Objective:To compare the consistency of microarray chemiluminescent protein chip and immunoblotting in the autoantibody spectrum of patients and the diagnostic efficacy of systemic lupus erythematosus(SLE), and to explore the correlation between the detection results of protein microarray and clinical indicators and lymphocyte subsets.Methods:Serum autoantibodies in 649 samples collected between December 2023 and December 2024 in Nanjing Drum Tower Hospital were analyzed using the microarray chemiluminescent protein chip method, with 401 samples simultaneously tested by immunoblotting. Kappa coefficient assessed inter-method consistency. Diagnostic performance was compared via ROC curves. Spearman correlation analysis evaluated relationships between autoantibody levels and SLEDAI-2000 scores, clinical parameters, and lymphocyte subsets.Results:The two methods demonstrated good consistency across 14 antinuclear antibodies, with optimal agreement for anti-SSA/Ro ( Kappa=0.845, P<0.001), anti-SSB ( Kappa=0.825, P<0.001), and anti-CENP B ( Kappa=0.851, P<0.001). The protein chip method significantly improved SLE diagnostic efficacy, particularly for anti-dsDNA (AUC difference=0.291, P<0.001) and anti-Sm antibodies (AUC difference=0.295, P<0.001). Combined detection of anti-SSA/Ro and anti-nRNP/Sm antibodies achieved superior diagnostic performance (AUC=0.927). Anti-dsDNA, anti-histone, and anti-nucleosome antibodies positively correlated with SLEDAI-2000 ( r=0.408, 0410, 0.384, all P<0.001), complement ( P<0.001), and 24-hour urinary protein ( r=0.374, 0.387, 0.301, all P<0.001). Immunological analysis showed that the proportion of NK cells was generally negatively correlated with antinuclear antibodies such as anti-dsDNA ( r=-0.352, P<0.001) and anti-Sm ( r=-0.328, P<0.001) antibodies. Meanwhile, the proportion of CD8 + T cells was positively correlated with anti-nRNP/Sm ( r=0.229, P=0.002) and anti-Sm antibodies ( r=0.211, P=0.005). The proportion of CD4 + T cells was negatively correlated with anti-SSA/Ro ( r=-0.239, P<0.001), while the proportion of B cells was positively correlated with anti-dSDNA antibody ( r=0.300, P<0.001). Conclusion:The protein chip method showed strong consistency with immunoblotting for detecting 14 autoantibodies but demonstrated superior SLE diagnostic efficacy. The combined use of multiple detection methods can enhance the reliability of clinical diagnosis.

ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

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

Objective:To compare the consistency of microarray chemiluminescent protein chip and immunoblotting in the autoantibody spectrum of patients and the diagnostic efficacy of systemic lupus erythematosus(SLE), and to explore the correlation between the detection results of protein microarray and clinical indicators and lymphocyte subsets.Methods:Serum autoantibodies in 649 samples collected between December 2023 and December 2024 in Nanjing Drum Tower Hospital were analyzed using the microarray chemiluminescent protein chip method, with 401 samples simultaneously tested by immunoblotting. Kappa coefficient assessed inter-method consistency. Diagnostic performance was compared via ROC curves. Spearman correlation analysis evaluated relationships between autoantibody levels and SLEDAI-2000 scores, clinical parameters, and lymphocyte subsets.Results:The two methods demonstrated good consistency across 14 antinuclear antibodies, with optimal agreement for anti-SSA/Ro ( Kappa=0.845, P<0.001), anti-SSB ( Kappa=0.825, P<0.001), and anti-CENP B ( Kappa=0.851, P<0.001). The protein chip method significantly improved SLE diagnostic efficacy, particularly for anti-dsDNA (AUC difference=0.291, P<0.001) and anti-Sm antibodies (AUC difference=0.295, P<0.001). Combined detection of anti-SSA/Ro and anti-nRNP/Sm antibodies achieved superior diagnostic performance (AUC=0.927). Anti-dsDNA, anti-histone, and anti-nucleosome antibodies positively correlated with SLEDAI-2000 ( r=0.408, 0410, 0.384, all P<0.001), complement ( P<0.001), and 24-hour urinary protein ( r=0.374, 0.387, 0.301, all P<0.001). Immunological analysis showed that the proportion of NK cells was generally negatively correlated with antinuclear antibodies such as anti-dsDNA ( r=-0.352, P<0.001) and anti-Sm ( r=-0.328, P<0.001) antibodies. Meanwhile, the proportion of CD8 + T cells was positively correlated with anti-nRNP/Sm ( r=0.229, P=0.002) and anti-Sm antibodies ( r=0.211, P=0.005). The proportion of CD4 + T cells was negatively correlated with anti-SSA/Ro ( r=-0.239, P<0.001), while the proportion of B cells was positively correlated with anti-dSDNA antibody ( r=0.300, P<0.001). Conclusion:The protein chip method showed strong consistency with immunoblotting for detecting 14 autoantibodies but demonstrated superior SLE diagnostic efficacy. The combined use of multiple detection methods can enhance the reliability of clinical diagnosis.

