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.

AIM:To evaluate the effectiveness of EYESI binocular indirect ophthalmoscope simulation system as a training platform for fundus examination skills of general practitioner.METHODS:Prospective randomized study. A total of 40 general practitioners who received clinical ophthalmology training at Shenzhen Eye Hospital from January 2021 to December 2024 were selected and randomly divided into two groups by random number table method, with 20 cases in the study group and 20 cases in the control group. The study group was trained by EYESI binocular indirect ophthalmoscope simulation system and the control group was trained by conventional teaching. Training effects of the two groups were analyzed.RESULTS: The general information of the two groups was comparable. Through training with the EYESI binocular indirect ophthalmoscope simulator, the study group showed significant improvements in total examination and drawing scores compared to pre-training results(all P<0.001). Additionally, examination duration, retinal light exposure time, and drawing time were all significantly shorter than those before training(all P<0.001).The study group achieved significantly higher total examination and drawing scores than the control group during the EYESI binocular indirect ophthalmoscope simulator assessment(all P<0.001). Furthermore, examination duration, retinal light exposure time, and drawing time were all significantly shorter in the study group compared to the control group(all P<0.001). Moreover, ratings for the novelty of the training method and overall satisfaction with the training were significantly higher in the study group than in the control group(all P<0.001); while the perceived psychological stress during training was significantly lower in the study group(P<0.001).CONCLUSION:The EYESI binocular indirect ophthalmoscope simulaton system effectively enhances both the proficiency in fundus examination skills and overall training satisfaction among general practitioners.

Objective To investigate the clinical value of serum hsa_circRNA_0002980 and hsa_circRNA_104348 expression in the diagnosis and prognosis evaluation of liver cancer patients.Methods From April 2020 to April 2022,a total of 105 liver cancer patients and 105 liver cirrhosis patients admitted in the hospital were selected as the liver cancer group and cirrhosis group,and another 105 healthy volunteers who underwent physical examinations in the hospital were selected as the control group.Real-time fluorescence quantitative PCR(qPCR)was applied to detect the expression of serum hsa_circRNA_0002980 and hsa_circRNA_104348.Receiver operating characteristic(ROC)curve was applied to evaluate the diagnostic value and prognostic val-ue of serum hsa_circRNA_0002980 and hsa_circRNA_104348 expression in liver cancer.Multivariate COX re-gression was performed to analyze the influencing factors of prognosis in liver cancer.Results The expression levels of serum hsa_circRNA_0002980 in the liver cancer group,liver cirrhosis group,and control group in-creased sequentially(P＜0.05),while the expression levels of serum hsa_circRNA_104348 decreased sequen-tially(P＜0.05).The levels of alanine aminotransferase and aspartate aminotransferase in the liver cancer group and the liver cirrhosis group were higher than those in the control group(P＜0.05),and the level of al-bumin was lower than that in the control group(P＜0.05).The area under the curve(AUC)for the diagnosis of liver cancer by hsa_circRNA_0002980 combined with hsa_circRNA_104348 was 0.888(95％CI:0.838-0.928),which was obviously higher than those of hsa_circRNA_0002980(Z=3.526,P＜0.001)and hsa_cir-cRNA_104348 alone(Z=2.184,P=0.029).The expression level of serum hsa_circRNA_0002980 in the poor prognosis group was lower than that in the good prognosis group(P＜0.05),and the expression level of ser-um hsa_circRNA_104348 and the proportion of TNM stage Ⅲ+Ⅳ were higher than those in the good progno-sis group(P＜0.05).The AUC for predicting prognosis in liver cancer patients by the combination of hsa_cir-cRNA_0002980 and hsa_circRNA_104348 was 0.870(95％CI:0.790-0.928),and there was no statistically significant difference compared to the AUC predicted separately by hsa_circRNA_0002980 and hsa_circRNA_104348(P＞0.05).The expression of serum hsa_circRNA_0002980,hsa_circRNA_104348 and TNM stage were influencing factors for the prognosis of liver cancer patients(P＜0.05).Conclusion The expression lev-el of hsa_circRNA_0002980 in the serum of liver cancer patients is relatively low,while the expression level of hsa_circRNA_104348 is relatively high.Both have certain clinical significance in the diagnosis and prognosis e-valuation of liver cancer.

