A long-term follow-up non-randomized controlled study was conducted to evaluate the medium- and long-term efficacy of the Jianpi Huogu (Kanggu) Formula in treating early-stage (ARCO Ⅰ-Ⅱ stage) femoral head necrosis, thereby providing evidence for the early prevention and treatment of the disease with TCM, improvement of symptoms, and delay of disease progression. Patients who received Jianpi Huogu (Kanggu) Formula (experimental group, n = 61) or formula combined with TCM infusion therapy (control group, n = 168) between January 2003 and June 2020, with a follow-up of ≥3 years, were included. Clinical and imaging data at baseline and annual follow-ups were collected, and 40 matched pairs (80 cases) were selected using propensity score matching. The primary endpoints were clinical efficacy (hip pain scores, hip flexion function scores, walking distance scores, and total scores of clinical efficacy) and the Beijing University of Chinese Medicine X-ray Evaluation (BUCMXE), including femoral head morphology scores, osteoarthritis scores, necrotic lesion density scores, and total scores of BUCMXE. The efficacy of the two groups was compared before treatment and at 3, 5, and 10 years post-treatment. Clinical efficacy showed that, compared with pre-treatment, both groups had significantly reduced hip pain scores and improved hip flexion function scores, walking distance scores, and total scores of clinical efficacy at 3, 5, and 10 years (P<0.001). Imaging evaluation showed that, compared with pre-treatment, femoral head morphology scores in experimental group increased at 3 (0.65±1.00, P<0.05), 5 (0.70±1.02, P<0.001) and 10 years (0.80±1.08, P<0.05); osteoarthritis scores increased at 3 (0.32±0.66, P<0.05) and 5 years (0.32±0.67, P<0.05); necrotic lesion density scores decreased at 3 (1.18±0.50, P<0.05) and 5 years (1.19±0.52, P<0.05); total scores of BUCMXE increased at 3 (2.15±1.29, P<0.05) and 5 years (2.22±1.32, P<0.05). Compared with control group, the femoral head morphology scores increased in experimental group (P<0.05). These results confirm that the Jianpi Huogu (Kanggu) Formula can significantly improve clinical symptoms (pain and joint function) in patients with ARCO Ⅰ-Ⅱ stage femoral head necrosis. Medium- and long-term imaging data suggest slow disease progression (scores not reaching grade Ⅰ pathological criteria). For patients with ARCO Ⅰ stage or mild disease, monotherapy with this formula may be considered.

This study aims to investigate the antifungal secondary metabolites produced by the endophytic fungus Aspergillus sp. FH-1 isolated from Valeriana officinalis via a high-salt rice medium. Compounds were isolated and purified by silica gel and ODS column chromatography, semi-preparative HPLC, and other techniques. The chemical structures were elucidated through analysis of physicochemical properties and spectroscopic data of nuclear magnetic resonance (NMR), infrared (IR), and mass spectrometry (MS). The inhibitory effects of all the compounds against Colletotrichum gloeosporioides were evaluated via the mycelial growth rate method. Eight compounds were obtained from the ethyl acetate extract of Aspergillus sp. FH-1. They were identified as asperchoried A (1), butyrolactone Ⅱ (2), isobutyrolactone Ⅱ (3), aspernolide A (4), butyrolactone Ⅴ (5), clavatone (6), 1-hydroxy-6,8-dimethoxy-3-methylanthracene-9,10-dione (7), and (S) -7-methoxy-2, 5-dimethyl-2, 3-dihydrobenzofuran-6-ol (8). Among them, compound 1 is a novel chlorinated butanolide derivative and was designated asperchoried A. Compounds 1, 2, 6, and 7 possessed inhibitory effects on C. gloeosporioides, with EC₅₀ values of 15.08, 77.19, 89.94, and 62.02 μg·mL^-1, respectively.

