The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

ObjectiveTo identify the pharmacodynamic material basis of Ruyi Zhenbaowan in relieving neuropathic pain by integrating the calculation of biological network proximity and pharmacokinetic characterization. MethodThe interaction network of "drug candidate target-related gene of disease" was constructed by Cytoscape 3.8.2， and the average shortest path value of each drug putative target acting on neuropathic pain-related genes in this network was calculated by Pesca 3.8.0 tool so as to evaluate the network proximity between them， and screen prescription candidate targets with strong intervention efficiency and their corresponding potential effect components. After that， plasma and cerebrospinal fluid samples were collected from rats after administration of Ruyi Zhenbaowan at set time points， and the contents of potential effect components in samples was quantified by ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry（UPLC-Q-TRAP/MS）， and drug concentration-time curves were plotted， then the pharmacokinetic parameters were calculated by DAS 2.1.1. ResultBy evaluating the network proximity between candidate targets and neuropathic pain-related genes in the interaction network， a total of 40 putative targets of Ruyi Zhenbaowan with strong intervention effects on neuropathic pain-related genes， such as estrogen receptor 1（ESR1）， cyclic adenosine monophosphate（cAMP）-dependent protein kinase catalytic subunit alpha（PRKACA） and protein kinase B1 （Akt1）， and 10 corresponding potential effect components， such as glycyrrhizic acid and betulinic acid， were obtained. Pharmacokinetic characterization showed that among the 10 potential effect components， gallic acid， apigenin-7-O-glucuronide， glycyrrhizic acid and apigenin were well absorbed and metabolized in plasma and cerebrospinal fluid， with long onset time and good bioavailability. ConclusionFrom the perspective of efficacy-target-constituent-pharmacokinetic， this study analyzes the main effective materials of Ruyi Zhenbaowan， such as glycyrrhizic acid， gallic acid， apigenin-7-O-glucuronide and apigenin， which have a high exposure in plasma or cerebrospinal fluid and have a strong intervention effect on neuropathic pain. The related results provide reliable experimental evidences for clarifying the material basis and developing quality standards of Ruyi Zhenbaowan.

Objective:To investigate the change and clinical significance of serum alkaline phosphatase (ALP) level in patients with acute spontaneous intracerebral hemorrhage(AICH).Methods:81 patients with AICH admitted to the Neurosurgery Department of Tianjin Third Central Hospital from January 2019 to October 2020 were retrospectively analyzed. 81 patients with non cerebral hemorrhage who came from the health examination center or complained of dizziness and had no hepatobiliary and skeletal diseases were selected as the control group. The clinical data of all the patients were recorded, including gender, age, Glasgow Coma Scale (GCS) score, hemorrhage location, liver function indexes, the history of hypertension, diabetes, heart disease, smoking, drinking, and so on. The differences in clinical data between the two groups were compared. Pearson correlation was used to analyze the correlation between liver function indexes and GCS score. The independent risk factors for AICH were screened by binary logistic regression, and the receiver operating characteristic (ROC) curve was used to evaluate the value of serum ALP in predicting intracerebral hemorrhage.Results:Serum ALP level in AICH group was significantly higher than that in the control group [85.0(70.0, 103.0) U/L vs 65.0(54.5, 71.5)U/L, Z=6.740, P<0.001]. Pearson correlation analysis showed that serum ALP had a negative correlation with GCS score ( r=0.255, P=0.022). Binary logistic regression analysis showed that hypertension ( OR=20.440, 95% CI 8.572-48.737) and ALP ( OR=1.077, 95% CI 1.049-1.105) were risk factors for intracerebral hemorrhage. Serum ALP level was an independent risk factor ( OR=1.069, 95% CI 1.038-1.101) for AICH after adjusting for confounding variables including age, AST, history of hypertension. ROC curve showed that the area under the curve (AUC) of serum ALP in predicting intracerebral hemorrhage was 0.807 (95% CI 0.740-0.873, P<0.001), with sensitivity of 67.9% and specificity of 81.5%. Conclusions:Serum ALP level may be related to the occurrence and severity of AICH. Therefore, serum ALP level can be used as a reference index to evaluate the occurrence, severity of patients with AICH.