OBJECTIVE To investigate the effects of anlotinib on the malignant phenotype of glioma cells by regulating the nuclear factor-κB （NF-κB） signaling pathway. METHODS Human glioma T98G cells were cultured in vitro， and 5-fluorouracil was used as positive control to investigate the effects of different concentrations of anlotinib （5， 10， 20 μmol/L） on the ability of proliferation， adhesion， migration and invasion， the expressions of epithelial-mesenchymal transition （EMT） related proteins [E-cadherin， N-cadherin， vimentin and fibronectin （FN）]. NF- κB signaling pathway inhibitor （BAY 11-7082） and activator （prostratin） were additionally used to verify the possible mechanism of the above effects of anlotinib. RESULTS Anlotinib with 5， 10， 20 μmol/L could significantly decrease the activity of cell proliferation （except for 5 μmol/L anlotinib group）， migration rate， and the number of adherent cells and invasive cells， could significantly up-regulate the expression of E-cadherin protein while down-regulate the expressions of N-cadherin， vimentin and FN protein （P＜0.05）； the effect of 20 μmol/L anlotinib was similar to that of positive control （P＞0.05）. Compared with 10 μmol/L anlotinib， pathway inhibitor could significantly decrease the ability of proliferation， adhesion， migration and invasion， and the expressions of N-cadherin， vimentin， FN and phosphorylated NF-κB p65 protein， while could significantly up-regulate the expression of E-cadherin protein （P＜0.05）； above indexes were reversed significantly by pathway activator （P＜0.05）. CONCLUSIONS Anlotinib may inhibit the proliferation， adhesion， migration and invasion of human glioma T98G cells， which may be associated with the inhibition of the NF-κB signaling pathway， thus inhibiting cell EMT-like processes.

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 and objective Lung cancer is a common malignant tumor of the lung.To explore the molecular mechanism of the occurrence and development of lung cancer is a hot topic in current research.Cyclic RNA D1(CircCCND1)is highly expressed in lung cancer and may be a potential target for the treatment of lung cancer.The aim of this study was to investigate the effect of CircCCND1 on the malignant biological behaviors of lung cancer cells by regulat-ing the miR-340-5p/transforming growth factor β-induced factor homeobox 1(TGIF1)axis.Methods The expression of CircCCND1,miR-340-5p,and TGIF1 mRNA in human normal lung epithelial cells BEAS-2B and human lung cancer H446 cells were detected.H446 cells cultured in vitro were randomly divided into control group,CircCCND1 siRNA group,miR-340-5p mimics group,negative control group,and CircCCND1 siRNA+miR-340-5p inhibitor group.Cell proliferation,mito-chondrial membrane potential,apoptosis,migration,and invasion were detected,and the expressions of CircCCND1,miR-340-5p,TGIF1 mRNA,BCL2-associated X protein(Bax),cleaved Caspase-3,N-cadherin,E-cadherin,and TGIF1 proteins in each group were detected.The targeting relationship of miR-340-5p with CircCCND1 and TGIF1 was verified.Results Compared with BEAS-2B cells,CircCCND1 and TGIF1 mRNA were increased in H446 cells,and miR-340-5p expression was decreased(P＜0.05).Knocking down CircCCND1 or up-regulating the expression of miR-340-5p inhibited the proliferation,migration and invasion of H446 cells,decreased the expression of TGIF1 mRNA and TGIF 1 protein,and promoted cell apop-tosis.Down-regulation of miR-340-5p could antagonize the inhibitory effect of CircCCND1 knockdown on the malignant bio-logical behavior of H446 lung cancer cells.CircCCND1 may target the down-regulation of miR-340-5p,and miR-340-5p may target the down-regulation of TGIF 1.Conclusion Knocking down CircCCND1 can inhibit the malignant behaviors of lung cancer H446 cells,which may be achieved through the regulation of miR-340-5p/TGIF1 axis.

Objective: To analyze the characteristics of a norovirus outbreak in a kindergarten, and factors affecting the detoxification time, so as to provide a scientific basis for targeted control measures. Methods: On February 24,2023, the basic personal information, clinical manifestations，morbidity and treatment of 16 kindergarten cases with a norovirus outbreak in Wuhan were collected. Anal swabs were collected every 7 d after the outbreak to detect norovirus. Chisquare test was used for comparison of intergroup rates. The comparison of detoxification time between different groups was conducted by Logrank test, and the influencing factors of detoxification time in cases were analyzed by Cox multiple regression analysis. Results: From February 19-28, 2023, a total of 18 cases were reported and 16 of them participated in the detoxication time monitoring. In the first, second, third and fourth sampling after the outbreak, the positive rates were 60.00%, 100.00%, 75.00% and 0, respectively. The reverse transcriptionpolymerase chain reaction cycle threshold (Ct values) were (25.83±5.74, 28.83±5.55, 36.13±4.30), and undetected, respectively. The median time of detoxification was 19.42 d with 95%CI=(18.21-20.64)d. The results of Cox regression showed that the detoxication time was shorter in the treatment group than in the nontreatment group[HR(95%CI)=5.09(1.39-18.58), P<0.05]. Conclusion Children infected with norovirus has a long duration of detoxification,and case management, which could be shortened by drugs, and disinfection should be strengthened after the case returned to school.

