BACKGROUND:Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells,promoting the phagocytosis of myelin debris by microvascular endothelial cells,affecting the migration and infiltration of microglia,promoting the recovery of damaged neurons,and decreasing neuronal apoptosis after spinal cord injury,but the mechanism of this is still not clear. OBJECTIVE:To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2(TREM2)and PI3K/Akt signaling pathways in mice following spinal cord injury. METHODS:Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group,a model group and a Wen-Shen-Tong-Du Decoction group,with 12 mice in each group.In the model and Wen-Shen-Tong-Du Decoction groups,mouse models of T10 spinal cord injury were prepared by the modified Allen's method.On the 1st day after modeling,the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage,and the sham-operation group and the model group were given saline by gavage once a day for 28 days.During the drug administration period,mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test.On the 7th and 28th days after modeling,hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice;immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1(IBA1)and TREM2;and western blot assay was used to detect the expression of TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,Bax and Caspase3 in spinal cord tissue. RESULTS AND CONCLUSION:Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury,and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury.Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group,manifesting as reduced degrees of dorsal white matter and neuronal atrophy,decreased cytoplasmic vacuolization,and reduced inflammatory cell infiltration.Immunofluorescence double staining results showed that on the 7th day after modeling,the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05);on the 28th day after modeling,the protein expression of TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05).Western blot results analysis demonstrated that on the 7th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,and Bcl2/Bax(P＜0.05),as well as a significant increase in p-Akt,Bax and p-Akt/Aktp-PI3K(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,p-PI3K/PI3K,p-Akt/Ak,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax and Caspase3 protein expression(P＜0.05).On the 28th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2 and Bcl2/Bax(P＜0.05),as well as a significant increase in Bax protein expression(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,Akt,p-Akt,Bcl2,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax protein expression(P＜0.05).To conclude,Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia,and then inhibit neuronal apoptosis,thus exerting neuroprotective effects and promoting the repair of spinal cord injury.

The 5-hydroxytryptamine 2A receptor (5-HT_2AR) is one of the key targets in the development of novel antidepressants. To develop new antidepressants targeting the 5-HT_2A receptor, this study established a high-throughput screening method for drugs targeting the 5-HT_2A receptor based on the principle of detecting calcium flux signals. The immunofluorescence assay and western blotting were employed to evaluate receptor expression levels in the 5-HT_2AR-CHO cell line. The reaction system parameters, including cell seeding density, DMSO concentration, and dye incubation time, were optimized with Z'-factor and signal window values as evaluation indicators. The specificity, precision, stability, and applicability of the method were assessed. Results indicated that the 5-HT_2AR-CHO cell line stably expressed high levels of the 5-HT_2A receptor. The optimized screening method involved a reaction system with 10 000 cells/well, 0.2% DMSO, and 2 h incubation with Calcium 6 dye. The method demonstrated excellent specificity, with inter-batch precision below 10% for the detection of 5-hydroxytryptamine (5-HT) at low, medium, and high concentrations. Testing four compounds that target the 5-HT_2A receptor- agonists 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD), along with the antagonist MDL100907-yielded Z'-factors (at EC₈₀) greater than 0.85 and signal window values over 0.91. The EC₅₀ values of these compounds were in the nanomolar range, and their potency rank order aligned with previously reported data, confirming the reliability of the established method. When being applied to the detection of 38 known active compounds, the method efficiently identified 5-HT_2A receptor agonists and antagonists while showing no response to non-target compounds. In conclusion, this study successfully constructs a high-throughput screening approach for 5-HT_2A receptor-targeting drugs based on calcium flux signals. The method possesses strong specificity, high sensitivity, and robust stability, being suitable for screening antidepressants targeting the 5-HT_2A receptor.
High-Throughput Screening Assays/methods* ; Receptor, Serotonin, 5-HT2A/metabolism* ; Animals ; CHO Cells ; Cricetulus ; Calcium Signaling/drug effects* ; Antidepressive Agents/pharmacology* ; Humans ; Serotonin 5-HT2 Receptor Antagonists/pharmacology* ; Calcium/metabolism*

