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Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a growing global health concern with no effective pharmacological treatments. SNP-630, a newly developed synthetic molecule with multiple mechanisms of action, and a mixture of two of its active metabolites (SNP-630-MS) inhibit CYP2E1 expression to prevent reactive oxygen species generation, thereby reducing the accumulation of hepatic triglycerides and lowering chemokine levels. This study investigated the SNP-630's potential to alleviate the liver injury in MASH and its efficacy in both a mouse model and patients with MASH to identify a drug candidate that targets multiple pathways implicated in MASH., Methods: SNP-630 and SNP-630-MS were separately administered to the MASH mouse model. The tolerability, safety, and efficacy of SNP-630-MS were also evaluated in 35 patients with MASH. The primary endpoint of the study was assessment of the changes in serum alanine aminotransferase (ALT) levels from baseline to week 12, while the secondary endpoints included the evaluation of liver inflammation, steatosis, and fibrosis parameters and markers., Results: SNP-630 treatment in mice improved inflammation, liver steatosis, and fibrosis compared with that in the MASH control group. Both SNP-630 and SNP-630-MS treatments markedly reduced ALT levels, hepatic triglyceride content, and the expression of inflammatory cytokines monocyte chemoattractant protein 1 and fibrotic collagen (i.e., Col1a1, Col3a1, and Timp1) in mice. In the clinical trial, patients treated with SNP-630-MS exhibited significant improvement in ALT levels at week 12 compared with baseline levels, with no reports of severe adverse events. This improvement in ALT levels surpassed that achieved with most other MASH candidates. SNP-630-MS demonstrated potential antifibrotic effects, as evidenced by a significant decrease in the levels of fibrogenesis-related biomarkers such as CCL4, CCL5, and caspase 3. Subgroup analysis using FibroScan measurements further indicated the efficacy of SNP-630-MS in ameliorating liver fibrosis., Conclusions: SNP-630 and SNP-630-MS demonstrated favorable results in mice. SNP-630-MS showed excellent tolerability in mice and patients with MASH. Efficacy analyses indicated that SNP-630-MS improved liver steatosis and injury in patients with MASH, suggesting that SNP-630 and 630-MS are promising therapeutic options for MASH. Larger scale clinical trials remain warranted to assess the efficacy and safety of SNP-630 in MASH., Trial Registration: ClinicalTrials.gov NCT03868566. Registered 06 March 2019-Retrospectively registered, https://clinicaltrials.gov/study/NCT03868566., (© 2024. The Author(s).)

Objective: To detect the pharmacokinetic (PK) parameters of coagulation factor Ⅷ (FⅧ) in adult patients with severe hemophilia A, identify the potential factors influencing FⅧ PK, and optimize the use of FⅧ in individual prophylaxis regimens., Methods: PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults. The correlation of patients' characteristics including age, von Willebrand factor antigen (vWF:Ag), blood group, weight, body mass index (BMI) and FⅧ genotype, with FⅧ PK were evaluated. Individual prophylaxis regimens were given based on FⅧ PK parameters., Results: The mean terminal half‑life (t 1/2 ) of FⅧ was 20.6±9.3 h, ranged from 11.47 h to 30.12 h. The age ( r =0.580) and vWF:Ag ( r =0.814) were significantly positively correlated with t 1/2 of FⅧ. The mean area under the plasma concentration curve (AUC) of FⅧ was 913±399 (328-1 878) IU·h/dl, and the AUC of FⅧ was positively correlated with age ( r =0.557) and vWF:Ag ( r =0.784). The mean residence time (MRT) of FⅧ was 24.7±12.4 (13.2-62.2) h, and the MRT of FⅧ was positively correlated with age ( r =0.664) and vWF:Ag ( r =0.868). The mean in vivo recovery (IVR) of FⅧ was 2.59±0.888 (1.5-4.29) IU/dl per IU/kg, the mean clearance (CL) of FⅧ was 3±1.58（0.97-7.18）ml/(kg·h)，and there was no significant correlation of IVR and CL with age and vWF:Ag. According to the individual PK parameters, ultra low-dose, low-dose and moderate-dose FⅧ were applied to 15, 6, 2 adults patients with severe hemophilia A for prophylaxis, respectively., Conclusion: There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A. The older the patient, the higher the vWF:Ag level, and the longer the FⅧ half-life. Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.

The impact of milk on bone health in rural preschoolers is under-researched. This study, through a clinical trial and a meta-analysis, finds that milk supplementation enhances forearm and calcaneus bone acquisition in children, supporting the benefits of daily milk consumption., Purpose: This study evaluated the impact of dairy supplementation on bone acquisition in children's limbs through a cluster-randomized controlled trial and a meta-analysis., Methods: The trial involved 315 children (4-6 year) from Northwest China, randomized to receive either 390 ml of milk daily (n = 215) or 20-30 g of bread (n = 100) over 12 months. We primarily assessed bone mineral density (BMD) and content (BMC) changes at the limbs, alongside bone-related biomarkers, measured at baseline, the 6th and 12th months. The meta-analysis aggregated BMD or BMC changes in the forearm/legs/calcaneus from published randomized trials involving children aged 3-18 years supplemented with dairy foods (vs. control group)., Results: Of 278 completed the trial, intention-to-treat analysis revealed significant increases in BMD (4.05% and 7.31%) and BMC (4.69% and 7.34%) in the left forearm at the 6th and 12th months in the milk group compared to controls (P < 0.001). The calcaneus showed notable improvements in BMD (2.01%) and BMC (1.87%) at 6 months but not at 12 months. Additionally, milk supplementation was associated with beneficial changes in bone resorption markers, parathyroid hormone (- 12.70%), insulin-like growth factor 1 (6.69%), and the calcium-to-phosphorus ratio (2.22%) (all P < 0.05). The meta-analysis, encompassing 894 children, indicated that dairy supplementation significantly increased BMD (SMD, 0.629; 95%CI: 0.275, 0.983) and BMC (SMD, 0.616; 95%CI: 0.380, 0.851) (P < 0.05) in the arms, but not in the legs (P > 0.05)., Conclusion: Milk supplementation significantly improves bone health in children's forearms, underscoring its potential as a strategic dietary intervention for bone development. Trial registration NCT05074836., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Cancer immunotherapy has recently emerged as a key strategy for cancer treatment. TREM2, a key target for regulating the tumor immune microenvironment, is important in cancer treatment and progression. TREM2 is an immune signaling hub that regulates multiple pathological pathways. It not only suppresses anti-tumor immune responses by inhibiting T cell-mediated immune responses, but it also influences tumorigenesis by affecting NK cell-mediated anti-tumor immunity. Noticeably, TREM2 expression levels also vary significantly among different tumor cells, and it can regulate tumor progression by modulating various signaling pathways. Above all, by summarizing the role of TREM2 in cancer immunotherapy and the mechanism by which TREM2 regulates tumor progression, this paper clarifies TREM2's role in both tumor progression and cancer therapy, identifying a new therapeutic target for oncology diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lei, Gou, Hao and Huang.)