This study aimed to elucidate the therapeutic effects and molecular mechanisms of Periplaneta americana extract (PAE) on ground-glass nodule (GGN) -type early-stage lung adenocarcinoma (LUAD) using patient-derived organoid (PDO) models. GGN-type patient-derived early-stage LUAD organoid (GGN-PDO) were successfully established. At the level of drug quality control and component analysis, the content of free amino acids and peptides in PAE were determined by high-performance liquid chromatography (HPLC), and the main components were further analyzed by liquid chromatography-mass spectrometry (LC-MS). Analysis of variance was used to evaluate the similarity between drugs of the same batch (Pearson correlation coefficient 0.87-0.99) and ensure quality control. At the histopathological level, hematoxylin-eosin (HE) staining and immunohistochemical (IHC) analysis of key molecular markers, including cytokeratin 7 (CK7), thyroid transcription factor-1 (TTF-1), and Ki-67, confirmed that the organoids recapitulated the tumor characteristics of parental tissues. Pharmacodynamic evaluation demonstrated that PAE significantly inhibited the proliferation and viability of GGN-PDOs in a dose-dependent manner, while immunofluorescence (IF) staining showed a marked reduction in the proliferation marker Ki-67. Flow cytometry further confirmed that PAE induced apoptosis in GGN-PDO, and Western blot analysis demonstrated that PAE downregulated the anti-apoptotic protein Bcl-2 and upregulated the pro-apoptotic protein Bax, thereby activating the apoptotic pathway. Notably, for the first time, the pro-apoptotic mechanism of PAE was shown to involve inhibition of the Janus kinase 1 (JAK1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, as evidenced by markedly decreased protein levels of JAK1, PI3K, p-PI3K, AKT, and p-AKT following PAE treatment. In summary, this study is the first to use a clinically relevant GGN-PDO models to demonstrate that PAE induces apoptosis in early-stage LUAD via JAK1/PI3K/AKT pathway inhibition, providing a solid theoretical and experimental basis for developing innovative pharmacotherapies and non-surgical interventions against GGNs.

Mitochondrial dysfunction is a key pathological mechanism in metabolic-associated fatty liver disease (MAFLD), and regulating mitochondrial function to restore normal activity is an important therapeutic strategy. The theory of "harmful hyperactivity and responding inhibition" is a classical TCM principle that explains cyclical patterns in nature, interprets physiological and pathological phenomena in the human body, and guides TCM clinical diagnosis and treatment. The mechanism of mitochondrial dysfunction closely aligns with the process described in this theory as when the responding element fails to control, the hyperactive element becomes harmful. Based on the relationship between mitochondrial function and the TCM pathogenesis of MAFLD, and applying the "harmful hyperactivity and responding inhibition" framework, this study proposes that MAFLD originates from spleen deficiency impairing nutrient transport and failing to disperse essence, kidney Yang deficiency leading to impaired Qi transformation, and insufficient mutual regulation of the two, resulting in pathological products such as excessive accumulation of phlegm-turbidity, dampness, and blood stasis. These pathological changes manifest as mitochondrial dysfunction, including mtDNA damage, hepatocyte injury, lipid peroxidation, and mitochondrial accumulation. Clinically, MAFLD treatment follows the principle of regulating the responding element and restraining the hyperactive element: reinforcing the spleen earth to restore regulation, strengthening kidney water to nourish the kidneys and harmonize the liver, and addressing phlegm-stasis obstruction and hyperactivity through blood-activating and phlegm-resolving therapies. By modulating mitochondrial structure and function, this approach improves hepatic lipid metabolism, reduces oxidative stress, and alleviates inflammatory responses, achieving multi-target therapeutic effects. This study provides new theoretical foundations and practical strategies for integrated TCM-western medicine treatment of MAFLD.

This study aims to investigate the effects of glycyrrhizic acid and calcium ions from adjuvant solutions on the toxic lectin in Pinelliae Rhizoma Praeparatum and clarify the processing detoxification mechanism. Molecular docking and molecular dynamics simulations were employed to construct a 3D model of lectin and evaluate the interactions of glycyrrhizic acid and/or calcium ions with lectin. Wild-type and mutant lectin proteins were produced via a prokaryotic expression system in Escherichia coli. The interactions of glycyrrhizic acid and/or calcium ions with the lectin proteins were verified by Bio-Layer Interferometry (BLI), and the irritant toxicity was assessed via a rabbit model of conjunctival irritation. The findings revealed that the ternary complex formed by glycyrrhizic acid, calcium ions, and lectin exhibited greater stability. This complex showed significantly reduced root mean square deviation (RMSD), root mean square fluctuation (RMSF), solvent-accessible surface area (SASA), radius of gyration (Rg), Gibbs free energy of solvation (ΔGSOLV), and total binding free energy (ΔTOTAL), but significantly increased number of hydrogen bonds and gas-phase free energy (ΔGGAS). The combined action of glycyrrhizic acid and calcium ions led to a significant increase in the number of interactions in the amino acid residue region 51-56, 170-175, and 232-237 of lectin, with enhanced Coulomb interaction-short range (Coul-SR) and Lennard-Jones-short range (LJ-SR). When the wild-type lectin protein co-bound with glycyrrhizic acid and calcium ions, the affinity constant was 8.10×10^-6 mol·L^-1, which was significantly lower than that of the binary complex of wild-type lectin with glycyrrhizic acid or calcium ions and the ternary complex of mutant lectin with glycyrrhizic acid and calcium ions. Additionally, lectin soaked in a mixed solution of glycyrrhizic acid and calcium ions did not significantly exacerbate the irritation of the rabbit conjunctiva when being combined with toxic needle crystals. In conclusion, glycyrrhizic acid and calcium ions demonstrate a synergistic effect in forming a structurally stable and non-toxic supramolecular complex with lectin, thereby achieving the processing detoxification of Pinelliae Rhizoma Praeparatum.

