Inhibition of HSP70 release by geniposide improves angiogenesis in moist heat arthralgia spasm syndrome collagen induced arthritis rats / 中国药理学通报

Aim To investigate the relation between the effect of geniposide (GE) in improving angiogenesis in arthralgia spasm syndrome collagen induced arthritis (CIA) rats and the modulation of heat shock proteins 70 (HSP70) release. Methods A CIA model was constructed by multiple intradermal injections of complete Freund's adjuvant (CFA) and an equal volume mixture of chicken type II collagen (CCII) into the dorsal and caudal root regions of rats, on the basis of which a rheumatic fever stimulus was given to build up a moist heat arthralgia spasm syndrome in CIA rats. After successful modeling, the groups were randomly grouped, and the administered groups were gavaged with GE (60, 120 mg · kg

Application of artificial intelligence to digital-rapid on-site cytopathology evaluation during endoscopic ultrasound-guided fine needle aspiration: A proof-of-concept study.

BACKGROUND: During endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), cytopathology with rapid on-site evaluation (ROSE) can improve diagnostic yield and accuracy. However, ROSE is unavailable in most Asian and European institutions because of the shortage of cytopathologists. Therefore, developing computer-assisted diagnostic tools to replace manual ROSE is crucial. Herein, we reported the validation of an artificial intelligence (AI)-based model (ROSE-AI model) to substitute manual ROSE during EUS-FNA. METHODS: A total of 467 digitized images from Diff-Quik (D&F)-stained EUS-FNA slides were divided into training (3642 tiles from 367 images) and internal validation (916 tiles from 100 images) datasets. The ROSE-AI model was trained and validated using training and internal validation datasets, respectively. The specificity was emphasized while developing the model. Then, we evaluated the AI model on a 693-image external dataset. We assessed the performance of the AI model to detect cancer cells (CCs) regarding the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The ROSE-AI model achieved an accuracy of 83.4% in the internal validation dataset and 88.7% in the external test dataset. The sensitivity and PPV were 79.1% and 71.7% in internal validation dataset and 78.0% and 60.7% in external test dataset, respectively. CONCLUSION: We provided a proof of concept that AI can be used to replace manual ROSE during EUS-FNA. The ROSE-AI model can address the shortage of cytopathologists and make ROSE available in more institutes.

To explore the quality markers of Huangqin Qingre Chubi capsule in the treatment of rheumatoid arthritis based on network pharmacology combined with pharmacokinetics and target verification / 药学学报

As an effective prescription for the treatment of rheumatoid arthritis (RA), Huangqin Qingre Chubi capsule (HQC) is still blank in quality control. This study aims to explore quality markers (Q-markers) for HQC in the treatment of RA by integrating network pharmacology and pharmacokinetics. By constructing the visualization network of "pharmacodynamic ingredient-target-pathway", the potential Q-Marker of HQC treatment for RA was preliminatively predicted. A rat model of rheumatic heat obstruction syndrome collagene-induced arthritis (CIA) was established to elucidate the dynamic quantification law of pharmacodynamic components of HQC in the disease state of rats. To establish the inflammatory model of RA synovial fibroblasts (MH7A) induced by tumor necrosis factor-α (TNF-α) in vitro. The effects of active ingredients on protein expression of sphingosin kinase-1 (Sphk1) and p-SphK1 were detected. The network pharmacological results showed that baicalin, geniposide, luteolin, coixol and amygdalin were the important active components of HQC treatment for RA. Quantitative analysis results further verified the measurability of these five components. The expression of Sphk1 and p-SphK1 was significantly inhibited by geniposide and baicalin by Western blotting. The above studies determined that the above 5 components could be used as Q-markers in the treatment of RA by HQC. This experiment was approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). All procedures were conducted in strict accordance with the principles of animal use and care.

