OBJECTIVE: To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma. METHODS: In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously. RESULTS: In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01). CONCLUSIONS Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.
Aristolochic Acids/toxicity* ; Animals ; Humans ; NAD(P)H Dehydrogenase (Quinone)/genetics* ; HEK293 Cells ; Kidney/pathology* ; Cytochrome P-450 CYP1A2/genetics* ; Mice, Inbred C57BL ; DNA Adducts/drug effects* ; Male ; Kidney Diseases/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Prunus armeniaca ; Plant Extracts

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively.Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques.There has been a decrease in intravenous thrombolysis rates, from 12% in 2017–2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for noncardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective To explore the potential mechanism of action of paeoniflorin in diabetes mellitus,the related targets and pathways were preliminarily discussed,based on the network pharmacology and molecular docking technology.Methods Analyze the potential targets of paeoniflorin using the Swiss Target Prediction database.Genecards and OMIM databases yielded the genes of diabetes-related illnesses.After taking the intersection of the two,protein-protein interaction network(PPI)was established using STRING and Cytoscape programs to search for key genes with strong correlation and complete gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Use AutoDockTools and Pymol programs to complete protein molecule docking validation.Results The pharmacologically-related study revealed 63 targets associated with paeoniflorin,4 758 genes related to diabetes,and 50 intersection targets.15 key genes including vascular endothelial growth factor A(VEGFA),epidermal growth factor receptor(EGFR),V-Ha-ras harvey(HRAS),V-src sarcoma(SRC)and heat shock protein hs 90-alpha(HSP90AA1)were screened.RAs-associated protein 1,Ras,calcium and other signaling pathways were obtained by KEGG pathway analysis.Molecular docking results showed that paeoniflorin had good binding ability with key genes.Conclusion Paeoniflorin can treat diabetes through multiple targets and pathways,and this mechanism can provide a basis for the application of paeoniflorin in anti diabetes and drug research and development.

Mycobacterium intracellular CHPC 1.5701 strain was isolated from the sputum specimen of the patient.This study attempted to establish a guinea pig infection model to evaluate its virulence,so as to provide basic scientific basis for the prevention and treatment of Mycobacterium intracellular infection.Mycobacterium intracellular CHPC 1.5701 was cultured in 7H10 medium.The morphology of the colony changed from colorless to light yellow smooth colony,and the acid-fast staining was positive.Mycobacterium intracellular suspension was diluted with 0.9％sodium chloride solution to 1 × 1010 CFU/mL,1×109 CFU/mL,1 × 108 CFU/mL,1 × 107 CFU/mL and 1 × 106 CFU/mL,respectively.Healthy Hartly guinea pigs with negative skin test of pure protein derivatives of tuberculin were selected and randomly divided into 6 groups with 10 guinea pigs in each group,half male and half female.Guinea pigs in the ex-perimental group were divided into 5 groups,which were intra-peritoneally injected with 5 different concentrations of 1.0 mL suspension/guinea pig,and those in the control group were in-traperitoneally injected with 0.9％sodium chloride solution 1.0 mL suspension/guinea pig.The guinea pigs was then observed,weighed every week,dissected 5 weeks later,lung,spleen and liver tissues were taken,and the tissue lesions were analyzed by hematoxylin-eosin(HE)staining,and the bacteria load was detected by tissue homogenate culture in 7H10 medium.The results showed that Mycobacterium intracellular challenge test had no significant effect on body weight of male guinea pigs(P＞0.05),but could reduce body weight of female guinea pigs(P＜0.01).No pathological changes of organ tissues were ob-served in guinea pigs in the control group,while HE staining of lung,spleen and liver tissues of guinea pigs in challenge experi-mental groups showed alveolar wall alveolar epithelial hyperplasia,monocyte infiltration in liver and spleen,granulomatous in-flammation and other pathological changes,and the degree of pathological changes was related to the injection dose of Mycobac-terium intracellular.Mycobacteria intracellular could be isolated from tissue culture of some organs,among which the spleen had a large amount of bacteria.Intrabitoneal injection of Mycobacteria intracellular CHPC 1.5701 can affect the body weight of female guinea pigs and cause lung,liver and spleen infection of guinea pigs,but no caseous necrosis of guinea pigs was ob-served.Compared with the reported data of Mycobacterium tuberculosis virulence test,it is concluded that Mycobacterium in-tracellular has certain virulence to guinea pigs and belongs to low virulence and low pathogenicity bacteria...

