ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

OBJECTIVE:The main clinical manifestations of knee osteoarthritis are pain,swelling,stiffness,and limited activity,which have a serious impact on the life of patients.Exercise therapy can effectively improve the related symptoms of patients with knee osteoarthritis.This paper uses the method of network meta-analysis to compare the efficacy of different exercise types in the treatment of knee osteoarthritis. METHODS:CNKI,WanFang,PubMed,Embase,Cochrane Library,Web of Science,Scopus,Ebsco,SinoMed,and UpToDate were searched with Chinese search terms"knee osteoarthritis,exercise therapy"and English search terms"knee osteoarthritis,exercise".Randomized controlled trials on the application of different exercise types in patients with knee osteoarthritis from October 2013 to October 2023 were collected.The outcome measures included visual analog scale,Western Ontario and McMaster Universities Osteoarthritis Index score,Timed Up and Go test,and 36-item short form health survey.Literature quality analysis was performed using the Cochrane Manual recommended tool for risk assessment of bias in randomized controlled trials.Two researchers independently completed the data collection,collation,extraction and analysis.RevMan 5.4 and Stata 18.0 software were used to analyze and plot the obtained data. RESULTS:A total of 29 articles with acceptable quality were included,involving 1 633 patients with knee osteoarthritis.The studies involved four types of exercise:aerobic training,strength training,flexibility/skill training,and mindfulness relaxation training.(1)The results of network meta-analysis showed that compared with routine care/health education,aerobic training could significantly improve pain symptoms(SMD=-3.26,95%CI:-6.33 to-0.19,P<0.05);strength training(SMD=-0.79,95%CI:-1.34 to-0.23,P<0.05)and mindfulness relaxation training(SMD=-0.79,95%CI:-1.23 to-0.34,P<0.05)could significantly improve the function of patients.Aerobic training(SMD=-1.37,95%CI:-2.24 to-0.51,P<0.05)and mindfulness relaxation training(SMD=-0.41,95%CI:-0.80 to-0.02,P<0.05)could significantly improve the functional mobility of patients.Mindfulness relaxation training(SMD=0.70,95%CI:0.21-1.18,P<0.05)and strength training(SMD=0.42,95%CI:0.03-0.81,P<0.05)could significantly improve the quality of life of patients.(2)The cumulative probability ranking results were as follows:pain:aerobic training(86.6%)>flexibility/skill training(60.1%)>strength training(56.8%)>mindfulness relaxation training(34.7%)>routine care/health education(11.7%);Knee function:strength training(73.7%)>mindfulness relaxation training(73.1%)>flexibility/skill training(56.1%)>aerobic training(39.9%)>usual care/health education(7.6%);Functional mobility:aerobic training(94.7%)>mindfulness relaxation training(65.5%)>strength training(45.1%)>flexibility/skill training(41.6%)>routine care/health education(3.2%);Quality of life:mindfulness relaxation training(91.3%)>strength training(68.0%)>flexibility/skill training(44.3%)>aerobic training(34.0%)>usual care/health education(12.3%). CONCLUSION:(1)Exercise therapy is effective in the treatment of knee osteoarthritis,among which aerobic training has the best effect on relieving pain and improving functional mobility.Strength training and mindfulness relaxation training has the best effect on improving patients'function.Mindfulness relaxation training has the best effect on improving the quality of life of patients.(2)Limited by the quality and quantity of the included literature,more high-quality studies are needed to verify it.

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

The chemical constituents in dried roots of Atractylodes macrocephala were investigated in this study. Through utilizing normal-phase silica gel and ODS column chromatography, TLC, and semi-preparative HPLC, 4 new sesquiterpenoids were purified from the ethyl acetate extract of A. macrocephala. By various spectroscopic techniques, such as 1D and 2D NMR, HR-ESI-MS, IR, UV, and CD, their structures were identified as atractylmacron A (1), 9β-hydroxyasterolide (2), atractylenolide H (3), atractylenolide J (4). Compound 1 possesses a rare 6/7 bicyclic skeleton.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*