Objective:To explore the prognostic value of systemic immune-inflammatory index(SII)combined with tumor burden score (TBS) (hereinafter referred to as STS) in patients with intrahepatic cholangiocarcinoma (ICC) after radical resection, and to construct a nomogram model.Methods:The clinical data (including the degree of tumor differentiation, vascular cancer thrombus, and lymph node metastasis, etc.) of 258 ICC patients who received radical resection at People′s Hospital of Zhengzhou University (170 cases, training set) and Cancer Hospital of Zhengzhou University (88 cases, validation set) from January 1, 2016 to January 31, 2020 were retrospectively analyzed and graded by SII, TBS and STS. Multivariate Cox regression analysis were used to identify independent factors affecting the prognosis of patients with ICC. Kaplan-Meier survival curve and receiver operating characteristic curve (ROC) were drawn to evaluate the predictive efficiency of SII, TBS and STS in the overall survival of patients with ICC after radical resection. The nomogram prediction model was constructed and evaluate the performance of nomogram model using consistency index (C-index) and calibration curve.Results:Among 170 ICC patients in the training set, there were 106 cases of SII grade 1 and 64 cases of SII grade 2; 137 cases of TBS grade 1 and 33 cases of TBS grade 2; and 98 cases of STS grade 1, 47 cases of STS grade 2, and 25 cases of STS grade 3. Among 88 ICC patients in the validation set, there were 33 cases of SII grade 1 and 55 cases of SII grade 2; 66 cases of TBS grade 1 and 22 cases of TBS grade 2; and 30 case of STS grade 1, 39 cases of TBS grade 2, and 19 cases of TBS grade 3.The multivariate Cox regression analysis showed that tumor differentiation degree (highly differentiated vs. moderately differentiated HR=0.157, 95% confidence interval(95% CI) 0.045 to 0.546, highly differentiated vs. poorly differentiated HR=0.452, 95% CI 0.273 to 0.750), STS (grade 3 vs. grade 2 HR=1.966, 95% CI 1.148 to 3.469; grade 3 vs. grade 1 HR=1.405, 95% CI 0.890 to 2.216), vascular cancer thrombus ( HR=2.006, 95% CI 1.313 to 3.066), nerve invasion ( HR=1.865, 95% CI 1.221 to 2.850), and lymph node metastasis ( HR=1.802, 95% CI 1.121 to 2.896) were independent influencing factors of overall survival in ICC patients after radical resection (all P<0.05). The Kaplan-Meier survival curve showed that SII, TBS, and STS were independent influencing factors of overall survival in ICC patients (all P<0.05). The results of ROC analysis showed that the areas under the curve of SII, TBS and STS in predicting overall survival of ICC patients after radical resection were 0.566 (95% CI 0.479 to 0.652), 0.585 (95% CI 0.499 to 0.672), and 0.657 (95% CI 0.522 to 0.692), respectively. Tumor differentiation, vascular tumor thrombus, nerve invassion, lymph node metastasis, and STS were included to constract the nomogram model. The C-indexes of the training set and validation set based on the nomogram model were 0.792 (95% CI 0.699 to 0.825) and 0.776 (95% CI 0.716 to 0.833), respectively. The calibration curves of the survival rate of the training set and the validation set were close to the reference lines, and the nomogram model had better predictive ability in both the training set and the validation set. Conclusions:Preoperative STS grading is an effective and practical predictor of overall survival in ICC patients after radical section. Compared with SII and TBS alone, it has better predictive value for the prognosis of patients with ICC.

Objective:To investigate the clinical characteristics and potential predisposing factors of the external cervical resorption(ECR).Methods:22 ECR cases with 38 affected teeth from 2016 to 2022 were retrospectively reviwed.Descriptive analysis combined with single factor analysis was used to study the clinical characteristics and influencing factors of ECR.Results:Maxillary anterior teeth(34.2％)were the most affected by ECR.Univariate analysis showed that ECR was more commonly noted in teeth without percussion pain and palpation pain,the probing depth of the periodontal pocket was greater than 3mm,with pulp activity reaction,without forma-tion of abscess and/or sinus tract,and without periapical lesions.There were statistically significant differences in percussion tender-ness,palpation tenderness and probing depth among the different Heithersary stages(P＜0.05).In the advanced cases,deep periodon-tal pockets and abscess formation were observed.The most common related dental factors of ECR were orthodontic treatment(15.87％)and dental traumatic injury(28.57％).Conclusion:ECR affected teeth often lack of clinical signs and symptoms.Radiology is the key to early diagnosis.