Objective To investigate the alterations of cerebral blood flow(CBF)in type 2 diabetic mellitus(T2DM) patients without cognitive impairment by using arterial spin labeling(ASL)technique.Methods A total of 23 T2DM patients without cognitive impairment and 23 healthy controls(HC)matched by age,sex,and education attainment were recruited.Their clinical data were collected,and neuropsychological tests and cerebral magnetic resonance imaging were performed.Then,the outcomes of clinical features,neuropsychological tests,and global and regional CBF were compared between the two groups.The significant regional zCBF(z-transformed relative CBF)values were extracted and correlated with clinical data and neuropsychological scores in T2DM patients,controlling age,sex,and education.Results No significant difference was found in whole brain CBF between the two groups(P=0.155),while significantly higher CBF was identified in the left superior temporal gyrus and left insula in the T2DM group(Gaussian random field correction,initial threshold P < 0.001,cluster level P < 0.05).No correlation was observed between the significant regional zCBF values and the clinical data or the neuropsychological scores in T2DM patients(all P>0.05).Conclusion Alterations in cerebral hemodynamics may precede cognitive function changes in T2DM,suggesting that the ASL technique is promising for early monitoring of cerebral hemodynamic changes associated with cognitive impairment in patients with T2DM.
Humans ; Diabetes Mellitus, Type 2/physiopathology* ; Cerebrovascular Circulation ; Middle Aged ; Male ; Female ; Magnetic Resonance Imaging ; Case-Control Studies ; Cognitive Dysfunction ; Neuropsychological Tests ; Aged

Objective To explore the difference in efficacy of metoprolol versus ivabradine in the treatment of postural orthostatic tachycardia syndrome(POTS)in the elderly after COVID-19 infection.Methods A total of 110 patients diagnosed with POTS at our department from Decem-ber 1,2022 to January 31,2023 were included.According to their drug regimen,they were divided into metoprolol group(62 patients)and ivabradine group(48 patients).On the 28th day of out-patient follow-up,the resting heart rate,heart rate of 10 min of standing,symptom disappearance rate,hospitalization rate,and mortality rate were compared between the two groups.Results On the 28th day of treatment,the resting heart rate and postural heart rate for 10 min were decreased in both groups when compared with the levels at initial diagnosis(P＜0.01).And there were no significant differences in the two types of heart rate between the two groups on the 28th day(71.0±7.0 vs 72.1±7.0,P=0.401;76.5±7.2 vs 77.4±7.6,P=0.573).No obvious differences were observed between the two groups in symptom disappearance rate,hospitalization rate,or mortality rate(88.7％vs 89.6％,3.2％vs2.1％,0％vs 0％,P＞0.05).Conclusion Metoprolol and ivabradine can effectively treat POTS in the elderly patients after COVID-19 infection.

Objective To mine and analyze the adverse event data of polatuzumab vedotin(Pola)and fam-trastuzumab deruxtecan-nxki(T-Dxd),so as to provide reference for clinical medication safety.Methods The adverse events reported from January 1,2004 to June 7,2023 were extracted based on openFDA database.The suspicious risk signals were screened by the Open Vigil 2.1 data platform and ranked by signal strength and frequency of occurrence;then ADEs were classified by reference to the MedDRA 26.0.Results A total of 7 164 and 22 870 ADE reports related to Pola and T-Dxd were obtained,and 104 and 95 suspicious ADE signals were detected,respectively.According to the signal intensity,cytomegalovirus enterocolitis(ROR=416.94)for Pola and interstitial lung disease[reporting odds ratio(ROR)=82.55]for T-Dxd ranked first,both of which were recorded in the drug instructions.According to the frequency of occurrence,the two drugs were most frequently associated with death(n=111)and nausea(n=285),respectively.The risk of Pola was associated with 12 systems/organs,of which 26 risk signals were not documented in the drug instruction,and the risk of T-Dxd was associated with 13 systems/organs,of which 18 risk signals were not documented in the drug instruction.Conclusion By tapping the ADE after real-world administration of Pola and T-Dxd,physicians are prompted to pay attention to the risk of adverse reactions in clinical use and actively take preventive and therapeutic measures to ensure the safety of patients'medication.