Objective: Fibroblast-like synoviocytes (FLS) play a critical role on the exacerbation and deterioration of rheumatoid arthritis (RA). Aberrant activation of FLS pyroptosis signaling is responsible for the hyperplasia of synovium and destruction of cartilage of RA. This study investigated the screened traditional Chinese medicine berberine (BBR), an active alkaloid extracted from the Coptis chinensis plant, that regulates the pyroptosis of FLS and secretion of inflammatory factors in rheumatoid arthritis., Methods: First, BBR was screened using a high-throughput drug screening strategy, and its inhibitory effect on RA-FLS was verified by in vivo and in vitro experiments. Second, BBR was intraperitoneally administrated into the collagen-induced arthritis rat model, and the clinical scores, arthritis index, and joint HE staining were evaluated. Third, synovial tissues of CIA mice were collected, and the expression of NLRP3, cleaved-caspase-1, GSDMD-N, Mst1, and YAP was detected by Western blot., Results: The administration of BBR dramatically alleviated the severity of collagen-induced arthritis rat model with a decreased clinical score and inflammation reduction. In addition, BBR intervention significantly attenuates several pro-inflammatory cytokines (interleukin-1β, interleukin-6, interleukin-17, and interleukin-18). Moreover, BBR can reduce the pyroptosis response (caspase-1, NLR family pyrin domain containing 3, and gasdermin D) of the RA-FLS in vitro, activating the Hippo signaling pathway (Mammalian sterile 20-like kinase 1, yes-associated protein, and transcriptional enhanced associate domains) so as to inhibit the pro-inflammatory effect of RA-FLS., Conclusion: These results support the role of BBR in RA and may have therapeutic implications by directly repressing the activation, migration of RA-FLS, which contributing to the attenuation of the progress of CIA. Therefore, targeting PU.1 might be a potential therapeutic approach for RA. Besides, BBR inhibited RA-FLS pyroptosis by downregulating of NLRP3 inflammasomes (NLRP3, caspase-1) and eased the pro-inflammatory activities via activating the Hippo signaling pathway, thereby improving the symptom of CIA., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

The Qinghai-Tibet Plateau is the key and largest ecological hotspot globally with enormous multiple ecosystem services. The vast and unique alpine ecosystems in this area have been subjected to the increased human disturbances, such as intensified land use. To explore the magnitude, spatiotemporal pattern and transformation process of land use in the Qinghai-Tibet Plateau and their impacts on the major ecosystem services during 1980-2020, we used the Integrated Valuation of Ecosystem Services and Trade-offs model to simulate the spatiotemporal variations of three types of ecosystem services, including habitat quality, carbon storage, and water yield. We analyzed the impacts of land use change on ecosystem services. The findings revealed that land use pattern remained generally stable from 1980 to 2020, with alpine grassland and desert as the dominant land use types. Habitat quality had generally enhanced, while carbon storage and water yield increased firstly and then declined. The magnitudes of three services gradually increased from the northwest to the southeast, corresponding to the spatial transformation pattern from desert via grassland to forest. The correlation between land use intensity and ecosystem services showed significant spatial heterogeneity, particulaly in counties greatly affected by land use intensity which concentrated predominantly in the mid-west, southern, and mid-east regions of the Qinghai-Tibet Plateau. The results have certain guiding significance for formulating land use policy and regulating land use pattern of alpine ecosystems in the Qinghai-Tibet Plateau.

Recent studies have demonstrated that ovarian granular cells (OGCs) pyroptosis is present in the ovaries of polycystic ovary syndrome (PCOS) mice and that NLRP3 activation destroys follicular functions. Metformin has been shown to protect against PCOS by reducing insulin resistance in women, whereas its role in OGC pyroptosis is unknown. This study aimed to investigate the impact of metformin on OGC pyroptosis and the underlying mechanisms. The results showed that treating a human granulosa-like tumor cell line (KGN) with metformin significantly decreased LPS-induced expression of miR-670-3p, NOX2, NLRP3, ASC, cleaved caspase-1, and GSDMD-N. Cellular caspase-1 activity; ROS production; oxidative stress; and the secretion of IL-1β, IL-6, IL-18, and TNF-α were also diminished. These effects were amplified by adding N-acetyl-L-cysteine (NAC), a pharmacological inhibitor of ROS. In contrast, metformin's anti-pyroptosis and anti-inflammatory effects were robustly ameliorated by NOX2 overexpression in KGN cells. Moreover, bioinformatic analyses, RT-PCR, and Western blotting showed that miR-670-3p could directly bind to the NOX2 (encoded by the CYBB gene in humans) 3'UTR and decrease NOX2 expression. Metformin-induced suppression of NOX2 expression, ROS production, oxidative stress, and pyroptosis was significantly alleviated by transfection with the miR-670-3p inhibitor. These findings suggest that metformin inhibits KGN cell pyroptosis via the miR-670-3p/NOX2/ROS pathway.

Dairy foods are crucial for adequate calcium intake in young children, but scarce data are available on the effects of formula milk on bone acquisition. This cluster-randomized controlled trial investigated the effects of the supplementation of formula milk on bone health in rural children accustomed to a low-calcium diet between September 2021 and September 2022. We recruited 196 healthy children aged 4-6 years from two kindergartens in Huining County, Northwest China. A class-based randomization was used to assign them to receive 60 g of formula milk powder containing 720 mg calcium and 4.5 µg vitamin D or 20-30 g of bread per day for 12 months, respectively. Bone mineral density (BMD) and bone mineral content (BMC) at the left forearm and calcaneus, bone biomarkers, bone-related hormones/growth factors, and body measures were determined at baseline, 6, and 12 months. A total of 174 children completed the trial and were included in the analysis. Compared with the control group, formula milk intervention showed significant extra increments in BMD (3.77% and 6.66%) and BMC (4.55% and 5.76%) at the left forearm at 6th and 12th months post-intervention (all p < 0.001), respectively. Similar trends were observed in BMD (2.83%) and BMC (2.38%) in the left calcaneus at 6 months ( p < 0.05). The milk intervention (vs. control) also showed significant changes in the serum concentrations of osteocalcin level (-7.59%, p = 0.012), 25-hydroxy-vitamin-D (+5.54%, p = 0.001), parathyroid hormone concentration (-15.22%, p = 0.003), and insulin-like growth factor 1 (+8.36%, p = 0.014). The percentage increases in height were 0.34%, 0.45%, and 0.42% higher in the milk group than in the control group after 3-, 6-, and 9-month intervention, respectively ( p < 0.05). In summary, formula milk supplementation enhances bone acquisition at the left forearm in young Chinese children.

The application of high hydrostatic pressure (HHP) technology in the food industry has generated potential safety hazards due to sub-lethally injured (SI) pathogenic bacteria in food products. To address these problems, this study explored the repair mechanisms of HHP-induced SI Escherichia coli O157:H7. First, the repair state of SI E. coli O157:H7 (400 MPa for 5 min) was identified, which was cultured for 2 h (37 °C) in a tryptose soya broth culture medium. We found that the intracellular protein content, adenosine triphosphate (ATP) content, and enzyme activities (superoxide dismutase, catalase, and ATPase) increased, and the morphology was repaired. The transcriptome was analyzed to investigate the molecular mechanisms of SI repair. Using cluster analysis, we identified 437 genes enriched in profile 1 (first down-regulated and then tending to be stable) and 731 genes in profile 2 (up-regulated after an initial down-regulation). KEGG analysis revealed that genes involved in cell membrane biosynthesis, oxidative phosphorylation, ribosome, and aminoacyl-tRNA biosynthesis pathways were enriched in profile 2, whereas cell-wall biosynthesis was enriched in profile 1. These findings provide insights into the repair process of SI E. coli O157:H7 induced by HHP.

