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.

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.

Objective To identify high-risk factors for healthcare-associated infection(HAI)in patients in inten-sive care units(ICUs),and develop a quick response(QR)code-based APP prediction tool.Methods Information of inpatients in general ICUs of three hospitals in Guizhou Province from January to December 2024 were collected.Risk factors were analyzed with a logistic regression model.QR code-based APP was constructed and validated.Results A total of 1 782 patients in general ICUs of three hospitals in Guizhou Province in 2024 were included in the analysis,out of which 410 were HAI cases,and the incidence of HAI was 23.01％.Multivariate logistic regre-ssion analysis results of HAI in ICU inpatients showed that regional gross domestic product(GDP)≥58 685 Yuan,performing pathogen culture during this hospitalization,history of diabetes mellitus,history of cancer,length of hospital stay ≥7 days before infection,and duration of persistent fever＞5 days before infection were independent risk factors for HAI in ICU patients(all P＜0.05).The discrimination of the model(area under the receiver operating characteristic curve[AUC]of 0.841),calibration(Brier score of 0.129),and clinical effectiveness(net benefit of 11.4％when the risk threshold was 5％-74％)all performed well.Conclusion The QR code-based APP prediction tool is of great significance for scientific research transformation and precise HAI control.

Objective:To analyze the molecular characteristics of prevalent Bordetella pertussis (Bp) isolates in Liaocheng City, Shandong Province in 2024. Methods:From March to August 2024, oropharyngeal swabs were collected from suspected pertussis cases at Liaocheng People′s Hospital in Shandong Province for Bp isolation. A total of 99 Bp isolates were obtained. Whole-genome sequencing was performed on all isolates, followed by Multilocus Sequence Typing (MLST), vaccine antigen-related gene typing (including ptxP, ptxA, ptxB, ptxC, ptxD, ptxE, fhaB, fim2, fim3, and prn), 23S rRNA gene typing, and phylogenetic analysis. To capture the differences between Bp isolates and vaccine strains in Liaocheng City, the international vaccine strain Tohama I and the Chinese vaccine strain CS were included in the analysis. Antimicrobial resistance testing against 11 agents was performed on 52 isolates. Results:The throat swabs of 99 Bp isolates were collected from patients aged 44 days to 42 years, and the median age of the patients was 7 (5, 8) years. All isolates ptxP were ptxP3 type. 74 isolates (74.75%) carried the prn150, while 21 isolates (21.21%) were prn-deficient. The predominant antigenic profile was ptxP3/ ptxA1/ ptxB1/ ptxC4/ ptxD1/ ptxE4/ fhaB1/ fim2-1/ fim3-1/ prn150, found in 72 isolates (72.73%). All 99 isolates carried the A2047G mutation in the 23S rRNA gene. Antimicrobial susceptibility testing showed that the MICs of macrolides and clindamycin for all 52 Bp isolates were all >256 mg/L. However, the isolates showed low MIC for seven other antimicrobials tested, including trimethoprim-sulfamethoxazole, amoxicillin, and levofloxacin. MLST typing revealed that 94 isolates (94.95%) were identified as ST-2, while 5 isolates (5.05%) belonged to a novel sequence type (ST-118). Phylogenetic analysis demonstrated that all 99 Bp isolates were highly homologous but clustered in evolutionary branches distinct from vaccine strains. Conclusion:In 2024, Bordetella pertussis isolates in Liaocheng City exhibit distinct clonal epidemic characteristics, with the predominant antigenic genotype being ptxP3/ ptxA1/ ptxB1/ ptxC4/ ptxD1/ ptxE4/ fhaB1/ fim2-1/ fim3-1/ prn150. All isolates are resistant to macrolide antibiotics.