Objective:To explore the differences of immune reconstitution between peripheral blood stem cell transplantation and umbilical cord blood transplantation.Methods:A total of 300 patients (aged 18 (8, 33), 163 males and 137 females) with malignant hematological diseases who received allogeneic hematopoietic stem cell transplantation in the First Affiliated Hospital of University of Science and Technology of China from January 2018 to March 2020 were enrolled in this study, including 255 cases of umbilical cord blood transplantation and 45 cases of peripheral blood stem cell transplantation. Multicolor flow cytometry was applied to analyze lymphocyte subsets of the percentages and absolute counts in the two donor types and peripheral blood of patients after receiving hematopoietic stem cell transplantation. The differences between the two grafts were compared, and the lymphocyte subsets results were evaluated at 1, 2, 3, 4, 6, 9, 12, and 18 months after transplantation. 18-month disease-free survival (DFS) within the 300 patients under the two transplantation types were retrospectively analyzed.Results:1. The proportion of NKT cells in peripheral blood group was significantly higher than that in cord blood group (2.79% vs 0.24%, P<0.001). 2. The proportion of helper T cells in the UCBT group was higher than that in the PBSCT group, as well as the counts 6 months after transplantation ( P<0.05). 3. The proportion of NK1 cells (3 rd to 9 th month) and count (4 th to 12 th month) in UCBT group were significantly higher than those in PBSCT group ( P<0.05). 4. NKT cells in the UCBT group were lower than those in the PBSCT group (proportion and count) throughout the monitoring process ( P≤0.001). 5. The proportion of DNT cells (within 1 year) and count (within 6 months) in the UCBT group were significantly lower than those in the PBSCT group ( P<0.05). Conclusions:Compared with the peripheral blood stem cell transplantation group, the umbilical cord blood transplantation patients had a faster rate of lymphocyte reconstitution, and patients received umbilical cord blood transplantation had a stronger ability of immune reconstitution and could achieve long-term hematopoiesis.

Objective:To study the changes of urinary metabolic profile, screen metabolic ions characterization with clinical diagnostic value, and a disease differentiation model establishment, in an attempt to help the clinical diagnosis of hepatocellular carcinoma patients.Methods:A case-control study was conducted. Ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) were used to analyze urine samples of 32 patients with hepatocellular carcinoma, 28 patients with liver cirrhosis and 28 healthy persons, respectively. The orthogonal partial least squares discriminant analysis (OPLS-DA) and the principal component analysis (PCA) model were constructed using MZmine2.0 and SIMCA-P + 12.0.1.0 software for preliminary screening of metabolites. The metabolic ions selected in the final test were analyzed by SPSS, and the markers were analyzed and screened by one-way analysis of variance. Finally, the sensitivity and specificity of the selected markers were analyzed by calculating the area under the receiver operating characteristic (ROC) curve. One-way analysis of variance was used to compare quantitative indicators between groups.Results:OPLS-DA model parameters were R2X = 35.3%, R2Y = 86.9%, and Q2 = 72.2%, which had a good identification value. A total of 26 characteristic ions were screened, of which 17 were identified. 14, 19-Dihydroaspidospermatine had a high value in distinguishing healthy person with hepatocellular carcinoma patients, and the area under the receiver operating characteristic curve was higher than 0.9. The area under the ROC curve for distinguishing liver cancer with liver cirrhosis patients was 0.88, which was higher than the ROC curve of alpha-fetoprotein (0.75).Conclusion:Based on the UPLC-MS platform, the PCA and OPLS-DA models were successfully constructed, and the characteristic metabolic ions in the urine were extracted and identified, which has a certain value in assisting clinical screening of hepatocellular carcinoma patients.

Objective To investigate the cytogenetic and clinical features of acute myeloid leukemia (AML) with CD7 positive. Methods Among 788 AML patients in the First Affiliated Hospital of USTC from January 2008 to December 2012, a total of 140 AML patients with CD7 positive were enrolled, and their clinical and cytogenetic characteristics were analyzed respectively. Results According to French-American-British (FAB) classification systems, M5[47.1 % (66/140)] and M2[27.1 % (38/140)] were often detected in 140 AML patients with CD7 positive. The positive rate of CD7 in M0patients [(60.9±13.2) %] was the highest, followed by (53.1±29.5) % in M1patient. Karyotype analysis showed that 72 (51.4 %) AML patients with CD7 positive had unfavorable karyotypes. Thirty-one (22.1 %) AML patients with CD7 positive simultaneously showed the expressions of lymphoid antigens. Clinically, some AML patients with CD7 positive was accompanied by hyperleukocytosis [75.0 % (105/140)] (white blood count ≥20×109/L) and hepatosplenomegaly [82.1 % (115/140)]. The proportion of elder patients (above 65 years old) and complete remission rate of AML with CD7 positive were lower than those of AML with CD7 negative [25.7 % (36/140) vs. 39.4 % (255/648);12.1 % (17/140) vs. 24.7 % (160/648), respectively], and there were statistical differences (χ 2＝ 8.62, P＝0.03; χ 2＝ 9.70, P＝ 0.01, respectively). Conclusion AML patients with CD7 positive have specific cytogenetic and clinical characteristics, and poor prognosis.

