Objective:To evaluate the potential causal relationship between tinnitus and the risk of Alzheimer's disease(AD)onset using the two-sample Mendelian randomization(MR)method and to clarify its mechanism of action,so as to provide new ideas for early warning of AD.Methods:Genome-wide association study(GWAS)database was used to search the keywords"tinnitus"and"Alzheimer"to obtain the related datasets of exposure factor tinnitus and outcome AD;the tinnitus datasets included ukb-d-4803_11,ukb-d-4803_12,ukb-d-4803_13,ukb-b-14254 and ukb-a-384;the AD datasets included ieu-b-5067,ieu-b-2,ieu-a-297,ebi-a-GCST90027158 and ebi-a-GCST002245.The single nucleotide polymorphisms(SNPs)closely and independently associated with tinnitus were screened as instrumental variables(IVs),and the SNPs associated with AD were used as outcomes.Inverse variance weighted(IVW)method was used to conduct MR analysis to evaluate its odds ratio(OR)value,95%confidence interval(CI)and P value;P<0.05 indicated significant causal relationship.Sensitivity detection used Cochran's Q test to detect the heterogeneity of IVs to evaluate its Q value,df value and P value;when IVW method P>0.05,it indicated no significant heterogeneity;MR-Egger intercept was used to detect horizontal pleiotropy;when the intercept was 0 or close to 0 and P>0.05,it indicated no significant horizontal pleiotropy;meanwhile,leave-one-out method was used for sensitivity analysis.Finally,visualization results were performed using forest plot,scatter plot,funnel plot and leave-one-out plot.Results:A total of 286 SNPs were screened as IVs.All instrumental variables satisfied F>10,suggesting no weak instrumental variable;after screening by PhenoScanner web tool,all SNPs were unrelated to confounding factors.When the tinnitus and AD datasets were ukb-d-4803 and ebi-a-GCST90027158 respectively,there was a significant positive correlation between tinnitus and the risk of AD onset(IVW:OR=1.842,95%CI:1.065-3.188,P=0.029);Cochran's Q test suggested no significant heterogeneity of IVs(Q=9.788,df=10.000,P=0.459);MR-Egger intercept indicated no horizontal pleiotropy(Egger intercept=-0.006,P=0.147);leave-one-out method showed stable results,and no SNP with significant influence on the results was detected.Conclusion:There is a positive causal relationship between tinnitus and the risk of AD onset.Neuroinflammation accompanied by persistent microglial activation to varying degrees may be the common pathogenesis of tinnitus and AD;in addition,depression may also act as an upstream factor to hyperactivate the hypothalamic-pituitary-adrenal(HPA)axis,leading to the progression of relationship between tinnitus and AD.

This paper explores the traditional Chinese medicine （TCM） pathomechanism， as well as pattern differentiation and treatments for sundowning syndrome in Alzheimer's disease through midnight-noon and ebb-flow theory. The syndrome's onset aligns with three critical time periods governed by three specific channels， including the bladder channel （3：00—5：00 pm， Shen period）， the kidney channel （5：00—7：00 pm， You period）， and the pericardium channel （7：00—9：00 pm， Xu period）. It is believed that when the symptoms occurred at the bladder channel （Shen period）， the pathomechanism manifested as yang qi floating upward and internal heat-blood stasis， and the treatment should supplement the kidney and essence， expelling stasis and discharging heat， as well as returning fire to its origin， using modified Taohe Chengqi Decoction （桃核承气汤） combined with Erzhi Pill （二至丸）. When the symptoms occurred at the kidney channel （You period）， the pathomechanism characterized by marrow sea deficiency and yin failing to anchor yang， so treatment follows the principles of supplementing the kidney and filling essence， as well as calming the mind and subduing yang， using modified Liuwei Dihuang Pill （六味地黄丸） combined with Erzhi Pill （二至丸）. When the symptoms occurred at the pericardium channel （Xu period）， the pathomechanism characterized as phlegm-turbidity clouding the mind and obstructing the brain， then the intervention need clear heat and dissolve phlegm， as well as open the orifices and calm the mind， using modified Wendan Decoction （温胆汤）. Additionally， comprehensive therapy combining oral administration of TCM decoctions with acupuncture， pressure pills on ear points， and point application therapy， which provides clinical insights for the treatment of this disease.

