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 construct and evaluate a radiomics model for predicting perineural invasion in patients with intrahepatic cholangiocarcinoma (ICC).Methods:Clinical data of 144 patients with ICC undergoing surgery in the People’s Hospital of Zhengzhou University ( n=113) and the Affiliated Cancer Hospital of Zhengzhou University ( n=31) from January 2018 to June 2023 were retrospectively analyzed, including 80 males and 64 females, aged (58.8±10.1) years. The patients were randomly divided into a training set ( n=100) and a test set ( n=44) at a ratio of 7: 3. The former set was used to build the model for predicting perineural invasion, and the latter was used to evaluate the model. Enhanced CT images and clinical data of the patients were collected, and features related to perineural invasion were screened. A light gradient boosting machine was used to construct an imaging genomics model. The model was evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results:Univariate and multivariate logistic regression analysis showed that none of the clinical features were associated with neural invasion in ICC patients (all P>0.05). Six, 25, 32, and 37 radiomics features were obtained by screening the intratumoral, 2 mm peritumoral, 5 mm peritumoral, and 8 mm peritumoral regions, respectively. The area under the ROC curve for predicting perineural invasion in ICC patients was 0.849 (95% CI: 0.774-0.923) in the training set and 0.745 (95% CI: 0.597-0.894) in the test set for the intratumoral model, 0.966 (95% CI: 0.938-0.995) and 0.750 (95% CI: 0.604-0.896) for the 5mm peritumoral model, 0.936 (95% CI: 0.892-0.980) and 0.792 (95% CI: 0.644-0.939) for the 2mm peritumoral model, and 0.961 (95% CI: 0.929-0.992) and 0.689 (95% CI: 0.526-0.853) for the 8mm peritumoral model. The area under the ROC curve, accuracy, sensitivity, and specificity of the combined intratumoral and 5mm peritumoral model for predicting perineural invasion were 0.927 (95% CI: 0.878-0.976), 88.0%, 84.5%, and 89.8% in the training set, and 0.849 (95% CI: 0.737-0.960), 77.3%, 85.2%, and 72.0% in the test set, respectively. The calibration curve showed a deviation between the calibration curve of the combined intratumoral and 5mm peritumoral model and the ideal line, but it could achieve basic consistency. DCA showed that when the threshold was between 0.18 and 0.70, the combined intratumoral and 5mm peritumoral model could bring clinical net benefit to patients when predicting neural invasion. Conclusion:The intratumoral and 5mm peritumoral imaging genomics model based on enhanced CT features can effectively predict neural invasion and offer clinical benefits in patients with ICC.

Objective:To analyze the clinical characteristics of patients with pregnancy-related chronic pain visiting the pain clinic.Methods:The number of pregnant patients who completed a pregnancy registration at the Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University from 2022 to 2024 was collected. The medical records were reviewed to identify the patients who visited the department of pain of our hospital due to chronic pain related to pregnancy. The clinical characteristics such as the visiting situation, gestational weeks, age and types of pain were analyzed.Results:From 2022 to 2024, the total number of registered pregnant patients was 64, 818, of which, 2, 224 cases visited the pain clinic, and the annual proportions of pregnancy-related chronic pain visits were 2.540%, 3.836% and 3.889% respectively. Among the patients who attended the clinic, 77.97% were pregnant (5.82% in early pregnancy, 41.93% in mid-pregnancy, and 52.25% in late pregnancy), and 21.03% were postpartum patients. A total of 83.72% were aged 20-34 yr. The types of pain were pelvic girdle pain (40.96%), limb joint pain (28.82%), low back pain (14.16%), cervical spondylosis (3.64%), peripheral nerve entrapment syndrome (3.42%), headache (2.97%), chest and back pain (2.79%), pelvic and perineal pain (1.66%), neuralgia (0.94%) and other pains (0.63%).Conclusions:From 2022 to 2024, the proportion of registered pregnant women at our hospital who visited to the pain clinic due to pregnancy-related chronic pain increases year by year. The common types of pain are pelvic girdle pain, limb joint pain and low back pain.