Objective To investigate the effect of the combination of Hyssop and White Peony on the nuclear factor E2-related factor-2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway induced by the combination of NG-nitro-L-arginine methyl ester,hydrochloride(L-NAME)and Aconite in mice with hypertensive kidney injury and its therapeutic mechanism.Methods A total of 80 KM mice were randomly divided into blank group,model group and experimental A,B,C,D,E and F groups,with 10 mice per group.Except for the blank group,the remaining 7 groups were given aconite decoction+L-NAME by gavage to prepare a hypertensive kidney injury model.Experimental A,B,C,D,E,and F groups were given 6.83 g·kg-1·d-1 of different proportions of Hyssop-White Peony solution in different proportions with 5∶0,4∶1,3∶2,2∶3,1∶4,0∶5,respectively.Blank and model groups were given an equal volume of distilled water by gavage.All 8 groups of mice were intervened for 6 weeks.The blood pressure changes of mice in each group were compared;the levels of blood urea nitrogen(BUN)in serum and superoxide dismutase(SOD)in kidney tissue were detected by kit;and the expression of Nrf2 and HO-1 in kidney tissue was detected by immunohistochemistry.Results The systolic blood pressure levels of blank group,model group and experimental C,D groups were(99.56±4.13),(140.11±7.33),(106.23±8.41)and(105.97±6.43)mmHg;the blood urea nitrogen contents were(172.00±15.90),(352.64±17.23),(201.76±12.14)and(192.72±12.77)μg·mL-1;BUN contents were(232.14±8.58),(165.44±6.17),(205.06±5.34)and(182.94±9.91)μg·mL-1;the expression levels(optical density)of Nrf2 were 2.06±0.14,2.25±0.22,2.63±0.22 and 2.83±0.21;the expression levels(optical density)of HO-1 were 2.18±0.12,2.25±0.10,2.64±0.16 and 2.65±0.28,respectively.The above indexes in experimental C and D groups were statistically significant compared with those of the model group(all P＜0.01).Conclusion Hyssop and White Peony can enhance the ability of L-NAME and Aconite to resist oxidative stress in mice with hypertensive kidney injury induced by the combination of Nrf2/HO-1 pathway,and inhibit the process of apoptosis of kidney cells caused by kidney injury caused by hypertension,thereby exerting its protective effect on the kidney.

Objective To investigate the effect of the combination of Hyssop and White Peony on the nuclear factor E2-related factor-2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway induced by the combination of NG-nitro-L-arginine methyl ester,hydrochloride(L-NAME)and Aconite in mice with hypertensive kidney injury and its therapeutic mechanism.Methods A total of 80 KM mice were randomly divided into blank group,model group and experimental A,B,C,D,E and F groups,with 10 mice per group.Except for the blank group,the remaining 7 groups were given aconite decoction+L-NAME by gavage to prepare a hypertensive kidney injury model.Experimental A,B,C,D,E,and F groups were given 6.83 g·kg-1·d-1 of different proportions of Hyssop-White Peony solution in different proportions with 5∶0,4∶1,3∶2,2∶3,1∶4,0∶5,respectively.Blank and model groups were given an equal volume of distilled water by gavage.All 8 groups of mice were intervened for 6 weeks.The blood pressure changes of mice in each group were compared;the levels of blood urea nitrogen(BUN)in serum and superoxide dismutase(SOD)in kidney tissue were detected by kit;and the expression of Nrf2 and HO-1 in kidney tissue was detected by immunohistochemistry.Results The systolic blood pressure levels of blank group,model group and experimental C,D groups were(99.56±4.13),(140.11±7.33),(106.23±8.41)and(105.97±6.43)mmHg;the blood urea nitrogen contents were(172.00±15.90),(352.64±17.23),(201.76±12.14)and(192.72±12.77)μg·mL-1;BUN contents were(232.14±8.58),(165.44±6.17),(205.06±5.34)and(182.94±9.91)μg·mL-1;the expression levels(optical density)of Nrf2 were 2.06±0.14,2.25±0.22,2.63±0.22 and 2.83±0.21;the expression levels(optical density)of HO-1 were 2.18±0.12,2.25±0.10,2.64±0.16 and 2.65±0.28,respectively.The above indexes in experimental C and D groups were statistically significant compared with those of the model group(all P＜0.01).Conclusion Hyssop and White Peony can enhance the ability of L-NAME and Aconite to resist oxidative stress in mice with hypertensive kidney injury induced by the combination of Nrf2/HO-1 pathway,and inhibit the process of apoptosis of kidney cells caused by kidney injury caused by hypertension,thereby exerting its protective effect on the kidney.