Baicalin inhibits PDK1 to mediate glucose metabolism reprogramming and intervene rheumatoid arthritis synovial inflammation / 药学学报

This study started from the effect of baicalin (BC), the main active component of the labiaceae plant Scutellaria baicalensis, on collagen-induced arthritis (CIA) in rats, to explore the mechanism of glucose metabolism reprogramming in fibroblast like synoviocytes (FLSs), a key effector cell of synovial inflammation in rheumatoid arthritis (RA). First of all, CIA rats and tumor necrosis factor-α (TNF-α)-induced RASFs in vitro and in vivo models were established, the arthritis index (AI) score and histopathological changes of CIA rats after BC administration were observed, and the levels of inflammatory factors in serum and cell supernatant were quantified by ELISA, immunocytochemistry and Western blot were used to detect the expression of G-protein-coupled receptor 81 (GPR81) and pyruvate dehydrogenase kinase 1 (PDK1) proteins. In addition, the kit was used to measure the levels of key products and enzyme activities in glucose metabolism reprogramming. The results showed that BC (50, 100 and 200 mg·kg-1) could alleviate the symptoms of arthritis in CIA rats in a dose-dependent manner, inhibit synovial hyperplasia, alleviate the infiltration of inflammatory cells, down-regulate the levels of pro-inflammatory factors TNF-α and interleukin (IL)-1β, and up-regulate the levels of anti-inflammatory factor IL-10 in CIA rats. At the same time, the secretion levels of lactate, pyruvate, acetyl-CoA, citrate and the activity of lactate dehydrogenase B (LDH-B) were decreased, and the expressions of GRP81 and PDK1 were down-regulated, suggesting that BC mediated the reprogramming process of glucose metabolism. However, when GPR81 inhibitor 3-OBA inhibited lactate uptake, the activity of LDH-B was significantly increased, suggesting that BC inhibited the expression of PDK1, a key enzyme in the reprogramming metabolism from glycolysis to oxidative phosphorylation. All animal experiments in this study were conducted in accordance with the ethical standards of the Laboratory Animal Care Center of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). These studies revealed that baicalin mediated metabolic reprogramming of RASFs from glycolysis to oxidative phosphorylation by inhibiting PDK1 protein expression, and alleviated joint inflammation in CIA rats.

Dahuang Lingxian Prescription Regulates Effect of TAK1 and TRAF6 Interaction and Co-localization on Inflammatory Response of Bile Duct Cells / 中国实验方剂学杂志

ObjectiveTo observe the repair effect of Dahuanglingxian prescription （DHLX） on bile duct epithelial cells of rats. To explore whether its mechanism of action is to adjust the mutual binding of transforming growth factor -β （TGF-β） activated kinase 1（TAK1） and tumor necrosis factor receptor-associated factor 6 （TRAF6）， and regulate the activation of the nuclear transcription factor -κB （NF-κB）/mitogen-activated protein kinase （MAPK） signaling pathway. MethodThe 20 SD rats were randomly divided into normal group and DHLX group， 10 rats in each group， were given saline and DHLX （320 mg·kg-1·d-1） for 8 days， to prepare normal serum and DHLX serum. Biliary epithelial cells were extracted from normal SD rats and divided into 9 groups： Normal group， model group （20 mg·L-1）， LPS+DHLX group （20 mg·L-1+10% DHLX）， LPS+PDTC group （20 mg·L-1+200 μmol·L-1）， LPS+SB203580 group （20 mg·L-1+0.5 μmol·L-1）， LPS+PDTC+SB203580 group （20 mg·L-1+200 μmol·L-1+0.5 μmol·L-1）， LPS+PDTC+DHLX group （20 mg·L-1+200 μmol·L-1+10% DHLX serum）， LPS+SB203580+DHLX group （20 mg·L-1+0.5 μmol·L-1+10% DHLX serum）， LPS+PDTC+SB203580 +DHLX group （20 mg·L-1+200 μmol·L-1+0.5 μmol·L-1+10% DHLX serum）. The microscopic observation of morphological changes in each group of cells after drug intervention. Enzyme-linked immunosorbent assay（ELISA） was used to detect the expression of （IL）-1β and IL-6 in each group of cells. Western blot detected the expression levels of TAK1 and TRAF6 proteins in each group of cells， Co-IP detected the interaction between TAK1 and TRAF6， and further observed the distribution and co-localization of TAK1 and TRAF6 using Laser confocal microscope. ResultAfter the action of LPS， the cell synapses are reduced， the cell body becomes significantly rounded and smaller， but the cell morphology of each group tends to be normal after medication. Compared with normal group， the expression levels of IL-1β and IL-6 in model group were significantly increased （P<0.05）， while the expression level of TAK1 was decreased while the expression level of TRAF6 was increased （P<0.05）. The content of TAK1-TRAF6 protein complex showed a decreasing trend， and the two proteins co-located in the cytoplasm. Compared with model group， the expression levels of IL-1β and IL-6 in LPS+DHLX group were significantly decreased （P<0.05）， the expression level of TAK1 was increased and the expression level of TRAF6 was decreased （P<0.05）， the content of TAK1-TRAF6 protein complex was significantly increased （P<0.01）， and the two proteins were significantly co-located in cytoplasm. Compared with LPS+DHLX group， the expression levels of IL-1β and IL-6 in other groups were significantly decreased （P<0.05，P<0.01）. TAK1-TRAF6 protein complex content in each group was significantly decreased after pathway blocker intervention （P<0.05）， while TAK1-TRAF6 protein complex content in each group was significantly increased after pathway blocker combined with DHLX intervention （P<0.05）. Co-localization of the TAK1-TRAF6 in cytoplasm was not obvious. ConclusionIn the LPS-induced inflammatory response of bile duct cells， the binding of TAK1 and TRAF6 showed a weakening trend， but DHLX could reverse the phenomenon， we think the mechanism of action may be related to promoting the mutual binding of TAK1 and TARF6 to inhibit the activation of the NF-κB/MAPK signaling pathway.