Objective To investigate the efficacy of plantamajoside(PMS)on diabetic peripheral neuropathy(DPN)and to explore its mechanism of action from mitochondrial autophagy.Methods Mice(C57BL/6J)were randomly divided into 6 groups(n=10):normal group(Control),model group(Model),positive drug group(LA),and low(L-PMS),medium(M-PMS),and high(H-PMS)dosage groups.High-sugar and high-fat diet with intraperitoneal injection of streptozotocin was used to duplicate the DPN model.After successful model duplication,the intervention was administered by gavage for 4 weeks.Sciatic nerve was taken,and pathological changes were observed by HE and Nissl staining;oxidative stress indexes SOD,MDA,GSH-Px and inflammatory factors such as IL-1β,IL-6,TNF-αin sciatic nerve tissues were detected by kits,and the expression of VDAC1,TOM20,COX IV,PINK1,Parkin,and autophagy proteins of Beclin1,LC3,P62 in mouse sciatic nerves was detected by Western blotting.Results PMS dose-dependently improved the behavioral indexes of DPN mice,reduced the pathological damage of sciatic nerve,and resulted in tightly arranged sciatic nerve fibers,clearly visible myelin structure,uniform coloration,and increased number of Schwann cells as well as Nissl bodies.Compared with the model group,both the M-PMS group and the H-PMS group increased the expression levels of SOD and GSH-Px(P<0.05),while decreased the expression of MDA(P<0.05);the M-PMS group and the H-PMS groups reduced the expression of IL-1β,IL-6,and TNF-α(P<0.05);the L-PMS group,M-PMS group,and H-PMS group reduced the expression levels of VDAC1,TOM20,and COX IV proteins(P<0.05);the L-PMS group,M-PMS group,and H-PMS group could differentially increase the expression of PINK1,Beclin1,Parkin,and LC3 proteins(P<0.05),and decrease the expression of P62 proteins(P<0.05).Conclusion PMS can play a role in ameliorating neurological injury in DPN mice by promoting PINK1/Parkin pathway-mediated mitochondrial autophagy and alleviating oxidative stress-related inflammatory injury.

Objective:To evaluate the efficacy and safety of radiotherapy combined with sintilimab and bevacizumab (anti-angiogenic agent) in patients with unresectable advanced hepatocellular carcinoma (HCC).Methods:Clinical data of 80 patients with unresectable advanced HCC admitted to Shanghai Mengchao Cancer Hospital from January 2021 to September 2023 were retrospectively analyzed. All patients were divided into two groups based on treatment regimens: the systemic therapy group ( n=41) receiving sintilimab combined with bevacizumab, and combined radiotherapy group ( n=39) receiving radiotherapy plus sintilimab and bevacizumab. Efficacy was evaluated using the response evaluation criteria in solid tumors (RECIST) 1.1 version and modified RECIST for HCC. Treatment-related adverse events (TRAE) were assessed by the common terminology criteria for adverse events (CTCAE) 4.03 version. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and TRAE. Independent sample t-test was used for normally distributed quantitative data, and Chi-square test for qualitative data. Survival analysis was performed via Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression models were applied to analyze prognostic factors. Results:In terms of efficacy, no patient obtained complete response (CR) in the systemic therapy group, while 2 cases achieved CR in the combined radiotherapy group. The ORR was 22% (9/41) in the systemic therapy group and 59% (23/39) in the combined radiotherapy group ( P=0.001). The DCR was 85% (35/41) and 97% (38/39) in the two groups ( P=0.130), with the incidence of progressive disease of 15% (6/41) and 3% (1/39) ( P=0.130), respectively. The median PFS was 8.0 months (95% CI=6.8-9.2 months) in the combined radiotherapy group and 4.4 months (95% CI=4.1-4.7 months) in the systemic therapy group ( P=0.002). The median OS was 19.0 months (95% CI=15.5-22.5 months) in the combined radiotherapy group and 12.5 months (95% CI=9.4-15.6 months) in the systemic therapy group ( P=0.006). Radiotherapy was an independent protective factor for both PFS ( HR=0.474, 95% CI=0.289-0.778, P=0.003) and OS ( HR=0.403, 95% CI=0.218-0.744, P=0.004). The number of tumors >3 was an independent risk factor for both PFS ( HR=2.658, 95% CI=1.485-4.755, P=0.001) and OS ( HR=3.245, 95% CI=1.773-5.939, P=0.001). There was no significant difference in TRAE between two groups ( P > 0.05). Conclusions:Radiotherapy combined with sintilimab and bevacizumab shows high efficacy and acceptable safety in patients with unresectable advanced HCC.

Objective To explore the feasibility of protocol with low tube voltage,low contrast agent dose,low injection rate,and low trigger threshold based on body weight in coronary computed tomography angiography(CCTA).Methods Patients suspected with coronary heart disease who underwent 320 rows of CCTA were prospectively selected.They were divided into 4 groups:＜60 kg,60-70 kg,71-80 kg,＞80 kg based on different body weights,120 cases for each group,then were randomly divided into experimental group and control group using a random number table method,with 60 patients in each group.Each case in the control group had a tube voltage of 120 kV and a trigger threshold of 240 HU;each case in the experimental group had a tube voltage of 100 kV and a trigger threshold of 190 HU.According to the CCTA application guidelines,the iodine flow rate was used to determine the contrast agent injection rate in the control group,while the injection rate in the experimental group was reduced by 30%.Using an injection time of 12 s,the control group's contrast agent dose was obtained,and that of the experimental group decreased by 30%.Two radiologists evaluated the CT values,contrast-to-noise ratio(CNR),image quality score,and signal-to-noise ratio(SNR)of the middle segment of the right coronary artery,proximal segment of the left anterior descending branch,and proximal segment of the left circumflex branch,as well as compared the effective dose(ED)of volume scanning and threshold monitoring sequences.One-way ANOVA,independent sample t-test,and Mann-Whitney U-test were used to evaluate the differences in each parameter.Results There were no statistically significant differences in general information and subjective image scores between the experimental group and the control group(P＞0.05).There were no statistically significant differences in CT values,CNR,and SNR between the experimental group and the control group at different body weights for the middle segment of the right coronary artery,the proximal segment of the left anterior descending branch,and the proximal segment of the left circumflex branch(P＞0.05).In terms of radiation dose,the comparison between the control group and the experimental group at the same body weights showed statistically significant differences both in volume scanning and threshold monitoring sequences(P＜0.001),and the ED of the experimental group was significantly lower than that of the control group.Conclusion The protocol with low tube voltage,low contrast agent dose,low injection rate,and low trigger threshold determined based on different body weights can achieve satisfactory image quality for CCTA,while significantly reducing the radiation dose of volume scanning and threshold monitoring sequences.

