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Chao-Jin Chen,* De-Zhao Liu,* Wei-Feng Yao, Yu Gu, Fei Huang, Zi-Qing Hei, Xiang Li Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Purpose: Neuropathic pain is a complex chronic condition occurring post-nervous system damage. The transcriptional reprogramming of injured dorsal root ganglia (DRGs) drives neuropathic pain. However, few comparative analyses using high-throughput platforms have investigated uninjured DRG in neuropathic pain, and potential interactions among differentially expressed genes (DEGs) and pathways were not taken into consideration. The aim of this study was to identify changes in genes and pathways associated with neuropathic pain in uninjured L4 DRG after L5 spinal nerve ligation (SNL) by using bioinformatic analysis.Materials and methods: The microarray profile GSE24982 was downloaded from the Gene Expression Omnibus database to identify DEGs between DRGs in SNL and sham rats. The prioritization for these DEGs was performed using the Toppgene database followed by gene ontology and pathway enrichment analyses. The relationships among DEGs from the protein interactive perspective were analyzed using protein–protein interaction (PPI) network and module analysis. Real-time polymerase chain reaction (PCR) and Western blotting were used to confirm the expression of DEGs in the rodent neuropathic pain model.Results: A total of 206 DEGs that might play a role in neuropathic pain were identified in L4 DRG, of which 75 were upregulated and 131 were downregulated. The upregulated DEGs were enriched in biological processes related to transcription regulation and molecular functions such as DNA binding, cell cycle, and the FoxO signaling pathway. Ctnnb1 protein had the highest connectivity degrees in the PPI network. The in vivo studies also validated that mRNA and protein levels of Ctnnb1 were upregulated in both L4 and L5 DRGs.Conclusion: This study provides insight into the functional gene sets and pathways associated with neuropathic pain in L4 uninjured DRG after L5 SNL, which might promote our understanding of the molecular mechanisms underlying the development of neuropathic pain. Keywords: spinal nerve ligation, neuropathic pain, uninjured afferent, bioinformatic analysis, microarray

Chaoliang Tang,1 Juan Li,2 Wai Lydia Tai,3 Weifeng Yao,4 Bo Zhao,1 Junmou Hong,5 Si Shi,1 Song Wang,2 Zhongyuan Xia1 1Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 2Department of Anesthesiology, Anhui Provincial Hospital of Anhui Medical University, Hefei, Anhui Provence, 3Department of Anaesthesiology, The University of Hong Kong, Hong Kong SAR, 4Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, 5Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China Background: Sex differences have been increasingly highlighted in complex regional pain syndrome (CRPS) in clinical practice. In CRPS type I (CRPS-I), although inflammation and oxidative stress have been implicated in its pathogenesis, whether pain behavior and the underlying mechanism are sex-specific is unclear. In the present study, we sought to explore whether sex differences have an impact on inflammation, oxidative stress, and pain sensitivity in CRPS-I. Methods: Chronic post-ischemia pain (CPIP) was established in both male and female mice as an animal model of CRPS-I. Edema and mechanical allodynia of bilateral hind paws were assessed after reperfusion. Blood samples were analyzed for serum levels of oxidative stress markers and inflammatory cytokines. Results: Both male and female mice developed edema. Male mice developed CPIP at day 3 after reperfusion; female mice developed CPIP at day 2 after reperfusion. Female mice displayed significantly earlier and higher mechanical allodynia in the ischemic hind paw, which was associated with higher serum levels of IL-2, TNF-α, isoprostanes, 8 OhdG, and malondialdehyde at day 2 after reperfusion. Moreover, female mice showed significantly lower SOD and IL-4 compared to male mice at day 2 after reperfusion. Conclusion: Our results indicate that sex differences in inflammatory and oxidative stress states may play a central role in the sex-specific nociceptive hypersensitivity in CRPS-I, and offer a new insight into pharmacology treatments to improve pain management with CRPS. Keywords: sex differences, complex regional pain syndrome, chronic post-ischemia pain, inflammatory response, oxidative stress