The role of HIF-VEGF-Ang-2 signal transduction-mediated synovial angiogenesis in rheumatoid arthritis / 药学学报

Rheumatoid arthritis (RA) is an autoimmune disease with angiogenesis, inflammatory factor infiltration and joint destruction as the main pathological features. Angiogenesis promotes the development of RA and plays an important role in its pathogenesis. The hypoxia-inducible factor (HIF)-vascular endothelial growth factor (VEGF)-angiopoietin-2 (Ang-2) signal transduction is a critical pathway to induce synovial angiogenesis. Targeting HIF-VEGF-Ang-2 signal transduction to inhibit synovial angiogenesis is a promising approach for RA treatment. This article reviews the role and mechanism of HIF-VEGF-Ang-2 signal transduction-mediated synovial angiogenesis in RA, in order to provide a new target and strategy for RA treatment.

Transnational policy migration, interdisciplinary policy transfer and decolonization: Tracing the patterns of research ethics regulation in Taiwan.

Research ethics regulation in parts of the Global North has sometimes been initiated in the face of biomedical scandal. More recently, developing and recently developed countries have had additional reasons to regulate, doing so to attract international clinical trials and American research funding, publish in international journals, or to respond to broader social changes. In Taiwan, biomedical research ethics policy based on 'principlism' and committee-based review were imported from the United States. Professionalisation of research ethics displaced other longer-standing ways of conceiving ethics connected with Taiwanese cultural traditions. Subsequently, the model and its discursive practices were extended to other disciplines. Regulation was also shaped by decolonizing discourses associated with asserting Indigenous peoples' rights. Locating research ethics regulation within the language and practices of public policy formation and transfer as well as decolonization, allows analysis to move beyond the self-referential and attend to the social, economic and political context within which regulation operates.

