This study aims to explore the screening and mechanisms of action of traditional Chinese medicine(TCM) monomer compounds targeting transient receptor potential vanilloid 4(TRPV4) against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). Based on a machine learning method using the pre-trained protein language model ConPLex to predict drug-target binding properties, the study rapidly screened TRPV4-targeting TCM monomer compounds and ranked them by algorithm scores from highest to lowest. The cytotoxicity of candidate compounds was evaluated via cell counting kit-8(CCK-8), and the effects of glycycoumarin(GCM) on SARS-CoV-2 replication in African green monkey kidney cell line(Vero-E6) were analyzed through indirect immunofluorescence assay(IFA) and Western blot. A BALB/c mouse infection model with SARS-CoV-2/C57MA14 mouse-adapted strain was employed to assess the in vivo antiviral efficacy of GCM by examining the survival rate, pulmonary viral load, and pathological damage. To elucidate the molecular mechanism, Western blot was used to detect the protein expression of key signaling pathways, and enzyme-linked immunosorbent assay(ELISA) was applied to quantify concentrations of cytokines including interleu-kin-6(IL-6), tumor necrosis factor-alpha(TNF-α), C-X-C motif chemokine ligand 10(CXCL10), and monocyte chemoattractant protein-1(MCP-1) in serum. Molecular docking and molecular dynamics simulation techniques were employed to resolve the binding mode of GCM with the TRPV4 protein. In vitro experiments demonstrated that among 15 candidate compounds, GCM exhibited significant dose-dependent inhibition of SARS-CoV-2. In the animal model, the compound prolonged the survival time of infected mice and significantly alleviated virus-induced pulmonary pathological damage. Mechanistic studies revealed that GCM suppressed the TRPV4 expression, blocked nuclear translocation of nuclear factor kappa-B(NF-κB) triggered by SARS-CoV-2 infection, and subsequently downregulated the transcriptional level of pro-inflammatory factors such as IL-6 and TNF-α. Concurrently, the expression of IL-6, TNF-α, CXCL10, and MCP-1 in serum was markedly reduced after GCM intervention. The molecular docking and dynamics simulation confirmed that the GCM-TRPV4 compound exhibited excellent stability in both binding conformation and dynamic interactions. The study verified that GCM demonstrated potent anti-SARS-CoV-2 activity in both in vitro and in vivo models, effectively inhibiting viral replication while suppressing infection-induced cytokine storms. The results indicate that GCM is a highly promising anti-SARS-CoV-2 TCM monomer compound, which is worthy of further in-depth research and development.

Chronic obstructive pulmonary disease (COPD), a disease responsible for early mortality worldwide, is well accepted to be associated with periodontitis epidemiologically. Although both of the diseases are the multi-microbial inflammatory disease, the precise underlying mechanisms by which periodontitis influences the progression of COPD remains largely unknown. Here, we established COPD accompanied with periodontitis mouse models and observed the pronounced progress in pulmonary symptoms and histopathology, characterized by poorer respiratory function, thickened bronchial walls, and increased neutrophils infiltration in lung tissue. Mechanistically, periodontitis pathogen Porphyromonas gingivalis (P. gingivalis) relocated in the lung through the respiratory tract and LPS from P. gingivalis promoted the secretion of chemokines CXCL2 and G-CSF of alveolar epithelial cells through NF-κB and p38 MAPK pathways to recruit neutrophils. Furthermore, exposure to P. gingivalis of infiltrated neutrophils released matrix metallopeptidase-8 (MMP-8) and neutrophil elastase (NE), which aggravated airway inflammation and tissue damage. These findings indicated that periodontitis could exacerbate COPD via its pathogen P. gingivalis, which translocated in the lung and stimulated neutrophil chemotaxis and activation in the lung.