Objective To investigate the early diagnostic value of serum double cortin-like kinase 1(DCLK1),latent transforming growth factor binding protein 2(LTBP2)combined with transvaginal real-time shear wave elastography(SWE)for cervical cancer.Methods A total of 155 patients with cervical lesions treated in our hospital from August 2021 to December 2022 were selected as the research objects.Seventy-five patients with cervical cancer(the cervical cancer group)and 80 patients with cervical intraepithelial neoplasia(the CIN group)were diagnosed by surgical pathology,another 80 volunteers without cervical related diseases who participated in physical examinations at our hospital during the same period were selected as the control group.All subjects of each groups underwent serum DCLK1 and LTBP2 levels detection and transvaginal SWE examination.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum DCLK1 and LTBP2 for cervical cancer;the diagnostic value of serum DCLK1 and LTBP2 combined with transvaginal SWE for cervical cancer was analyzed by fourfold table analysis.Results The serum levels of DCLK1 and LTBP2 of patients in the cervical cancer group were obviously higher than those in the CIN group and the control group(P<0.05).Compared with before surgery,the serum levels of DCLK1 and LTBP2 1,3,and 6 months after surgery in cervical cancer patients gradually decreased,and there were statistical differences in pairwise comparisons at each time point(P<0.05).The area under the curve of serum DCLK1 and LTBP2 for diagnosing cervical cancer were 0.868 and 0.754,respectively,with sensitivity of 86.67% and 78.67%,specificity of 81.25% and 60.00%,and optimal cutoff values of 1.49 ng/mL and 19.02 μg/mL.The maximum and average elastic modulus of lesion tissue in the cervical cancer group were obviously higher than those in the CIN group(P<0.05).The positive rates of serum DCLK1,serum LTBP2,and transvaginal SWE in the diagnosis of cervical cance were 86.67%,78.67%,and 82.67%,respectively,which were consistent with the gold standard(Kappa=0.624,0.501,0.673,P<0.001),and the positive rate of the combination of them in the diagnosis of cervical cancer was 97.33%,which was highly consistent with the gold standard(Kappa=0.846,P<0.001).The sensitivity and accuracy of the three combined diagnosis were obviously higher than those of the single indicator diagnosis of serum DCLK1,LTBP2,and transvaginal SWE,the specificity of the three combined diagnosis was obviously higher than that of the single indicator diagnosis of serum DCLK1 and LTBP2,the misdiagnosis rate of the three combined diagnosis was obviously lower than that of the single indicator diagnosis of serum DCLK1 and LTBP2,and the differences were all statistically significant(P<0.05).Conclusion Serum DCLK1 and LTBP2 combined with transvaginal SWE has high application value in the diagnosis of cervical cancer,which can further improve the sensitivity and accuracy of diagnosis,and reduce the misdiagnosis rate.

Disharmony between nutritive qi(ying)and defensive qi(wei)is the core pathogenesis of insomnia.The normal function of ying-wei in the generation,dispersion,divergence and aggregation is the precondition for the realization of the coordination between ying and wei.The disordered function of ying-wei in the generation,dispersion,divergence and aggregation will cause the disharmony between ying and wei,and then the insomnia occurs.For the treatment of insomnia caused by the disordered function of ying-wei in the generation,Guizhi Decoction associated prescriptions are used for strengthening middle energizer and nourishing ying and wei.For the treatment of insomnia caused by the disordered function of ying-wei in the dispersion,Mahuang Decoction associated prescriptions are used to relieve the exterior and eliminate the pathogen for insomnia patients with the manifestations of the attack of exopathogens,and Xiao Chaihu Decoction associated prescriptions are used to dredge the triple energizer for insomnia patients with the dysfunction of the triple energizer.For the treatment of insomnia caused by the disordered function of ying-wei in the divergence,Rhei Radix et Rhizoma associated bitter-cold prescriptions are used to purge the interior heat for insomnia patients with abundant interior heat syndrome,Gypsum Fibrosum associated pungent-cold prescriptions are used to release muscles and clear heat for insomnia patients with the interior heat complicated by exterior syndrome,Natrii Sulfas Exsiccatus associated salty-cold prescriptions are used to clear heat,moisten dryness and dissipate the masses for insomnia patients with interior heat complicated by dryness syndrome,sour-cold medicines are used to clear heat and remove retained water,supplement deficiency and relieve exterior for insomnia patients with interior heat complicated by water-retention syndrome,deficiency syndrome and exterior syndrome,and Ophiopogonis Radix associated prescriptions and Lillli Bulbus associated prescriptions are used to clear heat and nourish ying for insomnia patients with the consumption of ying and yin.For the treatment of insomnia caused by the disordered function of ying-wei in the aggregation,the compatibility of Poria and Cinnamomi Ramulus is used for warming yang and resolving fluid retention in patients with fluid retention,Taohong Siwu Decoction associated prescriptions are used to activate blood and remove stasis in patients with predominance of blood stasis syndrome,the compatibility of Poria and Paeoniae Radix Alba are used to treat retained water and blood stasis in patients with water-blood co-morbidity.Treating insomnia caused by disharmony between ying and wei from the perspective of the function of ying-wei in the generation,dispersion,divergence and aggregation is aimed at the core pathogenesis of insomnia,which makes the treatment easy to be carried out,and can provide reference for clinical differentiation and treatment of insomnia.

