ObjectiveTo evaluate the effect of neuromuscular electrical stimulation (NMES) on pain, quadriceps strength and motor function of patients after total knee arthroplasty (TKA). MethodsThe databases of CNKI, Wanfang data, VIP, PubMed, Embase, Cochrane, Web of Science and Scopus were retrieved from inception to April, 2025. Randomized controlled trials (RCT) related to the intervention of NMES after TKA were collected. The quality of the included literature was evaluated using the Cochrane Risk of Bias Assessment Tool and the Physical Therapy Evidence Database (PEDro) scale. Meta-analysis was performed with RevMan 5.4. ResultsA total of twelve RCT were included, involving 772 subjects. The PEDro scale score ranged from four to seven. NMES improved postoperative quadriceps muscle strength (SMD = 0.61, 95%CI 0.34 to 0.88, P < 0.001) and knee flexion range of motion (SMD = 1.35, 95%CI 0.30 to 2.41, P = 0.010), and reduced the Timed Up and Go Test (TUGT) time (SMD = -0.86, 95%CI -1.45 to -0.26, P = 0.005). Compared with the control group, the intervention group achieved better outcomes in the 2-Minute Walk Test (2MWT) (SMD = 19.44, 95%CI 10.44 to 30.43, P < 0.001), 3-Minute Walk Test (SMD = 23.57, 95%CI 14.77 to 32.36, P < 0.001), 6-Minute Walk Test (SMD = 42.29, 95%CI 9.71 to 74.86, P = 0.010), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (SMD = -0.52, 95%CI -1.00 to -0.04, P = 0.040), as well as the Physical Component Summary (PCS) (SMD = 2.90, 95%CI 0.73 to 5.06, P = 0.009) and Mental Component Summary (MCS) (SMD = 2.84, 95%CI 1.40 to 4.28, P = 0.040) of the 36-Item Short Form Health Survey (SF-36). Subgroup analysis demonstrated that two to four weeks after surgery, NMES enhanced patients' quadriceps muscle strength (SMD = 0.90, 95%CI 0.58 to 1.21, P < 0.001), shortened TUGT time (SMD = -1.28, 95%CI -2.57 to -0.02, P < 0.05) and increased walking distance in 2MWT (SMD = 20.43, 95%CI 10.44 to 30.43, P < 0.001). For patients followed up for two to three months, NMES yielded improvements in WOMAC scores (SMD = -0.44, 95%CI -0.79 to -0.09, P = 0.010) and SF-36 MCS scores (SMD = 4.17, 95%CI 2.43 to 5.91, P < 0.001). ConclusionNMES can significantly improve the quadriceps strength and walking ability of the TKA patients two to four weeks after surgery, and enhance the quality of life of patients two to three months after surgery.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

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.

Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.

In this study, the pharmacokinetic characteristics and tissue distribution of cannabidiol(CBD)/γ-polyglutamic acid-g-cholesterol(γ-PGA-g-CHOL) nanomicelles [CBD/(γ-PGA-g-CHOL)NMs] were investigated by pharmacokinetic experiments, and the effect of CBD/(γ-PGA-g-CHOL)NMs on the lipopolysaccharide(LPS)-induced inflammatory damage of cells was evaluated by cell experiments. CBD/(γ-PGA-g-CHOL)NMs were prepared by dialysis. The CBD concentrations in the plasma samples of male SD rats treated with CBD and CBD/(γ-PGA-g-CHOL)NMs were investigated, and the pharmacokinetic parameters were calculated and compared. UPLC-MS/MS was employed to determine the concentration of CBD in tissue samples. The heart, liver, spleen, lung, kidney, and muscle samples were collected at different time points to explore the tissue distribution of CBD and CBD/(γ-PGA-g-CHOL)NMs. The Caco-2 cell model of LPS-induced inflammation was established, and the cell viability, transepithelial electrical resistance(TEER), and secretion levels of inflammatory cytokines were determined to compare the anti-inflammatory activity between the two groups. The results showed that CBD/(γ-PGA-g-CHOL)NMs had the average particle size of(163.1±2.3)nm, drug loading of 8.78%±0.28%, and encapsulation rate of 84.46%±0.35%. Compared with CBD, CBD/(γ-PGA-g-CHOL)NMs showed increased peak concentration(C_(max)) and prolonged peak time(t_(max)) and mean residence time(MRT_(0-t)). Within 24 h, the tissue distribution concentration of CBD/(γ-PGA-g-CHOL)NMs was higher than that of CBD. In addition, both CBD and CBD/(γ-PGA-g-CHOL)NMs significantly enhanced Caco-2 cell viability and TEER, lowered the secretion levels of inflammatory cytokines, and alleviated inflammation. Moreover, CBD/(γ-PGA-g-CHOL)NMs demonstrated stronger anti-inflammatory effect. It can be inferred that γ-PGA-g-CHOL blank nanomicelles are good carriers of CBD, being capable of prolonging the circulation time of CBD in the blood, improving the bioavailability and tissue distribution concentration of CBD, and protecting against LPS-induced inflammatory injury. The findings can provide an experimental basis for the development and clinical application of oral CBD preparations.
Animals ; Cannabidiol/administration & dosage* ; Polyglutamic Acid/analogs & derivatives* ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Anti-Inflammatory Agents/administration & dosage* ; Micelles ; Caco-2 Cells ; Cholesterol/pharmacokinetics* ; Tissue Distribution ; Nanoparticles/chemistry*

