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Wen-Jie Cong,1,* Zhi-Peng Liu,2,* Yi-Xin Liang,2 Sheng-Lie Ye,2 Zhong-Ming Cai,2 Hao-Man Chen,2 Cheng-Wei Liao,2 Qun-Li Lin,3 Ren-Qian Feng,2 Xu-Dong Zhou,4 Yan-Zhi Wu,2 Le-Qiu Sun,5 Xue-Rong Huang,6 Man-Man Zhang,7 Gui-Qian Huang,8 Bei-Lei Zhu7 1Department of Acupuncture and Physiotherapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2The First Clinical School, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Neurology, Yongjia People’s Hospital, Wenzhou, Zhejiang, People’s Republic of China; 4Department of Neurology, Pingyang People’s Hospital, Wenzhou, Zhejiang, People’s Republic of China; 5Department of Neurology, Affiliated Yueqing Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 6Department of Neurology, Ruian People’s Hospital, Wenzhou, Zhejiang, People’s Republic of China; 7Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang People’s Republic of China; 8School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bei-Lei Zhu, Tel +86 13567896076, Email doczbl@163.comPurpose: To explore the predictive value of nutritional risk for all-cause death and functional outcomes among elderly acute stroke patients.Patients and Methods: A total of 479 elderly acute stroke patients were enrolled in this study. The nutritional risk of patients was screened by the GNRI and NRS-2002. The primary outcome was all-cause death, and the secondary outcome was poor prognosis defined as a modified Rankin Scale (mRS) score ≥ 3.Results: Based on the NRS-2002, patients with nutritional risk had a higher risk of all-cause death at 3 months (adjusted OR: 3.642, 95% CI 1.046~12.689) and at 3 years (adjusted OR: 2.266, 95% CI 1.259~4.076) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.748, 95% CI 1.518~4.972. Based on the GNRI, compared to those without nutritional risk, patients with mild malnutrition also had a higher risk of all-cause death at 3 months (adjusted OR: 7.186, 95% CI 1.550~33.315) and at 3 years (adjusted OR: 2.255, 95% CI 1.211~4.199) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 1.947, 95% CI 1.030~3.680), so patients with moderate and severe malnutrition had a higher risk of all-cause death at 3 months (adjusted OR: 6.535, 95% CI 1.380~30.945) and at 3 years (adjusted OR: 2.498, 95% CI 1.301~4.799) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.213, 95% CI 1.144~4.279).Conclusion: Nutritional risk increases the risk of poor short-term and long-term outcomes in elderly patients with acute stroke. For elderly stroke patients, we should pay attention to early nutritional risk screening, and effective intervention should be provided to improve the prognosis of such patients.Keywords: acute stroke, malnutrition, nutritional screening, all-cause death, GNRI, NRS-2002

Juan Long,1 Chunjing He,1 Hong Dai,2 Xinguo Kang,1 Jinfeng Zou,1 Shengli Ye,1 Qian Yu21Department of Pain, Guizhou Province People‘s Hospital, Guiyang, People’s Republic of China; 2Department of Neurology, Guizhou Province People‘s Hospital, Guiyang, People’s Republic of ChinaObjective: To observe the effects of transection of cervical sympathetic trunk (TCST) on the cognitive function of traumatic brain injury (TBI) rats and the potential mechanisms.Methods: A total of 288 adult male SD rats were divided into 3 groups using a random number table: TBI group (n=96), TBI + TCST group (n=96) and Sham group (n=96). The water maze test was performed before TBI (T0) and at day 1 (T1), day 2 (T2), day 3 (T3), 1 week (T4), 2 weeks (T5), 6 weeks (T6) and 12 weeks (T7) after TBI. The levels of α1-adrenergic receptors (α1-ARs), α2-adrenergic receptors (α2-ARs), toll-like receptor 4 (TLR-4) and P38 in hippocampi were detected by real-time PCR. Hippocampal P38 expression was assayed by Western blot. The expressions of interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and brain-derived neurotrophic factor (BDNF) were examined by immunohistochemistry. Noradrenaline (NE) expression in plasma was evaluated by ELISA. The respiratory control ratio (RCR) of brain mitochondria was detected using a Clark oxygen electrode.Results: TCST effectively improved the cognitive function of TBI rats. TCST significantly inhibited sympathetic activity in the rats and effectively inhibited inflammatory responses. The expression of BDNF at T1-T6 in TBI+TCST group was higher than that in TBI group (P

Haitham Amal,1,‡ Lu Ding,2,‡ Bin-bin Liu,3,‡ Ulrike Tisch,1 Zhen-qin Xu,2 Da-you Shi,2 Yan Zhao,3 Jie Chen,3 Rui-xia Sun,3 Hu Liu,2 Sheng-Long Ye,3 Zhao-you Tang,3 Hossam Haick1 1Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa, Israel; 2Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; 3Liver Cancer Institute and Zhong-shan Hospital, Fudan University, Shanghai, China ‡These authors have equal contribution to the manuscriptBackground: Hepatocellular carcinoma (HCC) is a common and aggressive form of cancer. Due to a high rate of postoperative recurrence, the prognosis for HCC is poor. Subclinical metastasis is the major cause of tumor recurrence and patient mortality. Currently, there is no reliable prognostic method of invasion.Aim: To investigate the feasibility of fingerprints of volatile organic compounds (VOCs) for the in-vitro prediction of metastasis.Methods: Headspace gases were collected from 36 cell cultures (HCC with high and low metastatic potential and normal cells) and analyzed using nanomaterial-based sensors. Predictive models were built by employing discriminant factor analysis pattern recognition, and the classification success was determined using leave-one-out cross-validation. The chemical composition of each headspace sample was studied using gas chromatography coupled with mass spectrometry (GC-MS).Results: Excellent discrimination was achieved using the nanomaterial-based sensors between (i) all HCC and normal controls; (ii) low metastatic HCC and normal controls; (iii) high metastatic HCC and normal controls; and (iv) high and low HCC. Several HCC-related VOCs that could be associated with biochemical cellular processes were identified through GC-MS analysis.Conclusion: The presented results constitute a proof-of-concept for the in-vitro prediction of the metastatic potential of HCC from VOC fingerprints using nanotechnology. Further studies on a larger number of more diverse cell cultures are needed to evaluate the robustness of the VOC patterns. These findings could benefit the development of a fast and potentially inexpensive laboratory test for subclinical HCC metastasis.Keywords: hepatocarcinoma, metastasis, volatile organic compound, sensor, GC-MS

