BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

Nanoparticle delivery systems have good application prospects in the field of precision therapy, but the preparation process of nanomaterial has problems such as short in vivo circulation time, easy recognition, and clearance by the immune system in the body. In recent years, biomimetic nanoparticle delivery systems mediated by natural cell membranes have become a research hotspot to address these issues. The natural membrane biomimetic nanoparticle delivery system cleverly integrates the advantages of natural biofilm "autologous" and "artificial" functional carriers by using endogenous cell membranes to modify the surface of nanocarriers, endowing them with characteristics such as tumor targeting, low immunogenicity, and long blood circulation. Currently, biomimetic nanoparticle delivery systems have been used in the treatment of malignant tumors, cardiovascular diseases, bacterial infections, and other diseases. This paper analyzes the development status and current research hotspots of natural cell membrane camouflaged biomimetic nanoparticle delivery systems mainly reviews the latest research progress of red blood cell membrane camouflaged biomimetic nanoparticle delivery systems in the field of disease treatment in recent years. It focuses on exploring the advantages, future development prospects, and limitations of biomimetic nanoparticle delivery systems based on red blood cell membrane camouflage in improving drug delivery, to provide a reference for the in-depth research and development of this system.

ObjectiveTo investigate the improvement effect of Qibai Pingfei capsules on pulmonary vascular remodeling in rats at different stages of chronic obstructive pulmonary disease （COPD） and to analyze its possible mechanism of action. MethodsMale Sprague-Dawley （SD） rats were randomly divided into a normal group， an early COPD model group， an advanced COPD model group， an early-intervention high-dose group， a late-intervention high-dose group， an early-intervention low-dose group， a late-intervention low-dose group， an early-intervention pyrrolidine dithiocarbamate （PDTC） group， and a late-intervention PDTC group， with 15 rats in each group. A rat model of early COPD was constructed by using cigarette smoke combined with airway infusion using lipopolysaccharide（LPS）， and a rat model of advanced COPD was constructed by using airway infusion with LPS， cigarette smoke， and hypoxia. All groups except the normal group were given LPS airway drops on days 1 and 14 of the experiment， smoked for 1 h per day， and administered the drug once a day for 40 weeks from day 15 onward. In the high- and low-dose groups， rats were given 1 g·kg^-1 and 250 mg·kg^-1 Qibai Pingfei capsules， respectively by gavage， and in PDTC groups， rats were given 100 mg·kg^-1 of PDTC by intraperitoneal injection. The advanced COPD model group underwent 6 h of hypoxia per day in weeks 5-6. Lung function and mean pulmonary artery pressure were tested in rats. Morphologic changes in lung tissues were detected by hematoxylin-eosin（HE）staining. Collagen deposition in lung tissues was examined by Masson staining， and the levels of inflammatory factors including interleukin-1β（IL-1β）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α）in lung tissues were detected by enzyme-linked immunosorbent assay （ELISA）. The number of inflammatory cells in the alveolar lavage fluid of rats in each group was detected by Giemsa staining， and the protein expression of Toll-like receptor 4（TLR4）， myeloid differentiation factor 88（MyD88）， nuclear factor-κB（NF-κB）， TNF-α， vascular endothelial-cadherin（VE-cadherin）， α-smooth muscle actin（α-SMA）， and platelet endothelial cell adhesion molecule-1（CD31） was detected by Western blot in the lung tissues of rats. ResultsCompared with the normal group， the model group showed significantly decreased forced expiratory volume in 0.3 s （FEV_0.3）， forced vital capacity （FVC）， and FEV_0.3/FVC ratio related to lung function （P<0.05）， thickening of pulmonary vasculature， increased collagen deposition in the lungs， and enhanced mean pulmonary arterial pressure and expression levels of IL-6， IL-1β， and TNF-α （P<0.05）. Additionally， the model group also exhibited increased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， significantly higher protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05）， and significantly lower protein expression of VE-cadherin and CD31 （P<0.05）. Lung function was significantly improved in the Qibai Pingfei capsules groups compared with the model group （P<0.05）， with mean pulmonary arterial pressure reduced and pulmonary vascular thickening and collagen deposition in the lungs ameliorated. The Qibai Pingfei capsules groups also showed reduced expression levels of IL-6， IL-1β， and TNF-α （P<0.05） and decreased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， as well as reduced protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05） and elevated protein expression of VE-cadherin and CD31 （P<0.05） in rat lung tissues. ConclusionQibai Pingfei capsules inhibits inflammatory response and endothelial-to-mesenchymal transition probably by regulating the TLR4/NF-κB signaling pathway， thus improving pulmonary vascular remodeling in COPD model rats and showing therapeutic effects in the early stage of COPD.