Objective To identify high-risk factors for healthcare-associated infection(HAI)in patients in inten-sive care units(ICUs),and develop a quick response(QR)code-based APP prediction tool.Methods Information of inpatients in general ICUs of three hospitals in Guizhou Province from January to December 2024 were collected.Risk factors were analyzed with a logistic regression model.QR code-based APP was constructed and validated.Results A total of 1 782 patients in general ICUs of three hospitals in Guizhou Province in 2024 were included in the analysis,out of which 410 were HAI cases,and the incidence of HAI was 23.01％.Multivariate logistic regre-ssion analysis results of HAI in ICU inpatients showed that regional gross domestic product(GDP)≥58 685 Yuan,performing pathogen culture during this hospitalization,history of diabetes mellitus,history of cancer,length of hospital stay ≥7 days before infection,and duration of persistent fever＞5 days before infection were independent risk factors for HAI in ICU patients(all P＜0.05).The discrimination of the model(area under the receiver operating characteristic curve[AUC]of 0.841),calibration(Brier score of 0.129),and clinical effectiveness(net benefit of 11.4％when the risk threshold was 5％-74％)all performed well.Conclusion The QR code-based APP prediction tool is of great significance for scientific research transformation and precise HAI control.

Objective:To compare the safety, number of lymph nodes removed, rate of lymph node metastasis, and prognosis between proximal gastrectomy (PG) and total gastrectomy (TG) in patients with Siewert types II and III adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, clinical data of patients diagnosed with adenocarcinoma of the esophagogastric junction at Changzhi People's Hospital, affiliated with Changzhi Medical College, between December 2019 and November 2022, were collected. Patients who had received neoadjuvant therapy, had multiple malignant lesions in the stomach, had concomitant malignancies in other organs, had incomplete clinical data, or had been lost to follow-up were excluded. The study cohort comprised 308 patients, 99 in the PG group and 209 in the TG group. To reduce confounding bias, propensity score matching was performed, matching patients for age, sex, body mass index, tumor diameter, and pathological stage in a 1:1 ratio, resulting in 73 patients in each group. The primary outcomes assessed were operative details, number of lymph nodes dissected, rate of lymph node metastasis, postoperative complications, duration of hospital stay, and follow-up and survival outcomes.Results:The PG group had a significantly shorter median operative time than did the TG group (250 vs. 280 minutes, Z = -4.970, P<0.001), with fewer cases of intraoperative blood loss >100 mL (30.1%[22/73] vs. 46.6%[34/73], χ2=4.171, P=0.041), and a smaller number of lymph nodes removed (median 33 vs. 46, Z =-4.774, P<0.001); all of these differences are statistically significant (all P<0.05). Differences between the two groups in postoperative hospital stay and postoperative complications were not statistically significant (both P>0.05). Furthermore, no statistically significant differences were found between the PG and TG groups in the number of lymph nodes dissected or the lymph node metastasis rates at stations No. 1, No. 2, No. 3, No. 4sa, No. 4sb, and No. 7 (all P> 0.05). Among the 209 patients in the TG group, analysis of risk factors for metastasis to distal perigastric lymph nodes (No.4d, No.5, and No.6) showed that patients with tumor diameters ≤4 cm and T1–T3 stage disease had significantly lower rates of metastasis to these lymph nodes than did patients with tumor diameters >4 cm and/or T4 stage disease (0/78 vs. 12/131 [9.2%]); these differences are statistically significant ( P=0.014). The median duration of follow-up for the entire cohort was 26 months. The 3-year overall survival rates for the PG and TG groups were 62.5% and 63.3%, respectively; this difference is not statistically significant (χ 2=0.330, P = 0.565). Multivariate analysis showed that older age ( P = 0.035) and advanced pathological stage ( P = 0.018) were significant independent risk factors that affected overall survival in patients with Siewert type II and III adenocarcinoma of the esophagogastric junction. Conclusions:PG is safe and feasible for patients with Siewert types II and III adenocarcinoma of the esophagogastric junction. The number of lymph nodes dissected and metastasis status were similar in the TG and PG groups.