The role of radiotherapy in the treatment of intrahepatic cholangiocarcinoma is controversial. We undertook this study to determine if radiotherapy is appropriate for patients with unresectable or lymph node metastatic intrahepatic cholangiocarcinoma. METHODS AND MATERIALS: The records of 75 patients with intrahepatic cholangiocarcinoma were reviewed and analyzed by Kaplan-Meier method and Cox proportional hazards analysis. Thirty-eight patients who received limited local external-beam radiotherapy were classified as the radiotherapy group. This group included nine patients with resected intrahepatic cholangiocarcinoma with macroscopic residual lymph nodes receiving postoperative external-beam radiotherapy, seven patients with postoperative recurrences in lymph nodes receiving external-beam radiotherapy for salvage failure after treatment with surgery alone, and 22 patients with unresectable intrahepatic cholangiocarcinoma. The median total dose was 50 Gy (range, 30-60 Gy) in daily doses of 2 Gy/fraction, five times a week. Thirty-seven patients with intrahepatic cholangiocarcinoma (including 14 with resectable disease and synchronous or asynchronous lymph node metastases, and 23 with unresectable disease) who did not receive external-beam radiotherapy were selected from hospitalized patients in the same period and were classified as the nonexternal-beam radiotherapy group. Parameters observed included survival rates and tumor response to external-beam radiotherapy demonstrated both by clinical symptoms and by computed tomography scan/magnetic resonance image. RESULTS: Objective responses to external-beam radiotherapy were 36.4% for intrahepatic tumors in 22 patients with unresectable intrahepatic cholangiocarcinoma, and 52% for lymph node metastases in 25 patients with resectable or unresectable intrahepatic cholangiocarcinoma. Pain was relieved in 90% of the patients who received external-beam radiotherapy. The survival rates at 1 and 2 years for patients with unresectable intrahepatic cholangiocarcinoma treated with external-beam radiotherapy (n = 22) compared with those who did not receive external-beam radiotherapy (n = 23) were 36.1% versus 19.0% and 5.2% versus 4.7%, respectively (log-rank P = 0.021). The survival experience of the 16 patients with lymph node metastases (synchronous or asynchronous) who underwent hepatectomy combined with external-beam radiotherapy was superior to that of the group (n = 14) who did not receive external-beam radiotherapy (median survival, 468 and 211 days, respectively; log-rank P = 0.075). These results show that external-beam radiotherapy influenced the survival in the patients with unresectable intrahepatic cholangiocarcinoma or lymph node metastases. The most common reason for death was liver failure caused by uncontrolled intrahepatic disease. Grade 3 toxicity in the external-beam radiotherapy group was infrequent. CONCLUSION: External-beam radiotherapy seems to improve the prognosis of patients with unresectable intrahepatic cholangiocarcinoma and deserves further study. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a common type of poorly prognosticated malignant tumor. Surgical resection is the preferred treatment method for early-stage HCC. However, at the time of the initial diagnosis, fewer than 30% of patients with liver cancer are suitable for radical therapy. Systemic therapy plays an important role in the treatment process of patients with intermediate- to advanced-stage HCC, as it can effectively extend patients' survival time. With an emphasis on the status and role of systemic therapy for comprehensive management of HCC, this article summarizes the latest progress at home and abroad in the past five years, including first-line combined immunotherapy for advanced-stage HCC, second-line therapy selection, perioperative systemic therapy application, and combined therapy of systemic and local. Currently, the treatment model combined with local therapy has already become a new research hotspot in the treatment of advanced-stage HCC. Nevertheless, in the future, individualized and precise systemic therapeutic strategies will need further exploration.

Background: AAA is a fatal condition that commonly occurs during vascular surgery. Nutritional status exerts a significant influence on the prognosis of various pathological conditions Scores from the CONUT screening tool have been shown to predict outcomes of certain malignancies and chronic diseases. However, the ramifications of nutritional status on AAA patients undergoing EVAR have not been elucidated in prior studies. In this study, we aimed to elucidate the correlation between CONUT scores and postoperative prognostic outcomes in patients with AAA undergoing EVAR., Methods: This was a retrospective review of 177 AAA patients treated with EVAR from June 2018 to November 2019 in a single center. Patient characteristics, CONUT scores, and postoperative status were collected. These patients were stratified into groups A and B according to CONUT scores. Subsequently, a comparative analysis of the baseline characteristics between the two cohorts was conducted. Cox proportional hazards and logistic regression analyses were employed to identify the autonomous predictors of mid-term mortality and complications, respectively., Results: Compared with group A, patients in group B had higher midterm mortality ( p  < 0.001). Univariate analysis showed that CONUT scores; respiratory diseases; stent types; preoperative Hb, CRP, PT, and Fb levels were risk factors for death. Multivariate analysis confirmed that CONUT score [HR, 1.276; 95% CI, 1.029-1.584; p  = 0.027] was an independent risk factor for mortality. Logistic regression analysis showed that prior arterial disease, smoking, and D-dimer levels were risk factors, although multivariate analysis showed smoking (OR, 3.492; 95% CI, 1.426-8.553; p  = 0.006) was an independent risk factor. Kaplan-Meier curves showed that patients in group B had shorter mid-term survival than those in group A (log-rank p  < 0.001)., Conclusion: Malnutrition was strongly associated with mid-term mortality in patients with infrarenal AAA treated with EVAR., 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 Ye, Xu, Wang, Han, Jiang, Tang, Song, Du, Hu and Li.)

RNA-cleaving ribozymes are promising candidates as general tools of RNA interference (RNAi) in gene manipulation. However, compared with other RNA systems, such as siRNA and CRISPR technologies, the ribozyme tools are still far from broad applications on RNAi due to their poor performance in the cellular context. In this work, we report an efficient RNAi tool based on chemically modified hammerhead ribozyme (HHR). By the introduction of an intramolecular linkage into the minimal HHR to reconstruct the distal interaction within the tertiary ribozyme structure, this cross-linked HHR exhibits efficient RNA substrate cleavage activities with almost no sequence constraint. Cellular experiments suggest that both exogenous and endogenous RNA expression can be dramatically knocked down by this HHR tool with levels comparable to those of siRNA. Unlike the widely applied protein-recruiting RNA systems (siRNA and CRISPR), this ribozyme tool functions solely on RNA itself with great simplicity, which may provide a new approach for gene manipulation in both fundamental and translational studies.

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5 th edition of the World Health Organization Classification of Tumours of the Digestive System., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Objective: To first induce chronic deep venous thrombosis in the left iliac veins of canines and porcines and then compare these two models to validate endovascular treatment devices., Methods: Thrombin and fibrinogen were used to produce a solid thrombus in the left iliac veins of a stenosis model. The researchers used venous angiography and histological staining to investigate the progression of thrombosis., Results: A left iliac vein thrombus was successfully formed in all experimental animals, including six Labrador dogs and three Bama miniature pigs, and there was minimal surgical bleeding. All dogs survived until 90 days, and three pigs died on Days 29, 33, and 58., Conclusion: The researchers first established the models and then observed the progression of chronic deep venous thrombosis of the iliac vein in large animals for up to 90 days. Dogs are better suited for chronic deep venous thrombosis models due to their uncomplicated anatomy, excellent obedience, and proneness to physical activity compared with pigs., (© 2023. The Author(s).)

