ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang （SWDK） on cognitive dysfunction in mice suffering from Alzheimer's disease （AD） and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group， total ginsenoside group（0.04 g·kg^-1）， high-， medium-， and low-dose groups of SWDK （32.60， 16.30， 8.15 g·kg^-1）， with 10 mice in each group， and ten wild-type mice of the same age were used as the normal group， male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin （HE） staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin （SYP） and postsynaptic dense substance 95 （PSD95） in mice serum were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expression of brain-derived neurotrophic factor（BDNF） in the dentate gyrus （DG） region of mouse brain tissue was observed by immunohistochemistry （IHC）. The protein levels of BDNF， Wnt family member 3A（Wnt3a）， and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice， the model group of mice had significantly more complex swimming routes and lower swimming speed （P<0.01）， significantly lower percentage of time spent in the target quadrant （P<0.01）， and a significantly lower percentage of freezing time （P<0.05）. The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95（P<0.01） in the serum of mice were reduced， and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice were obviously reduced （P<0.05， P<0.01）. Compared with the model group， the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes， the high- and medium- dose SWDK groups significantly higher swimming speeds （P<0.01）， significantly higher percentage of time spent in the target quadrant （P<0.01）， obviously higher percentage of Freezing time （P<0.05）， and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP （P<0.05， P<0.01）， PSD95 （P<0.01）， increased BDNF-positive cells in the DG region of brain tissue， and obviously elevated levels of BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice （P<0.05， P<0.01）. ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice， and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway， which promotes BDNF expression and thereby enhances synaptic plasticity， allowing neuronal signaling to be restored.

ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang （SWDK） on cognitive dysfunction in mice suffering from Alzheimer's disease （AD） and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group， total ginsenoside group（0.04 g·kg^-1）， high-， medium-， and low-dose groups of SWDK （32.60， 16.30， 8.15 g·kg^-1）， with 10 mice in each group， and ten wild-type mice of the same age were used as the normal group， male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin （HE） staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin （SYP） and postsynaptic dense substance 95 （PSD95） in mice serum were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expression of brain-derived neurotrophic factor（BDNF） in the dentate gyrus （DG） region of mouse brain tissue was observed by immunohistochemistry （IHC）. The protein levels of BDNF， Wnt family member 3A（Wnt3a）， and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice， the model group of mice had significantly more complex swimming routes and lower swimming speed （P<0.01）， significantly lower percentage of time spent in the target quadrant （P<0.01）， and a significantly lower percentage of freezing time （P<0.05）. The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95（P<0.01） in the serum of mice were reduced， and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice were obviously reduced （P<0.05， P<0.01）. Compared with the model group， the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes， the high- and medium- dose SWDK groups significantly higher swimming speeds （P<0.01）， significantly higher percentage of time spent in the target quadrant （P<0.01）， obviously higher percentage of Freezing time （P<0.05）， and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP （P<0.05， P<0.01）， PSD95 （P<0.01）， increased BDNF-positive cells in the DG region of brain tissue， and obviously elevated levels of BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice （P<0.05， P<0.01）. ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice， and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway， which promotes BDNF expression and thereby enhances synaptic plasticity， allowing neuronal signaling to be restored.

Precancerous lesions of gastric cancer is a key stage in the development of gastric cancer.The reprogramming of glucose metabolism is a prominent feature of precancerous lesions of gastric cancer.Hypoxic microenvironment and hypoxia-inducible factors are important factors influencing the occurrence of glucose metabolic reprogramming.This article summarized the relationship between hypoxic microenvironment and the reprogramming of glucose metabolism in precancerous lesions of gastric cancer,and concluded the relevant research on TCM compounds and effective components to improve hypoxic microenvironment and further regulate glycolysis for the treatment of this disease.It was concluded that the mechanism may be the inhibition of angiogenesis,regulation of signaling pathways and key proteins of glycolysis,expression of multiple enzymes,reduction of lactate secretion,inhibition of cell malignant proliferation and invasion.It explored the mechanism of Chinese materia medica in improving hypoxic microenvironment and regulating glycolysis,so as to provide reference for the prevention and treatment of precancerous lesions of gastric cancer.

