By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis* ; Neural Networks, Computer

Traditional Chinese medicine(TCM), a treasure of the Chinese nation, contains abundant chemical components and demonstrates unique pharmacological activities, showing important values in clinical applications. With profound connotations and broad application prospects, TCM urgently needs us to further explore and conduct systematic research. Puerarin is a small-molecule natural isoflavonoid carbon glycoside extracted from plants of Pueraria. It is also the main active ingredient of Puerariae Lobata Radix, a Chinese herbal medicine with both medicinal and edible values. Puerarin has a variety of pharmacological effects such as blood pressure-lowering, anti-atherosclerosis, anti-ischemia-reperfusion injury, antithrombotic, anti-tumor, anti-inflammatory, liver-protecting, nerve cell-protecting, and intestinal microbiota-regulating effects. It is also an active ingredient that has been widely studied. This article comprehensively reviews the research progress in the pharmacological effects and molecular mechanisms of puerarin over the years, aiming to provide references and theoretical support for the in-depth research and development as well as clinical application of puerarin.
Isoflavones/chemistry* ; Humans ; Animals ; Drugs, Chinese Herbal/chemistry* ; Pueraria/chemistry*

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

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.

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.

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.

Taxifolin (Tax) has been proved to be a medicinal edible substance with protective effects against alcoholic liver injury, however, its poor hydrophilicity and permeability have hindered the clinical application of Tax. In this study, we prepared taxifolin-phosphatidylcholine/sodium deoxycholate/PVP-K30 micells (Tax-MLs). Box-Behnken test was used to obtain the optimal preparation process, and Tax-MLs were characterised by transmission electron microscopy and fourier transform infrared spectroscopy. Physicochemical parameters such as proximate micelle concentration, equilibrium solubility and oil-water partition coefficient were determined, and the release pattern of Tax-MLs was investigated by in vitro digestion simulation. Alcoholic liver injury model to explore the in vivo efficacy of Tax-MLs. The results showed that the average particle size, polydispersity index (PDI) and zeta potential of Tax-MLs were 36.90 ± 4.57 nm, 0.194 ± 0.01 and -32.6 ± 0.35 mV, respectively, and the uniform size and distribution of Tax-MLs were observed by transmission electron microscopy. The formation of Tax-MLs was proved by differential scanning calorimetry and fourier transform infrared spectroscopy. In terms of physicochemical properties, the solubility of Tax-MLs in water increased by 92.02 times compared with Tax, and its oil-water partition coefficient in water increased from 0.43 to 1.14, which proved that Tax-MLs could improve its solubility and permeability. The in vivo pharmacodynamic results showed that compared with the Tax group, Tax-MLs low, medium and high dose groups showed a significant reduction in liver indices and serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < 0.05), and enhanced the activities of superoxide dismutase (SOD) and glutathione (GSH), and lowered the levels of malondialdehyde (MDA) more significantly in the hepatic tissues. Tax-MLs effectively improved drug solubility and permeability, and enhanced the protective effect against alcoholic liver injury. Animal experiments were conducted with approval from the Animal Ethics Committee of Changchun University of Traditional Chinese Medicine (approval number: 2023601).

Five saponins were isolated from the kernels of Momordica cochinchinensis, by macroporous resin, silica gel, ODS column chromatography, and semi preparative HPLC. Based on MS and NMR analysis, combining with alkaline hydrolysis and acid hydrolysis, their structures were identified as: gypsogenin-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (1), quillaic acid-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (2), gypsogenin-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (3), quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (4), 18α-quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside (5). Compounds 1-5 were new compounds, and named as mubezhisides A, B, C, D, E, respectively. They all could obviously inhibited the growth of Candida albicans, C. parapsilosis, and C. tropicalis.

Objective: To investigate the situation and influencing factors of school bullying experienced by primary and middle school students, so as to provide the basis for formulating school bullying intervention measures and promoting students' physical and mental health development. Methods: All the counties (cities, districts) in Zhejiang Province were stratified to urban and suburban areas, primary, junior high and senior high school students were selected using a stratified cluster sampling method. Basic information, lifestyle and school bullying were collected through questionnaire surveys. Factors affecting school bullying experienced by primary and middle school students were analyzed using a multivariable logistic regression model. Results: Totally 137 846 valid questionnaires were recovered, with an effective recovery rate of 97.17%. There were 72 526 males (52.61%) and 65 320 females (47.39%). There were 47 561 primary school students (34.50%), 47 701 junior high school students (34.61%) and 42 584 senior high school students (30.89%). A total of 3 987 students suffered from school bullying, accounting for 2.89%. The proportions of being maliciously teased, being intentionally excluded from group activities/isolated, being teased about physical defects or appearance, being hit/kicked/pushed/shoved/locked in a room, being threatened, and being extorted for money were 2.04%, 1.18%, 1.11%, 0.86%, 0.84% and 0.83%, respectively. Multivariable logistic regression analysis showed that the students who were males (OR=1.122, 95%CI: 1.048-1.202), lived in suburban areas (OR=1.322, 95%CI: 1.233-1.418), lived in areas with medium (OR=1.086, 95%CI: 1.006-1.173) or underdeveloped (OR=1.298, 95%CI: 1.191-1.415) economic level, had higher academic levels (junior high school, OR=1.380, 95%CI: 1.270-1.499; senior high school, OR=1.210, 95%CI: 1.083-1.351), lived on campus (OR=1.489, 95%CI: 1.372-1.616), engaged in fights (OR=6.029, 95%CI: 5.585-6.509), attempted to smoke (OR=1.320, 95%CI: 1.128-1.545), drank (OR=1.735, 95%CI: 1.575-1.912), were scolded and beaten by parents (OR=1.972, 95%CI: 1.822-2.135) and were obese (OR=1.240, 95%CI: 1.132-1.360) were more likely to experience school bullying. Conclusion The harm of school bullying to the physical and mental health of primary and middle school students should be taken seriously, and active policy measures should be adopted to strengthen intervention.

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.