Background: and Purpose Although amyloid positron emission tomography (PET) might provide a molecular diagnosis for cerebral amyloid angiopathy (CAA), it does not have sufficient specificity for this condition relative to incipient Alzheimer’s disease (AD). To identify a regional amyloid uptake pattern specific to CAA, we attempted to reduce this overlap by selecting “pure CAA” (i.e., fulfilling the criteria for probable CAA but without tau PET AD signature) and “pure AD” (i.e., positive amyloid PET and presence of tau PET AD signature, but without lobar hemorrhagic lesions). We hypothesized that occipital tracer uptake relative to the whole cortex (WC) would be higher in patients with pure CAA and may serve as a specific diagnostic marker. Methods: Patients who fulfilled these criteria were identified. In addition to the occipital region of interest (ROI), we assessed the frontal and posterior cingulate cortex (PCC) ROIs that are sensitive to AD. Amyloid PET uptake was expressed as the absolute standardized uptake value ratio (SUVR) and ROI/WC ratio. The diagnostic utility of amyloid PET was assessed using the Youden index cutoff. Results: Eighteen patients with AD and 42 patients with CAAs of comparable age were eligible. The occipital/WC was significantly higher in CAA than AD (1.02 [0.97–1.06] vs. 0.95 [0.87–1.01], P=0.001), with an area under curve of 0.762 (95% confidence interval [CI] 0.635–0.889) and a specificity of 72.2% (95% CI 46.5–90.3) at Youden cutoff (0.98). The occipital lobe, frontal lobe, PCC and WC SUVRs were significantly lower in CAA than in AD. The frontal/WC and PCC/WC ratios did not differ significantly between the groups. Conclusion Using stringent patient selection to minimize between-condition overlap, this study demonstrated the specificity of higher relative occipital amyloid uptake in CAA than in AD.

Background: and Purpose Although amyloid positron emission tomography (PET) might provide a molecular diagnosis for cerebral amyloid angiopathy (CAA), it does not have sufficient specificity for this condition relative to incipient Alzheimer’s disease (AD). To identify a regional amyloid uptake pattern specific to CAA, we attempted to reduce this overlap by selecting “pure CAA” (i.e., fulfilling the criteria for probable CAA but without tau PET AD signature) and “pure AD” (i.e., positive amyloid PET and presence of tau PET AD signature, but without lobar hemorrhagic lesions). We hypothesized that occipital tracer uptake relative to the whole cortex (WC) would be higher in patients with pure CAA and may serve as a specific diagnostic marker. Methods: Patients who fulfilled these criteria were identified. In addition to the occipital region of interest (ROI), we assessed the frontal and posterior cingulate cortex (PCC) ROIs that are sensitive to AD. Amyloid PET uptake was expressed as the absolute standardized uptake value ratio (SUVR) and ROI/WC ratio. The diagnostic utility of amyloid PET was assessed using the Youden index cutoff. Results: Eighteen patients with AD and 42 patients with CAAs of comparable age were eligible. The occipital/WC was significantly higher in CAA than AD (1.02 [0.97–1.06] vs. 0.95 [0.87–1.01], P=0.001), with an area under curve of 0.762 (95% confidence interval [CI] 0.635–0.889) and a specificity of 72.2% (95% CI 46.5–90.3) at Youden cutoff (0.98). The occipital lobe, frontal lobe, PCC and WC SUVRs were significantly lower in CAA than in AD. The frontal/WC and PCC/WC ratios did not differ significantly between the groups. Conclusion Using stringent patient selection to minimize between-condition overlap, this study demonstrated the specificity of higher relative occipital amyloid uptake in CAA than in AD.

Background: and Purpose Although amyloid positron emission tomography (PET) might provide a molecular diagnosis for cerebral amyloid angiopathy (CAA), it does not have sufficient specificity for this condition relative to incipient Alzheimer’s disease (AD). To identify a regional amyloid uptake pattern specific to CAA, we attempted to reduce this overlap by selecting “pure CAA” (i.e., fulfilling the criteria for probable CAA but without tau PET AD signature) and “pure AD” (i.e., positive amyloid PET and presence of tau PET AD signature, but without lobar hemorrhagic lesions). We hypothesized that occipital tracer uptake relative to the whole cortex (WC) would be higher in patients with pure CAA and may serve as a specific diagnostic marker. Methods: Patients who fulfilled these criteria were identified. In addition to the occipital region of interest (ROI), we assessed the frontal and posterior cingulate cortex (PCC) ROIs that are sensitive to AD. Amyloid PET uptake was expressed as the absolute standardized uptake value ratio (SUVR) and ROI/WC ratio. The diagnostic utility of amyloid PET was assessed using the Youden index cutoff. Results: Eighteen patients with AD and 42 patients with CAAs of comparable age were eligible. The occipital/WC was significantly higher in CAA than AD (1.02 [0.97–1.06] vs. 0.95 [0.87–1.01], P=0.001), with an area under curve of 0.762 (95% confidence interval [CI] 0.635–0.889) and a specificity of 72.2% (95% CI 46.5–90.3) at Youden cutoff (0.98). The occipital lobe, frontal lobe, PCC and WC SUVRs were significantly lower in CAA than in AD. The frontal/WC and PCC/WC ratios did not differ significantly between the groups. Conclusion Using stringent patient selection to minimize between-condition overlap, this study demonstrated the specificity of higher relative occipital amyloid uptake in CAA than in AD.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals ; Drugs, Chinese Herbal/chemistry* ; Depression/genetics* ; Mice ; Network Pharmacology ; Metabolomics ; Male ; Disease Models, Animal ; Humans ; Protein Interaction Maps/drug effects* ; Antidepressive Agents