Objective:To construct and validate a machine learning model for preoperative prediction of perineural invasion (PNI) status in intrahepatic cholangiocarcinoma (ICC).Methods:Clincial data of 329 patients, including 245 admitted to Zhengzhou University People's Hospital from January 2018 to June 2023 and 84 admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2013 to January 2020 were retrospectively analyzed. Patients were divided into a training set ( n=231) and a validation set ( n=98). Clinicopathological data including age, gender, hepatitis B virus (HBV) infection status were collected. Predictive variables were determined using least absolute shrinkage and selection operator (LASSO) regression analysis. Six machine learning algorithms including random forest (RF), logistic regression, and linear kernel-based support vector machine were selected to construct the preoperative prediction model for PNI in ICC. Performance metrics of the model were calculated using a confusion matrix, and the final model was selected. The model performance was evaluated in the validation set. Calibration curves were plotted to evaluate the final model, and a Pareto chart was used to visualize the importance of predictive variables. Results:LASSO regression identified nine predictive variables included in the prediction model, including carbohydrate antigen 19-9 (CA19-9), HBV infection status, alkaline phosphatase, alanine aminotransferase, prothrombin time, total bilirubin, albumin, neutrophil times gamma-glutamyl transferase to lymphocyte ratio, and tumor burden score. Among the trained six models, the area under the curve (AUC) of the RF model was 0.909, with a sensitivity of 0.842 and an accuracy of 0.870. Compared with the AUC of the RF model, the AUCs of the other 5 models were lower (all P<0.05). The AUC of the RF model for predicting PNI in ICC in validation set was 0.736. Calibration curves showed good fit of the RF model's prediction of PNI in ICC in both training and validation sets. The Pareto chart showed that CA19-9 was the most important predictive variable in the model, followed by HBV infection status. Conclusion:The machine learning model based on the RF algorithm has a high accuracy in preoperative prediction of PNI status in ICC.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective:To explore the influence of tumor-associated macrophages (TAMs) on endocrine resistance in breast cancer through the forkhead box M1 (FOXM1) /Wnt/ β-catenin pathway. Methods:Tamoxifen-resistant breast cancer cells were cultured, THP-1 cells were induced into macrophages (MΦ), and further induced into TAMs. After being cultured in the conditioned medium (CM) of MCF-7 cells for 24 hours, MΦ were defined as MS cells. After being cultured in the CM of MCF-7R cells for 24 hours, MΦ were defined as MR cells. MCF-7 cells, after being cultured in the CM of macrophages for 24 hours, were defined as MCF-7 (MΦ) cells. MCF-7 cells, after being cultured in the CM of MS cells for 24 hours, were defined as MCF-7 (MS) cells. MCF-7 cells, after being cultured in the CM of MR cells for 24 hours, were defined as MCF-7 (MR) cells. Cell viability and invasion ability were evaluated using CCK-8 and Transwell assays. The protein levels of CD163, Wnt1, β-catenin, and FOXM1 in different groups were examined by qRT-PCR and Western blot. Results:Compared to the MS group (mRNA: 1.49±0.12, protein: 1.15±0.12), CD163 expression was higher in the MR group (mRNA: 2.33±0.16, protein 1.52±0.11) ( t=7.28, P=0.002) ( t=3.94, P=0.017), indicating that tamoxifen-resistant breast cancer cells can induce polarization of more MΦ into TAMs. TAMs increased the expression of FOXM1 in breast cancer cells, which further activated the Wnt/ β-catenin pathway. Compared to the MCF-7 (MΦ) group, the MCF-7 (MS) and MCF-7 (MR) groups showed enhanced cell viability and invasion, with the most significant increase observed in the MCF-7 (MR) group. Compared with MCF-7 (MΦ) cells, the levels of Wnt1, β-catenin, and FOXM1 in MCF-7 (MS) and MCF-7 (MR) cells were significantly increased, with the highest levels observed in the MCF-7 (MR) group with the most TAM polarization. Compared to the MCF-7 group, both the MCF-7 (MR) and MCF-7+pcDNA-FOXM1 groups showed increased levels of Wnt1 and β-catenin, enhanced cell viability and invasion. Compared to the MCF-7 (MR) group, the MCF-7 (MR) + si-FOXM1 group showed reduced levels of Wnt1 and β-catenin, weakened cell viability and invasion. Conclusion:TAMs promote endocrine resistance in breast cancer by upregulating FOXM1 and activating the Wnt/ β-catenin pathway.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objective: To explore the biological effects of electromagnetic pulse (EMP) with different high intensities on condylar cartilage in rats. Methods: SD rats were randomly divided into a sham group (Sham) and an irradiation group (EMP1: 500 kV/m, 10 Hz; EMP2: 270 kV/m, 10 Hz). Then, they were sacrificed at 1 h, 3 h, 12 h, 24 h and 3 d after irradiation. The degree of cartilage degeneration was evaluated by HE, safranine O-fast green, type Ⅱ collagen immunohistochemistry and TUNEL staining. Immunohistochemistry and western blot were performed to detect the expression of the matrix degradation factors: matrix metalloproteinase-13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5) and the apoptosis key factor cleaved-cysteinyl aspartate specific proteinase (cleaved-Caspase3) in condylar cartilage. Results : HE staining showed that, compared with the Sham group, a small amount of exfoliation was found on the fibrous surface layer of the cartilage after irradiation in the EMP1 and EMP2 groups. Compared with the Sham group, the percentage of safranine O-fast green-positive area decreased significantly at 12 h and 24 h (both P<0.01) in the EMP1 group and 12 h and 24 h in the EMP2 group (both P<0.05); the percentage of type Ⅱ collagen-positive area decreased significantly at 3 h and 12 h (P<0.05, P<0.001) in the EMP1 group. In addition, the number of TUNEL-positive apoptotic cells increased significantly at 1 h, 3 h, 12 h, and 24 h in the EMP1 group and 1 h, 3 h, and 12 h in the EMP2 group (P<0.05). Moreover, at different timepoints (except at 3 d) in the EMP1 group and EMP2 group, the percentage of MMP-13, ADAMTS-5- and cleaved Caspase3-positive chondrocytes and their protein levels in condylar cartilage increased significantly after irradiation (P<0.05). Conclusion EMP with a certain degree of high-intensity can induce early transient damage to condylar cartilage. This effect is dose-and time-dependent.