Background: Ruptured abdominal aortic aneurysms (rAAAs) are challenging for vascular surgeons because they have a high mortality rate. In many diseases, nutritional status is closely associated with prognosis. The Controlling Nutritional Status (CONUT) screening tool score is a prognostic factor in some malignant and chronic diseases; however, the impact of nutritional status on rAAA has not yet been reported. In this study, we explored the relationship between the CONUT score and the postoperative prognosis of patients with rAAA., Methods: This was a retrospective review of 39 patients with rAAA who underwent surgical treatment from March 2018 to September 2021 at one center. Patient characteristics, nutritional status (CONUT score), and postoperative status were recorded. The patients were divided into groups A and B based on the CONUT score. The baseline characteristics of the two groups were compared, and Cox proportional hazards and logistic regression analyses were used to determine independent predictors of mid-term mortality and complications, respectively., Results: The overall mid-term mortality rate was 28.21% (11/39). Compared with group A, group B had higher intraoperative ( P  = 0.047) and mid-term mortality ( P  = 0.033) rates. The univariate analysis showed that age [hazard ratio (HR), 1.098; 95% confidence interval (CI), 1.019-1.182; P  = 0.014], CONUT score (HR, 1.316; 95% CI, 1.027-1.686; P  = 0.03), and surgical procedure (HR, 0.127; 95% CI, 0.016-0.992; P  = 0.049) were associated with mid-term mortality, whereas the multivariate analysis showed that the CONUT score (HR, 1.313; 95% CI, 1.009-1.710; P  = 0.043) was an independent predictor of mid-term mortality. The multivariate logistic regression analysis did not reveal any associations with complications. The Kaplan-Meier curves showed that group B had a lower mid-term survival rate (log-rank P  = 0.024)., Conclusion: Malnutrition is closely associated with the prognosis of patients with rAAA, and the CONUT score can be used to predict mid-term mortality., 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., (© 2023 Ye, Xiang, Liu, Li, Tang, Qian, Li and Sun.)

Background: The aim of this study was to perform hemodynamic simulations of a three-dimension ideal inferior vena cava-iliac vein model with artificial stenosis to determine the degree of stenosis that requires clinical intervention., Methods: Four three-dimension stenosis models (30%, 50%, 70%, and 90% stenosis) were constructed using commercial software (Solidworks). The inlet flow rates were acquired from previous literatures to perform the hemodynamic simulations. Changes in the old blood volume fraction, as well conventional hemodynamic parameters including pressure, differential pressure, wall shear stress, and flow patterns, over time were recorded. The pressure at the telecentric region of the stenosis increased with increasing degree of stenosis., Results: For the 70% stenosis model, the pressure at the telecentric region of the stenosis reached 341 Pa, and the differential pressure between the two ends of the stenosis was 363 Pa (approximately 2.7 mmHg). Moreover, in the 70% and 90% stenosis models, there was a marked change in wall shear stress in the stenosis and the proximal end region, and the flow patterns began to show the phenomenon of flow separation. Blood stasis analysis showed that the 70% stenosis model had the slowest decrease in old blood volume fraction, while the proximal end region had the largest blood residue (15%)., Conclusion: Iliac vein stenosis of approximately 70% is associated with clinically relevant hemodynamic changes, and is more closely related to DVT than other degrees of stenosis., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Portal vein tumor thrombosis (PVTT), a common complication of advanced hepatocellular carcinoma (HCC), remains the bottleneck of the treatments. Liver cancer cells potentially experienced multi-steps during PVTT process, including cancer cells leave from cancer nest, migrate in extracellular matrix, invade the vascular barrier, and colonize in the portal vein. Accumulated evidences have revealed numerous of molecular mechanisms including genetic and epigenetic regulation, cancer stem cells, immunosuppressive microenvironment, hypoxia, et al. contributed to the PVTT formation. In this review, we discuss state-of-the-art PVTT research on the potential molecular mechanisms and experimental models. In addition, we summarize PVTT-associated clinical trials and current treatments for PVTT and suppose perspectives exploring the molecular mechanisms and improving PVTT-related treatment for the future., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Time in range (TIR) is a novel indicator of glycaemic control that has been reported to have an association with diabetic complications. The objective of the study was to explore the association of TIR with postoperative wound healing in patients with diabetic foot ulcers (DFUs). We retrospectively analysed the data of DFU patients who had undergone surgical treatment from 2015 to 2019. A 1:1 ratio in propensity score matching (PSM) was adopted to compare patients with TIR ≥50% with those <50%. Data were summarised using chi-squared, Fisher's exact, and Mann-Whitney U tests. Patients with TIR <50% underwent a higher rate of secondary surgery within a month (P = .032) and had a longer hospital stay (P = .045) with greater hospital charges (P < .001) than the TIR ≥50% group. Multivariate analysis revealed that TIR (P = .034), Wagner score (P = .009), diabetes treatment (P = .006), and type of surgery (P = .013) were independent risk factors for secondary surgery. Additionally, patient subgroups with TIR <50% and baseline HbA1c < 7.5% (P = .025), albumin level ≥ 30 g/L (P = .039), HDL < 1.16 (P = .021), or Wagner score ≥ 3 (P = .048) also experienced a higher incidence of secondary surgery. TIR was correlated with postoperative wound healing in patients with DFUs. Strict glycaemic targets should be established for surgical patients., (© 2021 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Exosomes are nanoscale endocytic vesicles, 30-150 nm in diameter, secreted by most cells. They mainly originate from multivesicular bodies formed by intracellular invagination of lysosomal microparticles, and released into the extracellular matrix after fusion of multivesicular bodies with cell membrane. Studies have shown that exosomes contain a variety of active molecules, such as proteins, lipids and RNAs (such as mRNA, miRNA, lncRNA, circRNA, etc.), which regulate the behavior of recipient cells and serve as circulating biomarkers of diseases, including thrombosis. Therefore, exosome research is important for the diagnosis, treatment, therapeutic monitoring, and prognosis of thrombosis in that it can reveal the counts, surface marker expression, protein, and miRNA cargo involved. Recent studies have shown that exosomes can be used as therapeutic vectors for tissue regeneration and as alternative vectors for drug delivery. In this review, we summarize the physiological and biochemical characteristics, isolation, and identification of exosomes. Moreover, we focus on the role of exosomes in thrombosis, specifically venous thromboembolism, and their potential clinical applications, including as biomarkers and therapeutic vectors for thrombosis., 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 Ye, Li, Li, Xiao, Ran, Chen, Li and Sun.)

Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients ( P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.

Background: Stroke is a leading cause of death and functional impairment in older people. To assess the prospective association between fasting blood glucose-to-glycated hemoglobin ratio and all-cause mortality and poor prognosis in stroke patients., Methods: A total of 971 Chinese inpatients with acute stroke (mean age of 65.7) were consecutively enrolled in the prospective clinical study and followed up for 12 months after discharge. Stress hyperglycemia was measured using the ratio of fasting blood glucose (FBG, mmol/L)/glycated hemoglobin (HbA1c, %). The primary outcome was all-cause mortality, and secondary outcomes were poor prognosis defined as infectious complications, a National Institutes of Health Stroke Scale (NIHSS) score ≥ 6, a Barthel Index score ≤ 60, or a modified Rankin Scale (mRS) score of 3-6, presented as multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) across the quartiles of the FBG/HbA1c ratio., Results: There were 35 (4.1%) all-cause deaths at 3 months and 85 (11.4%) at 12 months. The inpatients with the highest quartile of the FBG/HbA1c ratio had a higher risk of all-cause death at 3 months (adjusted OR: 5.16, 95% CI: 1.03-25.74) and at 12 months (adjusted OR: 2.59, 95% CI: 1.14-5.89)) and a higher risk of infectious complications (adjusted OR 2.37, 95% CI 1.27-4.43) and dysfunction (adjusted OR 1.79, 95% CI 1.06-3.01) during hospitalization than inpatients with the lowest quartile., Conclusions: Stress hyperglycemia, measured by the FBG/HbA1c ratio, was associated with an increased risk of adverse outcomes, including all-cause death, infectious complications, and dysfunction after stroke., (© 2022. The Author(s).)

