·min~(-1) to measure the content of norharmine(NHM) and harmanme(HM). Chemometric methods were applied to study the relationships and differences among the 57 batches of C. communis. Significant differences in alkaloid content were observed among C. communis from different regions, with the average total content decreasing in the order of North China, Northeast China, Northwest China, East China, Southwest China, Central China, and South China. Cluster analysis(CA) and principal component analysis(PCA) further revealed the quality differences of C. communis from various origins, and partial least squares discriminant analysis(PLS-DA) identified DNJ as a marker compound to distinguish the quality differences between different geographical sources of C. communis. It is recommended that the content limit of DNJ be set at no less than 0.055 9%, providing a reference for the quality evaluation and clinical application of C. communis medicinal materials.
Alkaloids/analysis* ; Drugs, Chinese Herbal/chemistry* ; China ; Chromatography, High Pressure Liquid ; Chemometrics/methods* ; Quality Control

As one of the chronic diseases with high incidence in contemporary society, cervical spondylosis has increasing patient groups who gradually present a low age, and it seriously affects social and public health. Although modern medicine has made great progress in the pathological research and clinical treatment of cervical spondylosis, patients still face gastrointestinal side effects of nonsteroidal anti-inflammatory drugs(NSAIDs), neck pain, limited mobility, upper limb numbness, and other symptoms after conservative or surgical treatment. In the theory of traditional Chinese medicine(TCM), cervical spondylosis belongs to the categories of "Bi syndrome" "stiff neck" "stiff Bi", etc. With the change of the times, the change of lifestyle, and the application of western medicine treatment, the etiology and pathogenesis of TCM in cervical spondylosis also show new characteristics. In terms of etiology and pathogenesis, it involves the invasion of wind, cold, and dampness, long-term strain, liver and kidney deficiency, Qi and blood stasis, which are associated with factors such as cervical degeneration, muscle tension and spasm, intervertebral disc herniation, and nerve root compression in modern medicine. In terms of the evolution of pathogenesis, in the early stage, wind, cold, and dampness, were more common in Xuanfu, resulting in unfavorable muscles and bones, poor flow of Qi and blood, and cervical spondylosis and radiculopathy. Medium-term phlegm stasis and internal knots, sluggish muscles and veins, and long-term weathering and fire are more likely to occur in the vertebral artery and sympathetic radiculopathy. In the later stage, the positive Qi is depleted; the true Yin is damaged, and the viscera Qi and blood are deficient, which is most common in cervical myelopathy. The strategy of treating cervical spondylosis with TCM classic formulas applies Gegen Decoction, Wutou Decoction, Qianghuo Shengshi Decoction, Mahuang Jiazhu Decoction to patients with wind, cold, and dampness. Patients with phlegm dampness and blood stasis are treated with Huoxue Xiaoling Dan, Jinlingzi Powder, Siwu Decoction, Banxia Baizhu Tianma Decoction, Shuanghe Decoction, etc. For those patients with liver, spleen, and kidney deficiency, Huangqi Guizhi Wuwu Decoction, Tianma Gouteng Decoction, Guishao Dihuang Pills, Shenling Baizhu Powder, and Lizhong Decoction are used to invigorate the spleen, nourish Qi and blood, and tonify liver and kidney. In clinical practice, the authors advocate a safe and effective treatment plan of classic formulas based on deficiency and excess, the integration of formulas and syndromes, and the combination of modern research results, so as to relieve symptoms, reduce recurrence, and reduce medical burden.