Background: Shizao decoction (SZD) consisted of Euphorbia kansui (EK), Euphorbia pekinensis (EP), Daphne genkwa (DG), and Fructus Jujubae (FJ) is a classic Chinese herbal medicine formula for treating malignant ascites, which is closely related to the modulation of gut microbiota by our previous study. For water-expelling members (WEM) including EK, EP, and DG may have side effects on the intestine, FJ is employed for detoxification and effectivity enhancement of WEM. However, the underlying mechanism for the compatibility of WEM and FJ is still unknown., Purpose: To investigate the effect of the compatibility of WEM with FJ in SZD on malignant ascites and elucidate the potential mechanism from the perspective of the modulation of gut microbiota and related metabolic function., Methods: Qualitative and quantitative evaluation of main components was conducted for comprehensive characterization of SZD and WEM. The effect of WEM and SZD was compared on malignant ascites effusion (MAE) rats. The intestinal injury was evaluated by HE staining and oxidative damage. Ascites weight, urine amount, fecal water content, the expression of aquaporins, and cytokines in ascites (IL-6, VEGF, and TNF-α) were measured to estimate the water-expelling activity. The intestinal flora was detected by 16S rDNA sequencing and the content of fecal short-chain fatty acids (SCFAs) was analyzed using gas chromatography-mass spectrometry. Pseudo-germ-free (PGF) and fecal bacteria transplantation animal experiments were subsequently employed to validate this finding. The fecal metabolomics and correlation analysis were finally conducted to explore the related metabolic changes., Results: 51 and 33 components were identified in SZD and WEM, respectively. Compared to WEM alone, the compatibility with FJ remarkably reduced intestinal oxidative damage in MAE rats. Ascites was also relieved by downregulating the expression of AQP3 in the colon and decreasing the levels of IL-6, TNF-α and VEGF in ascites. The diversity of gut microbiota was reversed with an increase in Lactobacillus and Clostridia_UCG-014 while a decrease in Colidextribacter. Under the PGF condition, compatibility of WEM with FJ failed to reduce intestinal injury and alleviate MA significantly, but this effect was further enhanced after FMT. 23 potential fecal metabolites were finally identified. Correlation analysis further showed that Lactobacillus and Clostridia_UCG-014 were positively correlated with SCFAs and l-tryptophan. Colidextribacter was negatively correlated with thymidine but positively correlated with ursodeoxycholic acid and deoxycholic acid., Conclusion: FJ cooperated with WEM reduced intestinal injury and alleviated malignant ascites by modulating gut microbiota, short-chain fatty and tryptophan metabolism. These findings provide a scientific basis for the clinical application of FJ from SZD and the safe usage of SZD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Background & Aims: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases., Methods: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications., Results: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis., Conclusion: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR., (© 2024. The Author(s).)

Background: Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF., Methods: The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (< 1). We compared the differences in morbidity rates between the two groups. Utilized logistic regression analysis to identify the risk factors associated with PHLF development and ROC curves to compare the predictive value of lactate ratio and other liver function indicators for PHLF., Results: A total of 203 patients were enrolled in the study. Overall morbidity and severe morbidity occurred in 64.5 and 12.8 per cent of patients respectively. 39 patients (19.2%) met the criteria for PHLF, including 15 patients (7.4%) with clinically relevant Post-hepatectomy liver failure (CR-PHLF). With a significantly higher incidence of PHLF observed in the lactate ratio ≥ 1 group compared to the lactate ratio < 1 group (n = 34, 26.8% vs. n = 5, 6.6%, P < 0.001). Multivariable logistic regression analysis revealed that a lactate ratio ≥ 1 was an independent predictor for PHLF (OR: 3.239, 95% CI 1.097-9.565, P = 0.033). Additionally, lactate ratio demonstrated good predictive efficacy for PHLF (AUC = 0.792)., Conclusions: Early assessment of peri-operative arterial lactate concentration level ratios may provide experience in early intervention of complications in patients with hepatocellular carcinoma, which can reduce the likelihood of PHLF occurrence and improve patient prognosis., (© 2024. The Author(s).)

Background and Aims: An increasing number of studies have confirmed that non-textbook outcomes (non-TO) are a risk factor for the long-term outcome of malignant tumors. It is particularly important to identify the predictive factors of non-TO to improve the quality of surgical treatment. We attempted to construct two nomograms for preoperative and postoperative prediction of non-TO after laparoscopic hepatectomy for hepatocellular carcinoma (HCC)., Methods: Patients who underwent curative-intent hepatectomy for HCC between 2014 and 2021 at two Chinese hospitals were analyzed. Using univariate and multivariate analyses, the independent predictors of non-TO were identified. The prediction accuracy is accurately measured by the receiver operating characteristic (ROC) curve and calibration curve. ROC curves for the preoperative and postoperative models, Child-Pugh grade, BCLC staging, and 8th TNM staging were compared relative to predictive accuracy for non-TO., Results: Among 515 patients, 286 patients (55.5%) did not achieve TO in the entire cohort. Seven and eight independent risk factors were included in the preoperative and postoperative predictive models by multivariate logistic regression analysis, respectively. The areas under the ROC curves for the postoperative and preoperative models, Child-Pugh grade, BCLC staging, and 8th TNM staging in predicting non-TO were 0.762, 0.698, 0.579, 0.569, and 0.567, respectively., Conclusion: Our proposed preoperative and postoperative nomogram models were able to identify patients at high risk of non-TO following laparoscopic resection of HCC, which may guide clinicians to make individualized surgical decisions, improve postoperative survival, and plan adjuvant therapy against recurrence., 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 © 2023 Xie, Liang, Ye, Xu, Wang, Xie, Zhang, Fu, Yao, Liu and Zhang.)