The article "MiR-124 affects the apoptosis of brain vascular endothelial cells and ROS production through regulating PI3K/AKT signaling pathway, by S.-W. Wang, L.-X. Deng, H.-Y. Chen, Z.-Q. Su, S.-L. Ye, W.-Y. Xu, published in Eur Rev Med Pharmacol Sci 2018; 22 (2): 498-505-DOI: 10.26355/eurrev&#95;201801&#95;14201-PMID: 29424909" has been withdrawn from the authors due to inaccuracies (there are some errors and incorrect data). The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14201.

Carotid and vertebral artery dissections are estimated to account for ∼20% of strokes in patients under 45-years-old. This meta-analysis compared the efficacy and safety of treatment with anticoagulants versus antiplatelet agents to determine the optimal therapy. We searched 4 electronic databases for clinical trials published from January 1, 1980 to August 25, 2021 that included patients who received anticoagulant or antiplatelet therapy for carotid and/or vertebral artery dissections. The curative effect was judged by recanalization evaluated by imaging. The primary outcomes were all cause death and ischemic stroke; secondary outcomes included hemorrhage and transient ischemic attack (TIA). Patients who received only a single drug treatment were divided into antiplatelet or anticoagulant groups; all received conservative treatment without surgical intervention. For this investigation, we pooled the available studies to conduct a meta-analysis, which included 7 articles with 1126 patients. The curative effect of vascular recanalization was not significantly different between the 2 treatment groups (odds ratio [OR] = 0.913, 95% confidence interval [CI]: 0.611-1.365, P  = .657); similarly, no significant differences were found regarding the primary outcomes all cause death (OR = 1.747, 95%CI: 0.202-15.079, P  = .612) and ischemic stroke (OR = 2.289, 95%CI: 0.997-5.254, P  = .051). Patients treated with anticoagulants were more likely to experience TIA (OR = 0.517, 95%CI: 0.252-1.060, P  = .072) and hemorrhage (OR = 0.468, 95%CI: 0.210-1.042, P  = .063), but the differences were not statistically significant. Overall, there were no statistically significant differences between anticoagulant therapy and antiplatelet therapy for the treatment of carotid and vertebral artery dissections.

Background: This study was aimed at systematically evaluating the clinical effect and safety of Xiao'er Xiaoji Zhike oral liquid in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children and providing evidence-based references for clinical application., Methods: The databases like Chinese Biomedical Literature Database, China Network Knowledge Infrastructure, Wan Fang Database, Chinese Scientific Journal Database, PubMed, EmBase, and the Cochrane Library were systematically investigated via searching clinical trials about Xiao'er Xiaoji Zhike oral liquid in treating MPP from the establishment of these databases to Jun 8, 2020, the valid data from which were entered meta-analysis. The quality of evidence was assessed by GRADE criteria., Results: Totally, 15 trials and 1500 patients were involved in this review. It showed that clinical efficacy of trial group was more superior than control group at the outcome measures of cough disappearance time, lung rale disappearance time, fever subsidence time, total effective rate, lung X-ray infiltrates disappearing time, reduction of hospital stay, immunological indexes, and some other measures. And the differences between groups were statistically significant. There was no statistical difference in the adverse effects between two groups. Lung X-ray infiltrates disappearing time and cough disappearance time were separately high- and moderate-quality evidences while lung rale disappearance time and fever subsidence time were all low in accordance with GRADE criteria., Conclusions: In accordance with trials with low methodological quality, Xiao'er Xiaoji Zhike oral liquid combined with azithromycin seems to be safe and superior to azithromycin alone for the treatment of MPP in children. However, further trials with rigorous methodology need to be implemented for these potential benefits., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2020 Gui-Min Zhang et al.)

The "top-down" method was used to measure the traffic carbon emissions from 1985 to 2016 in the Yangtze River Economic Belt and analyze its spatial pattern and temporal evolution characteristics. Considering the unexpected output, a three-stage DEA model was constructed to evaluate and compare the traffic carbon emission efficiency of the Yangtze River Economic Belt, excluding the influence of external environment variables and random errors. The study found that first, the total traffic carbon emissions in the Yangtze River Economic Belt showed a rising trend, among which the carbon emissions from petroleum energy consumption accounted for the largest proportion. Sichuan, Hubei, and Hunan and the Su-Zhe-Hu Region were the high-value areas of traffic carbon emissions in the upper, middle, and lower reaches of the Yangtze River, respectively. Second, from the east to west, the center of traffic carbon emissions generally showed a changing track of moving east first and then west; from the north to south, it highlighted the characteristics of increasing concentrated distribution along the Yangtze River in space. Third, there was an obvious spatial differentiation in the traffic carbon emission efficiency values of different provinces; from 2007 to 2016, the efficiency value of the eastern region was the highest, but the value of the central region changed from higher than that in the western region to lower than that in the western region. Finally, external environmental factors had a significant impact on the efficiency of traffic carbon emissions, in which the optimization of industrial structure was found to be conducive to the improvement of traffic carbon emission efficiency, while the influence of government intervention was changed from "innovation compensation" effect to "compliance cost" effect.

The Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement on the treatment strategy for patients with intermediate-stage hepatocellular carcinoma (HCC) was established on August 31, 2019, in Sapporo, Hokkaido during the 10th Annual APPLE Meeting. This manuscript summarizes the international consensus statements developed at APPLE 2019. Transarterial chemoembolization (TACE) is the only guideline-recommended global standard of care for intermediate-stage HCC. However, not all patients benefit from TACE because intermediate-stage HCC is a heterogeneous disease in terms of tumor burden and liver function. Ten important clinical questions regarding this stage of HCC were raised, and consensus statements were generated based on high-quality evidence. In intermediate-stage HCC, preservation of liver function is as important as achieving a high objective response (OR) because the treatment goal is to prolong overall survival. Superselective conventional TACE (cTACE) is recommended as the first choice of treatment in patients eligible for effective (curative) TACE, whereas in patients who are not eligible, systemic therapy is recommended as the first choice of treatment. TACE is not indicated as the first-line therapy in TACE-unsuitable patients. Another important statement is that TACE should not be continued in patients who develop TACE failure/refractoriness in order to preserve liver function. Targeted therapy is the recommended first-line treatment for TACE-unsuitable patients. Especially, the drug, which can have higher OR rate, is preferred. Immunotherapy, transarterial radioembolization, TACE + targeted therapy or other modalities may be considered alternative options in TACE-unsuitable patients who are not candidates for targeted therapy. Better liver function, such as albumin-bilirubin grade 1, is an important factor for maximizing the therapeutic effect of systemic therapy., Competing Interests: M.K. received lecture fees from Bayer, Eisai, MSD, and Bristol-Myers Squibb, research grants from Chugai, Otsuka, Takeda, Taiho, Daiichi Sankyo, Eisai, AbbVie, EA Pharma, Gilead Sciences, Astellas Pharma, and Bristol-Myers Squibb, and advisory consulting fees from MSD, Eisai, Bayer, Bristol-Myers Squibb, Roche, and Ono Pharmaceutical. K.-H.H. received lecture fees from Eisai, Gilead Sciences and AstraZeneca and research grants from Bristol-Myers Squibb, Eisai and Ono Pharmaceutical. S.-L.Y., Z.J., Y.-H.H., and S.-M.L. has no conflicts of interest to declare. C.-K.W. had no conflict of interest. M.I. received honoraria from Eisai, Bayer, and Lilly and received research funds from Lilly, Bayer, Takeda, Eisai, Bristol Myers Squibb, AstraZeneca, Novartis, Chugai, and Merck biopharma. S.L.C. received advisory consulting fees from Eisai, MSD, Ipsen, and AstraZeneca, and research fund from Eisai, Bayer, and MSD. S.P.C. received honoraria and consulting fees from Eisai, Bayer, BMS, Roche, Celgene and AstraZeneca. Also received speaker fees from BMS, Eisai and Lilly. S.M. received honoraria (speaker fees) from Eisai, Guerbet, Bayer, MSD, Bristol-Myers, Daiichi Sankyo, Asahi Intecc, Terumo, Philips, and Piolax. A.L.C. received consultant from Bristol-Myers Squibb, Bayer Schering Pharma, Novartis, Eisai, Ono Pharmaceutical, AstraZeneca, Genentech/Roche, CSR Pharma Group, Inc., MSD, BeiGene, Ltd., Bayer Yakuhin, ISPEN, and Eli Lilly., (Copyright © 2020 by S. Karger AG, Basel.)

Background: Malnutrition is confirmed to be associated with poor outcomes in stroke patients. The present study aimed to confirm that being at risk of malnutrition assessed by Nutritional Risk Screening Tool 2002 (NRS-2002) and the Controlling Nutritional Status (CONUT) score predicts poor outcomes at 3 months in acute ischemic stroke (AIS) patients., Methods: In total, 682 patients with AIS were recruited within 7 days of stroke onset consecutively and 110 were dropped out. They were screened for risk of malnutrition using NRS-2002 and the CONUT score. The primary outcome is the follow-up modified Rankin Scale (mRS) score. Poor outcomes were defined as an (mRS) score ≥ 3 at 3 months post discharge., Results: There was a significant difference in the mRS score at 3 months between patients at risk of malnutrition compared to those not at risk assessed by NRS-2002(P < 0.001) and CONUT (P = 0.011). The logistic regression model showed that the risk of malnourishment (according to NRS-2002), low risk of malnourishment (according to CONUT), and the moderate-to-severe risk of malnourishment (according to CONUT) were associated with higher risk of poor outcomes at 3 months (P < 0.001, P = 0.033, and P = 0.007). The multivariate logistic regression model (adjusted for confounding factors) demonstrated that the risk of malnourishment, according to the NRS-2002, was associated with the increasing risk of poor outcomes at 3 months (odds ratio = 2.31; 95% CI: 1.24-4.30; P = 0.008)., Conclusions: The risk of malnutrition assessed by NRS-2002 and CONUT can predict poor outcomes at 3 months in AIS patients. NRS-2002 is superior to CONUT in predicting poor outcomes at 3 months.

In this work, a fluorescent nanoparticles labeling-free fluorescence enzyme-linked immunoassay (FELISA) has been established for the ultrasensitive detection of microcystin-LR (MC-LR) in water and fish samples. Polyclonal antibody against MC-LR was labeled with horseradish peroxidase (HRP) and used as signal probe for binding with analyte in sample or for coating antigen. After washing of the unbound antibody, the substrate system (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS)/H 2 O 2 ) was added. The oxidation product of ABTS (ox-ABTS) catalyzed by HRP effectively caused the fluorescence quenching of subsequently added silane-doped carbon dots (Si-CDs), and the change in fluorescence intensity of Si-CDs was used to realize the quantitative detection of MC-LR. Under the optimum conditions, the Si-CDs based FELISA method showed a good linear relationship from 0.001 to 3.20 μg L -1 (R 2  = 0.994) and provided a low detection limit of 0.6 ng L -1 , which was approximately 30-fold lower than that of traditional indirect competitive ELISA. Average recovery values from 79.9% to 109.2% was obtained from spiked water and crucian samples, suggesting its potential application on the monitoring of MR-LR at a trace level., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose : The prognosis of patients with intermediate-stage hepatocellular carcinoma (HCC) treated by conventional TACE (cTACE) is greatly heterogeneous. This study aimed to develop a new survival prediction model to help select patients who would benefit better from cTACE treatment. Methods : We collected data of 848 treatment-naïve patients with BCLC B HCC who received cTACE as first-line therapy. The prognostic model's variables were derived from univariate and multivariate Cox regression analyses. The concordance index (C-statistic) calculated through cross-validation and bootstrap resampling was used for the model selection. The calibration of our final prediction model was also assessed. Results : The model showed a better discrimination ability than Bolondi's BCLC B1-B4 subclassification to predict the prognosis of BCLC B patients (C-statistic, 0.66 vs . 0.60; difference, 0.05, 95% CI, 0.03-0.07). In cross-validation, bootstrap resampling demonstrated that the model maintained sufficiently discriminant (an average of C-statistic, 0.66; 95% CI, 0.65-0.68). The model calibration was accurate in predicting survival of patients matched well with the observed outcomes. On the basis of the improved survival of 18 months or more as the responding patient, the observations of patients in each response category (responder and non-responder) were fair-moderately matched with those predicted by the model (κ=0.40, P <0.001). Conclusions : Based on clinically available features of patient, tumor and liver function, we developed an alternative prediction model with better performance than the Bolondi's substaging system for intermediate HCC patients after cTACE, which could help define the distinct subgroup of BCLC B patients who are suitable for cTACE treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The antibiofilm activity and molecular mechanism of a natural phenolic compound, 3- p-trans -coumaroyl-2-hydroxyquinic acid (CHQA) against Staphylococcus aureus were investigated in this study. Crystal violet staining and XTT reduction assay demonstrated that CHQA could prominently prevent the biofilm formation of S. aureus accompanied with decrease in metabolic activity of biofilm cells. Meanwhile, microscopic observations revealed that CHQA caused a huge collapse on the architecture of S. aureus biofilm. Moreover, CHQA specifically inhibited the initial attachment phase of biofilm development and reduced S. aureus adhesion to fibrinogen. Fluorescence resonance energy transfer assay and molecular simulation showed that CHQA inhibited the activity of S. aureus sortase A (SrtA) through binding to the active region via non-covalent interactions. Additionally, CHQA efficiently reduced S. aureus attachment to stainless steel. Hence, these results suggested CHQA as a potential bacterial biofilm inhibitor which achieved antibiofilm activity through affecting the attachment phase of biofilm formation by targeting SrtA., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Hepatocellular carcinoma (HCC) (about 85-90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people., Summary: This guideline presents official recommendations of the National Health and Family Planning Commission of the People's Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations., Key Messages: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

