1.Mechanism of Tibetan Medicine Sanwei Doukoutang to Improve Cognitive Dysfunction in 5×FAD Mice Based on Wnt/β-catenin Signaling Pathway
Shuran LI ; Yaxin WANG ; Jing SUN ; Lei BAO ; Zihan GENG ; Dan XIE ; Ronghua ZHAO ; Yanyan BAO ; Qiyue SUN ; Jingsheng ZHANG ; Xinwei WANG ; Xinying LI ; Xihe CUI ; Xiaowei YANG ; LIUXIAN ; Mengyao CUI ; Qingshan LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):54-60
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.
2.Mechanism of Tibetan Medicine Sanwei Doukoutang to Improve Cognitive Dysfunction in 5×FAD Mice Based on Wnt/β-catenin Signaling Pathway
Shuran LI ; Yaxin WANG ; Jing SUN ; Lei BAO ; Zihan GENG ; Dan XIE ; Ronghua ZHAO ; Yanyan BAO ; Qiyue SUN ; Jingsheng ZHANG ; Xinwei WANG ; Xinying LI ; Xihe CUI ; Xiaowei YANG ; LIUXIAN ; Mengyao CUI ; Qingshan LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):54-60
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.
3.Construction and evaluation of a radiomics model for predicting perineural invasion in intrahepatic cholangiocarcinoma
Kai ZHANG ; Gengping ZHOU ; Yang XU ; Chenxi XIE ; Pengyu CHEN ; Yangyang WANG ; Taiyang CHEN ; Qingshan LI ; Bo MENG ; Haibo YU
Chinese Journal of Hepatobiliary Surgery 2025;31(11):817-822
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.
4.Clinical characteristics of patients with pregnancy-related chronic pain visiting pain clinic
Dan WANG ; Qingshan LIU ; Lei HUA ; Kai SHA ; Beibei ZHOU ; Shu ZHANG ; Xiaofeng SHEN ; Li YUE
Chinese Journal of Anesthesiology 2025;45(10):1304-1308
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.
5.Correlation between serum residual cholesterol level and the expression of lipoprotein-associated phospholipase A2 with type 2 diabetes mellitus
Xiaoyan WANG ; Qingshan SHI ; Quan YE
Chinese Journal of Diabetes 2025;33(2):104-108
Objective To explore the correlation between residual cholesterol(RC)and lipoprotein-associated phospholipase A2(Lp-PLA2)in type 2 diabetes mellitus(T2DM).Methods A total of 362 T2DM patients visited our hospital from January 2022 to June 2023 were divided into RC≥0.78 mmol/L(HRC,n=196)group and RC<0.78 mmol/L(NRC,n=166)group based on the levels of RC.The clinical characteristics and related factors were compared between the two groups and the risk factors for RC were analyzed.Results Compared with NRC group,DM duration,SBP,DBP,TC,TG,rate of ACEI or ARBs use,non-HDL-C,Lp-PLA2 and IMT in HRC group increased(P<0.05)and LDL-C decreased(P<0.05).Pearson and Spearman correlation analysis showed that RC was positively correlated with age,DM duration,SBP,DBP,TC,TG,non-HDL-C,Lp-PLA2,IMT(P<0.05)and negatively correlated with LDL-C(P<0.05).Logistic multivariate regression analysis showed that TC,TG,LDL-C,non-HDL-C,Lp-PLA2 and IMT were the influencing factors of RC in T2DM patients.Receiver operating characteristic curve analysis showed that the cutoff value of RC was 0.85 mmol/L,and the cutoff value of Lp-PLA2 was 242 U/L.The predicted AUC of T2DM macroangiopathy respectively was 0.864 and 0.721,and the predicted AUC of RC combined with Lp-PLA2 was 0.896.Conclusions Serum RC is positively correlated with Lp-PLA2 in T2DM patients.The combined detection of these two indicators has a certain predictive value for T2DM macrovascular disease.