Background: The clinical education of interns on hepatocellular carcinoma (HCC) is both crucial and difficult in China, even if the education reform has advanced constantly over the years. The value of specific 3D printing model (3DPM) in clinical education of HCC is uncertain, and relevant literatures are very few. This study aimed to explore the effects of a patient-specific 3D printing liver model on the clinical education of HCC., Methods: Three laparoscopic hepatectomies were collected. For each case, a 3D virtual reconstruction (3DVR) and 3DPM were created using multi-detector computed tomography (MDCT) data, respectively. A total of 62 interns were randomly assigned to each group (3DPM, 3DVR, and MDCT groups) through a table of random numbers for random grouping. Following lecture-based HCC education, interns in each group selected a corresponding model of HCC. All interns were tested on the hepatic tumor locations, the vessels adjacent to them, surgical planning, and test time using the centesimal system score within 90 min. A questionnaire investigation on the degree of satisfaction, interest, and helpfulness for improving the comprehension ability of liver anatomy and 3D spatial structures was also recorded. The 3DPM group were compared with both 3DVR and MDCT group by theoretical examination scores and questionnaire survey satisfaction to evaluate the effects of 3DPM on the interns' clinical education in HCC., Results: All the interns completed the test and questionnaire. The 3DPM group gained significantly higher scores on the following test contents: indicating the correct tumor location (3DPM vs. 3DVR, MDCT: 36.7±4.8 vs. 33.2±5.8, 26.8±10.0, P=0.03, P<0.01, respectively), accurately identifying the relationship between the tumor and vessels (3DPM vs. 3DVR, MDCT: 37.1±4.6 vs. 31.6±3.7, 30.0±5.8, P<0.01, P<0.01, respectively), and designing appropriate surgical plans (3DPM vs. 3DVR, MDCT: 8±2.7 vs. 4.9±2.7, 5.9±3.8, P<0.01, P=0.04, respectively). The 3DPM group showed a higher degree of satisfaction (86.2%), interest (92.1%), and helpfulness (80.5%) for improving the comprehension ability of liver anatomy and 3D spatial structures., Conclusions: The clinical teaching by utilizing 3DPM can significantly improve the professional theoretical level, strengthen clinical thinking and comprehensive ability, and improve the teaching effects of HCC for medical interns., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-28/coif). All authors report that this study was supported by the Basic Public Welfare Research Project of Zhejiang Province (No. LGF20H030011) and the Zhejiang Medical and Health Science and Technology Plan (No. 2022RC096). The authors have no other conflicts of interest to declare., (2023 Journal of Gastrointestinal Oncology. All rights reserved.)

Background & Aims: The long-term prognosis of patients with metabolic syndrome (MS) and hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after radical hepatectomy remains unclear. The purpose of this study was to elucidate the effect of MS on long-term survival for patients with HBV-related HCC after hepatectomy., Methods: Patients with HBV-HCC after hepatectomy were included. Patients were stratified into MS-HBV-HCC and HBV-HCC groups. Clinical features and surgical outcomes were compared between the two groups, and COX regression analysis was used to determine independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS)., Result: 389 patients (MS-HBV-HCC group: n=50, HBV-HCC group: n=339) were enrolled for further analysis. Baseline characteristics showed that patients with MS-HBV-HCC were associated with a high rate of elderly patients, ASA score, and co-morbid illness, but a lower rate of anatomy hepatectomy. There were no significant differences in perioperative complications. After excluding patients who relapsed or died within 90 days after surgery, multivariate Cox regression analysis showed MS was an independent risk factor of OS (HR 1.68, 95% CI 1.05-2.70, P = 0.032) and RFS (HR 1.78, 95% CI 1.24-2.57, P = 0.002)., Conclusion: MS is an independent risk factor for poor OS and RFS in HBV-infected HCC patients after radical hepatectomy. This suggests that we need to strengthen postoperative follow-up of the relevant population and encourage patients to develop a healthy lifestyle., 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. The reviewer CL declared a shared affiliation with the author W-FL to the handling editor at the time of review., (Copyright © 2022 Zhang, Ye, Lu, Xu, Xie, Wang, Xiao, Liu, Yao, Cheng, Shen, Liu, Zhang, Huang and Liang.)