Humans ; Spondylosis/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Cervical Vertebrae/pathology*

Objective:To analyze the distribution characteristics of sports facilities in China using geographic information system (ArcGIS) and to investigate their association with mortality risk among residents.Methods:This prospective cohort study included 97 912 community residents from the Chinese Family Database (CFD) between 2013 and 2017. After excluding participants lost to follow-up and those with incomplete data, 53 937 individuals were retained for the analysis. The distribution characteristics of sports facilities in China was mapped using ArcGIS, and the death events were recorded via structured interviews and questionnaires. The Poisson regression was used to assess the association between the distribution characteristics of sports facilities near participants′ residences and their mortality risk.Results:In 2013, a total of 79 714 sports facilities were identified across 262 districts (counties) in China, with large-scale sports facilities accounting for the highest proportion (87.09%). The median number of sports facilities within the residential buffer zone was 17 (4, 30), and the median distance from the residence to the nearest sports facility was 453.2 (341.5, 1 863.5) m. Among the 53 937 community residents analyzed in this study, there were 27 761 males and 26 176 females, 1 326 deaths (2.5%) occurred during the follow-up. Poisson regression revealed that a higher number of sports facilities in the buffer zone (≥21 vs 0-2) was associated with lower mortality risk ( RR=0.74, 95% CI: 0.64-0.85; P0.05). Subgroup analyses showed that being≥60 years old ( RR=0.82, 95% CI: 0.70-0.95), males ( RR=0.78, 95% CI: 0.64-0.95), females ( RR=0.79, 95% CI: 0.64-0.97), having a junior high school education or less ( RR=0.84, 95% CI: 0.71-0.99), and having a urban residence ( RR=0.77, 95% CI: 0.66-0.90) were all negatively associated with residents′ mortality risk (all P0.05). After adjusting for age, greater distance to the nearest sports facility ( RR=1.41, 95% CI: 1.08-1.83) and failing to meet the"10-minute fitness circle"criterion ( RR=1.25, 95% CI: 1.02-1.53) were associated with higher mortality risk among males (both P0.05). After adjusting for age and gender, urban residents with a greater distance to the nearest sports facility ( RR=1.29, 95% CI: 1.04-1.60) or not meeting the 10-minute fitness circle ( RR=1.18, 95% CI: 1.00-1.38) showed a significantly higher mortality risk (both P0.05). Conclusions:The ArcGIS analysis revealed that the distribution of sports facilities in China is characterized by a high proportion of large-scale facilities. Lower facility density within residential buffer zone and greater distance to the nearest facility increase mortality risk among adults.

Objective:To investigate the efficacy of Saussurea involucrata injection (SII) in alleviating rheumatoid arthritis (RA) and to explore the mechanism of action of SII in alleviating RA through the Toll-like receptor 4 (TLR4)/nuclear factor-kappaBp65 (NF-κBp65) pathway-mediated M1 macrophage polarization.Methods:In vivo experiments were conducted using a collagen-induced arthritis (CIA) rat model. After successful modeling, the CIA rats were randomly assigned into five groups ( n=10 per group): CIA control group, MTX group, low-dose SII (L-SII) group, medium-dose SII (M-SII) group, and high-dose SII (H-SII) group. The efficacy of SII in alleviating RA was evaluated using arthritis index scores, histopathology, and ELISA to measure serum levels of nitric oxide (NO), interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Subsequently, Western blot analysis was used to detect the expression of inducible nitric oxide synthase (iNOS) and CD86 proteins in synovial tissue. In vitro experiments involved first isolating and inducing rat bone marrow-derived macrophages (BMDMs). Then, BMDMs were polarized toward the M1 phenotype using lipopolysaccharide (LPS) combined with interferon-γ (IFN-γ). Concurrently, cells were treated with SII and the TLR4 inhibitor TAK242. Subsequently, ELISA was used to detect NO, IL-1β, TNF-α levels in the cell culture supernatant via ELISA. RT-qPCR was used to detect the