6.Development and implementation of a new operation and management model of"one body,two wings and three drives"in a public hospital in Shenzhen
Yue QIU ; Xiaorou XIE ; Wei JIANG ; Qingshan GENG ; Bin DAI ; Yanhui KUANG ; Yunping WANG ; Jun SUN ; Haokai ZHAI
Modern Hospital 2025;25(5):734-737
Objective To assess the efficacy of an innovative operational management model in enhancing the refined operational management of a public hospital.Methods An innovative operational management model,"One Body,Two Wings and Three Drives",was developed,which involved establishing a systematic operational management system,strengthening per-formance and cost control,and reinforcing the supporting roles of discipline construction,scientific and technological innovation,and smart hospital initiatives.This comprehensive approach aimed to systematically promote hospital operational management re-forms and improve overall efficiency and quality.Results After using this model,the hospital presented continuous improve-ments in operational efficiency and medical quality,with key performance indicators trending positively.Over the past three years,the average annual growth rate of outpatient and emergency service visits reached 6.6%,inpatient service visits increased by 5.7%,and the Case Mix Index(CMI)rose by 0.22 over two consecutive years.Conclusion This model is highly systemat-ic,practical,and policy-compatible,providing a replicable path for the high-quality development of public hospitals.
7.Quantitative evaluation of the effectiveness of yttrium aluminum garnet laser vitreolysis for symptomatic vitreous opacities
Canfeng HUANG ; Linli WANG ; Jiafeng NING ; Run GAN ; Xiaohe YAN ; Qingshan CHEN
Chinese Journal of Experimental Ophthalmology 2025;43(1):47-51
Objective:To evaluate the effectiveness of yttrium aluminum garnet (Nd∶YAG) laser vitreolysis in the treatment of symptomatic vitreous opacity.Methods:An observational case series study was performed.Forty-four eyes of 44 patients diagnosed as physiological vitreous opacity in Shenzhen Eye Hospital from June 2021 to September 2022 and treated with Nd∶YAG laser vitreolysis were enrolled.Before treatment and 2 months after last treatment, best corrected visual acuity (BCVA) evaluated with standard logarithmic visual acuity chart, floater areas calculated through infrared fundus photography, and objective scattering index (OSI) obtained by the Optical Quality Analysis System (OQAS) were recorded.The occurrence of complications during the follow-up period was recorded.The differences in each indicator were compared, and a simple linear regression model was used to analyze the relationship between floater area and OSI.This study adhered to the Declaration of Helsinki and was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (No.2021-6-3).Patients were informed of the study methods and purposes.Written informed consent was obtained from each subject.Results:There was no significant difference in BCVA before and after Nd∶YAG laser vitreolysis ( t=-0.478, P=0.635).The floater area before laser treatment was (3.043±1.942)mm 2, which was significantly larger than (1.074±0.735)mm 2 after laser treatment ( t=0.769, P<0.001).The OSI before laser treatment was 1.976±0.975, which was significantly greater than 1.560±0.796 after laser treatment ( t=0.730, P<0.001).The results of linear regression analysis showed that the OSI=1.45+ 0.16× floater area ( F=5.681, P=0.020).No patient had visual acuity loss or intraocular pressure increase and no traumatic cataract or retinal damage occurred. Conclusions:After laser treatment, the floater area decreased, the OSI decreased, and the visual quality of patients improved.The OSI from OQAS Ⅱ and floater area can be used as quantitative evaluation indicators to objectively evaluate the effectiveness of Nd∶YAG laser vitreolysis.
8.Establishment of double-antigen sandwich chemiluminescent enzyme immunoassay for antibody detection against classical swine fever virus Erns antigen
Zihan YANG ; Zhongdi LIU ; Yixiao ZHANG ; Qingshan ZUO ; Qichao SONG ; Zunbao WANG ; Yidi GUO ; Changchun TU ; Wenjie GONG
Chinese Journal of Veterinary Science 2025;45(9):1834-1842
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.
