ObjectiveTo explore the effect of oral sodium butyrate on skeletal muscle atrophy in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism. MethodsSixty SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group (NC, n=18) and a ABX-depleted group (ABX, n=42). The ABX mice were pretreated with a quadruple antibiotic cocktail via oral gavage (0.2 ml per administration, once daily, 6 d per week, for 2 weeks), whereas NC received an equal volume of sterile water. The quadruple antibiotic cocktail consisted of metronidazole (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and gentamicin (1 g/L). Following successful pretreatment, six mice from each group were randomly selected for gut microbiota sequencing analysis and designated as the Abx group and the NC0 group, respectively. Theremaining mice in ABX were subcutaneously inoculated in the dorsum with 0.2 ml of CT26 cell suspension (at a cell density of 1×10⁷/ml). Then these mice were randomly allocated into three subgroups: a control tumor bearing model group (0_NaB, n=12), a tumor-bearing model group receiving low-dose oral sodium butyrate (L_NaB, n=12), a tumor-bearing model group receiving high-dose oral sodium butyrate (H_NaB, n=12). And mice in NC were inoculated at the same site with 0.2 ml of normal saline. The administration dose for L_NaB was 0.3 g/(kg·d), that for H_NaB was 0.5 g/(kg·d), while NC and 0_NaB were given the same volume of normal saline (0.2ml per time, once daily, 6 d per week, for 4 weeks). The general condition of mice was monitored, and forelimb grip strength gastrocnemius muscle mass and its muscle fiber cross-sectional area were measured for each group. The structural changes in gut microbiota were assessed by 16S rRNA sequencing of cecal contents. Pathological alterations in the intestinal wall were examined via HE staining. Serum and gastrocnemius muscle levels of TNF‑α, IL-6, IL-1β, and LPS were quantified using ELISA. The protein expression of ZO-1 and occludin in the small intestine, as well as proteins associated with the TLR4/MyD88/NF-κB signaling pathway in the gastrocnemius muscle, were detected by Western blot analysis. Results(1) The alpha-diversity in Abx was significantly lower than that in NC0 (P<0.01), a significant decrease of the mass and muscle fiber cross-sectional area of the gastrocnemius (P<0.01), with the majority of gut microbiota being effectively depleted. (2) Compared with NC, the subcutaneous tumors of mice in 0_NaB were prominent, a significant increase of the mass and muscle fiber cross-sectional area of the gastrocnemius, accompanied by a significant decrease in body weight at the end of the 3th and 4th week (P<0.05), and a significant weakening of the forelimb grasping strength at the 5th and 6th week (P<0.01). Compared with 0_NaB, the tumor mass of mice in L_NaB and H_NaB showed a significant decreasing trend, and the grip strength of the forelimbs significantly increased at the 5th and 6th week (P<0.05, P<0.01). (3) Compared with 0_NaB, the Shannon and Observed species indices in α diversity of L_NaB and H_NaB were significantly increased (P<0.05). At the genus level, compared with 0_NaB, L_NaB exhibited a significant decrease in the relative abundance of Parasutterella (P< 0.01), while H_NaB showed significant reductions in the relative abundances of both Escherichia-Shigella and Parasutterella (P < 0.01). (4) Compared with 0_NaB, the small intestinal tissue structure in L_NaB and H_NaB was more intact, the infiltration of inflammatory cells was significantly reduced, and the capillaries were slightly dilated. The expression levels of ZO-1 and occludin proteins in L_NaB were significantly increased (P<0.01). (5) The LPS concentration in the gastrocnemius muscle and the protein expression levels of TLR4, MyD88, p-IκBα, and p-NF‑κB p65 in L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05). The serum TNF‑α concentration in H_NaB and TNF-α concentration in the gastrocnemius muscle of the L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05, P<0.01, P<0.01). ConclusionOral administration of NaB can improve gut microbiota α diversity, adjusting its composition, improving intestinal mucosal barrier function, reducing the LPS-induced pro-inflammatory response, and delaying skeletal muscle atrophy. The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

