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Traditional Chinese medicine (TCM) formulations have proven to be advantageous in clinical treatment and prevention of disease. LiuWei DiHuang Pill (LWDH Pill) is a TCM that was employed to treat type 2 diabetes mellitus (T2DM). However, a holistic network pharmacology approach to understanding the active ingredients and the therapeutic mechanisms underlying T2DM has not been pursued. A network pharmacology approach including drug-likeness evaluation, oral bioavailability prediction, virtual docking, and network analysis has been used to predict the active ingredients and potential targets of LWDH Pill in the treatment of type 2 diabetes. The comprehensive network pharmacology approach was successfully to identify 45 active ingredients in LWDH Pill. 45 active ingredients hit by 163 potential targets related to T2DM. Ten of the more highly predictive components (such as :quercetin, Kaempferol, Stigmasterol, beta-sitosterol, Kadsurenone, Diosgenin, hancinone C, Hederagenin, Garcinone B, Isofucosterol) are involved in anti-inflammatory, anti-oxidative stress, and the reduction of beta cell damage. LWDH Pill may play a role in the treatment of T2DM and its complications (atherosclerosis and nephropathy) through the AGE-RAGE signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. Based on a systematic network pharmacology approach, our works successfully predict the active ingredients and potential targets of LWDH Pill for application to T2DM and helps to illustrate mechanism of action on a comprehensive level. This study provides identify key genes and pathway associated with the prognosis and pathogenesis of T2DM from new insights, which also demonstrates a feasible method for the research of chemical basis and pharmacology in LWDH Pill.

ObjectivesTo investigate the feasibility and diagnostic value of free-breathing, radial, stack-of-stars three-dimensional (3D) gradient echo (GRE) sequence (“golden angle”) on dynamic contrast-enhanced (DCE) MRI of gastric cancer.MethodsForty-three gastric cancer patients were divided into cooperative and uncooperative groups. Respiratory fluctuation was observed using an abdominal respiratory gating sensor. Those who breath-held for more than 15 s were placed in the cooperative group and the remainder in the uncooperative group. The 3-T MRI scanning protocol included 3D GRE and conventional breath-hold VIBE (volume-interpolated breath-hold examination) sequences, comparing images quantitatively and qualitatively. DCE-MRI parameters from VIBE images of normal gastric wall and malignant lesions were compared.ResultsFor uncooperative patients, 3D GRE scored higher qualitatively, and had higher SNRs (signal-to-noise ratios) and CNRs (contrast-to-noise ratios) than conventional VIBE quantitatively. Though 3D GRE images scored lower in qualitative parameters compared with conventional VIBE for cooperative patients, it provided images with fewer artefacts. DCE parameters differed significantly between normal gastric wall and lesions, with higher Ve (extracellular volume) and lower Kep (reflux constant) in gastric cancer.ConclusionsThe free-breathing, golden-angle, radial stack-of-stars 3D GRE technique is feasible for DCE-MRI of gastric cancer. Dynamic enhanced images can be used for quantitative analysis of this malignancy.Key Points• Golden-angle radial stack-of-stars VIBE aids gastric cancer MRI diagnosis.• The 3D GRE technique is suitable for patients unable to suspend respiration.• Method scored higher in the qualitative evaluation for uncooperative patients.• The technique produced images with fewer artefacts than conventional VIBE sequence.• Dynamic enhanced images can be used for quantitative analysis of gastric cancer.

Background Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a pivotal pathogen contributing to healthcare-associated infections. Identifying environmental risk factors associated with CRAB contamination is critical. Objectives To assess the associations of ward microclimate and procedure duration with CRAB contamination risks. Methods High-touch environment and exposure surface, and air samples were repeatedly measured. A total of 2330 high-touch environment surfaces, 345 exposure surfaces, and 366 air samples were collected. The generalized linear mixed-effects model and additive interaction analysis were employed to examine the associations of ward microclimate and procedural factors with environmental CRAB contamination risks. Results We found that compared to procedures lasting ≤15min, those lasting >15min were related to higher risks of CRAB contamination (OR: 1.435, 95% CI: 1.052, 1.954). Compared to the standard environmental conditions (22.5–25.5 °C for temperature and 30–60% for humidity), lower temperature (<22.5 °C) and lower humidity (<30%) were associated with increased CRAB contamination risks (ORs:1.568 and 1.602). However, there was no significant association between high temperature (>25.5°C) or high humidity (>60%) and CRAB contamination risks. The combination of lower temperature or humidity with prolonged procedures showed synergistical interaction on increased risks of CRAB contamination. Additionally, CRAB was consistently detected in air across all sampling scenarios (static conditions, real-time nursing care procedures, and real-time sanitation), with the nursing care procedures group showing the highest detection rate (29.66% vs. 13.95% for static conditions and 8.33% for real-time sanitation). Conclusions Temperature and humidity below standard thresholds, combined with prolonged procedures were associated with an increased risk of environmental CRAB contamination in ICUs.