Background: Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (LncRNA MALAT1) has been proven to promote osteogenesis in different health conditions. However, the role of plasma MALAT1 in postmenopausal osteoporosis (PMOP) has not been investigated., Objective: To investigate whether plasma MALAT1 expressions are associated with severity of PMOP., Methods: A total of 126 patients with PMOP and 126 healthy female control individuals were drafted into study participation. Plasma MALAT1 was detected using RT-PCR. Bone formation marker bone-specific alkaline phosphatase plasma concentration was determined using chemiluminescence immunoassay. Levels of bone absorption marker cross-linked N-telopeptidases of type I collagen were measured in duplicate using enzyme immunoassay. Bone mineral density (BMD) was examined in the total hips, femoral neck, and lumbar (L1-L4) spine using dual-energy x-ray absorptiometry. We used Genant semiquantitative (GSQ) criteria to assess the degree of vertebral deformity and fracture. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the potential diagnostic value of MALAT1 with regard to the GSQ grading. We used the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) to evaluate the symptomatic severity in and functional ability of the study participants., Results: Plasma MALAT1 expressions were significantly lower in patients with PMOP, compared with healthy controls. Plasma MALAT1 expressions in patients with PMOP were positively associated with total hip, femoral neck, and lumbar (L1-L4) spine BMD. In total, 95 patients experienced vertebral deformity or fracture (VF), and 31 had no fractures. Plasma MALAT1 expressions were markedly decreased in patients with VF, compared with patients without fractures. Plasma MALAT1 expressions were negatively related to GSQ grading in patients with VF. ROC curve analysis demonstrated that decreased plasma MALAT1 expression exhibits decent diagnostic value with regard to GSQ grading. Finally, we discovered that plasma MALAT1 expression was also negatively associated with VAS and ODI., Conclusion: Plasma MALAT1 expressions are negatively associated with severity of PMOP., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Recently, the effectiveness of "textbook outcomes (TO)" in the evaluation of surgical quality has been recognized by more and more scholars. This study tended to examine the association between preoperative albumin-bilirubin (ALBI) grades and the incidence of achieving or not achieving TO (non-TO) in patients with hepatocellular carcinoma (HCC) undergoing laparoscopic hepatectomy., Methods: The patients were stratified into two groups: ALBI grade 1 (ALBI ≤ -2.60) and ALBI grade 2/3 (ALBI > -2.60). The characteristics of patients and the incidence of non-TO were compared. Multivariate analyses were performed to determine whether ALBI grade was independently associated with TO., Results: In total, 378 patients were enrolled, including 194 patients (51.3%) in the ALBI grade 1 group and 184 patients (48.7%) in the ALBI grade 2/3 group. In the whole cohort, 198 patients (52.4%) did not achieve TO, and the incidence of non-TO in the ALBI grade 2/3 group was obviously higher than that in the ALBI grade 1 group ( n = 112, 60.9% vs . n = 86, 44.3%, P = 0.001). The multivariate analyses showed that ALBI grade 2/3 was an independent risk factor for non-TO (OR: 1.95, 95%CI: 1.30-2.94, P = 0.023)., Conclusions: More than half (52.4%) of the patients with hepatocellular carcinoma did not achieve TO after laparoscopic hepatectomy, and preoperative ALBI grade 2/3 was significantly associated with non-TO. Improving the liver function reserve of patients before operation, thereby reducing the ALBI grade, may increase the probability for patients to reach TO and enable patients to benefit more from surgery., 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 Xu, Ye, Wang, Xie, Zhang, Cheng, Xiao, Liu, Jiang, Yao, Shen, Liu, Zhang, Huang and Liang.)

Background: Osteoporosis (OP) is characterized as low bone mass, bone microarchitecture breakdown and bone fragility. The increase of oxidative stress could lead to breakdown in the balance of bone formation and resorption which gives rise to OP. Nrf2 is a transcription factor which takes part in oxidative stress and recently was reported that it can regulate the occurrence of OP. Salidroside (SAL) with the efficacies of anti-oxidation, anti-aging and bone-protection is one of the active ingredients in Ligustri Lucidi Fructus, a traditional Chinese medicinal herb. Nevertheless, few studies have explored the potential mechanism of SAL preventing OP development from the perspective of oxidative stress intervention., Purpose: This study aimed to investigate the pharmacological effect and molecular mechanisms of SAL on OP., Study Designs and Methods: A tert-butyl hydroperoxide (t-BHP)-induced oxidative stress model was applied for investigating the effects of SAL in vitro, and an ovariectomized (OVX) model was used for in vivo study on the effect of SAL for OP. Related pharmacodynamic actions and molecular mechanisms of SAL were explored in both rat osteoblasts (ROBs) and OVX rats. Network biology and cell metabolomics were performed for further investigating the correlation and association among potential biomarkers, targets and pathways., Results: SAL reduced levels of ROS and lipid peroxidation (LPO), increased activities of antioxidant enzymes like GPx and SOD, and enhanced osteogenic differentiation in t-BHP-induced ROBs and OVX rats. Mechanistic studies showed SAL prevented OP development and reduced oxidative damage in ROBs and OVX rats through up-regulating Nrf2 expression and facilitating its nuclear translocation. The joint analysis of network biology and cell metabolomics revealed that galactose metabolism and fatty acid metabolism could be the major influenced pathways following treatment with SAL., Conclusion: SAL could protect against OP by inhibiting oxidative stress, promoting osteogenesis through the up-regulation of Nrf2 and intervening galactose metabolism and fatty acid metabolism. Our study implied that SAL may be a potential drug to treat OP., (Copyright © 2022. Published by Elsevier GmbH.)

