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.

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.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

This study， anchored in the traditional Chinese medicine （TCM） syndrome differentiation and treatment principles alongside the clinical characteristics of sepsis in Western medicine， extensively gathers and meticulously dissects the latest research findings on sepsis animal models from both Chinese and international sources. Adhering strictly to TCM syndrome diagnostic criteria for sepsis， the study conducts a thorough evaluation of various animal models across multiple dimensions， including clinical manifestations， pathological changes， and biomarker expressions， so as to reflect the degree of resemblance these models have to human sepsis TCM syndromes. The results reveal that the colon stent implantation model exhibits a higher degree of congruence with both TCM and Western medicine standards， particularly aligning with the diagnosis of the "Fu-Qi obstruction syndrome". Conversely， the extraperitoneal sepsis model shows a higher degree of congruence with TCM， fitting more closely with the diagnosis of "acute deficiency syndrome" and emphasizing the core pathogenesis of Qi deficiency in sepsis. These findings not only augment the diversity of sepsis animal models but also highlight the necessity and potential of integrated TCM and western medicine research. Current sepsis animal models predominantly focus on western pathophysiological mechanisms， with limited direct incorporation of TCM syndrome differentiation elements. This underscores the need， in future study designs， to actively explore integrating TCM syndrome classification and intervention principles into model development. This could be achieved by manipulating model-inducing factors and observing more TCM-specific symptoms and signs among other strategies， so as to establish sepsis models that more closely resemble clinical reality and incorporate both TCM and western medical perspectives.

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with dysfunctions related to thinking, learning, and memory of the brain. AD has multiple pathological characteristics with complicated causes, constructing a suitable pathological model is crucial for the research of AD. Microfluidic chip technology integrates multiple functional units on a chip, which can realize microenvironmental control similar to the physiological environment. It is well applied in the construction of pathological model, early diagnosis as well as drug screening of AD. This paper focuses on the construction of AD microfluidic chips model from the perspective of cell type, culture formats and the chips structure as well as the research progress of microfluidic chips in AD application based on the pathological characteristics of AD, which will provide a reference for further elucidation of AD mechanism and drug development.

Objective: To investigate the expression of transient receptor polycystic protein 2(TRPP2) in oral squamous epithelial cell and its effect on the invasion and migration of oral squamous cell carcinoma(OSCC), and to explore the potential signaling pathway of TRPP2 affecting OSCC metastasis. Methods: The OSCC model with TRPP2 knockdown was constructed by CRISPR-Cas9 lentivirus plasmid transfection technique. The effect of TRPP2 protein knockdown was verified by Western blot. The effect of TRPP2 on OSCC proliferation was detected by CCK-8 assay and clone formation assay. RT-qPCR was used to detect the target genes associated with TRPP2 metastasis to OSCC. Western blot and RT-qPCR were used to detect the expression of EpCAM and its transcription factors associated with unfolded protein response(UPR). The effects of TRPP2 on the invasion and migration of OSCC were examined by invasion test and scratch test. Results: Compared with HOK in oral epithelial cells, the expression of TRPP2 in OSCC was significantly higher. When TRPP2 was knocked down, OSCC proliferation and clonalformation were significantly enhanced. Compared with the control group, a total of 494 differential genes were significantly expressed in TRPP2 knockdown transcription profile, among which 234 genes were up-regulated and 260 genes were down-regulated. The expression of EpCAM gene, which is related to cell adhesion, was up-regulated. In addition, UPR related genes PERK, ATF6, GRP78 were up-regulated, while ATF6 and EpCAM were down-regulated in OSCC compared to HOK cells. The expression of ATF6 and EpCAM in oral squamous cell carcinoma cells was up-regulated by TRPP2 knockdown, and the cell migration and invasion ability decreased. The ATF6 inhibitor ceapin-A7(5 μmol/L) restored the OSCC migration and invasion ability of TRPP2 knockdown. Conclusion TRPP2 is highly expressed in OSCC. When TRPP2 is knocked down, OSCC proliferation ability is enhanced, migration and invasion ability are inhibited. TRPP2 mediates the expression of EpCAM through activation of UPR, thus affecting the invasion and migration of oral squamous cell carcinoma.

Objective To observe the clinical efficacy of the modified Huangan Lipi Decoction(mainly composed of Sclerotium Poriae Pararadicis,Paeoniae Radix Alba,Atractylodis Macrocephalae Rhizoma,Polygalae Radix,Acori Tatarinowii Rhizoma,and Curcumae Radix)combined with acupuncture at Sifeng(EX-UE10)points in the treatment of children with tic disorders(TD).Methods Seventy cases of TD children with spleen deficiency and liver hyperactivity syndrome were randomly divided into the treatment group and the control group,with 35 cases in each group.The control group was treated with conventional western medicine of Tiapride Hydrochloride Tablets,while the treatment group was treated with the combination of the modified Huangan Lipi Decoction and acupuncture at Sifeng points.Both groups were treated for 8 weeks.The changes of the Yale Global Tic Severity Scale(YGTSS)item scores of tic muscle group,tic frequency,tic intensity,complexity and interference degree as well as their total scores in the two groups were observed before and after treatment.Moreover,the clinical efficacy and safety in the two groups were evaluated.Results(1)After 8 weeks of treatment,the total effective rate of the treatment group was 88.57%(31/35),and that of the control group was 68.57%(24/35).The intergroup comparison showed that the total effective rate(tested by chi-square test)and the overall therapeutic efficacy(tested by rank-sum test)of the treatment group were significantly superior to those of the control group,and the differences were statistically significant(P＜0.05).(2)After treatment,the YGTSS item scores of tic muscle group,tic frequency,tic intensity,complexity and interference degree as well as their total scores in the two groups were significantly lower than those before treatment(P＜0.01),and the effect on lowering the above scores of the treatment group was significantly superior to that of the control group,the differences being all statistically significant(P＜0.01).(3)During the treatment,the incidence of adverse reactions in the treatment group was 2.86%(1/35)and that in the control group was 8.57%(3/35).The intergroup comparison showed that the incidence of adverse reactions in the treatment group tended to be lower than that of the control group,but the difference was not statistically significant(P＞0.05).Conclusion Modified Huangan Lipi Decoction combined with acupuncture at Sifeng points exert certain effect in the treatment of TD children with spleen deficiency and liver hyperactivity syndrome,and its efficacy is superior to that of the western medicine Tiapride Hydrochloride Tablets.