Antibiotic treatment of endometritis was limited by the inevitable antibiotic residues and risk of bacterial resistance. Therefore, the development of safe and effective strategies for endometritis treatment is urgently needed. Syringa oblata Lindl. (SOL) showed great pharmacological potential against endometritis. However, the active components and underlying mechanism of SOL for endometritis treatment remain indeterminate. In our study, the active components and possible molecular mechanism of SOL against endometritis were predicted through computer data mining and biological networks construction. It was predicted that the main active components of SOL were luteolin, kaempferol, oleanolic acid, and rutin, and their anti-endometritis effect was mainly attributed to the TLRs/NF-κB signaling pathway. Furthermore, a green and efficient deep eutectic solvent combined with ultrasound-assisted extraction (DES-UAE) was performed and optimized to obtain high contents of total flavonoid, rutin, and luteolin. The four predicted active components in the SOL extracts were qualitatively and quantitatively analyzed by LC/MS and HPLC. Finally, the pharmacological effects of SOL and active components have been verified by Staphylococcus aureus -endometritis models in mice. H&E staining and bacterial load in uterus tissues assays initially validated the pharmacodynamic effects of SOL, and quantitative real-time PCR (RT-qPCR) and ELISA results confirmed that SOL and four active components could ameliorate the uterus injury caused by Staphylococcus aureus , the mechanism of action is related to the TLRs/NF-κB signaling pathway., (Copyright © 2022 Wang, Song, Liu, Xing, Wu, Zhang, Su, Hao, Chen, Zhang, Li and Liu.)

Background: Owing to limited data, the effect of cardiac dysfunction categorized according to the Killip classification on gastrointestinal bleeding (GIB) in patients with acute myocardial infarction (AMI) is unclear. The present study aimed to investigate the impact of cardiac dysfunction on GIB in patients with AMI and to determine if patients in the higher Killip classes are more prone to it., Methods: This retrospective study was comprised of patients with AMI who were admitted to the cardiac intensive care unit in the Heart Center of the Beijing Chaoyang Hospital between December 2010 and June 2019. The in-hospital clinical data of the patients were collected. Both GIB and cardiac function, according to the Killip classification system, were confirmed using the discharge diagnosis of the International Classification of Diseases, Tenth Revision coding system. Univariate and multivariate conditional logistic regression models were constructed to test the association between GIB and the four Killip cardiac function classes., Results: In total, 6,458 patients with AMI were analyzed, and GIB was diagnosed in 131 patients (2.03%). The multivariate logistic regression analysis showed that the risk of GIB was significantly correlated with the cardiac dysfunction [compared with the Killip class 1, Killip class 2's odds ratio ( OR ) = 1.15, 95% confidence interval ( CI ): 0.73-1.08; Killip class 3's OR = 2.63, 95% CI : 1.44-4.81; and Killip class 4's OR = 4.33, 95% CI : 2.34-8.06]., Conclusion: This study demonstrates that the degree of cardiac dysfunction in patients with acute myocardial infarction is closely linked with GIB. The higher Killip classes are associated with an increased risk of developing GIB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Feng, Wang, Liu, Ren, Hao, Li and Chen.)

Background: Biliary strictures after liver transplantation (LT) remain clinically arduous and challenging situations, and endoscopic retrograde cholangiopancreatography (ERCP) has been considered as the gold standard for the management of biliary strictures after LT. Nevertheless, in the treatment of biliary strictures after LT with ERCP, many studies show that there is a large variation in diagnostic accuracy and therapeutic success rate. Digital single-operator peroral cholangioscopy (DSOC) is considered a valuable diagnostic modality for indeterminate biliary strictures., Aim: To evaluate DSOC in addition to ERCP for management of biliary strictures after LT., Methods: Nineteen patients with duct-to-duct biliary reconstruction who underwent ERCP for suspected biliary complications between March 2019 and March 2020 at Beijing Chaoyang Hospital, Capital Medical University, were consecutively enrolled in this observational study. After evaluating bile ducts using fluoroscopy, cholangioscopy using a modern digital single-operator cholangioscopy system (SpyGlass DS™) was performed during the same procedure with patients under conscious sedation. All patients received peri-interventional antibiotic prophylaxis. Biliary strictures after LT were classified according to the manifestations of choledochoscopic strictures and the manifestations of transplanted hepatobiliary ducts., Results: Twenty-one biliary strictures were found in a total of 19 patients, among which anastomotic strictures were evident in 18 (94.7%) patients, while non-anastomotic strictures in 2 (10.5%), and space-occupying lesions in 1 (5.3%). Stones were found in 11 (57.9%) and loose sutures in 8 (42.1%). A benefit of cholangioscopy was seen in 15 (78.9%) patients. Cholangioscopy was crucial for selective guidewire placement prior to planned intervention in 4 patients. It was instrumental in identifying biliary stone and/or loose sutures in 9 patients in whom ERCP failed. It also provided a direct vision for laser lithotripsy. A space-occupying lesion in the bile duct was diagnosed by cholangioscopy in one patient. Patients with biliary stricture after LT displayed four types: (A) mild inflammatory change ( n = 9); (B) acute inflammatory change edema, ulceration, and sloughing ( n = 3); (C) chronic inflammatory change; and (D) acute suppurative change. Complications were seen in three patients with post-interventional cholangitis and another three with hyperamylasemia., Conclusion: DSOC can provide important diagnostic information, helping plan and perform interventional procedures in LT-related biliary strictures., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To design and develop a disposable superfine catheter system for visual examination of bile and pancreatic ducts and predict its clinical application value., Methods: The superfine triple-lumen catheter and miniature photography technology were used to design and produce a disposable superfine catheter for visual examination of bile and pancreatic ducts, and animal experiments were conducted to compare said catheter and SpyGlass™., Results: The designed and developed disposable superfine catheter for visual examination of bile ducts with a diameter of 2.4 mm could enter the third-order and fourth-order bile ducts in the animal liver and also the gallbladder via the cystic duct for observation. The said catheter has a water injection rate of 0.8 mL/s, 0.16 megapixels, a resolution of 400 × 400, a depth of field of 0.3 to 20 mm, and a tilting up angle >90°., Conclusion: The new disposable catheter for visual examination of bile ducts has a superfine diameter, easier operation, and clearer imaging, and is expected to have a higher clinical practical value., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hao, Zhang and Huang.)

BACKGROUND This retrospective study from 2 centers in Beijing, China aimed to assess the safety and efficacy of endoscopic radiofrequency therapy under direct vision in 59 patients with gastroesophageal reflux disease (GERD) using the gastroesophageal reflux disease questionnaire (GerdQ). MATERIAL AND METHODS Fifty-nine GERD patients who underwent endoscopic radiofrequency treatment were included. Patients were divided into 2 groups: the endoscopic radiofrequency therapy under direct vision group and the non-direct vision radiofrequency therapy group. Indicators such as GerdQ score, lower esophageal sphincter (LES) pressure, DeMeester score, acid exposure time, and proton pump inhibitors (PPIs) use were collected before and after radiofrequency treatment. Postoperative complications were also recorded. The efficacy and safety of endoscopic radiofrequency therapy under direct vision were evaluated by comparing the indicators of patients in the 2 groups. RESULTS At 3 months after radiofrequency treatment, patients in the endoscopic radiofrequency therapy under direct vision group improved significantly in GerdQ score, decreased from 11.0 (10.0, 12.0) to 6.0 (6.0, 8.0), better than patients in the non-direct vision radiofrequency therapy group, and the better improvements remained at 12 months after the procedure (P<0.05). At 6 months after treatment, patients in the endoscopic radiofrequency therapy under direct vision group had significant improvements in LES pressure, which increased from 8.15 (3.18, 12.88) mmHg to 15.20 (10.25, 27.03) mmHg (P<0.05). There were no severe complications in our trial. CONCLUSIONS When compared with non-visualized endoscopic radiofrequency therapy, treatment under direct vision was safer and improved the GerdQ score and LES pressure at up to 12 months.