BackgroundAtypical antipsychotics have been widely used in patients with chronic schizophrenia， and aripiprazole and risperidone are the most commonly used drugs. The mechanism of action of the two is different， while previous studies have provided insufficient credible evidence from multiple perspectives to support the comparative efficacy of the two drugs in improving symptoms in patients with chronic schizophrenia. ObjectiveTo compare the efficacy of aripiprazole and risperidone on the improvement of symptoms， prepulse inhibition （PPI）， cognitive functioning and neurotrophic factors in patients with chronic schizophrenia， so as to provide effective treatment regimens for these patients. MethodsA total of 86 patients with chronic schizophrenia attending the psychiatry department of the Third People's Hospital of Fuyang from March 2021 to March 2023 and fulfilling the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） were enrolled and grouped using random number table method， each with 43 cases. Aripiprazole group was given oral aripiprazole once daily at an initial dose of 5 mg for one week and then gradually increased to a maximum dose of 25 mg. Risperidone group received oral risperidone twice daily at an initial dose of 0.5 mg for one week and then gradually increased to a maximum dose of 3 mg. Treatment in both groups lasted 3 months. Before treatment and 3 months after treatment， Patients were required to complete Positive and Negative Symptom Scale （PANSS）， detection of both strong and weak PPIs in a startle modification passive attention paradigm， Wisconsin Card Sorting Test （WCST） and the measurement of neurotrophic factors at baseline and after treatment. The adverse reactions were recorded. Analysis of covariance was used to test the difference between the PANSS score， PPI， WCST and neurotrophic factor levels of the groups， with the pretest used as the covariate. Results3 months after treatment， no statistical difference was found in the scores of PANSS general psychopathology subscale， positive symptom subscale， negative symptom subscale and total score between two groups after treatment （F=0.621， 0.815， 0.743， 0.752， P>0.05）. There were no statistically significant differences between the two groups in PPI inhibition rate， single intense stimulus amplitude， single intense stimulus latency， prepulse inhibition amplitude， or prepulse inhibition latency （F=0.174， 0.001， 0.183， 0.171， 0.001， P>0.05）. There was no statistically significant difference in the total number of WCST tests between two groups （F=0.512， P>0.05）， whereas aripiprazole group reported significantly larger total numbers of categories completed and correct responses as well as smaller total numbers of random errors and perseverative errors compared to risperidone group （F=3.737， 4.621， 4.892， 5.130， P<0.05）. A significant increase in brain-derived neurotrophic factor （BDNF） and nerve growth factor （NGF） along with a reduction in glial fibrillary acidic protein （GFAP） were documented in risperidone group when compared to risperidone group （F=4.414， 3.781， 6.319， P<0.05）. No significant difference was demonstrated in the incidence of adverse reactions between the two groups （χ²=0.261， P>0.05）. ConclusionAripiprazole may be more beneficial than risperidone in improving cognitive functioning and neurotrophic factor levels in patients with chronic schizophrenia. ［Funded by Scientific Research Project of Fuyang Municipal Health Commission in 2021 （number， FY2021-147）］

Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans ; Capecitabine/adverse effects* ; Colorectal Neoplasms/mortality* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Middle Aged ; Female ; Aged ; Adult ; Treatment Outcome

Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Carcinoma, Hepatocellular/microbiology* ; Liver Neoplasms/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional

The therapeutic effects of Yueju Pills on depression and cardiovascular diseases have been widely recognized. Previous studies have shown that the drug can significantly improve depressive-like behaviors induced by chronic unpredictable mild stress(CUMS) combined with atherosclerosis(AS). Given the complex pathogenesis of psychocardiac diseases, this study integrated metabolomics and network pharmacology to systematically elucidate the mechanism of Yueju Pills in alleviating depressive symptoms in psychocardiac diseases. The results demonstrate that, after Yueju Pill intervention, the levels of 9 abnormal metabolites in the hippocampus restore to normal ranges, primarily involving key pathways or signaling pathways, including the cyclic adenosine monophosphate(cAMP), mammalian target of rapamycin(mTOR), glycine/serine/threonine metabolism, and aminoacyl-tRNA biosynthesis. In a high-fat diet-induced CUMS ApoE~(-/-) mouse model, Yueju Pills significantly increases adenosine monophosphate(AMP) levels and decreases L-alanine and D-glyceric acid levels in the hippocampus. In conclusion, Yueju Pills exert antidepressant effects by regulating multiple metabolic axes, including glycine/serine/threonine metabolism and the cAMP, mTOR signaling pathways. Network pharmacology predictions reveal that the treatment of CUMS combined with AS by its core active components may be realized through modulating pathways concerning neuroinflammation and synaptic plasticity, including serine/threonine-protein kinase 1(AKT1), mitogen-activated protein kinase 1(MAPK1), and prostaglandin-endoperoxide synthase 2(PTGS2). This study provides a theoretical reference for the clinical application of Yueju Pills in alleviating the depressive symptoms of psychocardiac diseases.
Animals ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Male ; Depression/genetics* ; Humans ; Hippocampus/drug effects* ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

ObjectivePrimary liver cancer, predominantly hepatocellular carcinoma (HCC), is a significant global health issue, ranking as the sixth most diagnosed cancer and the third leading cause of cancer-related mortality. Accurate and early diagnosis of HCC is crucial for effective treatment, as HCC and non-HCC malignancies like intrahepatic cholangiocarcinoma (ICC) exhibit different prognoses and treatment responses. Traditional diagnostic methods, including liver biopsy and contrast-enhanced ultrasound (CEUS), face limitations in applicability and objectivity. The primary objective of this study was to develop an advanced, light-weighted classification network capable of distinguishing HCC from other non-HCC malignancies by leveraging the automatic analysis of brightness changes in CEUS images. The ultimate goal was to create a user-friendly and cost-efficient computer-aided diagnostic tool that could assist radiologists in making more accurate and efficient clinical decisions. MethodsThis retrospective study encompassed a total of 161 patients, comprising 131 diagnosed with HCC and 30 with non-HCC malignancies. To achieve accurate tumor detection, the YOLOX network was employed to identify the region of interest (ROI) on both B-mode ultrasound and CEUS images. A custom-developed algorithm was then utilized to extract brightness change curves from the tumor and adjacent liver parenchyma regions within the CEUS images. These curves provided critical data for the subsequent analysis and classification process. To analyze the extracted brightness change curves and classify the malignancies, we developed and compared several models. These included one-dimensional convolutional neural networks (1D-ResNet, 1D-ConvNeXt, and 1D-CNN), as well as traditional machine-learning methods such as support vector machine (SVM), ensemble learning (EL), k-nearest neighbor (KNN), and decision tree (DT). The diagnostic performance of each method in distinguishing HCC from non-HCC malignancies was rigorously evaluated using four key metrics: area under the receiver operating characteristic (AUC), accuracy (ACC), sensitivity (SE), and specificity (SP). ResultsThe evaluation of the machine-learning methods revealed AUC values of 0.70 for SVM, 0.56 for ensemble learning, 0.63 for KNN, and 0.72 for the decision tree. These results indicated moderate to fair performance in classifying the malignancies based on the brightness change curves. In contrast, the deep learning models demonstrated significantly higher AUCs, with 1D-ResNet achieving an AUC of 0.72, 1D-ConvNeXt reaching 0.82, and 1D-CNN obtaining the highest AUC of 0.84. Moreover, under the five-fold cross-validation scheme, the 1D-CNN model outperformed other models in both accuracy and specificity. Specifically, it achieved accuracy improvements of 3.8% to 10.0% and specificity enhancements of 6.6% to 43.3% over competing approaches. The superior performance of the 1D-CNN model highlighted its potential as a powerful tool for accurate classification. ConclusionThe 1D-CNN model proved to be the most effective in differentiating HCC from non-HCC malignancies, surpassing both traditional machine-learning methods and other deep learning models. This study successfully developed a user-friendly and cost-efficient computer-aided diagnostic solution that would significantly enhances radiologists’ diagnostic capabilities. By improving the accuracy and efficiency of clinical decision-making, this tool has the potential to positively impact patient care and outcomes. Future work may focus on further refining the model and exploring its integration with multimodal ultrasound data to maximize its accuracy and applicability.