Voriconazole-induced hypoglycemia in non-diabetic patients has rarely been reported. We describe a non-diabetic man, aged 50 years, without hepatic or renal dysfunction who developed severe prolonged hypoglycemia about 28 hours after initiating therapeutic dose of intravenous (IV) voriconazole therapy for invasive pulmonary aspergillosis. He required continuous IV infusion of dextrose solutions to maintain euglycemia. He recovered from hypoglycemia after discontinuation of voriconazole. Higher than normal plasma insulin (30.4 μU/mL) as well as C-peptide (10.04 ng/mL) levels were observed, which reached normal levels after he recovered from hypoglycemia. The temporal association between voriconazole administration and hypoglycemia occurrence led to probability that it was voriconazole-induced. The voriconazole trough level (8.9 μg/mL) checked during the hypoglycemia episode was elevated. The mechanism of hypoglycemia may be strongly attributed to insulinemia resulting from high voriconazole concentration. There is a possibility of genetic polymorphisms in the hepatic cytochrome P450 2C19 isoenzyme in this patient, which altered the voriconazole metabolism, causing high trough levels associated with hypoglycemia. This case suggests that voriconazole has a propensity to alter glucose homeostasis in the absence of liver and kidney dysfunction, and it may induce hypoglycemia without drug over dosage or drug interaction that clinicians should be vigilant about.

To explore lung ultrasound (LUS) in the evolution of bronchopulmonary dysplasia (BPD) and the diagnostic value of LUS in BPD.

Newborn rats were randomly assigned to the room air (RA) group or the oxygen (O₂) group. LUS were performed at 12 h and on the 3rd, 7th, and 10th days to explore the LUS in BPD rats. Hematoxylin-eosin staining and immunohistochemical were analyzed to evaluate pathological characteristics.

LUS score (LUSs) in the O₂ group was significantly increased on the 7th and 10th days. In the early stage, LUS revealed multiple B-lines and air bronchograms. In the late stage, LUS revealed anechoic echoic areas on the pleural surface and scattered dot-like hyperechoic patterns in the lung field. The LUS findings were consistent with the pathological results.

There was a strong positive correlation between LUS and pathological findings. LUS can be used to monitor the evolution of BPD.

This study systematically revealed the inflammatory mechanism of action of the Qibai Pingfei Capsules in intervening in phlegm-stasis obstructing lung syndrome in chronic obstructive pulmonary disease(COPD) based on network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation. Core components such as kaempferol and inosine, as well as key targets such as hypoxia-inducible factor-1α(HIF-1α) and prostaglandin-endoperoxide synthase 2(PTGS2)/cyclooxygenase-2(COX-2), were identified via network pharmacology, and a multidimensional interaction network was constructed. Enrichment analysis suggested that these core targets may exert regulatory effects by modulating biological processes such as hypoxic stress response, inflammatory mediator release, and angiogenesis, with potential mechanisms related to the regulation of inflammation-related signaling pathways. Molecular dynamics simulations confirmed that the key components stably bound to targets such as HIF-1α, COX-2, and tumor necrosis factor-α(TNF-α). A rat model of COPD with phlegm-stasis obstructing lung syndrome was established using a composite stimulation method(hypoxia + swimming + cigarette smoke). The results demonstrated that Qibai Pingfei Capsules could significantly improve lung function, as evidenced by increased lung function parameters(FVC, FEV_(0.3), FEV_(0.3)/FVC), and reduced inflammatory cell infiltration in lung tissue. Pathological damage to bronchi and alveolar structures in the Qibai Pingfei Capsules group was significantly alleviated, characterized by reduced airway remodeling and thinning of alveolar septa. Qibai Pingfei Capsules inhibited the expression of HIF-1α and COX-2 proteins(P<0.01) and significantly downregulated the level of the pro-inflammatory factor TNF-α. Co-immunoprecipitation confirmed the interaction between HIF-1α and COX-2 proteins in rat lung tissue. In-depth analysis revealed that the therapeutic mechanism of Qibai Pingfei Capsules may involve targeting and regulating the HIF-1α/COX-2 signaling pathway to intervene in the hypoxic stress response, thereby modulating TNF-α-mediated inflammatory cascades. This mechanism effectively modulated hypoxic stress and the inflammatory microenvironment, promoted lung tissue repair, and significantly reduced pulmonary inflammation levels in the rat model of COPD with phlegm-stasis obstructing the lung syndrome.