Licorice (Glycyrrhiza glabra) is extensively used owing to the superior pharmacological effects. However, its maximum application potential has not been fully exploited due to the limitation of currently available extraction solvent and methods. In this study, an eco-friendly deep eutectic solvent (NADESs) based ultrasound-assisted extraction (DES-UAE) method was applied to prepare licorice extracts. The DES-UAE using choline chloride and lactic acid as solvent was optimized and modeled by using response surface methodology to maximize the extraction yields of glabridin (GLA) and isoliquiritigenin (ISL). The optimized extracts possessed higher contents of GLA and ISL than available extraction methods, and the enriched products showed superior pharmacological activities in vitro. Furthermore, scanning electron microscopy (SEM) and molecular dynamic simulation analyses were performed to deeply investigate the interaction between solvent and targeted compounds. This study not only provides an eco-friendly method for high-efficient extraction of GLA and ISL from licorice but also illustrates the mechanism of the increased extraction efficacy, which may contribute to the application of licorice and deep insight into extraction mechanism using DES., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: We aimed to establish a standardized procedure for white light gastroscopy (WLG) to screen gastric lesions including early gastric cancer (EGC) in China and to verify its efficacy and feasibility in clinical practice., Methods: A standardized WLG procedure for outpatients at nine tertiary hospitals in Beijing was established. Clinical information of the participants and details of the endoscopic procedures were recorded., Results: A total of 1051 participants were enrolled in a baseline conventional endoscopic survey between March 2014 and December 2015, while 2156 patients were enrolled in the standardized WLG operation from January 2016 to June 2017. The procedure time of the standardized procedure was significantly longer than that of the baseline conventional procedure (P = 0.003). More images were obtained during the standardized procedure compared with the baseline conventional procedure (P < 0.001). The overall detection rate of gastric lesions in the standardized procedure group was significantly higher than that in the baseline procedure group (52.5% vs 38.4%, P < 0.01). The satisfaction scores of both participants and endoscopists in the standardized procedure group were significantly higher than in the baseline procedure group., Conclusions: Compared with the conventional procedure, standardized WLG procedure significantly improves the detection rate of gastric lesions as well as the satisfaction score of participants and endoscopists despite its longer procedure time. It is effective and feasible in clinical practice in China for the use of currently available endoscopic equipment., (© 2021 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Limited data were available on the current trends in optimal medical therapy (OMT) after PCI and its influence on clinical outcomes in China. We aimed to evaluate the utilization and impact of OMT on the main adverse cardiovascular and cerebrovascular events (MACCEs) in post-PCI patients and analyzed the factors predictive of OMT after discharge., Methods: We collected data from 3812 individuals from 2016.10 to 2017.09 at TEDA International Cardiovascular Hospital. They were classified into an OMT group and a non-OMT group according to their OMT status, which was defined as the combination of dual antiplatelet therapy, statins, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after PCI. Multivariable Cox regression models were developed to assess the association between OMT and MACCEs, defined as all-cause mortality, nonfatal myocardial infarction, stroke, and target vessel revascularization. A logistic regression model was established to analyze the factors predictive of OMT., Results: Our results revealed that the proportion of patients receiving OMT and its component drugs decreased over time. A total of 36.0% of patients were still adherent to OMT at the end of follow-up. Binary logistic regression analysis revealed that baseline OMT (P < 0.001, OR = 52.868) was the strongest predictor of OMT after PCI. The Cox hazard model suggested that smoking after PCI was associated with the 1-year risk of MACCE (P = 0.001, HR = 2.060, 95% CI 1.346-3.151), while OMT (P = 0.001, HR = 0.486, 95% CI 0.312-0.756) was an independent protective factor against postoperative MACCEs., Conclusions: There was still a gap between OMT utilization after PCI and the recommendations in the evidence-based guidelines. Sociodemographic and clinical factors influence the application of OMT. The management of OMT and smoking cessation after PCI should be emphasized.

Objective: To investigate the effect of mild hypothermia therapy on liver after cardiopulmonary resuscitation. Methods: Thirty-three inbred Chinese Wuzhishan (WZS) minipigs, weighted (28±2) kg, were used to establish a ventricular fibrillation model. And 30 animals survived after cardiopulmonary resuscitation reached basic life support. The surviving animals were randomly divided into two groups: mild hypothermia group (group M, n= 15) and conventional treatment group (group C, n= 15). All the animals were observed for 24 hours. Blood samples were extracted at baseline, 0.5, 1, 2, 4, 6, 12 and 24 h after successful resuscitation. The concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected at the time points. The enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α). The data were compared between the two groups, LSD test was used when the variance was homogeneous, and Tamhane T2 test was used when the variance was uneven. Results: Eleven pigs (73.3%) in the group M and 8(53.3%) in the group C survived at 24 h after successful resuscitation, with no statistically significant difference between the two groups (χ(2)=1.229, P= 0.225). After successful resuscitation, the AST, ALT increased in both group but less in M group (all P< 0.05). After successful resuscitation, the concentrations of TFN-α and IL-6 in the blood increased in both groups, reached the peak at 4h, and then decreased gradually. The concentrations of TFN-α in group M were lower than those in group C at 0.5, 2, 4 and 6 h after successful resuscitation ( t= 0.01, 0.01, 0.87, 0.86, all P< 0.05). The concentrations of IL-6 in the group M were lower than those in group C at 0.5, 1, 2 and 4 h after successful resuscitation ( t= 0.23, 0.78, 0.11, 0.80, all P< 0.05). Conclusions: After successful resuscitation, the release of inflammatory mediators, such as TNF-α and IL-6, and cell apoptosis may involve in liver ischemia reperfusion injury. After successful resuscitation, the liver undergoes ischemia-reperfusion injury, which may be related to the release of inflammatory mediators such as TNF-α and IL-6. Mild hypothermia therapy can prevent the release of TNF-α, IL-6 to reduce the degree of liver damage after resuscitation.

The gut microbiota plays a critical role in obesity and lipid metabolism disorder. Chokeberry ( Aronia melanocarpa L . ) are rich in polyphenols with various physiological and pharmacological activities. We determined serum physiological parameters and fecal microbial components by using related kits, liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA gene sequencing every 10 days. Real-time PCR analysis was used to measure gene expression of bile acids (BAs) and lipid metabolism in liver and adipose tissues. We analyzed the effects of different Chokeberry polyphenol (CBPs) treatment time on obesity and lipid metabolism in high fat diet (HFD)-fed rats. The results indicated that CBPs treatment prevents obesity, liver steatosis and improves dyslipidemia in HFD-fed rats. CBPs modulated the composition of the gut microbiota with the extended treatment time, reducing the Firmicutes / Bacteroidetes ratio (F/B ratio) and increasing the relative abundance of Bacteroides , Prevotella , Akkermansia and other bacterial species associated with anti-obesity properties. We found that CBPs treatment gradually decreased the total BAs pool and particularly reduced the relative content of cholic acid (CA), deoxycholic acid (DCA) and enhanced the relative content of chenodeoxycholic acid (CDCA). These changes were positively correlated Bacteroides , Prevotella and negatively correlated with Clostridium , Eubacterium , Ruminococcaceae . In liver and white adipose tissues, the gene expression of lipogenesis, lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rats, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism. In addition, the mRNA expression of PPARγ, UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue (iBAT) after CBPs treatment. We confirmed that CBPs could reduce the body weight of HFD-fed rats by accelerating energy homeostasis and thermogenesis in iBAT. Finally, the fecal microbiota transplantation (FMT) experiment results demonstrated that FMT from CBPs-treated rats failed to reduce the weight of HFD-fed rats. However, FMT from CBPs-treated rats improved dyslipidemia and reshaped gut microbiota in HFD-fed rats. In conclusion, CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rats. The gut microbiota plays an important role in BAs metabolism after CBPs treatment, and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism, energy metabolism and thermogenesis., Competing Interests: Competing interestsThe authors declare no conflicts of interest., (© The Author(s) 2020.)

