ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

BACKGROUND:Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis,and there are further explorations in the mechanism against peri-implantitis.OBJECTIVE:To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.METHODS:Relevant literature was searched on PubMed,Web of Science,CNKI,and WanFang Data,using the search terms of"probiotics,peri-implantitis,flora imbalance,immunoregulation,inflammatory reaction,mechanism of action"in Chinese and English.A total of 90 articles were finally included.RESULTS AND CONCLUSION:Probiotics have the following mechanisms.They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors.They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins,reduce the pH value of biofilms,improve the composition of microorganisms in microecology,induce the change of bacterial community structure,and restore the balance of microbial population around implants.They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant.In addition,probiotics can produce antibacterial compounds,offset the adhesion of pathogenic microorganisms,and regulate immune function.Through the above mechanisms,probiotics have certain potential in the adjuvant treatment of peri-implantitis,which can improve the clinical parameters of peri-implantitis and affect the microbiota.Probiotic therapy provides a new treatment option,but more long-term prospective studies are needed to further verify its effect.

BACKGROUND:Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis,and there are further explorations in the mechanism against peri-implantitis.OBJECTIVE:To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.METHODS:Relevant literature was searched on PubMed,Web of Science,CNKI,and WanFang Data,using the search terms of"probiotics,peri-implantitis,flora imbalance,immunoregulation,inflammatory reaction,mechanism of action"in Chinese and English.A total of 90 articles were finally included.RESULTS AND CONCLUSION:Probiotics have the following mechanisms.They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors.They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins,reduce the pH value of biofilms,improve the composition of microorganisms in microecology,induce the change of bacterial community structure,and restore the balance of microbial population around implants.They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant.In addition,probiotics can produce antibacterial compounds,offset the adhesion of pathogenic microorganisms,and regulate immune function.Through the above mechanisms,probiotics have certain potential in the adjuvant treatment of peri-implantitis,which can improve the clinical parameters of peri-implantitis and affect the microbiota.Probiotic therapy provides a new treatment option,but more long-term prospective studies are needed to further verify its effect.

ObjectiveTo investigate the protective effect of magnolol ester derivative YW against cisplatin （Cis）-induced acute kidney injury （AKI） and to explore its effect and preliminary mechanisms on Cis-induced AKI. MethodsThe research group designed and synthesized the magnolol ester derivative YW using magnolol as the parent core. Molecular docking was employed to predict the binding interaction between YW and lysine acetyltransferase 7 （KAT7）. A Cis-induced AKI model was established in C57BL/6J mice. Mice were divided into the normal control group， model group， YW low/medium/high dose groups （17.5， 35， 70 mg/kg）， and the positive control amifostine group. Renal function was assessed by measuring serum creatinine （Scr） and blood urea nitrogen （BUN） levels. Pathological changes were evaluated via HE staining and scoring of kidney tissues. Protein expression levels of kidney injury molecule 1 （KIM-1）， lysine acetyltransferase 7 （KAT7）， and cyclin-dependent kinase inhibitor 1A （p21） in kidney tissues were detected by Western blot （WB）. HK-2 cells were treated with different concentrations of YW； cell viability was measured by CCK-8 assay. WB was used to detect the expression levels of the renal injury marker KIM-1， KAT7， and its downstream protein p21. Cellular senescence was assessed by senescence-associated β-galactosidase （SA-β-Gal） staining. ResultsYW could stably bind to KAT7. In vivo experiments showed that， compared with the model group， all YW dose groups， especially the medium and high doses， significantly reduced the elevated levels of Scr and BUN in AKI mice （P<0.001） and effectively ameliorated renal histopathological damage. YW significantly downregulated the protein expression levels of KIM-1， KAT7， and p21 in kidney tissues （P<0.05）. Concentrations of YW≤10 μmol/L had no significant effect on HK-2 cell viability. YW inhibited the Cis-induced decline in HK-2 cell viability （P<0.05）， suppressed the Cis-induced upregulation of KIM-1， KAT7， and p21 proteins （P<0.05）， and significantly decreased the percentage of SA-β-Gal-positive cells （P<0.01）. ConclusionYW suppresses the expression of KAT7 and p21 proteins and inhibits the decline in HK-2 cell viability in cisplatin-induced AKI， significantly mitigates HK-2 cell senescence， and improves renal function， providing preliminary experimental evidence for developing AKI treatment strategies based on structural optimization of natural products.