To explore the mechanism of action of Shengjiang Pingchuan Zhike Pills in the treatment of bronchial asthma, this study used proteomics technology to analyze the key proteins and molecular mechanisms of the ovalbumin(OVA)-induced bronchial asthma in rats and experimentally verified the core differential proteins. Sixty specific-pathogen free(SPF) rats were selected and divided into a blank group and a model group. The model was established by intraperitoneal injection and nebulization of OVA and aluminum hydroxide mixed solution. After successful modeling, the rats were divided into a blank group, a model group, a positive control group, and low-dose, medium-dose, and high-dose groups of Shengjiang Pingchuan Zhike Pills, with 10 rats in each group. The general conditions of the rats in each group were observed. The pathological changes of lung tissue were observed by hematoxylin-eosin(HE) staining, and mucus secretion, as well as basement membrane destruction and thickening were examined by periodic acid-Schiff(PAS) staining. Differentially expressed proteins and molecular mechanisms were analyzed by proteomics. The content of cytokines in bronchoalveolar lavage fluid(BALF) was verified by enzyme-linked immunosorbent assay(ELISA). The location of goblet cells and nuclear translocation of nuclear factor-κB(NF-κB) were measured by immunofluorescence, and the pathways and expression level of key proteins were verified by Western blot. Compared with those of the model group, after the intervention of Shengjiang Pingchuan Zhike Pills, the number of wheezing, stridor, and coughing times decreased; the hair luster and mental state improved; the activity increased; the breathing frequency tended to be stable; the response to external stimuli and flexibility increased, and the body weight showed an increasing trend. Pathological staining showed that after the intervention, the inflammatory infiltration of asthma rats was reduced; the thickening of airway smooth muscle was alleviated; the mucus secretion was decreased; the destruction of the basement membrane was ameliorated, and the inflammatory score and PAS score were decreased. ELISA results indicated that the expression level of interleukin-4(IL-4), interleukin-5(IL-5), interleukin-13(IL-13), and interleukin-17(IL-17) in the high-dose group decreased, and the expression level of interferon(INF)-γ increased. Immunofluorescence results showed that the number of goblet cells and mucus secretion in the high-dose group decreased; the fluorescence of phospho-NF-κB(p-NF-κB) in the nucleus weakened, and some were distributed from the nucleus to the cytoplasm. Western blot results showed that the high-dose group exhibited the down-regulated expression of cathepsin S(CTSS), mucin 5AC(MUC5AC), and p-NF-κB/NF-κB proteins and the up-regulated expression of low-affinity immunoglobulin γFc region receptor Ⅱ-b(FCGR2B) protein. In conclusion, Shengjiang Pingchuan Zhike Pills may alleviate OVA-induced airway inflammation, goblet cell metaplasia, and mucus secretion by inhibiting the NF-κB pathway, which may be related to the down-regulation of CTSS and up-regulation of FCGR2B protein expression, thereby regulating the immune balance of Th1/Th2/Th17 cells.

Dementia risk reduction through lifestyle modification has much potential but is not yet implemented in routine clinical care. Currently, there are no preventive interventions available for memory clinic patients. Therefore, the aim of The Lifestyle Intervention in the memory clinics of General and academic Hospitals Trial (LIGHT) is to examine the (cost)effectiveness of a multidomain intervention combining lifestyle coaching with risk self-management for patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI).

LIGHT is a 1-year multi-center randomized controlled trial for dementia risk reduction by improving brain health through lifestyle modifications in memory clinic patients without dementia. Starting early 2025, the trial aims to include 300 older adults (≥ 50 years) with SCD or MCI, with presence of ≥ 2 modifiable dementia risk factors, recruited via the memory clinics of Dutch hospitals. Participants are randomized 1:1 to either the intervention group or control group. The intervention consists of three components: (1) three individual sessions with a certified lifestyle coach to set and work on personal goals, (2) vouchers for access to brain-healthy services from local providers, and (3) access to an online self-management platform (www.breinzorg.nl) providing psychoeducation on dementia risk reduction through lifestyle. The control group receives general health advice. The primary outcome is 1-year change in modifiable dementia risk captured by the LIfestyle for BRAin Health 2 (LIBRA2) index consisting of coronary heart disease, diabetes, hypercholesterolemia, hypertension, depression, obesity, smoking, high physical activity, and chronic kidney disease, high alcohol intake, high cognitive activity, healthy diet, hearing impairment, sleep disturbances, and social participation. Secondary outcomes include cognitive functioning, health-related quality of life, activities of daily living, self-efficacy, care use, as well as change in individual risk factors.

LIGHT will provide insight into the implementation and (cost-)effectiveness of a lifestyle intervention for indicated prevention in a memory clinic setting.

Clinicaltrials.gov: NCT06832761 (date 2025-02-18), OMON: 57,198.