Objective:To compare the effects of different reference brain regions on the semi-quantitative SUV ratio (SUVR) of 18F-Florzolotau PET images of Alzheimer′s disease (AD). Methods:The 18F-Florzolotau PET images of 28 (13 males, 15 females, age (57.3±9.5) years) normal controls (NC), 19 patients (4 males, 15 females, age (73.3±7.3) years) with β-amyloid (Aβ)-positive mild cognitive impairment (MCI) and 40 patients (19 males, 21 females, age (61.9±9.1) years) with AD were collected from Huashan Hospital, Fudan University between November 2018 and July 2020. Six semi-quantitative reference brain regions were defined, including whole cerebellum (WC), cerebellar gray matter (GM), cerebellar white matter (WM), parametric estimation of reference signal intensity (PERSI), WC after partial volume correction (WC_pvc), cerebellar GM after partial volume correction (GM_pvc). SUVR was calculated for 14 ROIs, which included the whole brain defined by the automated anatomical labeling (AAL) template, fusiform, inferior temporal, lingual, middle temporal, occipital, parahippocampal, parietal, posterior cingulate, precuneus defined by the AAL template, and Meta ROI composed of the above brain regions, and braak_Ⅰ-Ⅱ, braak_Ⅲ-Ⅳ, braak_Ⅴ-Ⅵ defined by the Desikan Killiany template. AUC was used to evaluate the classification ability of SUVR, and the correlation between SUVR and clinical scale scores were assessed by Spearman rank correlation analysis. Results:The SUVRs of most brain regions showed a steady upward trend in the AD disease spectrum. In the classification task of NC and MCI, the overall performance of SUVR based on WC_pvc was relatively optimal (AUCs: 0.975-1.000). In the classification task of NC and AD, SUVRs of 10 ROIs based on the WC_pvc method showed the relatively best performance (AUCs: 0.976-1.000). The correlation between SUVR of fusiform based on cerebellar WM and mini-mental state examination (MMSE) score was the strongest ( rs=-0.72, P<0.001), and the SUVR of precuneus based on WC_pvc showed the strongest correlation with clinical dementia rating (CDR) score ( rs=0.78, P<0.001). Conclusion:The SUVR based on WC_pvc method performs well in classification and correlation tasks, and is recommended to be used in semi-quantification of 18F-Florzolotau PET images of AD.

Objective:A voxel-level quantification method based on the tau IQ algorithm and Braak staging, excluding β-amyloid (Aβ) imaging, was developed to achieve specific tau quantification. Methods:This cross-sectional study included 92 subjects (35 males, 57 females; age (62.9±10.4) years) from the Nuclear Medicine/PET Center of Huashan Hospital, Fudan University between November 2018 and July 2020. The cohort comprised 28 cognitively normal (CN) individuals, 20 patients with mild cognitive impairment (MCI), and 44 patients with Alzheimer′s disease (AD). All participants underwent 18F-florzolotau PET imaging, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) scoring. A longitudinal tau dataset was constructed based on Braak staging. Voxel-level logistic regression fitting provided a baseline matrix, decomposed via least squares to yield the Tau load coefficient. One-way analysis of variance (with post hoc Tukey) was used to compare Tau load and SUV ratio (SUVR) among groups. ROC curve analysis was used to evaluate classification between CN, MCI and AD. Spearman rank correlation was used to assess the relationships between Tau load, SUVR, and MMSE scores or CDR scores. Results:The Tau load in the CN group was close to 0 and significantly lower than that in the MCI and AD groups ( F=55.03, P<0.001; post hoc tests all P<0.001). Significant differences were also observed in the SUVR across all ROIs ( F values: 36.46-55.38, all P<0.001). Compared to SUVR, Tau load demonstrated greater intergroup differences. In ROC curve analyses between each pair of CN, MCI, and AD groups, Tau load consistently achieved the highest AUC (0.754-1.000). Both Tau load and SUVR for each ROI were negatively correlated with MMSE scores ( rs values: from -0.698 to -0.583, all P<0.05) and positively correlated with CDR scores ( rs values: 0.648-0.783, all P<0.05), with Tau load showing the highest absolute correlation coefficients. Conclusion:Compared to the traditional semi-quantitative SUVR method, the Braak-tau IQ algorithm does not require a specific reference brain region to achieve specific tau quantification.