Background: This study aimed to investigate the safety of sorafenib for the treatment of unresectable hepatocellular carcinoma in Chinese patients., Methods: A subgroup of 345 Chinese patients from the international database of the Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON) study was included in this analysis. Safety assessment measures were adverse events (AEs) and serious adverse events (SAEs) graded using the National Cancer Institute Common Terminology Criteria version 3.0., Results: Of 331 evaluable patients, 98% started sorafenib at 800 mg/day. The median treatment duration was 22 weeks (range, 0.1-116 weeks), and median overall survival (OS) was 322 days (10.7 months). Approximately 50% of patients had at least one adverse event, and 6% had grade 3-4 adverse events. Drug-related adverse events were experienced by 29% of patients, and 3.6% had grade 3-4 drug-related adverse events. Overall, 23% of patients (n = 77) experienced serious adverse events, among which only 1 event was drug-related (0.3%). No differences in overall adverse events, serious adverse events, and deaths were observed between Child-Pugh A and Child-Pugh B patients. The most frequent drug-related adverse events were dermatological/skin (24%), hand-foot skin reaction (20%), gastrointestinal (11%), and diarrhea (11%). The majority of adverse events occurred within 30 days of beginning sorafenib., Conclusion: Sorafenib has satisfactory efficacy and safety in Chinese Child-Pugh A and B patients with unresectable HCC using the recommended dosage of 800 mg/day, and the safety of sorafenib is not affected by liver function. Prophylaxis for gastrointestinal adverse events may help to decrease dose interruptions or discontinuation., Trial Registration: ClinicalTrials.gov ; Identifier: NCT00812175. Date of registration: December 19, 2008.

Transarterial chemoembolization (TACE) is the standard treatment for unresectable hepatocellular carcinoma (HCC). Hypoxia-induced angiogenesis by TACE is linked to treatment failure; however, whether the chemotherapeutic damage of TACE to HCC could increase tumor angiogenesis has not been explored. The molecular effects of chemotherapy-damaged HCC cells on the neo-angiogenesis were investigated in vitro and in vivo. The expression of growth differentiation factor 15 (GDF15) was significantly upregulated in HCC cells exposed to chemotherapeutic agents. GDF15 from chemotherapy-damaged HCC cells promoted the in vitro proliferation, migration, and tube formation of endothelial cells. The pro-angiogenic effect of GDF15 was through the activation of Src and its downstream AKT, MAPK, and NF-κB signaling, which was blocked by thalidomide. The use of thalidomide significantly attenuated the in vivo chemotherapy-damaged HCC cells-promoted angiogenesis in nude mice. In conclusion, the chemotherapeutic damage in TACE to HCC could promote tumor angiogenesis via the increased release of GDF15. Thalidomide could reverse these pro-angiogenic effects., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: The apoptosis of vascular endothelial cells (VEC) is related to ischemic stroke. Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT/PKB) signaling pathway can upregulate Bcl-2 expression, reduce reactive oxygen species (ROS) production, and induce apoptosis. The level of miR-124 was significantly increased after cerebral ischemia. This study aimed to investigate the role of miR-124 in regulating PI3K expression, brain VEC apoptosis, and ROS production., Materials and Methods: The expressions of miR-124, PI3K, p-AKT, and Bcl-2 in brain VEC of rats from the sham group and middle cerebral artery occlusion (MCAO) group were tested. Bioinformatics analysis showed the complementary binding site between miR-124 and PI3K mRNA. ROS content and cell apoptosis were detected by flow cytometry. Rat brain VEC were cultured in vitro and treated by oxygen-glucose deprivation (OGD) for 6 h. VECs were divided into four groups, including miR-NC, miR-124 inhibitor, pIRES2-blank, and pIRES2-PI3K groups, and were further treated by OGD., Results: MiR-124 expression, ROS content, and cell apoptosis were markedly increased, whereas the levels of PI3K, p-AKT, and Bcl-2 were markedly reduced in rat VECs from MCAO group compared with that in the sham group. OGD treatment significantly induced VECs apoptosis, upregulated miR-124 expression and ROS content, and down-regulated the levels of PI3K, p-AKT, and Bcl-2. MiR-124 inhibitor or transfection of pIRES2-PI3K plasmid apparently enhanced PI3K, p-AKT, and Bcl-2 expressions, alleviated cell apoptosis and decreased ROS content in VECs induced by OGD., Conclusions: Our data demonstrated that miR-124 induced the apoptosis of brain vascular endothelial cells via the down-regulation of PI3K/AKT signaling pathway and promotion of ROS production.

Background: Garzê and Aba form the second largest Tibetan-inhabited area of China. Blood services have never been reported for this region before., Objective: To assess the current situation and analyse whether a safe and adequate blood supply has been developed in both Garzê and Aba., Methods: We conducted a longitudinal survey covering the period 2011-2016. The subjects of interest were recruited from non-remunerated voluntary donation, blood testing, clinical transfusion practices and infrastructure of local blood service systems., Results: The donation rate and blood collection volume were below the average levels of both the Sichuan Province and mainland China. Component therapy was widely used, but inappropriate usage of whole blood existed. A lack of national specific standards for people on the plateaus led to local blood transfusions being conducted without full clinical assessment. Endemic and frequently occurring disease, such as hydatid disease and gastrointestinal disease, were inevitable risks for blood utilisation and safety. The potential influence of religious belief and traditions, like 'male-leaving marriages', of Tibetans on donor recruitment and blood safety requires further research., Conclusions: A relatively safe and complete blood service system has been developed in this region. However, there is still an urgent need for comprehensive and effective support from the government in terms of policies and finance. As an epidemic area of hydatid disease and sexually transmitted disease, this region needs to emphasise public health measures, such as blood safety and inappropriate usage of blood products., (© 2017 British Blood Transfusion Society.)

Background: Antiphospholipid syndrome (APS)-related immune factors are considered as an important cause of recurrent spontaneous abortion (RSA). Anticoagulant and anti-inflammatory treatments are believed to effectively improve adverse pregnancy outcomes by affecting the abnormal autoimmune response of the maternal-fetal interface. The aim of this study was to observe the clinical characteristics and treatment outcomes of anticoagulant regimens and anti-inflammatory plus anticoagulation regimens for APS-related RSA., Methods: APS-related RSA cases from September 2011 to September 2016 at Peking University Third Hospital were retrospectively analyzed. The patients were assigned to study group (anti-inflammation plus anticoagulation) and control group (simple anticoagulation). The incidence of repeat abortion, the incidence of placental dysfunction, the gestational weeks of pregnancy, and the mean weight of the fetus were observed., Results: The pregnancy and neonatal outcome indicators of the repeat pregnancy loss rate (11.11% vs. 22.70%), placental dysfunction-related diseases (6.35% vs. 15.60%), the mean birth weight of infants born after 24 weeks gestation (3152.41 ± 844.67 g vs. 2765.76 ± 816.40 g), full-term delivery weight (3456.28 ± 419.79 g vs. 3076.18 ± 518.79 g), the proportions of low birth weight infants (12.70% vs. 21.98%), and small for gestational age (6.35% vs. 14.18%) differed significantly between the study and control groups (all P< 0.05). The incidence of preterm delivery, term delivery, and stillbirth was not significantly different between the two groups, and there was no significant difference between the study and control groups in gestational age at birth (37.6 ± 3.3 weeks vs. 36.9 ± 3.2 weeks; P > 0.05)., Conclusion: The anti-inflammatory and anticoagulation regimen is more effective than the simple anticoagulation regimen in the treatment of APS recurrent abortion.