This study aimed to investigate the mechanisms by which Acanthopanax senticosus extract (ASH) exerts effects onα-synuclein (α-syn) overexpressing transgenic mouse model of Parkinson's disease (PD), with a focus on its regulation of brain lipid metabolism. Twenty PD model mice were randomly assigned to a model group or an ASH treatment group (45.5 mg·kg^-1 by gavage for 4 weeks), and 10 C57BL/6 mice served as a normal control group. Behavioral assessments revealed that, compared with controls, PD model mice showed prolonged pole test time, reduced spontaneous locomotor activity, shorter latency to fall in the rotarod test, and decreased total distance traveled in the open field test. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), caspase-9 were significantly elevated, B-cell lymphoma-2 (Bcl-2), and proliferating cell nuclear antigen (PCNA) expression was reduced, and marked neuronal damage was observed in brain tissue. ASH intervention significantly improved these behavioral and biochemical parameters and attenuated neuronal injury. Untargeted lipidomics analysis revealed significant alterations in sphingomyelin (SM), ceramide (Cer), phosphatidylcholine (PC), and phosphatidylserine (PS) across multiple brain regions (cortex, substantia nigra, cerebellum, and striatum) in PD mice, which were notably restored by ASH treatment. Pathway analysis indicated that these metabolites were predominantly involved in sphingolipid metabolism. Western blot further demonstrated that ASH downregulated the expression of key sphingolipid metabolic enzymes serine palmitoyltransferase long-chain base subunits 1 and 2 (SPTLC1 and SPTLC2) and upregulated UDP-glucose ceramide glucosyltransferase (UGCG), β-galactosylceramidase (GALC), and sphingosine kinase 2 (SPHK2), thereby suppressing abnormal SM and Cer accumulation in the substantia nigra and elevating PS and PC levels in the striatum. Spearman's correlation analysis supported the modulatory effect of ASH on brain lipid metabolic profiles. In conclusion, ASH improves behavioral deficits, exerts anti-inflammatory effects, and regulates sphingolipid metabolism to correct disordered lipid profiles, thereby providing neuroprotective effects in PD mice.

This study is aimed to investigate the therapeutic effects of Junren Bufei Yixin Granules (JRBF) on hypoxic pulmonary hypertension (HPH) and explore the therapeutic mechanism through the polypyrimidine tract-binding protein 1 (PTBP1)/pyruvate kinase isozyme type M2 (PKM2) signaling pathway. Sixty SPF-grade C57BL/6 male mice were randomized into normal, model, sildenafil, and low/medium/high-dose JRBF groups. HPH was induced by hypoxic exposure (10% O₂, 8 h/day) for 4 weeks. The right ventricular systolic pressure (RVSP) was measured by right cardiac catheterization. Echocardiography was employed record the pulmonary artery acceleration time (PAAT), pulmonary ejection time (PET), tricuspid annular plane systolic excursion (TAPSE), and right ventricular anterior wall thickness at diastole (RVAWd). The histopathological changes were observed by hematoxylin-eosin (HE) and Masson staining. Western blot was employed to measure the expression levels of PTBP1, PKM2, and PKM1 in the lung tissue. The immunofluorescence assay was employed to detect the co-localization of PTBP1 with the marker alpha-smooth muscle actin (α-SMA) of pulmonary arterial smooth muscle cells (PASMCs). The lactate assay kit was used to measure the lactate levels in the serum and lung tissue. In the cell experiments, the hypoxia model was established by exposing human pulmonary artery smooth muscle cells (hPASMCs) to 1% O₂ for 48 h. The optimal (10%) JRBF concentration for intervention was determined by the cell-counting kit-8 (CCK-8). The cell proliferation (EdU), migration (Transwell), PTBP1/PKM2/PKM1, and lactate production were analyzed. The results showed that JRBF significantly reduced the RVSP, improved the PAAT/PET ratio and TAPSE, and attenuated pulmonary arteriolar remodeling and myocardial fibrosis. Furthermore, JRBF suppressed PTBP1 and PKM2 expression and reduced the lactate accumulation in the lung tissue and PASMCs. The cell experiment results showed that the 10% JRBF-containing serum inhibited the proliferation and migration of hPASMCs, while decreasing the PTBP1/PKM2 expression and lactate production. In conclusion, JRBF mitigates HPH progression by suppressing the PTBP1/PKM2 axis and restoring the glycolytic flux.