Pien Tze Huang has the efficacy of clearing heat, removing toxins, cooling the blood, removing blood stasis, subduing swelling, and relieving pain. It is widely used in the treatment of acute viral hepatitis, carbuncles and furuncles, unidentified swelling and poison, blunt trauma, and various inflammations. To investigate the clinical efficacy and safety of Pien Tze Huang Capsules combined with Compound Pien Tze Huang Hemorrhoid Ointment in controlling the postoperative inflammatory response of wounds in patients undergoing surgery for mixed hemorrhoids, a multicenter, randomized, open-label, and positive-controlled clinical trial was conducted at 12 tertiary medical institutions in China. A total of 240 patients who underwent Milligan-Morgan hemorrhoidectomy for mixed hemorrhoids were enrolled and randomly assigned to the treatment or control group(1∶1). Both groups received sitz baths with Compound Jingjie for Fumigation and Washing as basic treatment. The treatment group additionally received Pien Tze Huang Capsules orally(2 capsules per dose, 3 times per day) and topical application of Compound Pien Tze Huang Hemorrhoid Ointment(2.5 g, twice per day), while the control group received topical Mayinglong Shexiang Hemorrhoid Ointment(2.5 g, twice per day). The treatment duration was 7 days. Primary efficacy endpoints included wound exudation scores, wound bleeding scores, and wound granulation tissue formation scores, and secondary endpoints included perianal edema scores, pain score using pain visual analogue scale(VAS) scores, postoperative analgesic use, and adverse events. RESULTS:: showed that in the full analysis set(FAS), the wound exudation scores on postoperative day 7 was significantly lower in the treatment group compared to that in the control group(P<0.05). In the per-protocol set(PPS), the wound exudation scores on postoperative days 3 and 7 was also significantly lower in the treatment group(P<0.05). While the treatment group showed lower perianal edema scores and pain VAS scores than the control group, the differences were not statistically significant. No statistically significant differences were observed between the two groups in wound bleeding scores, wound granulation tissue formation scores, analgesic use rate or amount, or incidence of adverse reactions. A total of 56 adverse events were observed, with 25 in the treatment group and 31 in the control group. The incidence of adverse reactions was comparable between groups, with no statistically significant difference. No serious drug-related adverse events were observed in either group. The results suggest that the Pien Tze Huang Capsules combined with Compound Pien Tze Huang Hemorrhoid Ointment can reduce wound exudation after surgery for mixed hemorrhoids, playing a beneficial role in controlling postoperative inflammation. The treatment offers good safety and tolerability, showing great potential as a postoperative adjunctive therapy integrating traditional Chinese medicine and western medicine.

Stroke is a leading cause of disability, with up to 80% of survivors experiencing motor impairments. These impairments are attributed to various factors, including reduced neural drive and altered motor unit firing patterns. Rehabilitation aims to restore motor function by enhancing motor unit recruitment and synchronization. High-density electromyography (HD-EMG) is a valuable tool for evaluating these changes in motor unit activity.

We tested a wearable HD-EMG forearm sleeve to investigate the relationship between motor function and motor unit properties including firing rate, motor unit module activation, and coherence. Seven individuals with chronic stroke and seven able-bodied individuals attempted 12 cued hand and wrist movements while EMG was recorded. Motor units were decomposed across all movements using convolutive blind source separation.

Fewer motor units were detectable in individuals with stroke compared to able-bodied participants. There was a significant reduction in motor unit firing rate during specific movements such as wrist flexion and hand open. Motor unit coupling and activation were altered following stroke, with reduced module activation in 8 of the 12 attempted movements. Furthermore, a reduction in coherence for gross movements and an increase in coherence for more dexterous thumb movements suggest altered neural drive to motor units after stroke that is differentially tuned to the complexity of movement. A combined neural control signature, consisting of multiple motor unit features, demonstrated strong correlation ([Formula: see text]) with clinical motor function scores.

This study demonstrates that HD-EMG can capture detailed motor unit activity and neural control characteristics across multiple forearm muscles in individuals with chronic stroke. By integrating multiple HD-EMG features, this approach provides new insights into neuromuscular alterations linked to hand motor function after stroke. These findings support the use of HD-EMG for monitoring recovery, predicting outcomes, and guiding more targeted rehabilitation, thus advancing both stroke research and patient care.