Lung carcinoma is the most common cause of malignant death worldwide. CD8 T cells, as critical elements in antitumor immunity, could function as good prognostic indicators in various kinds of cancers such as renal cell carcinoma and colorectal cancer, but its prognostic role in lung adenocarcinoma is still unclear. The objective of this study was to explore the prognostic role of CD8 expression in lung adenocarcinoma.Paired tumor and adjacent noncancerous tissues were obtained from 102 patients with lung adenocarcinoma, and CD8 expression of these samples was examined by immunohistochemistry. We evaluated the relationships between the expression of CD8 and pathological grade, TNM stage, clinical stage, as well as overall survival (OS).Expression of CD8 was significantly increased in lung adenocarcinoma compared with that in adjacent lung adenocarcinoma (P < .001). CD8 expression was negatively correlated with pathological grade (r = -0.216, P = .022) and N stage (r = -0.372, P < .001), while no statistical correlation with T stage, or clinical stage. Importantly, OS was numerically increased in patients with high expression of CD8 than the group of intermediate and low CD8 expression (P = .12). Furthermore, CD8 could significantly increase OS (P = .043, HR: .713, 95%CI: .515-.989) by univariate Cox's proportional hazards regression analysis.Our data indicated that expression of CD8, as a protective factor, is correlated with the outcome of patients with lung adenocarcinoma. Furthermore, CD8 might be a novel prognostic biological marker for patients with lung adenocarcinoma.

The purpose of this study was to examine the safety and efficacy of sorafenib in Chinese patients with unresectable hepatocellular carcinoma. Data of 338 Chinese patients from the Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib study database were included. Patients were divided into those who received and did not receive sorafenib prior to surgical resection and those with and without portal vein tumor thrombosis. In the non-surgery group, the median survival was 302 days (95% confidence interval: 244-371), and the median time from diagnosis to death was 428 days (95% confidence interval: 352-556); in the surgery group, half of the patients survived for 345 days and the median time from diagnosis to death was 1000 days (95% confidence interval: 750-2816). Median progression-free survival and median time to progression were not different between the two groups. Median overall survival was 360 days (95% confidence interval: 309-435) in the non-portal vein tumor thrombosis group and 240 days (95% confidence interval: 181-296) in the portal vein tumor thrombosis group; median time between hepatocellular carcinoma diagnosis and death was 750 days (95% confidence interval: 472-1000) and 420 days (95% confidence interval: 252-567), respectively, in the two groups. Median progression-free survival was 209 days (95% confidence interval: 166-264) for patients without portal vein tumor thrombosis and 154 days (95% confidence interval: 112-202) for patients with portal vein tumor thrombosis; median time to progression was 295 days (95% confidence interval: 209-463) and 221 days, respectively. Adverse events were generally comparable regardless of prior surgery and portal vein tumor thrombosis status. We thus conclude that earlier administration of sorafenib may result in improved outcomes in patients with unresectable hepatocellular carcinoma and portal vein tumor thrombosis.

Background & Aims: GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) is a prospective, observational registry study evaluating the safety of sorafenib and treatment practices in hepatocellular carcinoma patients. This large global database allowed for assessment of the use and tolerability of sorafenib in patients with liver dysfunction., Methods: Baseline characteristics and medical/treatment history were collected in patients for whom a decision to treat with sorafenib had been made. Adverse event, dosing, and outcomes data were collected during follow-up., Results: In the overall safety population (n=3202), 1968 patients (61%) had Child-Pugh A status and 666 (21%) had Child-Pugh B. The majority of Child-Pugh A (72%) and Child-Pugh B (70%) patients received an initial sorafenib dose of 800mg, consistent with the label, and dose reduction rates were 40% and 29%, respectively. The type and incidence of adverse events were generally consistent across Child-Pugh subgroups. The incidence of drug-related adverse events leading to discontinuation was similar between Child-Pugh A and Child-Pugh B patients (17% and 21%). In the intent-to-treat population (n=3213), median overall survival (months [95% confidence interval]) was longer in Child-Pugh A patients (13.6 [12.8-14.7]) compared with Child-Pugh B patients (5.2 [4.6-6.3])., Conclusions: In clinical practice, the safety profile of sorafenib appeared to be consistent across Child-Pugh A and Child-Pugh B patients. Findings suggest sorafenib may be safely used in some Child-Pugh B patients and indicate the importance of careful patient evaluation when making treatment decisions., Lay Summary: The GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) study is a large prospective registry of patients with liver cancer who were treated with sorafenib. The aims were to evaluate the safety and tolerability of sorafenib among those in which the liver was not functioning properly. The study showed that the safety profile of sorafenib was consistent across patients with preserved liver function and those in which the liver was not functioning properly, and therefore, suggesting that sorafenib may be a valid treatment for some patients with liver impairment., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Treatment approaches for hepatocellular carcinoma (HCC) vary across countries, but these differences and their potential impact on outcomes have not been comprehensively assessed. Data from the multinational GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) registry evaluated differences in patient characteristics, practice patterns and outcomes in HCC across geographical regions in patients who received sorafenib., Methods: GIDEON is a non-randomised, observational registry study conducted in 39 countries across five global regions. HCC patients in whom a decision to treat with sorafenib was made in clinical practice and according to local practices were included., Results: 3202 patients were evaluable for safety analysis: Asia-Pacific (n = 928), Japan (n = 508), Europe (n = 1113), USA (n = 563) and Latin America (n = 90). Patients in Japan had earlier-stage disease at initial diagnosis compared with patients in other regions (Barcelona Clinic Liver Cancer stage A; 43.7% vs 9.1-24.3%). Use of locoregional therapies before sorafenib, including transarterial chemoembolisation, was more common in Japan (84.4%) and Asia-Pacific (67.2%) compared with the USA (49.4%) and Europe (43.5%). Treatment patterns with respect to sorafenib also differed, with a shorter duration of treatment reported in the USA and Asia-Pacific. Time from initial diagnosis to death was longer in Japan compared with other regions (median, 79.6 months vs 14.8-25.0 months)., Conclusions: Data from GIDEON highlight regional variations in the management of HCC and patient outcomes. Greater standardisation of management may help optimise outcomes for HCC patients., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Conflicting results of the efficacy and safety of conventional transarterial chemo-embolization (cTACE) vs drug-eluting bead (DEB)-TACE have been reported. This meta-analysis aimed to update and re-evaluate the efficacy and safety of cTACE compared with those of DEB-TACE in patients with hepatocellular carcinoma (HCC)., Methods: Literature search was performed by two investigators independently in PubMed, MEDLINE and EMBASE to screen studies published from January 1990 to March 2015. Studies of parallel group designs comparing cTACE and DEB-TACE for HCC were reviewed. Complete response, partial response, objective response, disease control, overall survival and survival time were collected to evaluate the efficacy of each therapy., Results: DEB-TACE increased the complete response rate [odds ratio (OR) 1.38, 95% confidence interval (CI) 1.01-1.89], overall survival rate (OR 1.41, 95% CI 1.01-1.98) and survival time [weighted mean difference (WMD) 6.65, 95% CI 6.15-7.14) with less common adverse events (OR 0.59, 95% CI 0.41-0.84). However, DEB-TACE had a similar partial response rate (OR 1.00, 95% CI 0.67-1.49), objective response rate (OR 1.21, 95% CI 0.94-1.56), disease control rate (OR 1.14, 95% CI 0.81-1.58) and serious adverse events (OR 0.86, 95% CI 0.50-1.49) compared with cTACE., Conclusions: DEB-TACE has a higher complete response rate and a higher overall survival rate in patients with HCC than cTACE; however, the results should be interpreted with caution. Furthermore, DEB-TACE is safer and has less common adverse events than cTACE., (© 2016 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.)