Objective To construct and validate an interpretable machine learning model integrating contrast-enhanced venous phase CT radiomics and clinical features for preoperative prediction of central lymph node metastasis(CLNM)of papillary thyroid carcinoma(PTC).Methods A case-control study was conducted on 243 histologically confirmed PTC patients.Among them,196 patients from the First Affiliated Hospital of Army Medical University were randomly allocated into a training set(n=137)and an internal validation set(n=59)at a 7:3 ratio,while the left 47 patients from No.958 Hospital of PLA Army were assigned into an external validation set.All participants completed standardized preoperative contrast-enhanced neck CT scanning.Quantitative radiomic features were systematically extracted from venous phase CT images through an open-source big data AI platform.Six machine learning classifiers,eXtreme Gradient Boosting(XGBoost),Support Vector Machine(SVM),Random Forest(RF),Logistic Regression(LR),k-Nearest Neighbors(KNN),and Decision Tree(DT)were implemented to construct clinical-radiomics integration models.The predictive performance was quantitatively assessed through receiver operating characteristic(ROC)curve analysis,with area under the curve(AUC)values calculated for training,internal validation,and external validation sets.Model interpretability was achieved using Shapley additive explanations(SHAP)framework,with particular focus on elucidating feature contributions in the best-performing model.Results The XGBoost model had an AUC value of 0.936(95%CI:0.895～0.976),0.832(95%CI:0.724～0.941),and 0.772(95%CI:0.632～0.912)in training,internal and external validation sets,respectively.SHAP analysis revealed age as the most influential clinical predictor,with younger patients showing higher CLNM risk(OR=0.968,P=0.042).Conclusion Our machine learning-based clinic-radiomic prediction model demonstrates satisfactory performance in predicting CLNM of PTC,providing valuable references for clinical decision-making.

Objective:To investigate the value of transabdominal bowel ultrasonography (TBUS) in evaluating the active phase of Crohn′s disease (CD) and its complications, and to compare the diagnostic efficacy of the international bowel ultrasound segmental activity score (IBUS-SAS) and the multidetector computed tomography enterography (MDCTE) score in the active phase.Methods:A totle of 103 CD patients who were admitted to the Nanjing Drum Tower Hospital from March 2021 to May 2023 were retrospectively analyzed. All patients underwent TBUS and MDCTE examinations. TBU parameters such as bowel wall thickness (BWT), color Doppler imaging signal (CDS), inflammatory fat (i-fat), and bowel wall stratification (BWS) were recorded. The patients were divided into the remission group and the active group based on the Crohn′s disease activity index. The latter group was further divided into the mild active group and the moderate-to-severe active group.Receiver operating characteristic curves (ROC) were plotted, and the diagnostic efficacy of TBUS parameters and two scoring systems in assessment of the active phase of CD was evaluated by sensitivity, specificity, area under the curve (AUC), and optimal cut-off values. Endoscopic or histopathological results were served as the gold standard for the diagnosis of intestinal strictures. The diagnostic efficacy of TBUS and MDCTE in CD complicated with intestinal stenosis were evaluated by ROC analysis. Spearman correlation analysis was performed to analyze the correlation between TBUS parameters, imaging scores, and clinical laboratory indicators such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and faecal calprotectin (FC).Results:In distinguishing the active phase and the remission phase of CD, BWT (a sensitivity of 85.7%, specificity of 90.9%, and cut-off value of 4.4 mm), CDS (a sensitivity of 95.7%, and specificity of 63.6%), IBUS-SAS (a sensitivity of 91.4%, specificity of 84.8%, and cut-off value of 23.8), and MDCTE score (a sensitivity of 77.1%, specificity of 75.8%, and cut-off value of 6.5) had high diagnostic efficacies. In distinguishing mild and moderate-severe active phases