Coronary heart disease is a cardiovascular disease that affects coronary arteries. It presents high incidence and high mortality worldwide, bringing a serious threat to human health and quality of life. Salviae Miltiorrhizae Radix et Rhizoma derived from Salvia miltiorrhiza is widely used in the treatment of cardiovascular diseases, such as coronary heart disease. Salvianolic acid B is an active component in Salviae Miltiorrhizae Radix et Rhizoma extracts, and studies have shown that it has anti-inflammatory, antioxidant, apoptosis-and autophagy-regulating, anti-fibrosis, and metabolism-modulating effects. This article reviews the research progress regarding the therapeutic effect of salvianolic acid B on coronary heart disease in the recent decade. It elaborates on the role and mechanism of salvianolic acid B in treating coronary heart disease from multiple perspectives, such as the inhibition of thrombosis, improvement of blood circulation, reduction of myocardial cell injury, and inhibition of cardiac remodeling. This article provides a theoretical basis for the application of Chinese medicinal materials and TCM prescriptions containing salvianolic acid B in the treatment of coronary heart disease.
Humans ; Benzofurans/administration & dosage* ; Coronary Disease/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Salvia miltiorrhiza/chemistry* ; Animals ; Depsides

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

To investigate the effects and mechanisms of the water extract from Sorbus tianschanica(STE) on asthmatic airway inflammation, the mice were randomly divided into six groups, including a control group, a model group, a positive drug dexamethasone group(2 mg·kg~(-1)), a low-dose STE group(1 g·kg~(-1)), a medium-dose STE group(2 g·kg~(-1)), and a high-dose STE group(4 g·kg~(-1)). Except for the control group, all groups were subjected to ovalbumin induction to establish an asthma mouse model. The anti-inflammatory effects of STE were evaluated by examining pathological changes in lung tissue and measuring the levels of interleukin(IL)-4 and IL-5 in bronchoalveolar lavage fluid(BALF). Transcriptomic and proteomic methods were further employed to analyze differentially expressed genes and proteins, as well as their associated signaling pathways in lung tissue. Subsequently, the expression changes of key genes were verified by reverse transcription-quantitative polymerase chain reaction(RT-qPCR), and immunohistochemistry and Western blot methods were used to explore the regulatory mechanisms of STE in the pathogenesis of asthma in mice. Molecular docking was performed by using AutoDock Vina software to evaluate the binding affinity of the main active components in STE with the target proteins, including phosphatidylinositol-3-kinase catalytic subunit α(PIK3CA), Toll-like receptor 4(TLR4), protein kinase B1(Akt1), and matrix metallopeptidase 9(MMP9). The results showed significant inflammatory cell infiltration and fibrous tissue proliferation in the lung tissue of mice in the model group. However, these pathological changes were markedly reduced following STE intervention. Compared with those of the control group, the expression levels of IL-4 and IL-5 in the BALF of the model group were significantly increased but notably decreased following STE intervention. Transcriptomic and proteomic analyses identified key genes and proteins associated with allergic asthma, including tumor necrosis factor(TNF), IL-6, TLR4, PIK3CA, and MMP9. RT-qPCR validation revealed that high-dose STE intervention significantly downregulated the expressions of PIK3CA, IL-6, Akt1, MMP9, IL-13, nuclear factor-kappa B(NF-κB), TNF, CXC motif chemokine ligand 1(CXCL1), and TLR4 mRNAs and significantly upregulated the expression of signal transducer and activator of transcription 1(STAT1) mRNA. Western blot and immunohistochemical analyses confirmed that STE significantly downregulated the expressions of MMP9, TLR4, PIK3CA, and phosphorylated protein kinase B(p-Akt) in lung tissue of asthmatic mice. Moreover, molecular docking demonstrated that kaempferol-3,7-diglucoside, isoquercitrin, quercetin-3-gentiobioside, and hyperoside in STE exhibited stable binding affinities with PIK3CA, TLR4, Akt1, and MMP9, suggesting that the active components may exert anti-inflammatory effects by targeting and modulating asthma-related signaling pathways. In summary, STE exerts anti-asthmatic effects by inhibiting the expressions of PIK3CA, MMP9, p-Akt, and TLR4 and regulating the TLR4/PI3K/Akt/MMP9 signaling pathway.
Animals ; Asthma/metabolism* ; Toll-Like Receptor 4/metabolism* ; Signal Transduction/drug effects* ; Mice ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Matrix Metalloproteinase 9/metabolism* ; Mice, Inbred BALB C ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Humans ; Lung/immunology* ; Male