Euphorbiae pekinensis Radix (EP) is effective in treating various diseases, but it's toxicity is a major obstacle in use in clinical. Although EP was processed with vinegar to reduce it's toxicity, the detailed mechanism of toxicity in EP have not been clearly delineated. This study investigate the toxicity attenuation-mechanism of Euphorbiae pekinensis after being processed with vinegar (VEP) and the toxic mechanism of four compounds from EP on zebrafish embryos. The contents of four compounds decreased obviously in VEP. Correspondingly, slower development on embryos can be seen as some symptoms like reduction of heart rate, liver area and gastrointestinal peristalsis after exposed to the compounds. Some obvious pathological signals such as pericardial edema and yolk sac edema were observed. Furthermore, the compounds could increase the contents of MDA and GSH-PX and induce oxidative damage by inhibiting the activity of SOD. Also, four compounds could provoke apoptosis by up-regulating the expression level of p53, MDM2, Bax, Bcl-2 and activating the activity of caspase-3, caspase-9. In conclusion, the four compounds play an important role in the toxicity attenuation effects of VEP, which may be related to the apoptosis induction and oxidative damage. This would contribute to the clinical application and further toxicity-reduction mechanism research., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Vascular complications at the puncture site is a common complication after femoral artery puncture. It will not only affect the postoperative effect and patient comfort, but also may endanger the life of the patient. The effective compression hemostasis methods at the puncture site can improve the comfort of the patient, shorten the hospital stay, and reduce the burden on the medical staff. The purpose of this research is to evaluate the effectiveness and safety of different compression methods after femoral artery puncture., Methods: We will include all relevant randomized controlled trials by searching major Chinese and English databases and clinical trial registration platforms. Use Cochrane Collaboration's Risk of bias tool for bias risk analysis. Use the Grades of Recommendation, Assessment, Development, and Evaluation to assess the quality of evidence. Data analysis will be performed using Stata (V.15.0) and WinBUGS (V.1.4.3)., Results: Five hundred ninety-seven records were obtained by searching the database but no records were obtained by other means. After removing duplicate records, 377 records remain. We excluded 103 records through abstract and title, leaving 274 full-text articles., Conclusion: This study will compare the application effects of different compression methods after femoral artery puncture. We hope that this study will help guide clinical decision-making and provide evidence for the management of patients after femoral artery puncture., Protocol Registration Number: INPLASY2020120094., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Postprandial hyperglycemia was reported to play a key role in established risk factors of coronary artery diseases (CAD) and cardiovascular events. Serum 1,5-anhydroglucitol (1,5-AG) levels are known to be a clinical marker of short-term postprandial glucose (PPG) excursions. Low serum 1,5-AG levels have been associated with occurrence of CAD. However, the relationship between 1,5-AG levels and coronary plaque rupture has not been fully elucidated. The aim of this study was to evaluate 1,5-AG as a predictor of coronary plaque rupture in diabetic patients with acute coronary syndrome (ACS)., Methods: A total of 144 diabetic patients with ACS were included in this study. All patients underwent intravascular ultrasound examination, which revealed 49 patients with plaque rupture and 95 patients without plaque rupture in the culprit lesion. Fasting blood glucose (FBG), hemoglobin A 1c (HbA 1c ) and 1,5-AG levels were measured before coronary angiography. Fasting urinary 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) level was measured and corrected by creatinine clearance., Results: Patients with ruptured plaque had significantly lower serum 1,5-AG levels, longer duration of diabetes, higher HbA 1c and FBG levels than patients without ruptured plaque in our study population. In multivariate analysis, low 1,5-AG levels were an independent predictor of plaque rupture (odds ratio 3.421; P = 0.005) in diabetic patients with ACS. The area under the receiver-operating characteristic curve for 1,5-AG (0.658, P = 0.002) to predict plaque rupture was superior to that for HbA 1c (0.587, P = 0.087). Levels of 1,5-AG were significantly correlated with urinary 8-iso-prostaglandin F 2α levels (r = - 0.234, P = 0.005)., Conclusions: Serum 1,5-AG may identify high risk for coronary plaque rupture in diabetic patients with ACS, which suggests PPG excursions are related to the pathogenesis of plaque rupture in diabetes.

Previous studies report that (-)-epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic ingredient in green tea, has high efficacy against Alzheimer's disease (AD) in various in vivo and in vitro models. However, as a water-soluble component, how EGCG exerts its anti-AD effects in the brain was not elucidated. In the present study, we investigated the anti-AD mechanisms of EGCG in natural aging rats with cognitive impairments (CIs) assessed using Morris water maze. The rats were treated with EGCG (100 mg/kg per day, intragastrically) for 4 weeks. The expression of β-amyloid (Aβ 1-42 ) in the brain was detected with immunohistochemical staining. We showed that EGCG administration significantly ameliorated the CI in the aging rats with CI and decreased Aβ 1-42 plaque formation in their brains. Then we used an efficient ultra-performance liquid chromatography-tandem mass spectrometer method to evaluate EGCG concentrations in rat plasma and tissue distribution. We found that EGCG absorption was significantly increased in the aging with CI group compared with control young rats. After oral administration of EGCG (100 mg), EGCG could not be detected in the brain tissues of control young rats, but it was found in the brain tissue of aging rats with CI. By using Evans Blue assay, transmission electron microscopy, and Western blotting assay, we demonstrated that the permeability of blood-brain barrier (BBB) was significantly increased in aging rats with CI. These results suggest that the permeability change of BBB is the physiological structural basis for EGCG treatment to improve learning and memory, thus providing a solid evidence for EGCG druggability in anti-AD therapeutic field.