Proteus mirabilis is a significant foodborne pathogen that frequently causes diseases in humans and animals.Understanding the cytokine profile alterations following gastrointestinal in-fection with P.mirabilis is crucial for developing effective treatment strategies.This study em-ployed an intragastric infection model in mice to observe clinical symptoms and pathological chan-ges.Blood samples were collected at various time points post-infection,and the concentrations of 21 cytokines in the serum of both infected and control mice were quantitatively analyzed using the Bio-Plex suspension array system.The results of the infection experiment indicated that gastroin-testinal infection with P.mirabilis in mice led to splenic hemorrhage and significant splenomegaly.A notable difference in spleen index between the infected and control groups was observed at 24 hours post-infection(P=0.001 688),with the greatest difference occurring at 96 hours post-infec-tion(P=0.000 074).Cytokine analysis revealed significant elevations in IL-2,IL-17A,KC,Eotax-in,MCP-1,RANTES,MIP-1α,MIP-1β,IFN-γ,G-CSF,and IL-10 levels in the infected group.A-mong these,the pro-inflammatory cytokines IL-17A and G-CSF exhibited the most substantial changes,positively correlating with the splenomegaly,and peaking at 96 hours post-infection,with concentrations of(104.74±3.91)and(5 184.08±280.22)ng/L,respectively,which were 26.79 and 36.25 times higher than those in the control group.These findings indicate that IL-17A and G-CSF play significant roles in the pro-inflammatory response following gastrointestinal infection with P.mirabilis.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Recent studies have shown that an imbalance in iron metabolism can affect the composition and microstructural changes of bone, disrupting bone homeostasis and leading to osteoporosis(OP). The imbalance in iron metabolism, along with its induced local abnormal microenvironment and cellular iron death, has become a new focal point in OP research, drawing increasing attention from the academic community regarding the regulation of iron metabolism to prevent and manage OP. From the perspective of traditional Chinese medicine(TCM), iron metabolism imbalance has potential connections to TCM theories regarding internal organs, as well as treatments aimed at tonifying the kidney, strengthening the spleen, and activating blood circulation. Evidence is continually emerging that TCMs and effective components that tonify the kidney, strengthen the spleen, and activate blood circulation can prevent and manage OP by regulating iron metabolism. This article analyzes the relationship between iron and bone, as well as the effects of TCM formulations on improving iron metabolism and influencing bone metabolism, from the perspectives of iron metabolism mechanisms and TCM interventions, aiming to broaden existing clinical strategies for prevention and treatment and inject new momentum into the field of OP as it moves into a new era.
Osteoporosis/drug therapy* ; Humans ; Iron/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Medicine, Chinese Traditional ; Bone and Bones/drug effects*

This study explores the therapeutic differences and mechanisms of salt-processed Phellodendri Chinensis Cortex in improving insulin resistance(IR) based on network pharmacology, molecular docking, and cellular experiments. The components and intersection targets of Phellodendri Chinensis Cortex in improving IR were collected from databases, and a "drug-component-target-disease" network and protein-protein interaction(PPI) network were constructed to screen core components and targets. A total of 29 active components and 240 intersection targets were identified, of which 13 were core targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were used to identify key signaling pathways, and molecular docking was performed to validate the binding activity between core components and targets. An IR model in HepG2 cells was induced using insulin combined with high glucose, and the effects of Phellodendri Chinensis Cortex before and after salt-processing on cell glucose consumption were evaluated. The expression of proteins related to the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) signaling pathways was detected by Western blot. The cellular experimental results showed that, compared with the model group, glucose consumption in the drug-treated groups was significantly increased(P<0.01), the phosphorylation level of extracellular regulated protein kinase(ERK) was decreased(P<0.05), the phosphorylation levels of PI3K and AKT were increased, and the expression of glucose transporter 4(GLUT4) was also upregulated(P<0.05). Furthermore, the effect of salt-processed Phellodendri Chinensis Cortex was better than that of raw Phellodendri Chinensis Cortex. The study demonstrates that Phellodendri Chinensis Cortex, both before and after salt-processing, improves IR by regulating the expression of related proteins in the MAPK and PI3K-AKT signaling pathways, with enhanced effects after salt-processing.
Humans ; Network Pharmacology ; Phellodendron/chemistry* ; Insulin Resistance ; Drugs, Chinese Herbal/chemistry* ; Hep G2 Cells ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Glucose/metabolism*