Objective:To analyze the detection of colorectal advanced neoplasms in the population who underwent colonoscopy screening in Henan Province as part of the Urban China Cancer Screening Program and its influencing factors.Methods:A cross-sectional study design was employed. Based on the Cancer Screening Program conducted in Henan Province, the study enrolled 7 454 urban residents who manifested no symptoms and were recruited from eight cities in the province, including Zhengzhou, Zhumadian, Anyang, Luoyang, Nanyang, Jiaozuo, Xinxiang, and Puyang from October 2013 to October 2019, and participated in colonoscopy screening. The χ 2 test was used to compare the detection rates of colorectal advanced neoplasms among participants with different characteristics, and a multivariate logistic stepwise regression model was used to analyze the factors affecting the detection rates. Results:A total of 7 454 subjects underwent colonoscopy screening, and 112 cases of colorectal advanced neoplasms were detected. Multivariate logistic regression analysis suggested that older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative were risk factors for colorectal advanced neoplasms. The detection rate was significantly higher in people aged 60-74 years compared with those aged 40-49 years, with an odds ratio ( OR) of 2.04 (95% CI: 1.23-3.38).The rates were higher in people who smoked than those who did not smoke, with an OR of 2.21 (95% CI: 1.48-3.31), and in people who consumed more meat than those who consumed less, with an OR of 1.53 (95% CI: 1.04-2.26). Those with diabetes had a higher detection rate compared with those without, with an OR of 1.69 (95% CI: 1.07-2.69), and those with a first-degree family history of colorectal cancer had a higher detection rate than those without, with an OR of 1.64 (95% CI: 1.09-2.46). Conclusion:The detection rate of colorectal advanced neoplasms through colonoscopy screening in Henan Province covered by the Urban China Cancer Screening Program is 1.50%. Older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative are identified as risk factors for colorectal advanced neoplasms.

Objective:To analyze the 5-year relative survival rate of cancer in Henan province based on cancer registration data.Methods:Cancer survival data were extracted from the cancer registration database of Henan province with the diagnosis date between January 1, 2010 and December 31, 2019 were included. The closing date of follow-up was set as December 31, 2019. The 5-year relative survival rate of cancer was calculated using the period survival analysis method and the Ederer II method in the R package "periodR", and the interest period was between 2015 and 2019.Results:During the period of 2015-2019, the overall 5-year relative survival rate of cancer patients in Henan province was 43.6%, and after age-standardization, it was 40.2%. The overall 5-year relative survival rate showed the characteristics of higher survival rate in females than males (45.9% vs 34.7%, Z=39.60, P＜0.001) and higher survival rate in urban areas than rural areas (44.9% vs 39.1%, Z=12.97, P＜0.001). The 5-year relative survival rate for cancer patients among children aged 0-14 was 60.2%, and for adults aged 15 and above, it was 43.5%, which was standardized to 40.2% after age adjustment. There are two types of cancers with a standardized 5-year relative survival rate exceeding 70% (thyroid cancer at 82.2% and breast cancer at 71.6%), and four cancers with a rate below 30% (pancreatic cancer at 18.2%, liver cancer at 19.6%, lung cancer at 24.0%, and gallbladder cancer at 26.6%). Conclusion:The cancer 5-year survival rate in Henan Province is lower than that of the national average, indicating the need for continued enhancement of cancer prevention and control measures.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective·To analyze and explore the influencing factors that lead to cognitive deterioration in individuals with elevated fasting blood glucose(FBG)and the metabolic clues associated with changes in the risk of cognitive deterioration.Methods·Data from the Alzheimer's Disease Neuroimaging Initiative(ADNI)database were downloaded,and the samples with FBG and follow-up data were selected from the database.Clinical information,including age,gender,body mass index,education years,apolipoprotein E4(APOE4)genotype and race,and corresponding metabolic indicator data,including amino acids,fatty acids,proteins and others were obtained.Based on the FBG levels and diagnosis of cognitive impairment stages in Alzheimer's disease,the subjects were categorized into four groups:normal FBG without/with cognitive deterioration,and elevated FBG without/with cognitive deterioration.The univariate analysis method,the Cox proportional hazards model,orthogonal projections to latent structures discriminant analysis(OPLSDA),and Spearman correlation analysis were employed for data analysis.Results·A total of 1 317 subjects were included,among which 1 153 had normal FBG level(>3.9 mmol/L and<6.1 mmol/L)and 164 had elevated FBG level(≥6.1 mmol/L).In the normal FBG group,275 subjects showed cognitive deterioration,while in the elevated FBG group,53 subjects showed cognitive deterioration.Univariate analysis revealed significant differences in gender and race between the normal FBG and elevated FBG group,and significant differences in age,gender,and APOE4 genotype between the groups with and without cognitive deterioration(all P<0.05).Cox regression analysis indicated that primary influencing factors for cognitive deterioration were APOE4 positivity,elevated FBG,and increasing age in order(HR=2.22,HR=1.38,HR=1.02;all P<0.05).In the analysis of baseline metabolic indicators in the groups without and with cognitive deterioration,as well as metabolic indicators before and after cognitive deterioration at different FBG levels,the results of the analysis of variance revealed that in the cognitively deteriorated population,the ratio of phospholipids carried by high-density lipoproteins(HDL)to total lipids was significantly higher;low-density lipoprotein(LDL)particle concentration and the lipids carried by LDL were significantly higher after cognitive deterioration.Correlation analysis showed that valine and leucine were significantly correlated not only with FBG level but also with phosphorylated tau(pTau)level in the plasma in the cognitively deteriorated population.Cholesterol and the ratio of phospholipids to total lipids carried by HDL were significantly correlated with pTau levels in cerebrospinal fluid(CSF).Conclusion·Compared to the individuals with normal FBG level,those with high FBG level have a significantly higher risk of cognitive deterioration.Additionally,different metabolic indicators show significant differences between the groups without and with cognitive deterioration,as well as metabolic indicators before and after cognitive deterioration at different FBG levels.Overall,LDL and its lipid content,and HDL-carried phospholipids show an increasing trend during cognitive deterioration,and the branched-chain amino acids valine and leucine are significantly correlated with pTau levels in CSF and plasma,suggesting that these metabolic markers may play an important role in cognitive deterioration.