Objective: To investigate the frequency and clinical significance of RAS mutation in thyroid tumors with follicular differentiation. Methods: The samples and clinical data of 207 patients with thyroid follicular-differentiated tumors were collected at Shunyi Region Hospital of Beijing from January 2000 to December 2017, including 60 cases of follicular variant of papillary thyroid carcinoma (FVPTC), 42 cases of classical papillary thyroid carcinoma (CPTC), 26 cases of follicular thyroid carcinoma (FTC), 40 cases of follicular adenoma (FTA) and 39 cases of adenomatoid hyperplasia. BRAF V600E mutations were detected using immunohistochemical staining. FVPTC was divided into BRAF-like (BRAF V600E mutant) and RAS-like (without BRAF V600E mutant). Real-time fluorescence quantitative polymerase chain reaction was used to detect the RAS mutation in RAS-like FVPTC, CPTC, FTC, FTA and adenomatoid hyperplasia. The genetic differences in RAS mutation and their correlation with clinicopathological features were analyzed. Results: The average age of patients with benign and malignant tumors in thyroid with follicular differentiation was 53.2 years and 47.7 years, respectively. In these patients, 42 were male and165 were female. Most of the tumors had a maximum diameter of less than 4 cm, and rarely spread to the surrounding tissues of thyroid and were at early stage (stages Ⅰ and Ⅱ). The diameter of tumors in FTC was significantly larger than that in RAS-like FVPTC and CPTC groups ( P <0.01). Peripheral thyroid invasion was rare in the RAS-like FVPTC, CPTC and FTC groups, but the clinical stage of FTC was more advanced than that of RAS-like FVPTC group ( P <0.01) or CPTC group ( P <0.01). The real-time fluorescence quantitative PCR showed that the RAS mutation rate in FTC was the highest (61.5%), significantly higher than that in others ( P <0.01). The RAS mutation rate in CPTC was the lowest (4.8%), while those in RAS-like FVPTC, FTA and adenomatous hyperplasia were similar (about 15%). The Spearman rank correlation analysis showed that the RAS mutation was not correlated with age, sex or tumor size in benign lesions (FTA and adenomatous hyperplasia), nor was it associated with age, sex, tumor size, lymph node metastasis, spreading of tumors to thyroid and clinical stage in malignant tumors (RAS-like FVPTC, CPTC and FTC). Conclusions: RAS mutation can occur in both benign and malignant thyroid tumors with follicular differentiation, in which the incidence is the highest in FTC. Both morphologic and immunohistochemical changes should be taken into account. The molecular genetics of RAS-like FVPTC is similar to FTA and adenomatous hyperplasia. RAS gene mutation appears not to be a prognostic factor for thyroid diseases.

Gut microbiota constitute the largest reservoir of the human microbiome and are an abundant and stable ecosystem-based on its diversity, complexity, redundancy, and host interactions This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition of gut microbiota, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic-associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment., (© 2020 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

This study uses the national ambient air quality station data of Anyang City from 2014 to 2017 to analyze the characteristics and variation rules of ozone (O 3 ) in different functional zones (urban, suburban, and industrial), and also studies meteorological influencing factors and potential source distributions of O 3 pollution. The results showed that the O 3 concentration in Anyang increased significantly between 2014 and 2017, whereby pollution started to advance from 2015 and the earliest occurrence of an O 3 pollution episode was in April 2017. The 90 th percentile and average concentrations of O 3 in the industrial zone increased at faster rates (average annual growth of 16.0 μg·m -3 and 13.0 μg·m -3 , respectively) than of those in the urban and suburban zones. The O 3 concentrations at the suburban site showed the fastest increase of all zones at the 5 th percentile (average annual growth of 13.2 μg·m -3 ). The monthly variation in O 3 concentrations in Anyang showed an "M" pattern that varied spatially depending on the zone. Temperature played a leading role in O 3 concentrations; air temperatures >23℃, relative humidity <58%, and a wind speed of 5 m·s -1 in a south-southwesterly direction were closely related to the occurrence of high O 3 concentrations. Potential sources of O 3 in different seasons were significantly different, and mainly distributed in southern Hebei, northern Hubei, and northern Shenyang in summer. The first heavy O 3 pollution day in the studied period was in May 2017, at which time the highest O 3 concentration was found in the industrial zone (up to 405 μg·m -3 ). This heavy O 3 pollution episode was related to the continuous high temperature that was caused by the transfer of a dry, hot air mass in western China.

Background: Esophageal motility disorders which include achalasia, esophagogastric junction outflow obstruction (EGJ outflow obstruction), jackhammer esophagus (JE), distal esophageal spasm (DES), etc. are rare disease of unknown causes. The diagnosis is based on endoscopy, barium meal, and high-resolution manometry (HRM). With the development of endoscopy, peroral endoscopic myotomy (POEM) has emerged as a standard method for the treatment of achalasia., Purpose: The purpose of this article is to enable gastroenterologists to have a more comprehensive understanding of the application status, technical characteristics, clinical efficacy and future prospect of POEM in the treatment of esophageal motility disorders., Methods: Through a large number of reading literature, combined with clinical practice, summary and analysis of the indications, procedure, efficacy, complications, and controversies of POEM in the treatment of esophageal motility disorders, as well as the current and future perspectives of POEM were studied., Results: POEM is safe and effective in the treatment of esophageal motility disorders, but the GERD reflux rate is higher., Conclusions: POEM can be a new option for the treatment of esophageal movement disorders, but large sample, multi-center, long-term study reports are needed, and it promotes the development of NOTES technology.

Background: The Asia-Pacific Colorectal Screening (APCS) score is effective to screen high-risk groups of advanced colorectal neoplasia (ACN) patients but needs revising and can be combined with the fecal immunochemical test (FIT). This paper aimed to improve the APCS score and evaluate its use with the FIT in stratifying the risk of ACN., Methods: This prospective and multicenter study enrolled 955 and 1201 asymptomatic Chinese participants to form the derivation and validation set, respectively. Participants received the risk factor questionnaire, colonoscopy and FIT. Multiple logistic regression was applied, and C-statistic, sensitivity and negative predictive values (NPVs) were used to compare the screening efficiency., Results: A modified model was developed incorporating age, body mass index (BMI), family history, diabetes, smoking and drinking as risk factors, stratifying subjects into average risk (AR) or high risk (HR). In the validation set, the HR tier group had a 3.4-fold (95% CI 1.8-6.4) increased risk for ACN. The C-statistic for the modified score was 0.69 ± 0.04, and 0.67 ± 0.04 for the original score. The sensitivity of the modified APCS score combined with FIT for screening ACN high-risk cohorts was 76.7% compared with 36.7% of FIT alone and 70.0% of the modified APCS score alone. The NPVs of the modified score combined with FIT for ACN were 98.0% compared with 97.0% of FIT alone and 97.9% of the modified APCS score alone., Conclusions: The modified score and its use with the FIT are efficient in selecting the HR group from a Chinese asymptomatic population.