Objective:To explore the effect of behavior change wheel strategy based on information asymmetry in the postoperative rehabilitation of patients with thoracolumbar fracture.Methods:From June 2020 to May 2021, 164 patients with thoracolumbar fracture in Spine Surgery who were admitted to the First Affiliated Hospital of Xinxiang Medical University were selected by convenience sampling as the research object. The patients were divided into observation group and control group according to random number table, 82 cases each. The control group adopted routine postoperative nursing management, while the observation group implemented the behavioral change wheel strategy based on nurse patient information asymmetry on the basis of the control group. After three months of intervention, the differences of kinesiophobia and recovery of lumbar and back function between the two groups were compared.Results:After intervention, the scores of kinesiophobia and recovery of lumbar and back function in the observation group at the end of the first, second and third months were lower than those in the control group, with statistically significant differences ( P<0.05) . Conclusions:The behavior change wheel strategy based on nurse patient information asymmetry can effectively alleviate postoperative kinesiophobia of patients undergoing thoracolumbar fracture surgery, and improve the recovery of lumbar and back functions after surgery.

The thalamocortical (TC) circuit is closely associated with pain processing. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel is predominantly expressed in the ventral posterolateral thalamus (VPL) that has been shown to mediate neuropathic pain. However, the role of VPL HCN2 in modulating TC circuit activity is largely unknown. Here, by using optogenetics, neuronal tracing, electrophysiological recordings, and virus knockdown strategies, we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex (S1HL) as well as mechanical hypersensitivity following spared nerve injury (SNI)-induced neuropathic pain in mice. Either pharmacological blockade or virus knockdown of HCN2 (shRNA-Hcn2) in the VPL was sufficient to alleviate SNI-induced hyperalgesia. Moreover, shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL circuit. Together, our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.
Animals ; Mice ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics* ; Neuralgia ; RNA, Small Interfering ; Thalamus/metabolism* ; Up-Regulation

Objective:To retrieve and summarize the evidence on early enteral nutrition in critically ill patients with prone position ventilation.Methods:The relevant evidence on early enteral nutrition in critically ill patients with prone position ventilation was systematically searched through computer in domestic and foreign guideline websites, institutional websites and databases. The quality was assessed using the literature evaluation criteria and systematic review evaluation tools of the Joanna Briggs Institute (JBI) Evidence-Based Health Care Center in Australia. The retrieval time limit was from January 1, 2015 to November 11, 2020.Results:A total of 10 articles were included, involving one clinical decision, four guidelines, three systematic reviews, and two original literature. A total of 18 pieces of evidence from 7 aspects were summarized on early enteral nutrition assessment, restart timing, body position, feeding program (intake, transgastric/postpyloric feeding, nasogastric feeding rate, nutritional preparations) , monitoring (gastric residual volume, gastric antral motility index) , drug prevention, staffing and training.Conclusions:This study summarizes the evidence of early enteral nutrition in critically ill patients with prone position ventilation, and provides evidence-based evidence for nursing managers to formulate enteral nutrition plans scientifically.

Closed-loop hospital management can effectivly cope with the COVID-19 pandemic. In order to ensure the continuity of treatments for hemodialysis patients under closed-loop management and minimize possible medical and infection risks, Huashan Hospital affiliated to Fudan University and 9 hospitals in Shanghai established a hemodialysis alliance in January 2021.The alliance optimized hemodialysis resources within the region through overall planning by preparing sites, materials and personnel shifts in advance, and establishing management systems and work processes to ensure that patients could be quickly and orderly diverted to other blood dialysis centers for uninterrupted high-quality hemodialysis services, in case that some hemodialysis centers in the alliance under closed-loop management.From November 2021 to April 2022, 317 of 1 459 hemodialysis patients in the alliance were diverted to other centers for treatment, accumulating 1 215 times/cases of treatments without obvious adverse reactions. The practice could provide a reference for medical institutions to quickly establish mutual support mode under major public health events.

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

PURPOSE: Various inflammation-based prognostic biomarkers such as the platelet to lymphocyte ratio and neutrophil to lymphocyte ratio, are related to poor survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aims to investigate the prognostic value of the aspartate aminotransferase to neutrophil ratio index (ANRI) in ICC after hepatic resection. MATERIALS AND METHODS: Data of 184 patients with ICC after hepatectomy were retrospectively reviewed. The cut-off value of ANRI was determined by a receiver operating characteristic curve. Preoperative ANRI and clinicopathological variables were analyzed. The predictive value of preoperative ANRI for prognosis of ICC was identified by univariate and multivariate analyses. RESULTS: The optimal cut-off value of ANRI was 6.7. ANRI was associated with tumor size, tumor recurrence, white blood cell, neutrophil count, aspartate aminotransferase, and alanine transaminase. Univariate analysis showed that ANRI, sex, tumor number, tumor size, tumor differentiation, lymph node metastasis, resection margin, clinical TNM stage, neutrophil count, and carcinoembryonic antigen were markedly correlated with overall survival (OS) and disease-free survival (DFS) in patients with ICC. Multivariable analyses revealed that ANRI, a tumor size > 6 cm, poor tumor differentiation, and an R1 resection margin were independent prognostic factors for both OS and DFS. Additionally, preoperative ANRI also had a significant value to predict prognosis in various subgroups of ICC, including serum hepatitis B surface antigen‒negative and preoperative elevated carbohydrate antigen 19-9 patients. CONCLUSION: Preoperative declined ANRI is a noninvasive, simple, and effective predictor of poor prognosis in patients with ICC after hepatectomy.
Alanine Transaminase ; Aspartate Aminotransferases* ; Aspartic Acid* ; Biomarkers ; Blood Platelets ; Carcinoembryonic Antigen ; Cholangiocarcinoma* ; Disease-Free Survival ; Hepatectomy* ; Hepatitis B ; Humans ; Leukocytes ; Lymph Nodes ; Lymphocytes ; Multivariate Analysis ; Neoplasm Metastasis ; Neutrophils* ; Prognosis* ; Recurrence ; Retrospective Studies ; ROC Curve