Objective To establish a lumbar radiography image quality control model by using the deep learning algorithm and evaluate clinical images in real time and retrospectively based on the developed model.Methods The anteroposterior,lateral and oblique lumbar radiographs of 1389 patients collected between January 2018 to February 2021 at the The First Affiliated Hospital of Wenzhou Medical University were analyzed.The anatomical structures in the lumbar X-ray images were segmented using a full convolutional neural network based on U-Net,and the segmentation algorithm was utilized to establish an automatic evaluation model to detect substandard images.Dice similarity coefficient(DSC)was used to evaluate the performance of the model,and the lumbar radiography images were statistically evaluated after the application of the model.Results The accuracy of the model on the validation set was 0.971-0.990(0.98±0.10),the sensitivity was 0.714-0.933(0.86±0.13),and the specificity was 0.995-1.000(0.99±0.12).The quality control model had an excellent rate of 28.8%,an intermediate rate of 54.8%,and a failure rate of 16.4%for lumbar spine radiography in 2022.Conclusion The lumbar spine X-ray image quality control model based on artificial intelligence realizes accurate segmentation of lumbar spine anatomical structures and makes accurate evaluation of image quality,which is helpful to ensure the standardization of lumbar spine X-ray radiography operation by

Objective:To explore the clinical application of portable head and neck magnetic resonance imaging (MRI) device in neurosurgery.Methods:A total of 213 patients with brain diseases who were scanned by portable head and neck MRI device in Center of Neurosurgery, Zhujiang Hospital, Southern Medical University from June to September 2022 were selected. The portable head and neck MRI images and 3.0T conventional MRI images of 10 randomly selected patients were compared; the differences in signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of different sequences were analyzed. Thirty-one patients accepted tracheal intubation/tracheotomy, or ventilator-assisted breathing were selected as special patient group, and another 30 patients were as general patient group; the differences in comprehensive diagnostic scores of portable head and neck MRI images were compared. Noise intensity differences in different sequences between 3.0T conventional MRI and portable head and neck MRI were statistically compared. Twenty hospitalized volunteers with normal hearing in our center from July to August 2022 were selected, conventional 3.0T MRI and portable head and neck MRI were performed successively, and the noise intensity of different sequences in them was evaluated by using a 5-point system.Results:Compared with those in 3.0T conventional MRI images, the SNR and CNR of T1WI, T2WI, and Liquid attenuated reverse recovery sequence (FLAIR) sequences in portable head and neck MRI images were significantly lower ( P<0.05). No significant difference was noted in the comprehensive diagnostic scores of portable head and neck MRI images between special patients and general patients ( P>0.05). Compared with that in the 3.0T conventional MRI, the noise intensity of different sequences in portable head and neck MRI was significantly reduced ( P<0.05). These volunteers had significantly reduced noise intensity scores of different sequences in portable head and neck MRI compared with that in conventional 3.0T MRI ( P<0.05). Conclusion:Portable head and neck MRI device is easy to use, enjoying high safety, imaging quality and suitability, which meets the clinical needs for neurosurgery patients.