of CD, BWT, CDS and i-fat demonstrated high sensitivity (81.4%, 69.8% and 62.8%) and specificity (81.5%, 77.8% and 100.0%); IBUS-SAS (a sensitivity of 83.7%, specificity of 88.9%, and cut-off value of 40.0) and MDCTE score (a sensitivity of 83.7%, specificity of 85.2%, and cut-off value of8.5) had high diagnostic efficacy. In the diagnosis of CD complicated with intestinal stenosis, the AUC, sensitivity, specificity, and accuracy of MDCTE was 0.942, 94.0%, 94.3%, and 94.2%, respectively. The AUC, sensitivity, specificity, and accuracy of TBUS in the diagnosis of CD complicated with intestinal stenosis was 0.952, 96.0%, 94.3%, and 95.1%, respectively. The results of Spearman correlation analysis revealed that BWT, CDS, and i-fat have positively correlated with ESR, CRP, and FC ( r value: 0.252 to 0.451, all P<0.05). Conclusions:TBUS demonstrates good application value in evaluating the activity of CD and intestinal stenosis. IBUS-SAS has the potential application for precise assessment of CD activity.

Objective:To investigate the value of transabdominal bowel ultrasonography (TBUS) in evaluating the active phase of Crohn′s disease (CD) and its complications, and to compare the diagnostic efficacy of the international bowel ultrasound segmental activity score (IBUS-SAS) and the multidetector computed tomography enterography (MDCTE) score in the active phase.Methods:A totle of 103 CD patients who were admitted to the Nanjing Drum Tower Hospital from March 2021 to May 2023 were retrospectively analyzed. All patients underwent TBUS and MDCTE examinations. TBU parameters such as bowel wall thickness (BWT), color Doppler imaging signal (CDS), inflammatory fat (i-fat), and bowel wall stratification (BWS) were recorded. The patients were divided into the remission group and the active group based on the Crohn′s disease activity index. The latter group was further divided into the mild active group and the moderate-to-severe active group.Receiver operating characteristic curves (ROC) were plotted, and the diagnostic efficacy of TBUS parameters and two scoring systems in assessment of the active phase of CD was evaluated by sensitivity, specificity, area under the curve (AUC), and optimal cut-off values. Endoscopic or histopathological results were served as the gold standard for the diagnosis of intestinal strictures. The diagnostic efficacy of TBUS and MDCTE in CD complicated with intestinal stenosis were evaluated by ROC analysis. Spearman correlation analysis was performed to analyze the correlation between TBUS parameters, imaging scores, and clinical laboratory indicators such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and faecal calprotectin (FC).Results:In distinguishing the active phase and the remission phase of CD, BWT (a sensitivity of 85.7%, specificity of 90.9%, and cut-off value of 4.4 mm), CDS (a sensitivity of 95.7%, and specificity of 63.6%), IBUS-SAS (a sensitivity of 91.4%, specificity of 84.8%, and cut-off value of 23.8), and MDCTE score (a sensitivity of 77.1%, specificity of 75.8%, and cut-off value of 6.5) had high diagnostic efficacies. In distinguishing mild and moderate-severe active phases of CD, BWT, CDS and i-fat demonstrated high sensitivity (81.4%, 69.8% and 62.8%) and specificity (81.5%, 77.8% and 100.0%); IBUS-SAS (a sensitivity of 83.7%, specificity of 88.9%, and cut-off value of 40.0) and MDCTE score (a sensitivity of 83.7%, specificity of 85.2%, and cut-off value of8.5) had high diagnostic efficacy. In the diagnosis of CD complicated with intestinal stenosis, the AUC, sensitivity, specificity, and accuracy of MDCTE was 0.942, 94.0%, 94.3%, and 94.2%, respectively. The AUC, sensitivity, specificity, and accuracy of TBUS in the diagnosis of CD complicated with intestinal stenosis was 0.952, 96.0%, 94.3%, and 95.1%, respectively. The results of Spearman correlation analysis revealed that BWT, CDS, and i-fat have positively correlated with ESR, CRP, and FC ( r value: 0.252 to 0.451, all P<0.05). Conclusions:TBUS demonstrates good application value in evaluating the activity of CD and intestinal stenosis. IBUS-SAS has the potential application for precise assessment of CD activity.