Objective To explore the material basis and mechanism of the Chinese medicine Dingqing tablets in the treatment of leukemia.Methods The potential active ingredients of Dingqing tablets were retrieved through TCMSP and HERB Database and the targets of herbs were screened by Swiss TargetPrediction databases.The treatment targets of leukemia were searched from the GeneCards,OMIM and Disgenet databases.The protein-protein interaction network was used to construct the interactive target regulation function of Dingqing tablets and leukemia by STRING software,and the core subnetworks were filtered by the MCODE plug-in.A component-target pathway network was constructed by GO and KEGG enrichment analysis of the highest scoring Gene cluster 1 gene in the DAVID database.Molecular docking of the active components and core targets of Dingqing tablets was performed by AutoDock and the results were visualized.Results A total of 82 active ingredients and 439 targets of action of Dingqing tablets,and 1 878 leukemia-related targets were obtained through database retrieval,in which 169 common targets of active ingredients and diseases were mapped.Based on the degree values,the main active ingredients were determined as quercetin,luteolin,kaempferol,etc.The PPI core network indicated that the key targets for treating leukemia included TP53,MMP9,TNF,AKT1,CASP3,etc.The gene enrichment analysis of sub-networks and the component-target pathway network diagram showed that Dingqing tablets might exert therapeutic effects on leukemia by regulating signaling pathways such as TNF and IL-17.The molecular docking results showed fairly strong binding activity between the active ingredients and the targets.Conclusion The active ingredients of Dingqing tablets may participate in TNF,IL-17,and other signaling pathways by regulating genes such as TP53,AKT1,and CASP3,thereby exerting therapeutic effects on leukemia.

Objective:To analyze the detection of colorectal advanced neoplasms in the population who underwent colonoscopy screening in Henan Province as part of the Urban China Cancer Screening Program and its influencing factors.Methods:A cross-sectional study design was employed. Based on the Cancer Screening Program conducted in Henan Province, the study enrolled 7 454 urban residents who manifested no symptoms and were recruited from eight cities in the province, including Zhengzhou, Zhumadian, Anyang, Luoyang, Nanyang, Jiaozuo, Xinxiang, and Puyang from October 2013 to October 2019, and participated in colonoscopy screening. The χ 2 test was used to compare the detection rates of colorectal advanced neoplasms among participants with different characteristics, and a multivariate logistic stepwise regression model was used to analyze the factors affecting the detection rates. Results:A total of 7 454 subjects underwent colonoscopy screening, and 112 cases of colorectal advanced neoplasms were detected. Multivariate logistic regression analysis suggested that older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative were risk factors for colorectal advanced neoplasms. The detection rate was significantly higher in people aged 60-74 years compared with those aged 40-49 years, with an odds ratio ( OR) of 2.04 (95% CI: 1.23-3.38).The rates were higher in people who smoked than those who did not smoke, with an OR of 2.21 (95% CI: 1.48-3.31), and in people who consumed more meat than those who consumed less, with an OR of 1.53 (95% CI: 1.04-2.26). Those with diabetes had a higher detection rate compared with those without, with an OR of 1.69 (95% CI: 1.07-2.69), and those with a first-degree family history of colorectal cancer had a higher detection rate than those without, with an OR of 1.64 (95% CI: 1.09-2.46). Conclusion:The detection rate of colorectal advanced neoplasms through colonoscopy screening in Henan Province covered by the Urban China Cancer Screening Program is 1.50%. Older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative are identified as risk factors for colorectal advanced neoplasms.