9.Effect of TCF1+CD8+T cells on prognosis of nasopharyngeal carcinoma patients undergoing immunotherapy
Lifang WEI ; Shuyan ZHAO ; Qingshan ZHU ; Xinsen WANG
Chinese Journal of Immunology 2025;41(7):1610-1615
Objective:To investigate the effect of TCF1+CD8+T cells on the prognosis of nasopharyngeal carcinoma(NPC)pa-tients undergoing immunotherapy.Methods:A retrospective study was conducted on 108 NPC patients admitted to Anyang Cancer Hospital from January 2018 to April 2020.Pathological findings and clinical data were collected,and multiple immunofluorescence staining was utilized to detect TCF1+CD8+T cell levels in tumor tissue.Cell counts and the proportion of positive cells were measured,and the optimal cut-off value was determined using a time-dependent receiver operating characteristic(ROC)curve.Patients were clas-sified into high expression group and low expression group according to the cut-off value.The general information and survival status were compared between two groups,and univariate and multivariate Cox regression analysis were performed to screen the influencing factors of patient prognosis.Results:The optimal cut-off value was determined using ROC curve.A cut-off value of 0.34%for TCF1+CD8+T cell area under the curve(AUC)=0.653 resulted in a sensitivity of 73.5%and a specificity of 43.7%.Based on the opti-mal cut-off value,33 patients with TCF1+CD8+T cell beyond 0.34%were included in high expression group,and the remaining 75 pa-tients were included in low expression group.The proportion of TCF1+CD8+T cells was(0.43±0.09)%in high expression group and(0.21±0.08)%in low expression group.Comparison of general data yielded that the gender,age,body mass index(BMI),clinical stage,and pathological classification showed no statistical difference between two groups(P>0.05),while the percentage of patients with T stage of T3 and T4,N stage of N2 and N3,and M stage of M1 in high expression group were smaller than that in low expression group(P<0.05).The 24-month survival rate was 81.82%(27/33)in high expression group and 74.67%(56/75)in low expression group,with no statistical difference between two groups(χ2=0.658 8,P=0.417 0).Univariate and multivariate Cox regression analysis found that T stage,N stage and M stage were independent risk factors affecting the prognosis of patients,and TCF1+CD8+T expression was a protective factor.ROC curve indicated that the AUC,sensitivity and specificity of TCF1+CD8+T expression in predicting death of NPC patients undergoing immunotherapy was 0.674,69.7%and 65.3%,while the AUC,sensitivity and specificity of TCF1+CD8+T ex-pression combined with TNM stage in predicting death was 0.809,75.8%and 84.0%,respectively.Conclusion:NPC patients with higher proportion of TCF1+CD8+T cells and lower TNM stage have higher 24-month survival rate after immunotherapy,and the above parameters are of great predictive value for patient prognosis.
10.Quantitative evaluation of the effectiveness of yttrium aluminum garnet laser vitreolysis for symptomatic vitreous opacities
Canfeng HUANG ; Linli WANG ; Jiafeng NING ; Run GAN ; Xiaohe YAN ; Qingshan CHEN
Chinese Journal of Experimental Ophthalmology 2025;43(1):47-51
Objective:To evaluate the effectiveness of yttrium aluminum garnet (Nd∶YAG) laser vitreolysis in the treatment of symptomatic vitreous opacity.Methods:An observational case series study was performed.Forty-four eyes of 44 patients diagnosed as physiological vitreous opacity in Shenzhen Eye Hospital from June 2021 to September 2022 and treated with Nd∶YAG laser vitreolysis were enrolled.Before treatment and 2 months after last treatment, best corrected visual acuity (BCVA) evaluated with standard logarithmic visual acuity chart, floater areas calculated through infrared fundus photography, and objective scattering index (OSI) obtained by the Optical Quality Analysis System (OQAS) were recorded.The occurrence of complications during the follow-up period was recorded.The differences in each indicator were compared, and a simple linear regression model was used to analyze the relationship between floater area and OSI.This study adhered to the Declaration of Helsinki and was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (No.2021-6-3).Patients were informed of the study methods and purposes.Written informed consent was obtained from each subject.Results:There was no significant difference in BCVA before and after Nd∶YAG laser vitreolysis ( t=-0.478, P=0.635).The floater area before laser treatment was (3.043±1.942)mm 2, which was significantly larger than (1.074±0.735)mm 2 after laser treatment ( t=0.769, P<0.001).The OSI before laser treatment was 1.976±0.975, which was significantly greater than 1.560±0.796 after laser treatment ( t=0.730, P<0.001).The results of linear regression analysis showed that the OSI=1.45+ 0.16× floater area ( F=5.681, P=0.020).No patient had visual acuity loss or intraocular pressure increase and no traumatic cataract or retinal damage occurred. Conclusions:After laser treatment, the floater area decreased, the OSI decreased, and the visual quality of patients improved.The OSI from OQAS Ⅱ and floater area can be used as quantitative evaluation indicators to objectively evaluate the effectiveness of Nd∶YAG laser vitreolysis.

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