Radiomics offers a noninvasive avenue for predicting clinicopathological factors. However, thorough investigations into a robust breast cancer outcome-predicting model and its biological significance remain limited. This study develops a robust radiomic model for prognosis prediction, and further excavates its biological foundation and transferring prediction performance. We retrospectively collected preoperative dynamic contrast-enhanced MRI data from three distinct breast cancer patient cohorts. In FUSCC cohort ( n  = 466), Lasso was used to select features correlated with patient prognosis and multivariate Cox regression was utilized to integrate these features and build the radiomic risk model, while multiomic analysis was conducted to investigate the model’s biological implications. DUKE cohort ( n  = 619) and I-SPY1 cohort ( n  = 128) were used to test the performance of the radiomic signature in outcome prediction. A thirteen-feature radiomic signature was identified in the FUSCC cohort training set and validated in the FUSCC cohort testing set, DUKE cohort and I-SPY1 cohort for predicting relapse-free survival (RFS) and overall survival (OS) (RFS: p  = 0.013, p  = 0.024 and p  = 0.035; OS: p  = 0.036, p  = 0.005 and p  = 0.027 in the three cohorts). Multiomic analysis uncovered metabolic dysregulation underlying the radiomic signature (ATP metabolic process: NES = 1.84, p -adjust = 0.02; cholesterol biosynthesis: NES = 1.79, p -adjust = 0.01). Regarding the therapeutic implications, the radiomic signature exhibited value when combining clinical factors for predicting the pathological complete response to neoadjuvant chemotherapy (DUKE cohort, AUC = 0.72; I-SPY1 cohort, AUC = 0.73). In conclusion, our study identified a breast cancer outcome-predicting radiomic signature in a multicenter radio-multiomic study, along with its correlations with multiomic features in prognostic risk assessment, laying the groundwork for future prospective clinical trials in personalized risk stratification and precision therapy.

Pulmonary surfactant is a lipoprotein complex lining the alveolar surface to decrease the surface tension and facilitate inspiration. Surfactant deficiency is often seen in premature infants and in children and adults with respiratory distress syndrome. Mechanical stretch of alveolar type 2 epithelial (AT2) cells during lung expansion is the primary physiological factor that stimulates surfactant secretion; however, it is unclear whether there is a mechanosensor dedicated to this process. Here, we show that loss of the mechanosensitive channels TMEM63A and TMEM63B (TMEM63A/B) resulted in atelectasis and respiratory failure in mice due to a deficit of surfactant secretion. TMEM63A/B were predominantly localized at the limiting membrane of the lamellar body (LB), a lysosome-related organelle that stores pulmonary surfactant and ATP in AT2 cells. Activation of TMEM63A/B channels during cell stretch facilitated the release of surfactant and ATP from LBs fused with the plasma membrane. The released ATP evoked Ca2+ signaling in AT2 cells and potentiated exocytic fusion of more LBs. Our study uncovered a vital physiological function of TMEM63 mechanosensitive channels in preparing the lungs for the first breath at birth and maintaining respiration throughout life.

Preeclampsia (PE) is a common pregnancy-related complication, and polymorphisms in angiotensinogen ( AGT ), angiotensin-converting enzyme ( ACE ), and angiotensin II type 1 receptor ( AT1R ) are believed to contribute to PE development. We implemented a hybrid study to investigate the influence of maternal and fetal ACE I/D, ACE G2350A, AGT M235T, AGT T174M, and AT1R A1166C polymorphisms on PE in Han Chinese women. Polymorphisms were genotyped in 1,488 subjects (256 patients experiencing PE, along with their fetuses and partners, and 360 normotensive controls with their fetuses). Transmission disequilibrium tests revealed that ACE I/D ( P  = 0.041), ACE G2350A ( P  = 0.035), and AT1R A1166C ( P  = 0.018) were associated with maternal PE. The log-linear analyses revealed that mothers whose offspring carried the MM genotype of AGT M235T had a higher risk of PE (OR = 1.54, P  = 0.010), whereas mothers whose offspring carried the II genotype of ACE I/D or the GG genotype of ACE G2350A had a reduced risk (OR = 0.58, P  = 0.039; OR = 0.47, P  = 0.045, respectively). Our findings demonstrate that fetal ACE I/D, ACE G2350A, AGT M235T, and AT1R A1166C polymorphisms may play significant roles in PE development among pregnant Han Chinese women.