To elucidate the mechanism of soybean resistance to Al, physiological and biochemical indices and antioxidant enzyme expression and activities were systematically analyzed in Al-sensitive (Glycine max Merr., Yunnan Province of China, SB) and Al-resistant Dambo (Glycine max Merr., Kyoto of Japan, RB) black soybean plants. According to the results, the contents of hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) in RB root tips were significantly lower than those in SB root tips, though the opposite results occurred for soluble protein contents. Moreover, the expression and activities of superoxide dismutase (SOD, EC 1.15.1.1.1.1.1.1 ), peroxidase (POD, EC 1.11.1.7 ) and catalase (CAT, EC 1.11.1.6 ) under 0-400 μM Al for 0-96 h were greater in RB than in SB. However, below 100 μM Al, the activities of those enzymes in SB increased with increasing Al concentration and treatment duration, with SOD activity being lowest and CAT activity exceeding that of POD with increasing Al concentration. Overall, enzyme activity in SB treated with Al at concentrations greater than 200 μM was lower than that in the SB control (CK; not treated with Al) and decreased with treatment duration. Additionally, at Al concentrations lower than 200 μM, enzyme activities in RB were significantly greater than those in RB CK and increased with both Al concentration and treatment duration. Moreover, enzyme activity in RB treated with 400 μM Al was slightly greater than that in RB CK. Thus, CAT activity determines soybean resistance to Al. These results indicate that soybean resistance to Al can be enhanced by regulating the expression and activity of antioxidant enzymes to remove H 2 O 2 under Al stress., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

We analyzed the sequences of sirt4 and sirt6 and their changes in expression after oral glucose administration in blunt snout bream (Megalobrama amblycephala). We cloned sirt4 and sirt6 and found that their full-length cDNA sequences were 1530 bp and 1723 bp, respectively; their amino acid sequences were 93% and 92% identical to Danio rerio. Megalobrama amblycephala were fed a high glucose solution (3 g/kg). Normally, sirt4 expression is higher in spleen, intestine, and gill (P < .05), and sirt6 expression is higher in intestine and gill (P < .05). After oral glucose administration, sirt4 and sirt6 expression increased in liver and gill, and sirt4 expression increased in intestine at 0.5 h (P < .05). In contrast, sirt4 in kidney and sirt6 in head kidney were downregulated at 1 h (P < .05). Expression of sirt4 was upregulated in brain, head kidney, spleen, muscle, and liver 2 h, 4 h, 4 h/24 h, 8 h, and 24 h, respectively (P < .05). Expression of sirt4 was downregulated in kidney at 8 h-48 h (P < .05). Expression of sirt6 was upregulated in intestine, liver, muscle, kidney, and spleen at 4 h/24 h, 8 h/24 h, 12 h, 12 h, and 24 h, respectively (P < .05). We report that sirt4 and sirt6 are highly conserved in evolution and exhibit tissue-specific expression profiles. We demonstrate that the expression of sirt4 and sirt6 are tissue-specific, and depend upon tissue-specific responses to glucose metabolism., (Copyright © 2019 Elsevier Inc. All rights reserved.)

With the digestive endoscopic tunnel technique (DETT), many diseases that previously would have been treated by surgery are now endoscopically curable by establishing a submucosal tunnel between the mucosa and muscularis propria (MP). Through the tunnel, endoscopic diagnosis or treatment is performed for lesions in the mucosa, in the MP, and even outside the gastrointestinal (GI) tract. At present, the tunnel technique application range covers the following: (1) Treatment of lesions originating from the mucosal layer, e.g ., endoscopic submucosal tunnel dissection for oesophageal large or circular early-stage cancer or precancerosis; (2) treatment of lesions from the MP layer, per-oral endoscopic myotomy, submucosal tunnelling endoscopic resection, etc .; and (3) diagnosis and treatment of lesions outside the GI tract, such as resection of lymph nodes and benign tumour excision in the mediastinum or abdominal cavity. With the increasing number of DETTs performed worldwide, endoscopic tunnel therapeutics, which is based on DETT, has been gradually developed and optimized. However, there is not yet an expert consensus on DETT to regulate its indications, contraindications, surgical procedure, and postoperative treatment. The International DETT Alliance signed up this consensus to standardize the procedures of DETT. In this consensus, we describe the definition, mechanism, and significance of DETT, prevention of infection and concepts of DETT-associated complications, methods to establish a submucosal tunnel, and application of DETT for lesions in the mucosa, in the MP and outside the GI tract (indications and contraindications, procedures, pre- and postoperative treatments, effectiveness, complications and treatments, and a comparison between DETT and other operations)., Competing Interests: Conflict-of-interest statement: All authors have no financial relationships to disclose.

Flos Lonicerae was an important Chinese medicine. In this research, a microwave assisted extraction method was applied for the extraction of chlorogenic acid from Flos Lonicerae. The operating conditions were optimized using a Box-Behnken design test. Under the optimal conditions, the extraction yield of chlorogenic acid reached 32.52 ± 1.31 mg/g. Next, a direct analysis in real time mass spectrometry (DART-MS) method was utilized to quantify of chlorogenic acid in Flos Lonicerae extracts. The primary parameters were optimized to obtain maximum signal intensity. In the detection process of the actual samples, the results obtained by DART-MS are consistent with those obtained by HPLC method with short detection time and acceptable repeatability and precision (<15%). In addition, the DART-MS/MS method has several advantages, such as speed, low cost and simplicity. Therefore, the DART-MS method is an efficient method that can be applied in the quantification of chlorogenic acid in Flos Lonicerae., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Academic papers are an essential manner for describing new ideas and consolidating existing concepts in the field of military medicine. The academic impact of military medical publications reflects the extent and depth of recognition, acceptance and utilisation of the concepts transmitted in these publications. The aim of this research was to construct an evaluation index system suitable for evaluating the academic influence of scholars in the field of military medicine., Methods: Using the Delphi consensus methodology, 30 experts from the field of military medicine, military medical information and library and information science were asked during three rounds of questioning to score the feasibility and importance of indicators that could be used to determine academic impact. An analytic hierarchy process method was used to calculate the relative weighting of each indicator in determining the final level of academic impact., Results: Eight evaluation indicators were agreed on to potentially determine academic impact. These comprised: 'Web of Science documents', 'Citation impact', 'h-index', 'Percentage of international collaborations', 'Percentage of the top 10% of the cited frequency', 'Category normalised citation impact', 'Percentage of documents cited' and 'The number of F1000 Recommended papers'., Conclusions: The evaluation index system determined from this study combines the advantages of both qualitative and quantitative recognised evaluation indicators, which are subsequently weighted according to their importance in the field of military medicine. It is hoped that this framework will provide a manner in the future for comparing the potential academic impact of military medical scholars., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Guangdong, Guangxi and Chongqing are emerging sericulture areas in China where the production of mulberry leaves is huge. In order to identity high quality mulberry leaves that are suitable for healthy products to expand planting, 24 samples from three regions (Guangdong, Guangxi, Chongqing) in the south of China were quantified for two alkaloids (1-deoxynojirimycin and fagomine) and five phenols (chlorogenic acid, rutin, isoquercitrin, etc.) using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Additionally, the total phenolic and total flavonoid contents, antioxidant and glycosidase inhibitory activities (hypoglycemic activity) were tested using different assays (DPPH, ABTS, FRAP) to comprehensively evaluate the quality of the mulberry leaves. The contents of DNJ and fagomine ranged from 0.401±0.003 to 5.309±0.036 mg/g and from 0.279±0.031 to 2.300±0.060 mg/g, respectively. The main phenolic constituents were chlorogenic acid, rutin and isoquercitrin, with chlorogenic acid present in the highest concentrations, ranging from 3.104±0.191 to 10.050±0.143 mg/g. The antioxidant activity exhibited a tendency as follows: Guangxi > Guangdong > Chongqing, except for two samples from Chongqing, which showed the highest antioxidant activity. Based on our study, mulberry leaves from Guangdong and Guangxi could be future sources of natural hypoglycemic and antioxidant products., Competing Interests: The authors have declared that no competing interests exist.