Risk factors of hepatorenal syndrome in patients with acute on chronic liver failure / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To identify the risk factors of hepatorenal syndrome in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure(ACLF).</p><p><b>METHODS</b>A total of 726 hospitalized patients with HBV-ACLF were retrospectively analyzed. Data of demographic and clinical parameters (sex, age, family history, and presence of liver cirrhosis and diabetes), common complications (spontaneous bacterial peritonitis, pulmonary infection, hepatic encephalopathy, and upper gastrointestinal hemorrhage), and baseline biochemical parameters (albumin, globulin, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, cholesterol, cholinesterase, K+, Na+, plasma thromboplastin antecedent, alpha-fetoprotein, HBV DNA, white blood cell count, hemoglobin, and platelet count) were collected from the medical records database. Univariate and multiple regression analyses were performed to determine the risk factors of hepatorenal syndrome.</p><p><b>RESULTS</b>Multiple logistic regression analysis indicated that upper gastrointestinal hemorrhage [risk (R) = 1.313, relative hazard (RH) = 3.716, 95% confidence interval (CI): 2.156-6.404], hepatic encephalopathy (R = 1.120, RH = 3.065, 95% CI: 1.900-4.945), spontaneous bacterial peritonitis (R = 1.005, RH = 2.733, 95% CI: 1.379-5.417), pulmonary infection (R = 1.051, RH = 2.862, 95% CI: 1.783-4.592), and white blood cell count (R = 0.056, RH = 1.058, 95% CI: 1.010-1.107) were independent risk factors for hepatorenal syndrome development in patients with HBV-ACLF.</p><p><b>CONCLUSION</b>Several risk factors were significantly associated with the development of hepatorenal syndrome in HBV-ACLF, including upper gastrointestinal hemorrhage, hepatic encephalopathy, spontaneous bacterial peritonitis, pulmonary infection, and elevated white blood cell count.</p>

Clinical characteristics of and factors related to relapse in chronic hepatitis B patients after nucleoside analogues withdrawal / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics of and factors related to relapse in chronic hepatitis B (CHB) patients who had previously achieved cessation criteria and had been withdrawn from nucleoside analogues treatment.</p><p><b>METHODS</b>Sixty CHB patients who experienced relapse after nucleoside analogues withdrawal based on cessation criteria were enrolled in the study retrospectively. Each patient's data on biochemical, serological and viral characteristics corresponding to baseline (treatment initiation), withdrawal and relapse were collected. COX proportional hazard modeling was used to evaluate the factors related to relapse.</p><p><b>RESULTS</b>The hepatitis B e antigen (HBeAg)-positive and -negative patients had similar median antiviral treatment times (38 months (range: 24 - 80) vs. 35 months (30 - 60); Z = -1.313, P more than 0.05). For all patients, the median follow-up time was 12 months (2 - 72), during which 49 (81.7%) patients developed virological breakthrough and 17 (28.3%) developed HBeAg recurrence. The patients who experienced virological breakthrough or HBeAg recurrence had significantly higher baseline levels of HBV DNA than those patients who remained disease-free (t = 2.15 and -2.54 respectively; P less than 0.05). The median relapse time of the HBeAg-positive patients was significantly longer than that of the HBeAg-negative patients (14 months (3 - 72) vs. 6 months (3 - 36); Chi-square test = 7.045, P less than 0.01). HBeAg status at baseline was identified as an independent factor associated with relapse (relative risk = 1.937, 95% confidence interval = 1.14-3.28, P less than 0.05).</p><p><b>CONCLUSION</b>HBeAg-positive and-negative patients showed distinct clinical characteristics of relapse, with the latter being more prone to relapse soon after nucleoside analogues withdrawal. Prolonging the treatment course may be beneficial to HBeAg-negative patients, even if cessation criteria are achieved.</p>

Characterization of diethylnitrosamine-induced liver carcinogenesis in Syrian golden hamsters.

The aim of this study was to characterize hepatocarcinogenesis in diethylnitrosamine (DEN)-treated hamsters. Syrian golden hamsters (n=36) were administered DEN by hypodermic injection and addition to drinking water. Morphological analyses, including light microscopy and immunohistochemistry of α-fetal protein (AFP), were performed on liver and lung tissues. Primary cell culture and tumor transplantation were carried out to evaluate the potential application in hepatocellular carcinoma (HCC) research. From 25 to 50 weeks of treatment, liver tumors, including macronodular HCC and ascites, were found in one-third (4/12) of the animals treated with DEN. HCC was characterized by poor differentiation, frequent mitosis, AFP reaction, vessel invasion and potential application in primary cell culture and xenotransplantation. Pre-neoplastic lesions were hyperplastic nodules comprised of clear cells, bile duct proliferation, fatty metamorphosis and multilocular cysts. The DEN-treated hamsters also showed lung tumors consisting of AFP-negative, well-differentiated neoplastic cells. Characterization of DEN-induced HCC in hamsters provides insights into human hepatocarcinogenesis. This animal model has potential applications in HCC research.