Xuefu Zhuyu decoction has been used for treating traumatic brain injury and improving post-traumatic dysfunction, but its mechanism of action needs further investigation. This study established rat models of traumatic brain injury by controlled cortical impact. Rat models were intragastrically administered 9 and 18 g/kg Xuefu Zhuyu decoction once a day for 14 or 21 days. Changes in neurological function were assessed by modified neurological severity scores and the Morris water maze. Immunohistochemistry, western blot assay, and reverse-transcription polymerase chain reaction were used to analyze synapsin protein and mRNA expression at the injury site of rats. Our results showed that Xuefu Zhuyu decoction visibly improved neurological function of rats with traumatic brain injury. These changes were accompanied by increased expression of synaptophysin, synapsin I, and postsynaptic density protein-95 protein and mRNA in a dose-dependent manner. These findings indicate that Xuefu Zhuyu decoction increases synapsin expression and improves neurological deficits after traumatic brain injury.

Cognitive impairments severely affect the quality of life of patients who undergo brain irradiation, and there are no effective preventive strategies. In this study, we examined the therapeutic potential of electroacupuncture (EA) administered immediately after brain irradiation in rats. We detected changes in cognitive function, neurogenesis, and synaptic density at different time points after irradiation, but found that EA could protect the blood-brain barrier (BBB), inhibit neuroinflammatory cytokine expression, upregulate angiogenic cytokine expression, and modulate the levels of neurotransmitter receptors and neuropeptides in the early phase. Moreover, EA protected spatial memory and recognition in the delayed phase. At the cellular/molecular level, the preventative effect of EA on cognitive dysfunction was not dependent on hippocampal neurogenesis; rather, it was related to synaptophysin expression. Our results suggest that EA applied immediately after brain irradiation can prevent cognitive impairments by protecting against the early changes induced by irradiation and may be a novel approach for preventing or ameliorating cognitive impairments in patients with brain tumors who require radiotherapy.

Bushen Tiansui decoction is composed of six traditional Chinese medicines: Herba Epimedii, Radix Polygoni multiflori, Plastrum testudinis, Fossilia Ossis Mastodi, Radix Polygalae, and Rhizoma Acorus tatarinowii. Because Bushen Tiansui decoction is effective against amyloid beta (Aβ) toxicity, we hypothesized that it would reduce hippocampal synaptic damage and improve cognitive function in Alzheimer's disease. To test this hypothesis, we used a previously established animal model of Alzheimer's disease, that is, microinjection of aggregated Aβ25-35 into the bilateral brain ventricles of Sprague-Dawley rats. We found that long-term (28 days) oral administration of Bushen Tiansui decoction (0.563, 1.688, and 3.375 g/mL; 4 mL/day) prevented synaptic loss in the hippocampus and increased the expression levels of synaptic proteins, including postsynaptic density protein 95, the N-methyl-D-aspartate receptor 2B subunit, and Shank1. These results suggested that Bushen Tiansui decoction can protect synapses by maintaining the expression of these synaptic proteins. Bushen Tiansui decoction also ameliorated measures reflecting spatial learning and memory deficits that were observed in the Morris water maze (i.e., increased the number of platform crossings and the amount of time spent in the target quadrant and decreased escape latency) following intraventricular injections of aggregated Aβ25-35 compared with those measures in untreated Aβ25-35-injected rats. Overall, these results provided evidence that further studies on the prevention and treatment of dementia with this traditional Chinese medicine are warranted.

BackgroundHomologous recombination (HR) is a key pathway in DNA double-strand damage repair. HR deficiency (HRD) occurs more commonly in triple-negative breast cancers (TNBCs) than in other breast cancer subtypes. Several clinical trials have demonstrated the value of HRD in stratifying breast cancer patients into distinct groups based on their responses to poly(ADP ribose) polymerase inhibitors and chemotherapy.MethodsWe retrospectively collected TNBC samples to establish a multiomics cohort (n = 343) and explored the biological and phenotypic mechanisms underlying the better prognosis of patients with high HRD scores. Gene set enrichment analysis was conducted to elucidate the underlying pathways in patients with low HRD scores, and a radiomics model was established to predict the HRD score via a noninvasive method.ResultsMultivariable Cox analysis revealed the independent prognostic value of a low HRD score (hazard ratio 2.20, 95% confidence interval 1.05–4.59; p = 0.04). Furthermore, amino acid and lipid metabolism pathways were highly enriched in tumors from patients with low HRD scores, which was also demonstrated by differential abundant metabolite analysis. A noninvasive radiomics method was developed to predict the HRD status and it performed well in the independent validation cohort (support vector machine model: area under the curve [AUC] 0.739, sensitivity 0.571, and specificity 0.824; logistic regression model: AUC 0.695, sensitivity 0.571, and specificity 0.882).ConclusionsWe revealed the prognostic value of the HRD score, predicted the HRD status with noninvasive radiomics features, and preliminarily explored druggable targets for TNBC patients with low HRD scores.