The dried roots of Euphorbia kansui S.L.Liou ex S.B.Ho have long been used to treat edema in China. However, the severe toxicity caused by Euphorbia kansui (EK) has seriously restricted its clinical application. Although EK was processed with vinegar to reduce its toxicity, the detailed mechanisms of attenuation in toxicity of EK stir-fried with vinegar (VEK) have not been well delineated. Diterpenoids are the main toxic ingredients of EK, and changes in these after processing may be the underlying mechanism of toxicity attenuation of VEK. 3- O -(2' E ,4' Z -decadienoyl)-20- O -acetylingenol (3-O-EZ) is one of the diterpenoids derived from EK, and the content of 3-O-EZ was significantly reduced after processing. This study aims to explore the underlying mechanisms of toxicity reduction of VEK based on the change of 3-O-EZ after processing with vinegar. Based on the chemical structure of 3-O-EZ and the method of processing with vinegar, simulation experiments were carried out to confirm the presence of the product both in EK and VEK and to enrich the product. Then, the difference of peak area of 3-O-EZ and its hydrolysate in EK and VEK were detected by ultra-high-performance liquid chromatography (UPLC). Furthermore, the toxicity effect of 3-O-EZ and its hydrolysate, as well as the underlying mechanism, on zebrafish embryos were investigated. The findings showed that the diterpenoids (3-O-EZ) in EK can convert into less toxic ingenol in VEK after processing with vinegar; meanwhile, the content of ingenol in VEK was higher than that of EK. More interestingly, the ingenol exhibited less toxicity (acute toxicity, developmental toxicity and organic toxicity) than that of 3-O-EZ, and 3-O-EZ could increase malondialdehyde (MDA) content and reduce glutathione (GSH) content; cause embryo oxidative damage by inhibition of the succinate dehydrogenase (SDH) and superoxide dismutase (SOD) activity; and induce inflammation and apoptosis by elevation of IL-2 and IL-8 contents and activation of the caspase-3 and caspase-9 activity. Thus, this study contributes to our understanding of the mechanism of attenuation in toxicity of VEK, and provides the possibility of safe and rational use of EK in clinics.

Aims: Baicalin (BAI), a flavonoid compound isolated from the root of Scutellaria baicalensis Georgi, has been established to have potent anti-inflammation and neuroprotective properties; however, its effects during Alzheimer's disease (AD) treatment have not been well studied. This study aimed to investigate the effects of BAI pretreatment on cognitive impairment and neuronal protection against microglia-induced neuroinflammation and to explore the mechanisms underlying its anti-inflammation effects., Methods: To determine whether BAI plays a positive role in ameliorating the memory and cognition deficits in APP (amyloid beta precursor protein)/PS1 (presenilin-1) mice, behavioral experiments were conducted. We assessed the effects of BAI on microglial activation, the production of proinflammatory cytokines, and neuroinflammation-mediated neuron apoptosis in vivo and in vitro using Western blot, RT-PCR, ELISA, immunohistochemistry, and immunofluorescence. Finally, to elucidate the anti-inflammation mechanisms underlying the effects of BAI, the protein expression of NLRP3 inflammasomes and the expression of proteins involved in the TLR4/NF-κB signaling pathway were measured using Western blot and immunofluorescence., Results: The results indicated that BAI treatment attenuated spatial memory dysfunction in APP/PS1 mice, as assessed by the passive avoidance test and the Morris water maze test. Additionally, BAI administration effectively decreased the number of activated microglia and proinflammatory cytokines, as well as neuroinflammation-mediated neuron apoptosis, in APP/PS1 mice and LPS (lipopolysaccharides)/Aβ-stimulated BV2 microglial cells. Lastly, the molecular mechanistic study revealed that BAI inhibited microglia-induced neuroinflammation via suppression of the activation of NLRP3 inflammasomes and the TLR4/NF-κB signaling pathway., Conclusion: Overall, the results of the present study indicated that BAI is a promising neuroprotective compound for use in the prevention and treatment of microglia-mediated neuroinflammation during AD progression., (© 2018 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

The traditional processing method for the slices preparation of Rehmanniae roots is time- and energy-consuming and is prone to result in loss of active components during twice water-treatment (once for wash and the other for softening) and drying steps. In this study, we firstly explored an integrative processing technique for Rehmanniae Radix by 2x3 factorial experiment based on the contents of catalpol and verbascoside as measured by HPLC. The potential differences between the traditional stepwise processing technique and the integrative processing technique for catalpol and verbascoside in the prepared slices were investigated. To further confirm the effectiveness of drugs using the integrative processing technique, some pharmacological variables, such as rectal temperature, hematologic parameters (RBC, HGB, HCT, and blood viscosity), and coagulation parameters (TT, APTT, PT and FIB), were detected in a blood-heat and hemorrhage syndrome rat model. Two-way ANOVA analysis showed that drying for 18 h at 50°C was considered as the best combination of process conditions. The mean catalpol and verbascoside contents in the integrative method-processed samples (4.30% and 0.33%, respectively) were higher than those in the traditional method-processed samples (2.61% and 0.21%, respectively). Significant increases in rectal temperature, and hematologic parameters, TT, APTT, and FIB, were observed in the model group rats, compared to the blank group animals ( P <0.01). Both in the integrative groups and traditional groups, the extracts caused significant decreases in rectal temperature, RBC, HGB, and HCT with increased concentration compared to the model group animals. All coagulation parameters tested were shortened in model rats received two kind prepared slices. There were no significant therapeutic differences between the integrative and the traditional method-processed slices on the hemostasis and hemorheological parameters in this blood-heat and hemorrhage syndrome rat model, indicating that our integrative method may be a feasible technique for processing Rehmanniae Radix slices.

