Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

Purpose/Significance To deeply analyze the research progress on the application of medical knowledge graph in the field of stroke,to discuss the problems of the development of stroke knowledge graph in China,and to put forward suggestions for the construc-tion of stroke knowledge graph.Method/Process By reviewing and analyzing the relevant literature,the application of medical knowledge graph in the field of stroke is sorted out and summarized.Result/Conclusion There are still many deficiencies in the development of stroke knowledge graph in China,and in the future,in-depth research can be carried out from four aspects,namely,expanding the ap-plication scope of knowledge graph,promoting the fusion of knowledge graph,developing more efficient algorithms,and upgrading to cog-nitive graph by joint artificial intelligence(AI).

Objective:To investigate the expression of soluble CD40 ligand (sCD40L) in serum of children with Kawasaki disease at acute stage and its diagnostic value in coronary artery disease (CAL).Methods:This study adopts case-control study method. Select 127 children with Kawasaki disease admitted to Xuzhou Children's Hospital affiliated to Xuzhou Medical University from August 2021 to August 2022. They are divided into CAL group and non-CAL group according to the degree of coronary artery involvement. Select 30 healthy children who have physical examination in this hospital at the same time as the healthy control group, and select another 30 children with acute upper respiratory tract infection and fever admitted to this hospital at the same time as the fever control group.Compare the sex, age and laboratory indicators of children with Kawasaki disease with or without CAL, and compare the difference between the serum sCD40L level of children with Kawasaki disease with or without CAL and the fever control group and the healthy control group, the serum sCD40L level of children with different degrees of coronary artery dilation, and analyze the correlation between the serum sCD40L and various laboratory indicators of children with Kawasaki disease and the influencing factors of children with Kawasaki disease complicated with CAL, To evaluate the screening effect of serum sCD40L for Kawasaki disease complicated with CAL. The measurement data with normal distribution is expressed by xˉ± s, the comparison between the two groups adopts independent sample t-test, the comparison between multiple groups adopts one-way ANOVA, and the comparison between two groups adopts LSD method and Bonferroni correction; The measurement data of non-normal distribution is expressed by M( Q1, Q3), and the comparison between the two groups is conducted by Mann-Whitney U test. Pearson method and Spearman mothod were used for correlation analysis. Logistic regression model was used to analyze the influencing factors of children with Kawasaki disease complicated with CAL. The diagnostic value of serum sCD40L level in Kawasaki disease complicated with CAL was analyzed by drawing the ROC curve. Results:All 127 children with Kawasaki disease were divided into CAL group (45 cases) and non-CAL group (82 cases) according to the presence or absence of CAL. The serum level of sCD40L in CAL group was higher than that in non-CAL group, healthy control group and fever control group ((7.03±0.91) μg/L vs (4.66±1.23), (1.73±0.96), (2.21±1.08) μg/L), the difference was statistically significant (all P<0.001). The serum level of sCD40L in children with coronary artery dilation in CAL group was lower than that in children with small CAA, medium CAA and large CAA ((6.04±0.22) μg/L vs (6.95±0.69), (8.02±0.57), (8.23±0.26) μg/L), the difference was statistically significant (all P<0.001). Serum sCD40L level and platelet count (PLT), C-reactive protein (CRP), N-terminal pro brain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), IL-8 and tumor necrosis factor (TNF-α) in children with Kawasaki disease All were positively correlated ( r=0.31, P<0.001, r=0.32, P<0.001, r=0.26, P=0.003, r=0.58, P<0.001, r=0.27, P=0.002, r=0.39, P<0.001). Serum sCD40L, IL-6 and NT-proBNP were the risk factors of complicated CAL in children with Kawasaki disease (odds ratio 1.21, 1.06 and 1.01, 95% confidence interval 1.03-1.43, 1.01-1.12, 1.00-1.01, P values were 0.022, 0.011 and 0.039, respectively). The area under the curve of serum sCD40L in diagnosing Kawasaki disease complicated with CAL was 0.928 (95% confidence interval: 0.885-0.971), and the optimal critical value was 5.60 μg/L, the sensitivity was 97.8% and the specificity was 79.3%. Conclusions:The level of serum sCD40L increased in children with Kawasaki disease in acute phase, especially in children with CAL. The level of serum sCD40L increased with the severity of CAL, which is a risk factor for Kawasaki disease complicated with CAL, and has certain diagnostic value for Kawasaki disease complicated with CAL.

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

Humans ; Nails ; Hydroxyurea/adverse effects* ; Alopecia/chemically induced*

Localized peripheral neuropathy amyloidosis is a rare disease that mainly occurred in elder people who present with focal neurological symptoms. AL is the main type of amyloid protein. Biopsy is the golden standard for diagnosis. Mass spectrometry and immunohistochemical analysis help to confirm the type of amyloid protein. This paper retrospectively analyzes the clinical and imaging data, auxiliary examinations, histological, and immunohistochemical markers. The patient, a 34-year-old woman, presented with a right neck mass and weakness of the right arm. Brachial plexus magnetic resonance imaging (MRI) showed a tumor-like lesion in the nerve root at C5 and C6 and in upper trunk. Electrophysiological studies revealed damage in the upper trunk of the brachial plexus. Positive staining with Congo red was found in brachial plexus biopsy. Mass spectrometry showed that the type of amyloid protein was AHL(G-λ). The patient underwent nerve graft for treatment. Meanwhile, literature review revealed that the average onset age of localized spinal nerve amyloidosis was 62.4 years old.The radial nerve was the most susceptible, followed by the lumbosacral plexus. Fifty percent of the type of amyloid protein is AL.Until now, no consolidated treatment is available. Here, we summarize the clinical characteristics of localized peripheral neuropathy amyloidosis in order to raise the awareness of the disease.