[Studies on the chemical constituents of Rubus parvifolius].

OBJECTIVE: To study the chemical constituents of Rubus parvifoliu. METHODS: The constituents were isolated by column chromatography and their structures were elucidated through spectroscopic analysis such as 1H-NMR, 13C-NMR, FT-IR, et al. RESULTS: Seven compounds were isolated from the roots of Rubus parvifolius L., they were identified as p-sitosterol (I), lauric acid (II), O-nitrophenol (III), beta-daucosterol (IV), euscaphic acid (V), camelliagenin A (VI) and(+) -catech in (VII). CONCLUSION: Compounds III and VII are isolated from the plant for the first time.

The impact of early rapid virological response on the outcomes of hepatitis B associated acute on chronic liver failure during antiviral treatment / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the impact of early rapid virological response on the outcomes of hepatitis B associated acute on chronic liver failure during antiviral treatment.</p><p><b>METHODS</b>106 acute on chronic liver failure patients in our hospital from January 2008 to July 2010 were enrolled in present study retrospectively. Besides internal medicine therapy, all patients received lamivudine (100 mg/d) or entecavir (0.5 mg/d) treatment. The profile of liver biochemistry, prothrombin time activity and viral load were detected at baseline and week 4, respectively. The patients were divided into HBV DNA negative group and HBV DNA positive group according to the viral load at week 4. The clinical features and treatment outcomes were compared between groups. Frequency variables were compared by x2 test or Fisher's exact test. Continuous variables were compared using independent samples T-test. The factors that impact on the treatment outcomes were determined using stepwise multivariate logistic regression analysis.</p><p><b>RESULTS</b>At the week 4, the TBil and PTA in HBV DNA positive group [(261.6+/-205.6)mumol/L and 44.7%+/-19.7%, respectively] were significantly different from those in HBV DNA negative group [(160.1+/-173.4) mumol/L and 56.8%+/-23.1%, respectively] ( t = 2.190 and -2.077, respectively, P less than 0.05). The non-effective rate of HBVDNA positive group (50%, 9/18) was significantly higher than that of HBV DNA negative group (14.8%, 13/88) (x2 = 9.235, P less than 0.01). By using stepwise multivariate logistic regression analysis, the disease stage and HBV DNA undetectable at week 4 were the independent factor. The OR values of disease stage and HBV DNA undetectable were 6.559 and 0.209, respectively, and 95% CI was 2.316~18.576 and 0.058~0.747, respectively.</p><p><b>CONCLUSION</b>The rapid suppression of viral load by nucleotide analogue may improve the efficacy of hepatitis B associated acute on chronic liver failure treatment. The early rapid virological response within first 4 weeks may contribute to the prediction of the treatment outcomes.</p>

Distribution of CAG repeat number within androgen receptor gene in Chinese Han nationality and its application in genetic diagnosis for Kennedy's disease / 中华老年医学杂志

Objective To investigate the distribution of androgen receptor (AR) gene CAGrepeats in the Chinese Han nationality and its application in genetic diagnosis for Kennedy's disease (KD). MethodsRT-PCR,denaturing polyacrylamide gel electrophoresis (DPAGE) and gene sequencing were conducted for AR gene CAG repetition among 100 healthy controls and 28 patients diagnosed as motorneuron diseases,and the number of the repetition was counted. Results The healthy controls had a range of 15-31 times of CAG repetition,with an average of (23 ± 3) times.Among patients with motoneuron disease,3 cases with CAG repetition for more than 40 times (namely,46,47 and 47 times) were diagnosed as KD.The main clinical manifestations included slow progress of limb weakness,primarily in the proximal lower limbs,fatigue accompanied by myalgia,muscle jumping,muscle atrophy,elevated serum creatine kinase (CK) levels,neurogenic damage revealed by electromyogram (EMG) and androgen insensitivity.Conclusions The incidence of KDmay be underestimated in the Chinese population.Performing genetic diagnosis in patients with motor neuron disease for AR gene can improve clinical diagnosis and avoid misdiagnosis.