ObjectiveTo explore the correlation between the occurrence of cardiovascular events in rheumatoid arthritis（RA） and traditional Chinese medicine（TCM） syndrome. MethodsThe cross-sectional study selected 6713 RA patients from 122 centres nationwide， in which general information such as name， gender， age， height， body weight， and course of disease were collected by completing a questionnaire； patients were classified into eight types of syndrome according to the information of their four examinations，i.e. wind-dampness obstruction syndrome， cold-dampness obstruction syndrome， dampness-heat obstruction syndrome， phlegm-stasis obstruction syndrome， stasis-blood obstructing collateral syndrome， qi-blood deficiency syndrome， liver-kidney insufficiency syndrome， and qi-yin deficiency syndrome. According to the occurrence of cardiovascular events， they were divided into the occurrence group and the non-occurrence group， and the condition assessment data and laboratory examination indexes were recorded. The test of difference between groups was used to analyse the possible risk factors for the occurrence of RA cardiovascular events， and binary logistic regression was used to analyse the correlation between TCM syndromes and RA cardiovascular events. ResultsA total of 6713 RA patients were included， including 256 cases in occurrence group and 6457 in non-occurrence group. There was no statistically significant difference between groups in terms of height， gender， insomnia， appetite， white blood cell（WBC）， hemoglobin（HGB）， platelets（PLT）， rheumatoid factor（RF）， anti-cyclic peptide containing citrulline（CCP）， alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， γ-glutamyl transpeptidase（GGT）， urea creatinine（CREA）， and glucose（GLU）（P＞0.05）. The TCM syndromes between groups showed significant statistic differences（P＜0.05）. Patients in occurrence group had longer disease duration， heavier body weight， and older age； more severe conditions such as disease activity（DAS-28）， number of painful joints（TJC）， number of swollen joints（SJC）， health questionnaire scores（HAQ）， visual analog scores（VAS）， restlessness， and fatigue； higher blood sedimentation rate（ESR）， low-density lipoprotein（LDL-C）， triglyceride（TG）， total cholesterol（TC）， D-Dimer， and lower high-density lipoprotein（HDL-C）（P＜0.05）. The distribution of syndrome types showed that dampness-heat obstruction syndrome accounted for the largest proportion of patients in both groups and was higher in RA cardiovascular events. Logistic regression analysis showed that the occurrence of RA cardiovascular events was strongly associated with dampness-heat obstruction syndrome［OR=5.937， 95%CI （4.434， 7.949）， P＜0.001］. ConclusionThe occurrence of RA cardiovascular events were associated with TCM syndromes， and the probability of cardiovascular events in the RA patients with dampness-heat obstruction syndrome was 5.937 times higher than patients with other TCM syndromes.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

OBJECTIVE: To explore the current research status and hotspots in the field of biomechanics of diabetic foot by bibliometric analysis methods. METHODS: Literatures related to biomechanics of diabetic foot published in the Web of Scienc Core Collection (WoSCC) from 1981 to 2024 were searched. CiteSpace software and R language bibliometrics plugin were used to conduct a visual analysis of annual publication volume of the literature, including publication volume of each country and region, the publication situation of authors and institutions, the citation situation of individual literature, and the co-occurrence network of keywords. RESULTS: Totally 996 literatures were included, and the number of published papers increased steadily. The United States (261 papers) and China (89 papers) were the top two countries in terms of the number of published papers. The mediating centrality of the United States was 0.94, and that of China was 0.01. Scholars such as Cavanagh and institutions like the Cleveland Clinic were at the core of research in this field. High-frequency keywords include plantar pressure (plantar pressure), diabetic foot (diabetic foot), ulceration (ulcer), etc. The research focuses on plantar pressure, ulcer formation and prevention, etc. CONCLUSION Biomechanical research on diabetic foot mainly focuses on the pressure distribution on the sole of the foot, callus formation, mechanical analysis of soft tissues on the sole of the foot, and the study of plantar decompression caused by Achilles tendon elongation. The research trend has gradually shifted from focusing on joint range of motion to gait and the design of braces and assistive devices, and has begun to pay attention to muscle strength, gait imbalance and proprioception abnormalities.
Humans ; Diabetic Foot/physiopathology* ; Biomechanical Phenomena ; Bibliometrics

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*