OBJECTIVE：To establish the fingerprint of Jingu tongxiao pill ，and to determine the contents of 7 components. METHODS：HPLC method was adopted. The determination was performed on Cosmosil 5C18-MS-Ⅱ column with acetonitrile- 0.02％ phosphoric acid solution as mobile phase （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelength was 230 nm and the column temperature was set at 25 ℃. The sample size was 10 μL. HPLC fingerprint of 10 batches of Jingu tongxiao pill was established by using Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition），and common peak was identified by comparing with the mixed reference substance. The contents of corresponding components of the identified common peak were determined by the same HPLC method. RESULTS ：There were 20 common peaks in HPLC fingerprint of 10 batches of samples ，and the similarity with the control fingerprint was not less than 0.980. By comparing with the mixed reference substance， 7 components were identified ， which were loganic acid ，gentiopicroside，paeoniflorin，salvianolic acid B ， cryptotanshinone，tanshinone Ⅰ and tanshinone Ⅱ A. The linear range of the above 7 components were 4.509-45.090， 15.090-150.900，14.985-149.850，14.982-149.820，2.967-29.670，1.944-19.440，3.094-30.940 μg/mL（all r＞0.999），respectively. The limits of detection were 0.060 1，0.161 0，0.399 6，0.159 8，0.031 6，0.051 8，0.082 5 μg/mL，respectively. The limits of quantitation were 0.200 4，0.503 0，0.999 0，0.399 5，0.079 1，0.259 2，0.412 6 μg/mL，respectively. RSDs of precision ，stability （24 h） and reproducibility tests were all lower than 3.0％ （n＝6）. Average recoveries were 98.81％ -100.28％ ，RSDs were 0.20％-1.21％（n＝6）. In 10 batches of samples ，the contents of the above 7 components were 0.441 0-0.969 4，3.283 4-4.733 4， 1.947 7-3.674 9，1.336 6-2.270 9，0.293 2-0.372 1，0.190 2-0.293 9 and 0.352 8-0.518 8 mg/g，respectively. CONCLUSIONS ：In this study，HPLC fingerprint and content determination method of Jingu tongxiao pill are successfully established and can be used for quality control.

OBJECTIVE：To compare the chemical components in Sinapis alba before and after stir-frying. METHODS ： UPLC-Q-Exactive Obitrap MS was adopted to analyze chemical constituents of S. alba before and after stir-frying. The determination was performed on Waters CORTECS T 3 column with mobile phase consisted of methanol- 0.1％ formic acid solution （gradient elution ）at the flow rate of 0.25 mL/min. The column temperature was 30 ℃ and the sample size was 2 μL. High resolution MS adopted heating electrospray electron source ，positive ion scanning mode ，scanning range m/z 120-1 000. The chemical constituents of S. alba before and after stir-frying were identified by Compound Discover 3.2 software combined with relevant database ，and the content changes of chemical constituents were analyzed by using peak area. Chemometrics analysis was performed for the content changes of chemical constituents using peak area as variable. RESULTS ：A total of 54 chemical components were identified in S. alba ，mainly fatty acids （represented by erucic acid ），alkaloids（represented by sinapine ）， flavonoids. After stir-frying ，the contents of 19 chemical components changed significantly ，of which the contents of 10 components decreased significantly and those of 9 components increased significantly （P＜0.05）. Principal component analysis and orthogonal partial least squares discriminant analysis could clearly distinguish S. alba from stir-fried S. alba . CONCLUSIONS ：The contents of some chemical components of S. alba change significantly after stir-frying ，which may be one of the important reasons for the change of efficacy after stir-frying.

Unrestrained inflammation is harmful to tissue repair and regeneration. Immune cell membrane-camouflaged nanoparticles have been proven to show promise as inflammation targets and multitargeted inflammation controls in the treatment of severe inflammation. Prevention and early intervention of inflammation can reduce the risk of irreversible tissue damage and loss of function, but no cell membrane-camouflaged nanotechnology has been reported to achieve stage-specific treatment in these conditions. In this study, we investigated the prophylactic and therapeutic efficacy of fibroblast membrane-camouflaged nanoparticles for topical treatment of early inflammation (early pulpitis as the model) with the help of in-depth bioinformatics and molecular biology investigations in vitro and in vivo. Nanoparticles have been proven to act as sentinels to detect and competitively neutralize invasive Escherichia coli lipopolysaccharide (E. coli LPS) with resident fibroblasts to effectively inhibit the activation of intricate signaling pathways. Moreover, nanoparticles can alleviate the secretion of multiple inflammatory cytokines to achieve multitargeted anti-inflammatory effects, attenuating inflammatory conditions in the early stage. Our work verified the feasibility of fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage, which widens the potential cell types for inflammation regulation.
Escherichia coli ; Fibroblasts ; Humans ; Inflammation/drug therapy* ; Nanoparticles

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*