Chronic obstructive pulmonary disease (COPD) characterized by persistent airflow limitation is a heterogeneous lung condition prone to exacerbations and progression. Recent studies have revealed that gut microbiota dysbiosis can trigger metabolic disorders, immune abnormalities, and inflammatory responses, contributing to the pathogenesis and progression of COPD through the gut-lung axis. The spleen-tonifying and lung-replenishing therapy originates from the five elements theory of TCM, specifically the principle of tonifying the source in the case of deficiency. Enhancing the function of the spleen and stomach (earth element) indirectly nourishes the lungs (metal element), embodying the holistic concept of organ interdependence. The gut, as an extension of the transformation function of the spleen and stomach, reflects the modern interpretation of the spleen's role in transformation and transportation. When the spleen is deficient, gut microbiota dysbiosis leads to the accumulation of turbid toxins, which rise to affect the lungs, resulting in impaired flow of healthy Qi and the interplay of phlegm and stasis. The concept of tonifying the spleen not only involves tonifying the middle Qi but also encompasses multidimensional interventions such as improving gastrointestinal functions and regulating the gut microbiota to restore lung-spleen coordination. The spleen-tonifying and lung-replenishing therapy can influence the gut microbiota in COPD patients, effectively interrupting the pathological vicious cycle of spleen deficiency-microbiota dysbiosis-lung damage, slowing down disease progression, and reducing acute exacerbations. This method highlights the scientific value of the holistic thinking in TCM and provides a key pathway for integrating TCM and Western medicine in the prevention and treatment of COPD, underscoring the core clinical significance of tonifying the spleen and replenishing the lung.

Influenza viral pneumonia (IVP) is an infectious disease caused by influenza virus invading the lungs. With acute onset and rapid progression, it can lead to respiratory failure and even death in severe cases. Moreover, IVP is prone to cause large-scale incidence along with influenza epidemics, posing a serious threat to public health. The pathogenesis of IVP is complex, involving multiple pathological links such as viral replication, cytokine storm, immune imbalance, and oxidative stress. Studies have confirmed that the occurrence and development of IVP are closely related to signaling pathways including Toll-like receptors (TLRs)/nuclear factor-κB (NF-κB), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), NOD-like receptor pyrin domain-containing protein 3 (NLRP3), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase(PI3K)/protein kinase B (AKT), and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1). TCM characterized by multi-pathway, multi-component, and multi-target actions shows unique potential in regulating the above pathways and ameliorating pathological damage in the lungs. Accordingly, this article clarifies the IVP pathogenesis mediated by these pathways and systematically reviews the recent research on TCM active ingredients, single herbs, and compound preparations in preventing and treating IVP via regulating these pathways, with focuses on the roles of TCM in inhibiting viral replication, regulating inflammation, restoring immune homeostasis, and alleviating oxidative stress damage. It aims to comprehensively reveal the potential mechanisms of TCM in treating IVP, providing new insights for clinical diagnosis and treatment of IVP.

Attention deficit hyperactivity disorder (ADHD), a common neurodevelopmental disorder in children, is characterized by inattention, hyperactivity, and impulsivity. Epidemiological surveys show that the prevalence of ADHD in children is gradually increasing worldwide, and it is the most common childhood mental disorder in China. Because of the complex clinical symptoms, multiple co-morbidities, and unknown etiology, ADHD has far-reaching negative impacts on individuals, families, and the society. Behavioral interventions, as a pillar in the management of ADHD, play a targeted role in improving children's social functioning, with significant benefits supported by evidence. However, they are constrained by uneven resources, poor compliance, and insufficient continuity, Western medicine has multiple adverse effects and unclear long-term effects in the treatment of ADHD despite the definite efficacy. Accordingly, there is an urgent need to find safe and effective therapies suitable for children. With a holistic view and treatment based on syndrome differentiation, traditional Chinese medicine (TCM) has significant advantages in treating ADHD via multiple targets, which involves dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT), cyclic adenosine monophosphate (cAMP), brain-derived neurotrophic factor (BDNF) and other signaling pathways. Through these pathways, TCM can treat ADHD through the regulation of neurotransmitters, enhancement of prefrontal and striatal functions, enhancement of neuronal protection, attenuation of neuroinflammation, and reduction of neuronal apoptosis. However, a systematic study remains to be conducted. This paper summarizes the signaling pathways related to the treatment of ADHD by TCM in the past two decades, aiming to provide reference for delving into the mechanism and exploring effective TCM prescriptions for ADHD in children and to give full play to the advantages of the efficacy and characteristics of TCM.