expression of IL-1b, IL-6, and TNF-α genes in each group of cells. Western blot analysis was performed to detect the expression of iNOS, CD86, TLR4, myeloid differentiation primary response 88 (MyD88), and p-NF-κBp65/NF-κBp65 proteins in the cells. Data analysis between multiple groups was performed using one-way analysis of variance, and between pairs using LSD- t-tests. Results:In vivo experimental results showed that compared with the CIA group(7.90 ± 0.70), MTX and SII both improved the pathological symptoms of rats and reduced the ankle joint pathological score [MTX (4.40 ± 0.92), L-SII (7.00 ± 0.89), M-SII (5.10 ± 1.30), H-SII (4.90 ± 0.94), t=33.86, P<0.001; t=9.10, P<0.001; t=2.38, P=0.029; t=5.69, P<0.001; t=7.66, P<0.001], while downregulating serum levels of NO, IL-1β, IL-6, and TNF-α levels in serum, as well as iNOS [ t=30.01, P<0.001; t=6.17, P=0.003; t=10.86, P<0.001; t=28.95, P<0.001; t=19.03, P<0.001] and CD86 [ t=65.61, P<0.001; t=8.76, P<0.001; t=13.18, P<0.001; t=13.22, P<0.001; t=18.91, P<0.001] expression. In vitro experimental results showed that compared with BMDMs treated with LPS and IFN-γ, SII and TAK242 treatment reduced the levels of NO, IL-1β, IL-6, and TNF-α in the supernatant and decreased the expression of IL-1b, IL-6, and TNF-α genes. Additionally, SII and TAK242 treatment downregulated the expression of iNOS and CD86 proteins in cells, and simultaneously downregulated TLR4, MYD88, and p-NF-κBp65/NF-κBp65 expression ( t=35.84, P<0.001; t=15.69, P<0.001; t=21.99, P<0.001; t=23.64, P<0.001; t=22.50, P<0.001). Additionally, compared with the TAK242 group alone, TAK242 + H-SII showed no significant differences in the modulation of M1 macrophage polarization and TLR4/NF-κBp65 pathway-related indicators. Conclusion:SII exerts anti-inflammatory and anti-RA effects by inhibiting TLR4/NF-κBp65-mediated M1 macrophage polarization.

Objective:To develop and externally validate a nomogram prediction model for assessing the risk of treatment dropout in allergic rhinitis (AR) patients undergoing sublingual immunotherapy (SLIT).Methods:Between February 2016 and December 2019, data from 358 and 259 AR patients undergoing SLIT were collected from Guizhou Provincial People′s Hospital and Huangshi Central Hospital, respectively. The data included general patient information, dust mite sIgE levels, allergen types, and 22 other clinical variables. Data from Guizhou Provincial People′s Hospital were used as the training set, while data from Huangshi Central Hospital were served as the external validation set. A multivariable Cox regression model was used to identify independent factors associated with SLIT dropout and to develop a nomogram prediction model.Results:Multivariate Cox regression analysis identified several significant factors influencing SLIT dropout, including dust mite sIgE levels (Grade Ⅱ-Ⅳ; HR=1.48, 95% CI: 1.16-1.88), presence of other allergic diseases ( HR=0.47, 95% CI: 0.37-0.61), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score ( HR=0.98, 95% CI: 0.97-1.00), WeChat management ( HR=0.77, 95% CI: 0.60-0.98), treatment efficacy ( HR=0.72, 95% CI: 0.56-0.92), age (5-17 years, HR=0.50, 95% CI: 0.36-0.71;≥60 years, HR=1.42, 95% CI: 1.08-1.87), household income (<5 000 CNY, HR=1.44, 95% CI: 1.09-1.90;>20 000 CNY, HR=0.66, 95% CI: 0.44-0.99), allergen types (single dust mite, HR=0.70, 95% CI: 0.49-0.93; and combined pollen or mold, HR=1.45, 95% CI: 1.02-2.04), and time to efficacy <3 months ( HR=0.73, 95% CI: 0.56-0.94), all P<0.05. At the third-year follow-up, the area under curve (AUC) for the nomogram model was 0.913 (95% CI: 0.881-0.943) in the training group and 0.886 (95% CI: 0.838-0.933) in the validation group. Calibration and decision curve analyses demonstrated the model′s consistency with actual dropout rates and clinical benefit in both groups. Additionally, a Brier score of 0.29 further confirmed the model′s predictive accuracy. Conclusion:We successfully develop a nomogram-based prediction model for SLIT dropout in AR patients, which could assist healthcare professionals in effectively identifying high-risk patients and facilitate the development of more personalized and timely treatment plans aimed at enhancing patient compliance.