A scoping review was performed to systematically search and summarize the clinical research in the treatment of dysmenorrhea with oral Chinese patent medicines. The oral Chinese patent medicines for treating dysmenorrhea in three major drug lists, guidelines, and textbooks were screened, and the relevant clinical trials were retrieved from eight Chinese and English databases. The key information of the included trials was extracted and visually analyzed. A total of 50 Chinese patent medicines were included, among which oral Chinese patent medicines for the dysmenorrhea patients with the syndrome of Qi stagnation and blood stasis accounted for the highest proportion, and the average daily cost varied greatly among Chinese patent medicines. A total of 150 articles were included, involving 22 Chinese patent medicines, among which Guizhi Fuling Capsules/Pills, Sanjie Zhentong Capsules, and Dan'e Fukang Soft Extract were the most frequently studied. These articles mainly reported randomized controlled trial(RCT), which mainly focused on the comparison of the intervention effect between Chinese patent medicines combined with western medicine and western medicine alone, and the sample size was generally 51-100 cases. The high-frequency outcome indicators belonged to nine domains such as effective rate, adverse reactions, and laboratory examinations. This study showed that oral Chinese patent medicines had advantages in the treatment of dysmenorrhea, and the annual number of related clinical trials showed an overall growing trend. However, there were still problems such as insufficient safety information and vague description of traditional Chinese medicine(TCM) syndromes types in the instructions of Chinese patent medicines. The available clinical research had shortcomings such as uneven distribution of Chinese patent medicines, limited research scale, poor methodological rigor, and insufficient standardization of outcome indicators. In the future, it is necessary to deepen the development of high-quality clinical research and improve the contents of the instructions to ensure the effectiveness and safety of the clinical application of oral Chinese patent medicines in the treatment of dysmenorrhea.
Dysmenorrhea/drug therapy* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Administration, Oral ; Nonprescription Drugs/administration & dosage*

This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

Cervi Cornu Pantotrichum is a precious animal-derived Chinese medicinal material, while there are often adulterants derived from animals not specified in the Chinese Pharmacopeia in the market, which disturbs the safety of medication. This study was conducted with the aim of strengthening the quality control of Cervi Cornu Pantotrichum and standardizing the medication. To achieve digital identification of Cervi Cornu Pantotrichum from different sources, a digital identification model was constructed based on ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS~E) combined with an adaptive boosting algorithm(Adaboost). The young furred antlers of sika deer, red deer, elk, and reindeer were processed and then subjected to polypeptide analysis by UHPLC-QTOF-MS~E. Then, the mass spectral data reflecting the polypeptide information were obtained by digital quantification. Next, the key data were obtained by feature screening based on Gini index, and the digital identification model was constructed by Adaboost. The model was evaluated based on the recall rate, F_1 composite score, and accuracy. Finally, the results of identification based on the constructed digital identification model were validated. The results showed that when the Gini index was used to screen the data of top 100 characteristic polypeptides, the digital identification model based on Adaboost had the best performance, with the recall rate, F_1 composite score, and accuracy not less than 0.953. The validation analysis showed that the accuracy of the identification of the 10 batches of samples was as high as 100.0%. Therefore, based on UHPLC-QTOF-MS~E and Adaboost algorithm, the digital identification of Cervi Cornu Pantotrichum can be realized efficiently and accurately, which can provide reference for the quality control and original animal identification of Cervi Cornu Pantotrichum.
Animals ; Algorithms ; Antlers/chemistry* ; Boosting Machine Learning Algorithms ; Chromatography, High Pressure Liquid/methods* ; Deer ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Quality Control ; Reindeer ; Tandem Mass Spectrometry/methods* ; Tissue Extracts/analysis*