Background: The pro-inflammatory protein chemokine cytokine ligand 3 is well established as a vital regulator of bone resorption and osteoclast stimulation., Aims: To investigate if serum cytokine ligand 3 levels correlated with disease severity in postmenopausal osteoporotic women., Study Design: Cross-sectional study., Methods: Eighty-two postmenopausal osteoporotic women, 76 postmenopausal non-osteoporotic women, and 80 healthy women of childbearing age were recruited. The total hip, femoral neck, and L1-L4 spine bone mineral density were assessed by dual-energy X-ray absorptiometry. Serum cytokine ligand 3 concentrations were examined using a commercial enzyme-linked immunosorbent assay kit. Serum inflammatory cytokine interleukin-6, tumor necrosis factor-alpha, and the bone metabolic markers, carboxy-terminal crosslinked and tartrate-resistant acid phosphatase 5b were also examined. Scores on both the visual analogue scale and the Oswestry Disability Index were utilized to assess clinical severity., Results: Patients in the postmenopausal osteoporotic group had significantly increased serum cytokine ligand 3 levels compared with those in both the postmenopausal non-osteoporotic group (40.9±15.1 pg/mL vs 24.2±8.7 pg/mL, p<0.001) and control group (40.9±15.1 pg/mL vs 23.9±9.1 pg/mL, p<0.001). Serum cytokine ligand 3 levels negatively correlated with bone mineral density at the total hip (r=-0.345, p=0.002), femoral neck (r=-0.329, p=0.003), and L1-L4 lumbar spine (r=-0.354, p=0.001) and positively correlated with visual analogue scale scores (r=0.413, p<0.001) and the Oswestry Disability Index (r=0.360, p<0.001). Moreover, serum cytokine ligand 3 levels were correlated with increased tumor necrosis factor-alpha (r=0.305, p=0.005), interleukin-6 (r=0.288, p=0.008), terminal crosslinked and tartrate-resistant acid phosphatase 5b (r=0.371, p<0.001), and carboxy-terminal crosslinked (r=0.317, p=0.004) levels. All correlations were still significant after adjusting for both body mass index and age., Conclusion: Chemokine cytokine ligand 3 may be a useful biomarker that can be used to predict disease severity of postmenopausal osteoporosis. Therapies targeting cytokine ligand 3 and its related signaling pathways to inhibit and delay the osteoclastogenesis process deserve further investigation.

Background: The correlation between the atherogenic index of plasma (AIP) and waist circumference (WC) remains unknown., Methods: A total of 5351 middle-aged men living in Southeastern China were surveyed using the random stratified cluster sampling method. A WC of 90 cm or greater was indicative of abdominal obesity, and AIP was calculated as follows: log [triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C)]., Results: (1) A significantly higher AIP was observed in subjects with abdominal obesity than in those without abdominal obesity (P < 0·001). (2) Multivariate logistic regression analysis revealed an odds ratio of 1·93, 2·59 and 2·76 for abnormal AIP levels for the second, third and fourth WC quartiles, respectively (all P < 0·001) compared to the first WC quartile as a reference. (3) There was a linear correlation between WC and AIP, and a 1·0 cm increase in WC resulted in a 0·0175 rise in AIP. For AIP corresponding to moderate risk (0·12-0·21), WC was 85-90 cm; for AIP corresponding to high risk (> 0·21), WC was >90 cm., Conclusions: AIP of 0·12-0·21 or >0·21 indicates a likelihood of borderline abdominal obesity or abdominal obesity, respectively, and the combination of WC and AIP may increase the specificity and sensitivity for detection of abdominal obesity in clinical practice. The results suggest that AIP may be used as a reference to estimate abdominal obesity.

In this research, a new triterpenoid, tirucalla-8,24-diene-3β,11β-diol-7-one ( 1 ), and eupha-8,24-diene-3β,11β-diol-7-one ( 2 ), which was isolated from Euphorbia kansui for the first time, together with twelve other known compounds ( 3 - 14 ), were isolated from the ethyl acetate extract of Euphorbia kansui . Their structures were elucidated based on High resolution electrospray ionization mass spectrometry (HR-ESI-MS), Infrared Spectroscopy (IR), 1D and 2D Nuclear Magnetic Resonance (NMR) data. Both constituents 1 and 2 exhibited moderate cytotoxicity against colon cancer HCT-116, gastric cancer MKN-45 and breast cancer MCF-7., Competing Interests: The authors declare no conflicts of interest.

Objective: To study the prevalence of obstructive sleep apnea hypopnea syndrome (OSAHS) and its relationship with traffic accidents in the professional drivers. Methods: Questionnaires of OSAHS were sent to 950 professional drivers who had annual physical examination at the Central Hospital of Jiading District in Shanghai from October 2014 to September 2015. Those with moderate to severe snoring and/or Epworth Sleepiness Scale (ESS)≥9 performed the home sleep testing. All drivers were divided into OSAHS and non-OSAHS according to the survey and monitoring. The following parameters were compared such as driving ages, neck circumference, body mass index (BMI), average night sleep time, ESS, hypertension, diabetes, hypertrophy of tonsil and the incidence of traffic accidents. The risk factors of traffic accidents were analyzed by multivariate Logistic regression. Results: Totally 826 responses were eligible, including 578 (70.0%) with self-reported snoring. There was measurement failure involving 3 of 233 the home sleep testing due to sensor off, 823 subjects were included in the study. The prevalence of OSAHS was 13.5% (111/823). The mild, moderate and severe OSAHS were 47, 38 and 26 cases respectively. There were 712 drives without OSAHS. The neck circumference[(39.8±3.8) vs (39.0±3.0) cm]and BMI[(26.7±4.2) vs (24.4±3.8) kg/m 2 ]were significantly higher in the drivers suffering from OSAHS (all P <0.05). The percentage of ESS≥ 9 (57.7% vs 12.6%), hypertension (27.9% vs 5.9%), diabetes (4.5% vs 1.1%), hypertrophy of tonsil (7.2% vs 2.3%) were higher in the drivers with OSAHS (all P <0.05). There were no significant difference in driving ages and average night sleep time between two groups (all P >0.05). The overall incidence of traffic accidents was 5.8% (48/823) in a year. The percentage was respectively 17.1% (19/111) in OSAHS and 4.1% (29/712) in non-OSAHS ( P <0.001). Multiple logistic regression analysis showed that sleepiness ( OR =30.578, 95% CI: 10.699-87.394; P <0.001), OSAHS ( OR =14.062, 95% CI: 4.791-41.269; P <0.001) and vehicle years ( OR =2.345, 95% CI : 1.183-4.646; P <0.05)were the risk factors, while the average night sleep time ( OR =0.037, 95% CI : 0.014-0.098; P <0.001) was the protective factor. Conclusion: Professional drivers have higher prevalence of OSAHS, which contributes to the increased risk of traffic accidents.