ObjectiveTo investigate the association between insulin resistance （IR） and cardiovascular metabolic indicators， including blood pressure， blood lipids， and serum uric acid， in a middle-aged population. MethodsBased on the baseline survey of the Hong Sifang cohort of China National Salt Industry Group， a total of 575 participants were included. According to the homeostasis model assessment of insulin resistance， the participants were divided into an IR group （n=116） and a non-IR group （n=459）. Differences between the two groups were compared using the t-test and chi-square test. Multivariate logistic regression analysis was performed to evaluate the associations between IR and abnormalities in metabolic indicators. ResultsA total of 575 participants were included， including 390 men and 185 women， with a mean age of （48.58 ± 5.14） years and a mean body mass index （BMI） of （24.16 ± 2.97） kg/m². Blood pressure， serum uric acid， and blood lipid levels were significantly higher in the IR group than in the non-IR group （P<0.001）. After adjusting for potential confounders including age， sex， and BMI， IR was independently associated with hypertension， dyslipidemia， and hyperuricemia， with odds ratios （OR） and 95% confidence intervals （CI） of 2.57 （1.61-4.09）， 3.81 （2.36-6.17）， and 2.68 （1.53-4.71）， respectively （all P<0.001）. ConclusionInsulin resistance is significantly associated with multiple cardiovascular metabolic risk factors in the middle-aged population. Monitoring IR may contribute to the early prevention and control of cardiovascular diseases.

Based on the pharmacokinetics theory, this study investigated the pharmacokinetic characteristics of albiflorin, paeoniflorin, wogonoside, and wogonin in normal and febrile rats and summarized absorption and elimination rules of Dayuanyin in them to provide reference for further development and clinical application of Dayuanyin. Blood samples were taken from the fundus venous plexus of normal and model rats after intragastric administration of Dayuanyin at different time points. The concentration of each substance in blood was determined by ultra performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS) technique at different time points. DAS 2.0, a piece of pharmacokinetics software, was used to calculate the pharmacokinetic parameters of each component. The results show that the 4 components had good linear relationship in their respective ranges, and the results of methodological investigation met the requirements. The pharmacokinetic parameters of C_(max), T_(max), t_(1/2), AUC_(0-t), AUC_(0-∞), and MRT_(0-t) were calculated by the DAS 2.0 non-compartmental model. Compared with those in the normal group, C_(max) and AUC_(0-t) of the 4 components in the model group were significantly increased. There were significant differences in the pharmacokinetic characteristics between the normal and model groups, suggesting that the absorption and elimination of Dayuanyin may be affected by the changes of internal environment of the body in different physiological states.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Fever/metabolism* ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Glucosides/pharmacokinetics* ; Monoterpenes

Descurainiae Semen Lepidii Semen, also known as Tinglizi, originates from Brassicaceae plants Descurainia sophia or Lepidium apetalum. The former is commonly referred to as "Southern Tinglizi(Descurainiae Semen)", while the latter is known as "Northern Tinglizi(Lepidii Semen)". To scientifically and accurately identify the origin of Tinglizi medicinal materials and traditional Chinese medicine products, this study developed a specific DNA mini-barcode based on chloroplast genome sequences. By combining the DNA mini-barcode with DNA metabarcoding technology, a method for the qualitative and quantitative identification of Tinglizi medicinal materials and Chinese patent medicines was established. In this study, chloroplast genomes of Southern Tinglizi and Northern Tinglizi and seven commonly encountered counterfeit products were downloaded from the GenBank database. Suitable polymorphic regions were identified to differentiate these species, enabling the development of the DNA mini-barcode. Using DNA metabarcoding technology, medicinal material mixtures of Southern and Northern Tinglizi, as well as the most common counterfeit product, Capsella bursa-pastoris seeds, were analyzed to validate the qualitative and quantitative capabilities of the mini-barcode and determine its minimum detection limit. Additionally, the mini-barcode was applied to Chinese patent medicines containing Tinglizi to authenticate their botanical origin. The results showed that the developed mini-barcode(psbB) exhibited high accuracy and specificity, effectively distinguishing between the two authentic origins of Tinglizi and commonly encountered counterfeit products. The analysis of mixtures demonstrated that the mini-barcode had excellent qualitative and quantitative capabilities, accurately identifying the composition of Chinese medicinal materials in mixed samples with varying proportions. Furthermore, the analysis of Chinese patent medicines revealed the presence of the adulterant species(Capsella bursa-pastoris) in addition to the authentic species(Southern and Northern Tinglizi), indicating the occurrence of adulteration in commercially available Tinglizi-containing products. This study developed a method for the qualitative and quantitative identification of multi-origin Chinese medicinal materials and related products, providing a model for research on other multi-origin Chinese medicinal materials.
DNA Barcoding, Taxonomic/methods* ; Drugs, Chinese Herbal/chemistry* ; Drug Contamination ; Genome, Chloroplast ; Medicine, Chinese Traditional