To improve the release profile of peptide drugs, thermos-responsive triblock copolymer poly (ε-caprolactone-co-p-dioxanone)-b-poly (ethylene glycol)-b-poly (ε-caprolactone-co-p-dioxanone) (PECP) was prepared and end capped by succinic anhydride to give its carboxylic terminated derivative. Both PCEP block copolymer and its end group modified derivative showed temperature-dependent reversible sol-gel transition in water. The carboxylic end group could significantly decrease the sol-gel transition temperature by nearly 10 °C and strengthen the gel due to enhanced intermolecular force among triblock copolymer chains. Furthermore, compared with the original PECP triblock copolymer, HOOC-PECP-COOH copolymer displayed a retarded and sustained release profile for leuprorelin acetate over one month while effectively avoiding the initial burst. The controlled release was believed to be related to the formation of conjugated copolymer-peptide pair by ionic interaction and enhanced solubility of drug molecules into the hydrophobic domains of the hydrogel. Therefore, carboxyl terminated HOOC-PECP-COOH hydrogel was a promising and well-exhibited sustained release carrier for peptide drugs with the advantage of being able to develop injectable formulation by simple mixing., Competing Interests: The authors declare no conflict of interest.

In the present study, porous magnetic cellulose beads (CBs) were prepared and further modified using amines. The CBs appeared to have good spherical shape and three-dimensional (3D) porous structure. In the adsorption tests, the modified cellulose beads (MCBs) showed better adsorption capacities and shorter adsorption times on hyperin and 2'-O-galloylhyperin than the commercial resins. The adsorption may be due to the hydrogen bonding between the target compounds and the amine groups of MCBs. After adsorption and desorption, the contents of hyperin and 2'-O-galloylhyperin reached 1.32% and 3.92%, which were 4.08 and 4.23 times higher than those in the Pyrola extracts. Therefore, the prepared MCBs in this study make an excellent adsorbing material of hyperin and 2'-O-galloylhyperin, and it may have potential for the separation of other natural compounds., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective To observe clinical efficacy of raw rhubarbs (by intranasal jejuna injection) for moderately severe acute pancreatitis (MSAP) , and its effects on gastrointestinal tract and coagulation fibrinolysis. Methods Totally 84 MSAP patients were randomly assigned to the control group and the treatment group by random number table, 42 in each group. All patients received routine medica- tion. Enteral nutrition by intranasal jejuna injection was input under the endoscope within 48 h of onset. Pa- tients in the treatment group additionally used raw rhubarbs (by intranasal jejuna injection) , 100 mL each time, twice per day, with the treatment duration for 3 -7 days. The recovery of gastrointestinal tract func- tion (passage of gas by anus, recovery time of bowel sound, distension disappearance time, abdominal pain disappearance time) was observed, prothrombin time (PT) , activated partial thromboplastin time (APTT), thrombin time (TT) , fibrinogen (Fib) content, platelet (PLT) count, D-dimer (DD), protein C were determined. Clinical efficacy was assessed as well. Results Compared with the control group, time for gas passage by anus, recovery time of bowel sound, distension disappearance time, and ab- dominal pain disappearance time were shortened, PT, APTT, Fib content, thrombin time, and DD decreased, and protein C increased in the treatment group (P <0. 05). The incidence rate of complications was lower in the treatment group than in the control group (P <0. 05). The cure rate was elevated (P < 0. 05). There was no statistical difference in the total effective rate between the two groups (P >0. 05). Conclusion Intranasal jejuna injection of raw rhubarbs in treating moderately severe acute pancreatitis could improve symptoms of gastrointestinal tract and coagulation fibrinolysis.

Objective: To explore the four criteria, including bedside index for severity in acute pancreatitis(BISAP), Ranson score, modified CT severity index(MCTSI) and acute physiology and chronic health evaluation scoring systemⅡ(APACHE Ⅱ) in assessment of severity and prognosis of hyperlipidemic acute pancreatitis., Methods: A total of 326 patients with hyperlipidemic acute pancreatitis were studied retrospectively from August 2006 to July 2015. The discrepancy of the four criteria in assessment of severity and prognosis of hyperlipidemic acute pancreatitis was compared with chi-square test and receiver operating characteristic curve., Results: The incidences of moderately severe acute pancreatitis and severe acute pancreatitis, local complications and mortality of patients with BISAP score≥3, Ranson score≥3, APACHE Ⅱ score≥8 and MCTSI score≥4 were significantly higher than BISAP score<3, Ranson score<3, APACHE Ⅱscore<8 and MCTSI<4 respectively (all P<0.05). As far as severity was concerned, the sensitivity and AUC of APACHEⅡ were 57% and 0.814, which were higher than the other systems. The second most sensitive criterion was BISAP. In assessment of local complications, the sensitivity and AUC of MCTSI were 68% and 0.791, which were higher than the other three. The most sensitive criterion to predict mortality was BISAP with sensitivity 89% and AUC 0.867, which was followed by APACHE Ⅱ., Conclusions: All four criteria can be used to determine the severity, local complications and mortality. Generally, BISAP is simple and easy to practice, and better than the other three.

Phytosterols (PSs) are reported to lower the serum total cholesterol and low-density lipoprotein cholesterol concentrations enriched in some fatty foods, such as margarine. However, these high-fat foods are not very suitable for older people. Soy milk is the favorite food for elderly people in China; therefore, we hypothesized that the consumption of soy milk powder supplemented with PSs would decrease the serum cholesterol levels in older Chinese people independent of the genotypes of apolipoprotein E (ApoE). Mild to moderate hyperlipidemic patients (n = 170) were recruited from different communities and treated with placebo soy milk powder or 3.4 g PS esters-enriched soy milk powder (2.0 g/d free PS in 30 g soy milk powder). The fasting serum lipid profiles at the baseline and after 3 and 6 months of intervention were measured. The ApoE genotype was also determined. After 3 months of PS intervention, the serum lipid profile was not changed significantly in either group. The serum total cholesterol, low-density lipoprotein cholesterol, and non- high-density lipoprotein cholesterol levels decreased by 9.3%, 11.4%, and 12.6%, respectively, in the PS group at the end of the intervention (6 months) compared with the control group, whereas the serum high-density lipoprotein cholesterol and triglyceride levels were not affected significantly. In the PS group, both the ApoE3 and ApoE4 carriers had a similar response to PS consumption. These findings suggested that PS-fortified soy milk powder was effective in lowering the serum cholesterol levels in older Chinese volunteers with mild to moderate hypercholesterolemia in both the ApoE3 and ApoE4 carriers., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To compare retrospectively serum levels of thyroid hormones (THs) and thyroid stimulating hormone (TSH) between patients with biliogenic acute pancreatitis (BAP) and those with hyperlipidaemic acute pancreatitis (HLAP), in order to assess their value for predicting the severity of acute pancreatitis (AP)., Methods: Patients with AP were divided into BAP and HLAP groups, then further divided into either a mild AP (MAP) group or a moderately severe AP (MSAP) group. Routine blood parameters were measured. Free tri-iodothyronine (FT3), free thyroxine (FT4) and TSH levels were measured., Results: Seventy-six patients with AP were enrolled in the study. FT3 and TSH levels were significantly higher in patients with MAP than in patients with MSAP. FT4 and TSH levels were significantly lower in the HLAP group than in the BAP group. TSH levels in both MAP and MSAP patients were significantly lower in the HLAP group than in the BAP group. TSH was inversely correlated with triglyceride levels in patients with HLAP. FT3 was a risk factor for MSAP in patients with AP and also demonstrated moderate accuracy in predicting AP severity., Conclusions: THs and TSH decrease with the severity of AP, especially in patients with HLAP. FT3 may be a useful biomarker for the early assessment of the severity of AP., (© The Author(s) 2016.)