Objective To predict the lymph node metastasis status of patients with invasive pulmonary adenocarcinoma by constructing machine learning models based on primary tumor radiomics, peritumoral radiomics, and habitat radiomics, and to evaluate the predictive performance and generalization ability of different imaging features. Methods A retrospective analysis was performed on the clinical data of 1 263 patients with invasive pulmonary adenocarcinoma who underwent surgery at the Department of Thoracic Surgery, Jiangsu Province Hospital, from 2016 to 2019. Habitat regions were delineated by applying K-means clustering (average cluster number of 2) to the grayscale values of CT images. The peritumoral region was defined as a uniformly expanded area of 3 mm around the primary tumor. The primary tumor region was automatically segmented using V-net combined with manual correction and annotation. Subsequently, radiomics features were extracted based on these regions, and stacked machine learning models were constructed. Model performance was evaluated on the training, testing, and internal validation sets using the area under the receiver operating characteristic curve (AUC), F1 score, recall, and precision. Results After excluding patients who did not meet the screening criteria, a total of 651 patients were included. The training set consisted of 468 patients (181 males, 287 females) with an average age of (58.39±11.23) years, ranging from 29 to 78 years, the testing set included 140 patients (56 males, 84 females) with an average age of (58.81±10.70) years, ranging from 34 to 82 years, and the internal validation set comprised 43 patients (14 males, 29 females) with an average age of (60.16±10.68) years, ranging from 29 to 78 years. Although the habitat radiomics model did not show the optimal performance in the training set, it exhibited superior performance in the internal validation set, with an AUC of 0.952 [95%CI (0.87, 1.00)], an F1 score of 84.62%, and a precision-recall AUC of 0.892, outperforming the models based on the primary tumor and peritumoral regions. Conclusion The model constructed based on habitat radiomics demonstrated superior performance in the internal validation set, suggesting its potential for better generalization ability and clinical application in predicting lymph node metastasis status in pulmonary adenocarcinoma.

Objective To evaluate the protective effect of radiation protection safety education (RPSE) on patients with differentiated thyroid carcinoma (DTC) undergoing iodine-131 (¹³¹I) treatment. Methods The DTC patients who undergo ¹³¹I treatment were divided into the control group and the RPSE group using the convenience sampling method, with 142 patients in each group. Patients in the control group received routine health education, while the RPSE group received routine health education combined with RPSE. Dose equivalent rate (DER) on pillows, bed sheets, quilt covers, and household waste of patients were compared between the two groups upon discharge. Results The median (M) DERs of patients' pillows, bed sheets, quilt covers and household waste were 3.86, 3.63, 3.91 and 56.59 times higher in the control group compared with the environmental background level, respectively. The M DERs of patients' pillows, bed sheets, quilt covers were 2.23, 2.18, and 2.55 times higher in the RPSE group compared with the environmental background level, while the M DER of household waste was equivalent to the environmental background level. The DERs of patients' pillows, bed sheets, quilt covers, and household waste in the RPSE group were significantly lower than those in the control group (all P<0.001). The DERs of the above four items were lower in both male and female patients in RPSE group compared with same-gender patients in the control group (all P<0.001). The patients' DERs of the above indicators had no significant difference among different gender in both control group and RPSE group (all P>0.05), except for higher DER of household waste in female patients than that of male patients in the control group (P<0.05). There were no significant differences in the DERs of pillows, bed sheets, quilt covers, and household waste across subgroups, where patients received different treatment doses, of both the control group and the RPSE group (all P>0.05). Conclusion RPSE for DTC patients treated with ¹³¹I, reduces the DERs of pillows, bed sheets, quilt covers, and particularly household waste.