This study aims to investigate the optimal ratio of Astragali Radix-Curcumae Rhizoma(AC) for inhibiting the proliferation of 143B osteosarcoma cells, and to investigate the mechanism by which AC inhibits osteosarcoma growth and metastasis through angiogenesis and cell adhesion mediated by the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible factor-1α(HIF-1α) pathway. A subcutaneous 143B tumor-bearing nude mouse model was successfully established and randomly divided into the model group, and the AC 1∶1, 2∶1, and 4∶1 groups. Body weight, tumor volume, and tumor weight were recorded. Real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of PI3K, Akt, phosphorylated Akt(p-Akt), HIF-1α, vascular endothelial growth factor A(VEGFA), transforming growth factor-β1(TGF-β1), epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, matrix metalloproteinase 2(MMP2), matrix metalloproteinase 9(MMP9), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3 in the hypoxic core region of the tumor tissue. A cell hypoxia model was established, and the effects of AC-medicated serum(model group, AC 1∶1, 2∶1, and 4∶1 groups) on angiogenesis, proliferation, adhesion, invasion, and migration of 143B osteosarcoma cells were examined through CCK-8, flow cytometry, Transwell assay, cell adhesion assay, and HUVEC tube formation assay. The results showed that compared with the model group, the tumor weight and volume were smallest in the 2∶1 group. The expression levels of PI3K, Akt, p-Akt, HIF-1α, VEGFA, and TGF-β1 were significantly decreased, and the protein expression of E-cadherin was significantly increased, while the protein expression of N-cadherin, vimentin, MMP2, and MMP9 was significantly decreased. Additionally, the protein expression of Bax and caspase-3 was significantly increased, and Bcl-2 protein expression was significantly decreased. In vitro experiments showed that after intervention with AC-medicated serum at a 2∶1 ratio, the cell activity, adhesion, invasion, and migration of 143B cells were significantly reduced, apoptosis was significantly increased, and HUVEC tube formation was significantly decreased. In conclusion, the 2∶1 ratio of AC showed the most effective inhibition of 143B cell growth. AC can inhibit the growth and metastasis of osteosarcoma 143B cells by regulating the PI3K/Akt/HIF-1α signaling pathway, inhibiting angiogenesis and reducing cell adhesion, invasion, and migration.
Osteosarcoma/pathology* ; Animals ; Proto-Oncogene Proteins c-akt/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Humans ; Mice ; Cell Adhesion/drug effects* ; Cell Proliferation/drug effects* ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Phosphatidylinositol 3-Kinases/genetics* ; Cell Line, Tumor ; Mice, Nude ; Signal Transduction/drug effects* ; Astragalus Plant/chemistry* ; Bone Neoplasms/physiopathology* ; Male ; Rhizome/chemistry* ; Mice, Inbred BALB C ; Angiogenesis

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

Based on the ultra performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology, combined with related literature, databases, and reference material information, this study qualitatively analyzed the components of Dayuanyin in the tissue of rats after gavage and employed molecular docking technology to predict the rationality of the mechanism behind the antipyretic effect of the in vivo components in Dayuanyin. A total of 21, 26, 20, 21, 14, and 31 prototype components and 3, 16, 3, 7, 5, and 24 metabolites were identified from the heart, liver, spleen, lung, kidney, and hypothalamus of the rats, respectively, and the binding ability of key components and targets was further verified by molecular docking. The results showed that all components had good binding ability with targets. The established UPLC-Q-Exactive Orbitrap-MS could effectively and quickly identify the Dayuanyin components distributed in tissue and preliminarily identify their metabolites. Many components were identified in the hypothalamus, which suggested that the components delivered to the brain should be focused on in the study on Dayuanyin in the treatment of febrile diseases. The molecular docking technology was used to predict the rationality of the mechanism behind its antipyretic effect, which lays the foundation for the clarification of the material basis and action mechanism of Dayuanyin, the development of new preparations, and the prediction of quality markers.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Molecular Docking Simulation ; Male ; Antipyretics/metabolism* ; Rats, Sprague-Dawley ; Tissue Distribution ; Mass Spectrometry ; Chromatography, High Pressure Liquid ; Hypothalamus/metabolism*