Background: The chemokine (C-X3-C motif) ligand 1 (CX3CL1), also called fractalkine (FKN), has recently been reported to be involved in osteoclastogenic process and pathological bone destruction., Objective: This study aimed to investigate the link between serum CX3CL1/FKN levels with disease progression of postmenopausal osteoporotic patients., Methods: A total of 53 women with postmenopausal osteoporosis (PMOP group), 51 postmenopausal non-osteoporotic female patients (PMNOP group) and 50 premenopausal non-osteoporotic healthy women of childbearing age (control group) were enrolled in the study. The bone mineral density (BMD) for all subjects was determined via dual-energy X-ray absorptiometry of the lumbar spine, femoral neck, internal trochanter, total hip, greater trochanter and Ward's triangle. The levels of FKN in the serum were examined using the enzyme-linked immunosorbent assay method. The serum bone resorption markers TRACP-5b, NTX levels, inflammation markers IL-1β and IL-6 as well as oestrogen-2(E2) were also detected in all participants. The visual analogue scores (VAS) and Oswestry Disability Index (ODI) for low back pain were recorded in PMOP females for evaluation of osteoporotic pain and function., Results: FKN levels were significantly higher in postmenopausal osteoporotic patients compared with postmenopausal non-osteoporotic females (139.8 ± 44.3 pg/mL VS 116.5 ± 23.1 pg/mL, p < 0.05) and healthy controls (139.8 ± 44.3 pg/mL VS 109.7 ± 19.4 pg/mL, p < 0.05). Serum FKN concentrations were negatively associated with BMD at femoral neck (r = -0.394, p = 0.004), total hip(r = -0.374, p = 0.006), internal trochanter(r = -0.340, p = 0.013), greater trochanter(r = -0.376, p = 0.006), Ward's triangle(r = -0.343, p = 0.012), L1-L4 lumbar spine(r = -0.339, p = 0.013) and positively associated with VAS (r = 0.321, p = 0.019) and ODI (r = 0.377, p = 0.005) scores, bone turnover makers (TRACP-5b:r = 0.341, p = 0.012; NTX:r = 0.364, p = 0.007)as well as inflammation markers (IL-1β: r = 0.396, p = 0.003; IL-6:r = 0.355, p = 0.009) in postmenopausal osteoporotic patients., Conclusions: Serum FKN may serve as a novel biomarker for assessing disease progression and a new potential therapeutic target for anti-resorptive treatment in osteoporosis patients.

The aim of the present study was to investigate the protective effects of (-)-epigallocatechin-3-gallate (EGCG), the main polyphenolic constituent of green tea, in aging mice induced by D-galactose (D-gal). The aging mice model was induced by subcutaneous (s.c.) injection of D-gal (150 mg/kg) once daily for 6 weeks. EGCG (2 mg/kg or 6 mg/kg) was administered intragastrically (i.g.) once daily for 4 weeks after 2-week D-gal injection. The water maze test was used to evaluate the learning and memory function of mice. The activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) and the contents of malondialdehyde (MDA) in the hippocampus were measured using different biochemical kits to estimate the changes in the antioxidative ability of mice. TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining method was used to detect neuronal apoptosis, and the activation and expression of proapoptotic protein caspase-3 in the hippocampus were observed and analyzed using immunohistochemical staining and the Western blot method to evaluate apoptosis in the brain. The results indicated that subcutaneous injection of D-gal induced learning and memory impairment in mice, decreased T-SOD and GSH-Px activities, increased MDA contents in the hippocampus, and increased the cell apoptosis index and cleaved caspase-3 protein expression in the hippocampus. Oral administration of EGCG (2 mg/kg or 6 mg/kg) for 4 weeks significantly improved the cognitive deficits in mice and elevated T-SOD and GSH-Px activities, decreased MDA contents in the hippocampus, and reduced the cell apoptosis index and expression of cleaved caspase-3 in the mouse hippocampus. The results suggest that EGCG has potent neuroprotective effects on aging mice induced by D-gal through antioxidative and antiapoptotic mechanisms, indicating that EGCG is worthy of further study in aging.