To establish a highly specific,sensitive,and efficient method for detecting antibodies a-gainst the Erns protein of classical swine fever virus(CSFV),and to distinguish CSFV vaccine strains from wild strains infections in combination with the E2 subunit vaccine.The purified Erns protein of the CSFV expressed by baculovirus was conjugated to carboxylated magnetic beads as a solid-phase carrier and horseradish peroxidase(HRP),separately.A double-antigen sandwich chemiluminescent enzyme immunoassay(CLEIA)was developed by optimizing various reaction parameters using a fully automated chemiluminescence analyzer.This method was then applied to quantitatively detect Erns protein antibodies in sera from pigs infected with prevalent strains and those immunized with the CSFV E2 subunit vaccine and challenged with field strains.The results showed that the optimal conditions for coupling protein-to-magnetic bead were as follows:coupling buffer pH of 8.0,a protein coupling amount of 2.5 mg/g,blocking solution of 10％BSA,serum sample volume of 20 μL.The optimal dilution of enzyme-labeled antigen was at 1:500 with a one-step reaction time of 15 minutes.The cutoff value of the established CLEIA method for detecting CSFV Erns protein antibodies was 5.83 U/mL and a diagnostic sensitivity of 1:128.No cross-reac-tivity was observed with positive sera against African swine fever virus,pseudorabies virus,porcine circovirus type 2,porcine epidemic diarrhea virus,porcine reproductive and respiratory syndrome virus,or porcine gastroenteritis virus.Additionally,the method yielded negative results with sera from pigs immunized with the E2 subunit vaccine.In repeatability tests,the intra-assay coefficient of variation(CV)ranged from 0.77％to 11.56％,and the inter-assay CV ranged from 10.30％to 14.55％,both below 15％.The positive and negative concordance rates with a commercial CSFV Erns protein antibody detection kit were 95.24％and 92.71％,separately,with an overall concord-ance rate of 93.23％.The double-antigen sandwich chemiluminescence method established in this study exhibits high sensitivity,excellent repeatability,and suitability for automated detection,making it applicable for serological differentiation between CSFV E2 subunit vaccination and infec-tion with prevalent strains.

To establish a highly specific,sensitive,and efficient method for detecting antibodies a-gainst the Erns protein of classical swine fever virus(CSFV),and to distinguish CSFV vaccine strains from wild strains infections in combination with the E2 subunit vaccine.The purified Erns protein of the CSFV expressed by baculovirus was conjugated to carboxylated magnetic beads as a solid-phase carrier and horseradish peroxidase(HRP),separately.A double-antigen sandwich chemiluminescent enzyme immunoassay(CLEIA)was developed by optimizing various reaction parameters using a fully automated chemiluminescence analyzer.This method was then applied to quantitatively detect Erns protein antibodies in sera from pigs infected with prevalent strains and those immunized with the CSFV E2 subunit vaccine and challenged with field strains.The results showed that the optimal conditions for coupling protein-to-magnetic bead were as follows:coupling buffer pH of 8.0,a protein coupling amount of 2.5 mg/g,blocking solution of 10％BSA,serum sample volume of 20 μL.The optimal dilution of enzyme-labeled antigen was at 1:500 with a one-step reaction time of 15 minutes.The cutoff value of the established CLEIA method for detecting CSFV Erns protein antibodies was 5.83 U/mL and a diagnostic sensitivity of 1:128.No cross-reac-tivity was observed with positive sera against African swine fever virus,pseudorabies virus,porcine circovirus type 2,porcine epidemic diarrhea virus,porcine reproductive and respiratory syndrome virus,or porcine gastroenteritis virus.Additionally,the method yielded negative results with sera from pigs immunized with the E2 subunit vaccine.In repeatability tests,the intra-assay coefficient of variation(CV)ranged from 0.77％to 11.56％,and the inter-assay CV ranged from 10.30％to 14.55％,both below 15％.The positive and negative concordance rates with a commercial CSFV Erns protein antibody detection kit were 95.24％and 92.71％,separately,with an overall concord-ance rate of 93.23％.The double-antigen sandwich chemiluminescence method established in this study exhibits high sensitivity,excellent repeatability,and suitability for automated detection,making it applicable for serological differentiation between CSFV E2 subunit vaccination and infec-tion with prevalent strains.