Background: Coagulopathy and its association with disease severity in hyperlipidemia (HL)- and non-hyperlipidemia (NHL)-induced acute pancreatitis (AP) are not clear. The present study was to evaluate the relationship between coagulation homeostasis and AP., Methods: This study included 106 AP patients admitted to our hospital between October 2011 and January 2013. Stratified by disease severity, the patients were divided into two groups: a mild AP (MAP) group (n=69); and a moderately severe AP (MSAP) group (n=37). Based on disease etiology, there were 31 HL-induced AP (HLP) cases and 75 NHL-induced AP (NHLP) cases. The HLP and NHLP groups were compared for parameters of coagulation homeostasis, lipid metabolism, and disease severity. Correlations between disease severity and levels of D-dimer and protein C were investigated, and the prognostic potential of D-dimer was evaluated., Results: Compared with MAP patients, MSAP patients showed higher levels of D-dimer and lower levels of protein C. HLP patients had higher protein C levels than NHLP patients. Both D-dimer and protein C levels were significantly associated with the disease severity, not the disease etiology. D-dimer levels correlated positively with low density lipoprotein cholesterol levels and performed well as a sensitive and specific predictor of disease severity in AP patients, especially in HLP patients., Conclusions: The coagulation homeostasis is different between HLP and NHLP patients, and HL may be a contributing factor for thrombosis and fibrinolysis in HLP. D-dimer may be a robust marker of disease severity in HLP.

Objective. To investigate the esophageal function tests in British and Chinese patients with gastroesophageal reflux disease (GERD). Methods. Patients with GERD were selected from the functional gut clinic, London, and digestive department, Beijing Chao-Yang Hospital, after taking the examinations of High-resolution Manometry and Impedance (HRiM) and 24-hour Multi-Channel Intraluminal Impedance and pH Recording (MII/pH) between 2013 and 2014. Chinese healthy volunteers who undertook HRiM were also selected as control group. Results. Fifty-nine British and 82 Chinese patients with GERD and 62 Chinese healthy volunteers were entered. Values for British patients, Chinese patients, and healthy volunteers were as follows: Lower esophageal sphincter pressure (LESP) 16.0 ± 8.6, 16.5 ± 10.0, and 26.4 ± 10.9 mmHg, peristalsis (normal/small break/large break) 24/12/23, 44/10/28, and 57/1/4, total bolus transit time (TBTT) 7.3 ± 1.3, 7.6 ± 1.2, and 6.9 ± 0.9 s, and complete bolus transit rate (CBTR) 66.7 ± 37.8, 61.7 ± 36.4, and 90.3 ± 14.0%, respectively. Stepwise linear regression analysis showed that age, gender, and ethnicity did not have significant effect on LESP, TBTT, esophageal peristalsis, and CBTR in patients with GERD. Conclusions. British and Chinese patients with GERD presented similar values of LESP, TBTT, and impaired esophageal peristalsis and CBTR.

Background: To investigate the relationship between health-related quality of life (HRQOL) and survival in Chinese patients with chronic liver disease (CLD)., Methods: HRQOL was measured with the Chinese version of Short Form 36 (SF-36). SF-36 scores, demographic and clinical data were collected at baseline and after 18 months follow-up. Kaplan-Meier and Cox Proportional Hazard Regression survival analyses were used for interpretation of data. Surviving patients were censored in the analyses., Results: A total of 415 Chinese patients with CLD and 86 healthy controls were enrolled. During the follow-up period 50 patients died. SF-36 scores in healthy controls and surviving patients were higher compared with those in deceased patients. Scores of physical component summary (PCS) in healthy controls, surviving and deceased patients were 54.1 ± 5.2, 48.9 ± 7.7 and 33.5 ± 8.2 respectively (p < 0.001). Scores of mental component summary (MCS) in healthy controls, surviving and deceased patients were 56.6 ± 8.2, 53.0 ± 5.6 and 37.1 ± 12.1 (p < 0.001) respectively. Survival was significantly associated with PCS and MCS scores, and the presence of ascites., Conclusions: HRQOL was associated with survival in patients with CLD. PCS and MCS scores were predictors of survival.

Objective: To investigate the value of D-dimer and protein S plasma concentrations for diagnosis of portal vein thrombosis (PVT) in patients with liver cirrhosis., Methods: D-dimer and protein S were quantified, PVT was diagnosed by dynamic enhanced computed tomography and liver function was classified using the Child-Pugh system. Receiver operating curve analysis was performed., Results: D-dimer increased, and protein S decreased, with decreasing liver function in the total study population (n = 188). D-dimer concentrations were significantly higher and protein S concentrations were significantly lower in patients with (n = 51) than those without PVT (n = 137). D-dimer had high specificity and negative predictive value (NPV) in Child-Pugh class A or B patients (cut-off values>0.56 mg/l and >1.18 mg/l, respectively). In class C patients>0.77 mg/l D-dimer had high sensitivity and NPV. Protein S had high sensitivity but low specificity in class A or B patients (cut-off values < 17.4 mg/l and <19.2 mg/l, respectively)., Conclusion: Plasma D-dimer and protein S are potential biomarkers for PVT diagnosis in patients with cirrhosis. PVT can be excluded when D-dimer is low and protein S is elevated.

In the present study, we downregulated FANCF expression by small interfering RNA (siRNA) in OVCAR ovarian cancer cells to address the effects of decreased FANCF expression on the function of the Fanconi anemia (FA)/breast cancer susceptibility gene (BRCA) pathway. Furthermore, we investigated whether this method increases the sensitivity of OVCAR3 cells to adriamycin (ADM) and the possible mechanism(s). We found that silencing of FANCF inactivated the FA/BRCA pathway by decreasing the monoubiquitination and focus formation of FANCD2 and reduced the function of the FA/BRCA pathway, resulting in the inhibition of cell proliferation, increased cell apoptosis and DNA damage in OVCAR3 cells. Moreover, we observed that silencing of FANCF enhanced the antiproliferative effect of ADM in OVCAR3 cells and increased ADM intracellular accumulation consequently sensitizing OVCAR3 cells to ADM. Furthermore, silencing of FANCF increased cell apoptosis of OVCAR3 cells which was caused by decreased mitochondrial membrane potential (MMP)-induced DNA damage, activated Jun N-terminal kinase (JNK), increased release of cytochrome c, increased expression of cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP) dependent on JNK activation following treatment of ADM. Collectively, we confirm that silencing of FANCF sensitizes OVCAR3 ovarian cancer cells to ADM, suggesting that FANCF may serve as a potential target for therapeutic strategies in the treatment of ovarian cancer.

The receptor tyrosine kinase (RTK) Ror2 plays important roles in developmental morphogenesis and mediates the filopodia formation in Wnt5a-induced cell migration. However, the function of Ror2 in noncanonical Wnt signaling resulting in cancer metastasis is largely unknown. Here, we show that Ror2 expression is higher in the highly metastatic murine B16-BL6 melanoma cells than in the low metastatic variant B16 cells. Overexpression of Ror2 increases the metastasis ability of B16 cells, and knockdown of Ror2 reduces the migration ability of B16-BL6 cells. Furthermore, the inhibition of Src kinase activity is critical for the Ror2-mediated cell migration upon Wnt5a treatment. The C-terminus of Ror2, which is deleted in brachydactyly type B (BDB), is essential for the mutual interaction with the SH1 domain of Src. Intriguingly, the Neurotrophin receptor-interacting MAGE homologue (NRAGE), which, as we previously reported, can remodel the cellular skeleton and inhibit cell-cell adhesion and metastasis of melanoma and pancreatic cancer, sharply blocks the interaction between Src and Ror2 and inhibits Ror2-mediated B16 cell migration by decreasing the activity of Src and focal adhesion kinase (FAK). Our data show that Ror2 is a potential factor in the tumorigenesis and metastasis in a Src-dependent manner that is negatively regulated by NRAGE., (Copyright © 2012. Published by Elsevier Inc.)