To enhance the therapeutic efficacy of the baicalin-berberine complex(BA-BBR) in the treatment of ulcerative colitis(UC), BA-BBR nanocrystal microspheres(BA-BBR NC MS) were prepared using the dropping method. The microspheres were characterized in terms of morphology, particle size, differential scanning calorimetry(DSC), and powder X-ray diffraction(XRD). The release profiles of BA and BBR from the microspheres were measured, and the drug release mechanism was investigated. A rat model of UC was induced by 5% dextran sodium sulfate(DSS) and treated continuously for 7 days to evaluate the therapeutic effects of different formulations. The results showed that the prepared BA-BBR MS and BA-BBR NC MS were uniform gel spheres with particle sizes of(1.77±0.16) mm and(1.67±0.08) mm, respectively. After drying, the gels collapsed inward and exhibited a rough surface. During the preparation process, the BA-BBR nanocrystals(BA-BBR NC) were uniformly encapsulated within the microspheres. The release profiles of the microspheres followed a first-order kinetic model, and the 12-hour cumulative release of BA and BBR from BA-BBR NC MS was higher than that from BA-BBR MS. Compared with BA-BBR, BA-BBR NC, and BA-BBR MS, BA-BBR NC MS further alleviated UC symptoms in rats, most significantly reducing the levels of TNF-α, IL-1β, IL-6, and MPO, while increasing the level of IL-4 in colon tissues. These results indicate that BA-BBR NC MS, based on a "nano-in-micro" design, can deliver BA-BBR to the intestine and exert significant therapeutic effects in a UC rat model, suggesting it as a promising new strategy for the treatment of UC.
Animals ; Colitis, Ulcerative/metabolism* ; Rats ; Nanoparticles/chemistry* ; Microspheres ; Male ; Berberine/administration & dosage* ; Flavonoids/administration & dosage* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Particle Size ; Tumor Necrosis Factor-alpha/immunology* ; Drug Liberation ; Drug Compounding

This study established the HPLC fingerprints, characteristic chromatograms, and a multi-component content determination method for Bidens bipinnata and B. biternata. The chemical pattern recognition analysis was then employed to clarify the characteristic indexes of quality differences between the two original plants of Bidentis Herba, providing a reference for establishing the quality standards of Bidentis Herba. HPLC was launched on an Agilent Poroshell 120 EC-C_(18) chromatographic column(4.6 mm×250 mm, 4 μm) by gradient elution with a mobile phase of 0.1% aqueous phosphoric acid-acetonitrile at a flow rate of 0.7 mL·min~(-1), detection wavelength of 270 nm, column temperature of 25 ℃, and an injection volume of 5 μL. The similarity between the fingerprints of 18 batches of Bidentis Herba samples and the common pattern(R) ranged from 0.572 to 0.933. A total of 23 chromatographic peaks were calibrated. Through comparison with the reference substances, six components(neochlorogenic acid, chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, rutin, and hyperoside) were identified and subjected to quantitative analysis. The characteristic fingerprints of B. bipinnata and B. biternata were calibrated with 20 and 17 characteristic peaks, respectively. Among them, peaks 8, 9, 22, and 23 were the characteristic peaks of B. bipinnata, and peak 7 was the characteristic peak of B. biternata, which can be used to distinguish the two original plants of Bidentis Herba. The relative standard deviation of the content of the above-mentioned six components ranged from 36% to 123%. The cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) classified the 18 batches of Bidentis Herba samples into two categories. Additionally, through the analysis of variable importance in projection(VIP) under OPLS-DA, three characteristic indexes, rutin, isochlorogenic acid A, and isochlorogenic acid B, were identified. The analytical method established in this study can comprehensively evaluate the consistency of Bidentis Herba samples derived from different original plants, specifically identify the differential components between them, and effectively distinguish the two original plants of Bidentis Herba, providing a basis for the differentiation between different original plants and the quality control of Bidentis Herba.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Bidens/chemistry*