Abstract: To investigate the status and influencing factors of tooth loss among the elderly population in China, so as to provide insights into early prevention of tooth loss. Methods: Based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS), data of the elderly people aged 65 years and older who participated in the survey in 2018 were collected, including demographic information, lifestyle, dietary habits, medical history, number of teeth remaining and self-assessment indicators. The status of tooth loss among the elderly were described based on the standard of 28 teeth, and factors affecting tooth loss were analyzed using a multivariable ordinal logistic regression model. Results: A total of 5 260 people was recruited, including 3 346 males (63.61%) and 1 914 females (36.39%). The median age was 78.00 (interquartile range, 18.00) years. The median number of teeth remaining was 12.00 (interquartile range, 23.00), and the median number of missing teeth was 16.00 (interquartile range, 23.00). Multivariable ordinal logistic regression analysis showed that the elderly who were female (OR=1.270, 95%CI: 1.098-1.470), had advanced age (OR=1.090, 95%CI: 1.083-1.098), lived in rural areas (OR=1.369, 95%CI: 1.165-1.610) and urban areas (OR=1.208, 95%CI: 1.027-1.422), smoked (past, OR=1.471, 95%CI: 1.240-1.746; always, OR=1.545, 95%CI: 1.300-1.838) and brushed teeth less than once a day (OR=1.791, 95%CI: 1.488-2.160) had more missing teeth; while the elderly who had high levels of education (junior high school, OR=0.819, 95%CI: 0.681-0.972; high school, OR=0.626, 95%CI: 0.507-0.771; college and above, OR=0.468, 95%CI: 0.334-0.657), kept physical exercise (OR=0.840, 95%CI: 0.736-0.958) and were overweight/obese (OR=0.868, 95%CI: 0.769-0.980) had less missing teeth. Conclusion Gender, age, residence, educational level, smoking, physical exercise, teeth brushing frequency and overweight/obese are the influencing factors for tooth loss among the elderly in China.

Objective To investigate the correlation between interleukin 1β gene-511C/T polymorphism of and essential hypertension in the Yi ethnic group of Yunnan province.Methods-511C/T polymorphism of interleukin 1β gene was detected by PCR-RFLP in 85 Yi patients with essential hypertension(EH group)and 106 Yi healthy people(control group)in Shuanghe Township,Jinning County,Yunnan Province.Genotype and allele frequencies were analyzed by SPSS 27.0 software,and association analysis was performed.Results The frequency distribution of CC,CT and TT genotypes at the mutation site 511 of the IL-1βgene in EH group was 18.82%,44.71%and 36.47%,respectively,and it was 5.66%,26.42%and 67.92%in the control group.The difference in genotype frequency between the two groups was statistically significant(P＜0.05).The allele frequency of C and T in EH group was 41.18%and 58.82%,respectively,and the allele frequency of C and T in control group was 18.87%and 81.13%.The frequency difference of alleles between the two groups was statistically significant(P＜0.05).Both genotype frequency and allele frequency found in males and females had statistical differences(P＜0.05).Conclusions The distribution of IL-1β gene-511C/T polymorphism is related to the incident of essential hyper-tension among the Yi ethnic group Yunnan Province,and is the susceptibility gene of the Yi ethnic group to essen-tial hypertension.