Objectives This research explored the characteristics of changes in the serum metabolic profile of preeclampsia pregnancy(PE) to establish the disease distinguish model and screen characteristic metabolic markers with potential diagnostic value for preeclampsia.Methods From August 2014 to January 2016,samples in three groups were collected at Tianjin Third Central Hospital.Thirty-one clinically diagnosis patients with preeclampsia,25 normal pregnancy women and 29 healthy volunteers of childbearing age were enrolled.Ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze serum metabolites of PE group (31 patients with preeclampsia),P group (25 normal pregnancy women) and Normal group (29 healthy volunteers of childbearing age).Nonparametric test analyzes were used to analyze the data and find the specific metabolites.Results This research established the principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) disease distinguish model for PE group,P group and Normal group.To distinguish PE group,P group and Normal group,15 characteristic metabolites were identified.Eight kinds of glycerol phospholipid (including 7 kinds of hemolysis phosphatidyl choline and 1 kind of lysophospholipids acid) and 1 kind of sphingomyelin in PE group were higher than that of normal pregnancy group.The difference had statistically significant(Z of the metabolites were 2.32,3.34,3.21,2.60,2.22,3.40,3.58,5.84,2.70 respectively,all P<0.05).1,25-Dihydroxyvitamin D3-26,23-lactone and 24-Oxo-1alpha,23,25-trihydroxyvitamin D3 in PE group were higher than that of P group and Normal group,which had a statistics difference (Z of the metabolites were 2.01,3.89,3.26,2.34 respectively,all P<0.05).Conclusions Metabolomics distinguish model has a good ability to distinguish PE group,P group and Normal group.Serum characteristic metabolites can successfully reflect the status of fat,calcium and phosphorus metabolism of preeclampsia patients and provide high value for prediction,diagnosis and treatment.

Objective: To determine the diagnostic value of serum cystatin C (Cys C) for acute kidney injury (AKI) in patients with liver cirrhosis. Methods: Serum Cys C levels in 150 liver cirrhosis patients (88 AKI and 62 non-AKI patients) were measured by the Particle-Enhanced Nephelometric Immuno-Assay. The accuracy of serum Cys C for the diagnosis of AKI in liver cirrhosis was evaluated by the ROC curve. Results: Liver cirrhosis patients with AKI had significantly higher serum Cys C levels [2.37 (1.75-2.83) mg/L] than those without AKI [0.97 (0.85-1.09) g/L] (P <0.001). Serum Cys C level was highest in the acute tubular necrosis group [5.41 (2.77-6.19) mg/L], followed by the hepatorenal syndrome group [2.55 (2.28-3.59) mg/L] and prerenal azotemia group [2.07 (1.70-2.41) mg/L], and the serum Cys C level was significantly different between the three groups (P <0.001). In addition, patients with AKI were further divided into infection group and non-infection group. Serum Cys C level was significantly higher in the infection group than in the non-infection group (P <0.05). The area under the ROC curve of serum Cys C for the diagnosis of AKI in liver cirrhosis was 0.99 (0.98-1.00) at a cut-off value of 1.36 mg/L, and the sensitivity and specificity were 97% and 95%, respectively. Conclusion Serum Cys C is a good marker for detecting AKI in liver cirrhosis, and the different levels of increase in Cys C may be useful in differentiating the different types of AKI.

Objective:To establish a simple HPLC method for the determination of warfarin in human plasma and analyze the re-sults of 100 monitoring reports. Methods:Warfarin was extracted from the plasma samples by acetonitrile. The extract was separated on a ZORBAX Eclipse XDB-C8 column (150 mm × 4. 6 mm, 5 μm)with a mobile phase consisting of methanol and 0. 1% acetic acid (65∶35) at flow rate of 1. 0 ml·min-1 and detected by a diode array detector. The detection wavelength was at 308nm and the sample size was 20 μl. Results:The calibration curve was linear within the range of 0. 1-5. 12μg·ml-1 . The average recovery and RSD was ranged from 85. 0% to 102. 3% and 1. 2% to 3. 9%(n=6), respectively. Inter-and intra-day RSD were 1. 1%-1. 8% and 1. 6%-2. 9%, respectively. Conclusion:The proposed method is rapid, convenient and accurate in the detection of warfarinin concentration in plasma.