Mycobacterium intracellular CHPC 1.5701 strain was isolated from the sputum specimen of the patient.This study attempted to establish a guinea pig infection model to evaluate its virulence,so as to provide basic scientific basis for the prevention and treatment of Mycobacterium intracellular infection.Mycobacterium intracellular CHPC 1.5701 was cultured in 7H10 medium.The morphology of the colony changed from colorless to light yellow smooth colony,and the acid-fast staining was positive.Mycobacterium intracellular suspension was diluted with 0.9％sodium chloride solution to 1 × 1010 CFU/mL,1×109 CFU/mL,1 × 108 CFU/mL,1 × 107 CFU/mL and 1 × 106 CFU/mL,respectively.Healthy Hartly guinea pigs with negative skin test of pure protein derivatives of tuberculin were selected and randomly divided into 6 groups with 10 guinea pigs in each group,half male and half female.Guinea pigs in the ex-perimental group were divided into 5 groups,which were intra-peritoneally injected with 5 different concentrations of 1.0 mL suspension/guinea pig,and those in the control group were in-traperitoneally injected with 0.9％sodium chloride solution 1.0 mL suspension/guinea pig.The guinea pigs was then observed,weighed every week,dissected 5 weeks later,lung,spleen and liver tissues were taken,and the tissue lesions were analyzed by hematoxylin-eosin(HE)staining,and the bacteria load was detected by tissue homogenate culture in 7H10 medium.The results showed that Mycobacterium intracellular challenge test had no significant effect on body weight of male guinea pigs(P＞0.05),but could reduce body weight of female guinea pigs(P＜0.01).No pathological changes of organ tissues were ob-served in guinea pigs in the control group,while HE staining of lung,spleen and liver tissues of guinea pigs in challenge experi-mental groups showed alveolar wall alveolar epithelial hyperplasia,monocyte infiltration in liver and spleen,granulomatous in-flammation and other pathological changes,and the degree of pathological changes was related to the injection dose of Mycobac-terium intracellular.Mycobacteria intracellular could be isolated from tissue culture of some organs,among which the spleen had a large amount of bacteria.Intrabitoneal injection of Mycobacteria intracellular CHPC 1.5701 can affect the body weight of female guinea pigs and cause lung,liver and spleen infection of guinea pigs,but no caseous necrosis of guinea pigs was ob-served.Compared with the reported data of Mycobacterium tuberculosis virulence test,it is concluded that Mycobacterium in-tracellular has certain virulence to guinea pigs and belongs to low virulence and low pathogenicity bacteria...

This study aimed to explore the anti-inflammatory material basis and molecular mechanism of Artemisia stolonifera based on the analysis of the chemical components in different extracted fractions of A. stolonifera and their antioxidant and anti-inflammatory effects in combination with network pharmacology and molecular docking. Thirty-two chemical components were identified from A. stolonifera by ultra-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Among them, there were 7, 21 and 22 compounds in water, n-butanol and ethyl acetate fractions, respectively. The antio-xidant capacity of different extracted fractions was evaluated by measuring their scavenging ability against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) free radicals and total antioxidant capacity [ferric reducing antioxidant power(FRAP) assay]. The inflammatory model of RAW264.7 cells was induced by lipopolysaccharide(LPS), and the levels of nitrite oxide(NO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) in the supernatant and the mRNA expression of related inflammatory factors in cells were used to evaluate the anti-inflammatory effects. The results revealed that ethyl acetate fraction of A. stolonifera was the optimal antioxidant and anti-inflammatory fraction. By network pharmacology, it was found that flavonoids such as rhamnazin, eupatilin, jaceosidin, luteolin and nepetin could act on key targets such as TNF, serine/threonine protein kinase 1(AKT1), tumor protein p53(TP53), caspase-3(CASP3) and epidermal growth factor receptor(EGFR), and regulate the phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) and mitogen-activated protein kinase(MAPK) signaling pathways to exert the anti-inflammatory effects. Molecular docking further indicated excellent binding properties between the above core components and core targets. This study preliminarily clarified the anti-inflammatory material basis and mechanism of ethyl acetate fraction of A. stolonifera, providing a basis for the follow-up clinical application of A. stolonifera and drug development.
Antioxidants/chemistry* ; Molecular Docking Simulation ; Artemisia ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Anti-Inflammatory Agents/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Interleukin-6

This study intended to evaluate the efficacy and safety of single Hirudo prescriptions in the treatment of ischemic cerebrovascular disease(ICVD) by frequency network Meta-analysis and traditional Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library databases were searched to collect the randomized controlled trial(RCT) of single Hirudo prescriptions for ICVD from the inception of the databases to May 2022. The quality of the included literature was evaluated by Cochrane risk of bias tool. Finally, 54 RCTs and 3 single Hirudo prescriptions were included. Statistical analysis was conducted by RevMan 5.3 and Stata SE 15. Network Meta-analysis showed that in terms of the clinical effective rate, the surface under the cumulative ranking curve(SUCRA) of intervention measures was as follows: Huoxue Tongmai Capsules+conventional treatment>Maixuekang Capsules+conventional treatment>Naoxuekang Capsules+conventional treatment>conventional treatment. Traditional Meta-analysis revealed that in terms of the safety of ICVD treatment, Maixuekang Capsules+conventional treatment had higher safety than conventional treatment alone. According to the network Meta-analysis and traditional Meta-analysis, it was found that conventional treatment combined with single Hirudo prescriptions improved the clinical efficacy of ICVD patients, and compared with that of conventional treatment alone, the incidence of adverse reactions of combined treatment was low and the safety was high. However, the methodological quality of the articles included in this study was generally low and there were large differences in the number of articles on the three combined medication. Therefore, the conclusion of this study needed to be confirmed by subsequent RCT.
Humans ; Animals ; Capsules ; Network Meta-Analysis ; Combined Modality Therapy ; Leeches ; Prescriptions ; Cerebrovascular Disorders