Objective:To investigate the efficacy and feasibility of mechanical thrombectomy (MT) via carotid artery salvage puncture in patients with acute anterior circulation large vessel occlusive stroke. Methods:A retrospective analysis was performed. Eight patients with acute anterior circulation large vessel occlusive stroke underwent MT via carotid artery salvage puncture in Departments of Neurology, First People's Hospital of Xianyang, Xi'an Ninth Hospital, Xi'an Daxing Hospital and XD Group Hospital from June 2021 to September 2023 were enrolled. Occlusion location, time from onset to femoral artery puncture, causes of carotid artery salvage puncture, time from femoral artery puncture to carotid artery salvage puncture, time from successful carotid artery puncture to vascular recanalization, modified thrombolysis in cerebral infarction (mTICI) score immediately after MT, and scores of National Institutes of Health Stroke Scale (NIHSS) 24 h after MT and modified Rankin Scale (mRS) 90 d after MT were analyzed. Results:Of the 8 patients, 7 had M1 segment occlusion and 1 patient had M2 segment occlusion. Direct thrombectomy was not possible resulting from type III aortic arch in 3 patients, aortic arch replacement in 1 patient, right common carotid artery twisting angle in 1 patient, left common carotid artery twisting angle in 2 patients, and bilateral femoral artery occlusion in 1 patient. All 8 patients had successful carotid artery puncture under local anesthesia, including 7 with mTICI 3 and 1 patient with mTICI 2b. Average time from successful carotid artery puncture to vascular recanalization was about 35 min, ranged 10-90 min. All patients had decreased NIHSS score 24 h after MT compared with before MT, and no complications such as hematoma or airway compression occurred in carotid artery puncture site. Six patients had mRS scores of 0-2 and 2 had scores of 6 (death cause: pulmonary infection) 90 d after surgery.Conclusion:For patients with patients with acute anterior circulation large vessel occlusive stroke, MT via carotid artery salvage puncture is a safe and feasible method in cases of difficulty in establishing thrombectomy route via femoral artery such as type III aortic arch, common carotid artery twisting angle, abdominal aorta occlusion.

Objective:To reveal the effect of β-sitosterol on cerebral ischemia-reperfusion injury (CIRI) in rats and whether its mechanism is related to endoplasmic reticulum stress (ERS).Methods:Fifty-three CIRI rats (CIRI models established by modified Longa method) were randomly divided into model group ( n=14), β-sitosterol low-dose group ( n=13), β-sitosterol medium-dose group ( n=13) and β-sitosterol high-dose group ( n=13); 12 rats underwent the same operation without blocking the middle cerebral artery were selected as sham-operated group. Rats in the sham-operated group and model group were given intragastric administration of 1 mL 5 g/L sodium carboxymethyl cellulose daily. Rats in the β-sitosterol low-dose group, β-sitosterol medium-dose group and β-sitosterol high-dose group were given intragastric administration of 1 mL β-sitosterol at 10, 20 and 40 mg/kg/d (dissolved in 5 g/L sodium carboxymethyl cellulose), respectively, for 14 consecutive d. Neurological function was evaluated according to Zea Longa 5 method. Rats were sacrificed and brain tissues were collected. Volume of cerebral infarction was measured by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Brain injury and neuronal apoptosis were evaluated by HE staining, Nissl staining and TUNEL. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) contents were detected by water-soluble tetrazolium 1 (WST-1) method, colorimetric method or thiobarbituric acid (TBA) method, respectively. The mRNA and protein expression levels of protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme-1 (IRE-1), activated transcription factor-6 (ATF-6), glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and Caspase-12 in the brain tissues were detected by qRT-PCR or Western blotting. Results:Compared with the sham-operated group, the model group had significantly increased neurological function score, cerebral infarction volume and TUNEL positive rate, decreased SOD and GSH-Px content, increased MDA content, and increased mRNA and protein expressions of PERK, IRE-1, ATF-6, GRP78, CHOP and Caspase-12 ( P<0.05). Compared with the model group, the β-sitosterol low-dose group, β-sitosterol medium-dose group and β-sitosterol high-dose group had significantly decreased neurological function score, cerebral infarction volume, and TUNEL positive rate, increased SOD and GSH-Px content, and decreased MDA content ( P<0.05); the β-sitosterol low-dose group, β-sitosterol medium-dose group and β-sitosterol high-dose group had significantly decreased mRNA and protein PERK expressions (mRNA: 2.17±0.17, 1.79±0.07 and 1.33±0.07; protein: 5.11±0.52, 2.91±0.26 and 1.98±0.17), IRE-1 expressions (mRNA: 1.75±0.18, 1.65±0.08 and 1.32±0.08; protein: 5.00±0.31, 4.05±0.27 and 1.98±0.14), ATF-6 expressions (mRNA: 2.24±0.12, 1.77±0.14 and 1.37±0.13; protein: 4.93±0.45, 4.04±0.30 and 3.10±0.20), GRP78 expressions (mRNA: 2.67±0.16, 2.11±0.16 and 1.69±0.11; protein: 5.02±0.38, 2.97±0.26 and 2.05±0.22), CHOP expressions (mRNA: 2.01±0.16, 1.70±0.19 and 1.40±0.10; protein: 4.92±0.39, 4.02±0.27 and 3.08±0.22) and Caspase-12 expressions (mRNA: 1.85±0.09, 1.61±0.09 and 1.30±0.09; protein: 3.03±0.20, 2.19±0.11 and 1.82±0.11) compared with the model group (mRNA: 2.99±0.28, 2.27±0.12, 2.57±0.21, 3.46±0.20, 2.50±0.23 and 2.35±0.16; protein: 6.98±0.48, 6.03±0.58, 5.98±0.63, 7.10±0.45, 6.00±0.53 and 5.02±0.43, P<0.05). Conclusion:β-sitosterol attenuates CIRI in rats, whose mechanism may be related to inhibition of ERS signal pathway.

Objective To explore the application of olfactory assessment and substantia nigra ultrasonography in early diagnosis of Parkinson's disease (PD).Methods Thirty PD patients,admitted to our hospital from March 2015 to March 2017,were served as PD group and 30 healthy subjects were served as control group.Olfactory assessment tool Sniffm Sticks-1 6 and substantia nigra ultrasonography were performed;the sensitivity,specificity and positive predictive value of olfactory assessment,transcranial ultrasonography,and combined measurement for diagnosis of PD were calculated,respectively.Correlations of results of olfactory assessment,transcranial ultrasonography with age,gender,course of disease,and Unified Parkinson's Disease Rating Scale Ⅲ (UPDRS Ⅲ) scores were analyzed.Results There were 25 PD patients with olfactory test (SS-16) scores≤ 10 and 22 control subjects;the olfactory test (SS-16) scores in PD patients were 7.83±2.23,which were significantly lower as compared with those in control subjects (12.03±1.96,P＜0.05);the incidence of olfactory dysfunction in PD group was 83.33％ and that in control group was 26.67％,with statistical significance (P＜0.05).There were 23 PD patients with area of substantia nigra hyperecho≥ 0.20 cm2 and 26 control subjects;area of substantia nigra hyperecho was (0.22±0.06) cm2 in PD group,which was signfciantly increased as compared with control group ([0.11 ±0.07] cm2,P＜0.05);the incidence of pathological substantia nigra hyperecho in PD group was 76.67％ and that in control group was 13.33％,with significant difference (P＜0.05).The sensitivity of olfactory assessment,transcranial ultrasonography,and combined measurement for diagnosis of PD was 83.33％,76.67％,86.67％,indicating that combined measurement had significantly higher sensitivity that the other two method (P＜0.05).SS-16 scores and area of substantia nigra hyperecho were unrelated with gender,age,duration and UPDRS Ⅲ scores (P＞0.05).Conclusion Combination of olfactory test and substantia nigra hyperecho can improve the diagnosis sensitivity of PD.