Objective:To analyze the 5-year relative survival rate of cancer in Henan province based on cancer registration data.Methods:Cancer survival data were extracted from the cancer registration database of Henan province with the diagnosis date between January 1, 2010 and December 31, 2019 were included. The closing date of follow-up was set as December 31, 2019. The 5-year relative survival rate of cancer was calculated using the period survival analysis method and the Ederer II method in the R package "periodR", and the interest period was between 2015 and 2019.Results:During the period of 2015-2019, the overall 5-year relative survival rate of cancer patients in Henan province was 43.6%, and after age-standardization, it was 40.2%. The overall 5-year relative survival rate showed the characteristics of higher survival rate in females than males (45.9% vs 34.7%, Z=39.60, P＜0.001) and higher survival rate in urban areas than rural areas (44.9% vs 39.1%, Z=12.97, P＜0.001). The 5-year relative survival rate for cancer patients among children aged 0-14 was 60.2%, and for adults aged 15 and above, it was 43.5%, which was standardized to 40.2% after age adjustment. There are two types of cancers with a standardized 5-year relative survival rate exceeding 70% (thyroid cancer at 82.2% and breast cancer at 71.6%), and four cancers with a rate below 30% (pancreatic cancer at 18.2%, liver cancer at 19.6%, lung cancer at 24.0%, and gallbladder cancer at 26.6%). Conclusion:The cancer 5-year survival rate in Henan Province is lower than that of the national average, indicating the need for continued enhancement of cancer prevention and control measures.

Objective:To investigate the characteristics of 18F-FDG and 18F-9-fluoropropyl-(+ )-dihydrotetrabenazine (FP-(+ )-DTBZ; short for DTBZ) brain vesicular monoamine transporter type 2 (VMAT2) PET/CT imaging and analyze its clinical diagnostic value in Parkinson′s disease (PD) patients with or without rapid eye movement sleep behaviour disorder (RBD). Methods:From July 2022 to June 2023, 50 patients clinically confirmed with primary PD who underwent 18F-FDG and 18F-DTBZ PET/CT imaging in the First Affiliated Hospital of Zhengzhou University were prospectively collected. Among them, 18 patients with PD accompanied by RBD (PD-RBD(+ ) group; 16 males, 2 females, age (59.2±9.3) years); 32 patients without RBD (PD-RBD(-) group; 16 males, 16 females, age (57.7±10.2) years). Moreover, 10 healthy controls matched with the age of PD patients were included (5 males, 5 females, age (60.3±9.6) years). 18F-DTBZ specific uptake ratio (SUR) of bilateral striatum, caudate nucleus, anterior putamen, posterior putamen, nucleus accumbens, substantia nigra and other brain regions were obtained with occipital cortex as the reference region. Striatal anterior-posterior gradient and other related semi-quantitative indicators were calculated according to the corresponding formula. One-way analysis of variance (the least significant difference (LSD)- t test), Kruskal-Wallis rank sum test (Bonferroni correction), independent-sample t test and Mann-Whitney U test were used to analyze the data. Pearson correlation and Spearman rank correlation analyses were used to evaluate the correlations. ROC curve analysis was also performed. The differences in global glucose metabolism in two groups were compared using statistical parametric mapping (SPM). Results:PD-RBD(+ ) group had a significantly lower Mini-Mental State Examination (MMSE) or PD Sleep Scale (PDSS) score than PD-RBD(-) group ( z values: -3.12, -3.08, both P<0.01), and its contralateral striatal anterior-posterior gradient of the predominantly affected limbs was significantly lower than that in PD-RBD(-) group ( t=-2.73, P=0.009). SPM analysis showed that the glucose metabolism in the contralateral prefrontal lobe was higher than that in the PD-RBD (-) group ( t values: 3.11-3.57, all P<0.001). 18F-DTBZ SUR in the bilateral striatum, caudate nucleus, anterior putamen, posterior putamen, nucleus accumbens, substantia nigra were considerably lower in both groups compared to the healthy control group ( F values: 6.24-147.61, H values: 8.66-24.43, all P<0.05; post-hoc: LSD- t test, Bonferroni correction, all P<0.01). In the PD-RBD(-) group, contralateral striatal anterior-posterior gradient were negatively correlated with unified PD Rating Scale (UPDRS) score and modified Hoehn-Yahr (mH-Y) stage ( r=-0.35, P=0.048; rs=-0.39, P=0.026). The AUC for distinguishing PD-RBD(+ ) and PD-RBD(-) with a contralateral striatal anterior-posterior gradient was 0.706 (95% CI: 0.562-0.851, P=0.016), with the sensitivity and specificity of 59.4%(19/32) and 16/18, respectively. Conclusions:The decrease of contralateral striatal anterior-posterior gradient of VMAT2 is more obvious in patients with PD-RBD(+ ), and there are differences in brain metabolism between the two groups, suggesting that there may be different neuropathological changes and different pathophysiological mechanisms between PD patients with and without RBD. 18F-DTDZ PET/CT can provide imaging basis for the differential diagnosis of the disease subtypes.