Based on the α7 nicotinic acetylcholine receptor(α7nAChR), this study examined how tetrahydropalmatine(THP) affected BV2 microglia exposed to lipopolysaccharide(LPS), aiming to clarify the possible mechanism underlying the anti-depression effect of THP from the perspectives of preventing inflammation and regulating polarization. First, after molecular docking and determination of the content of Corydalis saxicola Bunting total alkaloids, THP was initially identified as a possible anti-depression component. The BV2 microglia model of inflammation was established with LPS. BV2 microglia were allocated into a normal group, a model group, low-and high-dose(20 and 40 μmol·L~(-1), respectively) THP groups, and a THP(20 μmol·L~(-1))+α7nAChR-specific antagonist MLA(1 μmol·L~(-1)) group. The CCK-8 assay was used to screen the safe concentration of THP. A light microscope was used to examine the morphology of the cells. Western blot and immunofluorescence were used to determine the expression of α7nAChR. qRT-PCR was performed to determine the mRNA levels of inducible nitric oxide synthase(iNOS), cluster of differentiation 86(CD86), suppressor of cytokine signaling 3(SOCS3), arginase-1(Arg-1), cluster of differentiation 206(CD206), tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. The experimental results showed that THP at concentrations of 40 μmol·L~(-1) and below had no effect on BV2 microglia. THP improved the morphology of BV2 microglia, significantly up-regulated the protein level of α7nAChR, significantly down-regulated the mRNA levels of iNOS, CD86, SOCS3, TNF-α, IL-6, and IL-1β, significantly up-regulated the mRNA levels of Arg-1 and CD206, and dramatically lowered the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. However, the antagonist MLA abolished the above-mentioned ameliorative effects of THP on LPS-treated BV2 microglia. As demonstrated by the aforementioned findings, THP protected LPS-treated BV2 microglia by regulating the M1/M2 polarization and preventing inflammation, which might be connected to the regulation of α7nAChR on BV2 microglia.
Berberine Alkaloids/chemistry* ; alpha7 Nicotinic Acetylcholine Receptor/chemistry* ; Microglia/metabolism* ; Mice ; Animals ; Cell Line ; Corydalis/chemistry* ; Humans ; Molecular Docking Simulation ; Inflammation/drug therapy* ; Nitric Oxide Synthase Type II/immunology* ; Tumor Necrosis Factor-alpha/immunology*

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective: We aimed to investigate whether 2-[ 18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[ 18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. Materials and Methods: This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[ 18F]FDG PET/CT for endoscopy-detected ampullary tumors 5–87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. Results: The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in earlyphase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13–36.18;P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80–13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41–19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00–14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16–21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874–0.956] vs. 0.815 [0.732–0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816–0.967) in candidates for endoscopic papillectomy. Conclusion Adding 2-[ 18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

Objective To understand the current situation and explore the influencing factors of delay in seeking medical treatment for common symptoms of residents in the rural areas of Sichuan province. Methods In July 2019,multi-stage random sampling was carried out in Zigong city,Sichuan province,and the data were collected by face-to-face questionnaire interview.The residents who had lived at hometown for more than half a year in the past year and had seen a doctor in the most recent month were surveyed.Logistic regression was adopted to predict the influencing factors of delay in seeking medical treatment. Results A total of 342 subjects were enrolled,and the incidence of delay in seeking medical treatment was 13.45%(46/342).Compared with the young and middle-aged(<65 years)people,the elderly(≥65 years)people were more likely to have delay in seeking medical treatment (OR=2.187,95%CI=1.074-4.457,P=0.031).The rural residents who gave higher score of the overall quality of township health centers were less likely to have delay in seeking medical treatment (OR=0.854,95%CI=0.735-0.992,P=0.039). Conclusions The occurrence of delay in seeking medical treatment for common symptoms of rural residents in Sichuan province is low.Age and the overall quality evaluation of township health centers affect the occurrence of delay in medical treatment among the rural residents in Sichuan province.Efforts should be made to improve the awareness of disease prevention among the elderly in rural areas.The investment in health resources in township health centers should be increased to strengthen the introduction and training of talents.These measures can improve the health services in township health centers,guide residents to make timely use of health resources,and reduce the occurrence of delay in seeking medical treatment.
Middle Aged ; Aged ; Humans ; Surveys and Questionnaires ; Logistic Models ; Rural Population ; China/epidemiology*

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.
Medicine, Chinese Traditional ; Reproducibility of Results ; China ; Quality Control ; Pharmaceutical Preparations