Objective To investigate the long-term effect of frailty on heart failure with reduced ejection fraction(HFrEF)in elderly patients.Methods A retrospective analysis was conducted on 245 HFrEF patients aged ≥75 years admitted to our hospital from October 2017 to October 2020 due to acute exacerbation of chronic heart failure(HF).Based on their clinical frailty scale(CFS)score,they were divided into frailty group(1-4,135 cases)and non-frailty group(5-9,110 cases).Their general clinical data,clinical medication,and prognosis were compared between the two groups,and the influencing factors for frailty and death were analyzed.Results Faster heart rate,higher NT-proBNP level,and larger proportions of male,diabetes,coronary heart disease,≥5 chronic diseases,LVEF ≤35％,anemia and increased troponin I level,while lower BMI,eGFR and score of activity of daily living scale were observed in the frailty group than the non-frailty group(P＜0.05,P＜0.01).The frail group had significantly lower utilization rates of angiotensin converting enzyme inhibitors(ACEI),angiotensin receptor blockers(ARB),angiotensin receptor enkephalin inhibitors(ARNI)β receptor blockers,and sodium-glucose cotransporter 2 inhibitors than the non-frailty group(P＜0.01).Additionally,the frailty group exhibited a higher incidence of emergency room visits/readmissions within 3 months and 2-year mortality than the non-frailty group(P＜0.05,P＜0.01).Binary logistic regression analysis revealed that ≥5 chronic diseases,LVEF ≤ 35％,BMI,and GFR were independent risk factors for frailty(OR=0.167,95％CI:0.064-0.453,P=0.000;OR=0.306,95％CI:0.160-0.586,P=0.000;OR=0.868,95％CI:0.786-0.958,P=0.005;OR=0.966,95％CI:0.943-0.991,P=0.007),while ≥5 chronic disea-ses and frailty were independent risk factors for death in HF patients(P＜0.05).Conclusion The incidence of frailty is high in elderly HF patients with HFrEF.They have poor compliance to guideline directed drug therapy(GDMT).Frailty is an independent risk factor for long-term mor-tality in the patients.

Objective To investigate the efficacy of utilizing Kaneka dual lumen microcatheter in combination with anchored balloon in treatment of bifurcation lesions in elderly patients with ra-dial artery 6 F catheter.Methods A retrospective analysis was performed on 168 patients(≥60 years)receiving bifurcation treatment with a 6 F catheter via the radial artery at the Heart Center of our hospital from January 2020 to January 2023.According to application of dual lumen micro-catheters and anchoring balloon technology or not,they were assigned into an anchoring group(81 cases old)and a control group(87 cases).A comparison was made between the two groups in terms of features of coronary artery disease,operation procedure,and MACE.Multivariate logistic regression analysis was employed.Results Lower incidence of dissection,shorter operation time,less X-ray exposure dose,and decreased contrast agent dosage were observed in the anchoring group when compared with the control group(P＜0.05,P＜0.01).There was no statistical differ-ence in the MACE incidence between the two groups(4.9％vs 8.0％,P＞0.05).The side branch dissection and final TIMI grade＜3 of side branch flow were independent risk factors for postop-erative MACE in elderly patients with bifurcation lesions after surgery(P＜0.05,P＜0.01).Conclusion Kaneka dual lumen microcatheter combined with anchored balloon technology via radial artery 6 F catheter has the advantages in effectively shorting operation time,minimizing X-ray exposure,reducing contrast agent usage,and diminishing the incidence of side branch dis-section in treatment of bifurcation lesions in elderly patients undergoing surgical treatment.

Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR-FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.