Objective: To evaluate the efficacy and safety of three different spinal rotation manipulations for the treatment of lumbar disc herniation., Methods: From September 2011 to April 2013,180 patients diagnosed as lumbar disc herniation were randomly divided into seat fixed rotation group (A), lateral position rotation group (B) and supine position rotation group (C) by using a digital table. Finally 10 patients were excluded and dropped, 170 patients were included in the study. There were 57 patients in group A, 57 patients in group B and 56 patients in group C. Baseline demographic characteristics of patients, clinical findings and indexes of health status had no statistically differences among three groups (P > 0.05). The manipulation was performed every other day, and the treatment duration for all patients was 3 weeks. Body pain (BP), Physical function (PF) in SF-36, Oswestry Disability Index (ODI) and adverse reactions were observed statistically 6 weeks, 3 months, 6 months, one year and two years after finishing treatment., Results: BP, PF scores in 3 groups were significantly improved and ODI scores were significantly lower than those before treatment and the differences were statistically significant (P < 0.05); However, there was no significant difference among three groups in the BP, PF and ODI scores (P > 0.05). There were no obvious and serious adverse reactions among these groups., Conclusion: Based on the theory of dislocation of bone joints in TCM, three kinds of spinal rotation manipulations can be used safely for the treatment of lumbar disc herniation, and the efficacy was similar.

Purpose: To evaluate transarterial chemoembolization (TACE) use prior to and concomitantly with sorafenib in patients with unresectable hepatocellular carcinoma (HCC) across different global regions., Materials and Methods: GIDEON is an observational registry study of more than 3000 HCC patients. Patients with histologically, cytologically, or radiographically diagnosed HCC, and for whom a decision had been made to treat with sorafenib, were eligible. Patients were enrolled into the registry from 39 countries beginning in January 2009, with the last patient follow-up in April 2012. Detailed data on treatment history, treatment patterns, adverse events, and outcomes were collected. All treatment decisions were at the discretion of the treating physicians. Documented approval from local ethics committees was obtained, and all patients provided signed informed consent. Descriptive statistics, including minimum, median, and maximum, were calculated for metric data, and frequency tables for categorical data. Kaplan-Meier estimates with 95% confidence intervals were calculated for survival end points., Results: A total of 3202 patients were eligible for safety analysis, of whom 2631 (82.2%) were male. Median age was 62 years (range, 15-98 years). A total of 1511 (47.2%) patients underwent TACE prior to sorafenib; 325 (10.1%) underwent TACE concomitantly. TACE prior to sorafenib was more common in Japan and Asia-Pacific compared with all other regions (362 [71.3%] and 560 [60.3%] vs 12-209 [13.3%-37.1%]). Adverse events were reported in 2732 (85.3%) patients overall, with no notable differences in the incidence of adverse events, regardless of TACE treatment history. Overall survival was 12.7 months in prior-TACE patients, 9.2 months in non-prior-TACE patients, 21.6 months in concomitant-TACE patients, and 9.7 months in non-concomitant-TACE patients., Conclusion: Global variation exists in TACE use in sorafenib-treated HCC patients. The combination of TACE with sorafenib appears to be a well-tolerated and viable therapeutic approach., ((©) RSNA, 2016 Online supplemental material is available for this article.)

Objective: To introduce co-word analysis into the analysis of the current research status of childhood tuberculous meningitis, to compare the similarities and differences in research topics of the field in China and abroad over the past decade, and to discover the advantages and weak links in the study field in China., Methods: PubMed, CNKI, VIP, and Wanfang Data were searched for the articles which met the inclusion criteria. Ucinet 6.0 and Netdraw were used for co-occurrence analysis, and the co-article relationship between high-frequency key words was visualized., Results: A total of 226 articles abroad and 186 Chinese articles on childhood tuberculous meningitis were obtained. The figures for co-occurrence analysis of high-frequency key words in research articles on childhood tuberculous meningitis in China and abroad were successfully plotted. Compared with the studies in China, the studies abroad were more sophisticated and well-developed, with more studies on drug-resistant tuberculosis, the relationship between tuberculosis and AIDS, and the epidemiology of tuberculosis. The key words listed in the studies abroad were more standard. The studies in China on childhood tuberculous meningitis concentrated on vaccination and nursing., Conclusions: In general, the studies on childhood tuberculous meningitis in China and abroad have the same directions. The studies abroad have a complicated network and use more standard key words. The studies on childhood tuberculous meningitis are well conducted in China. However, more studies are needed for drug-resistant tuberculosis, the relationship between tuberculosis and AIDS, and the epidemiology of tuberculosis in future.

Objectives: Liver-specific MRI is a fast-growing field, with technological and protocol advancements providing more robust imaging and allowing a greater depth of information per examination. This article reports the evidence for, and expert thinking on, current challenges in liver-specific MRI, as discussed at the 7th International Forum for Liver MRI, which was held in Shanghai, China, in October 2013., Methods: Topics discussed included the role of gadoxetic acid-enhanced MRI in the differentiation of focal nodular hyperplasia from hepatocellular adenoma and small hepatocellular carcinoma (HCC) from small intrahepatic cholangiocarcinoma (in patients with chronic liver disease), the differentiation of low-grade dysplastic nodule (DN) from pre-malignant high-grade DN and early HCC, and treatment planning and assessment of treatment response for patients with HCC and colorectal liver metastasis. Optimization of the gadoxetic acid-enhanced MRI protocol to gain robust arterial and hepatobiliary phase images was also discussed., Results and Conclusions: Gadoxetic acid-enhanced MRI demonstrates added value for the detection and characterization of focal liver lesions and shows promise in a number of new indications, including regional liver functional assessment and patient monitoring after therapy; however, more data are needed in some areas, and further developments are needed to translate cutting-edge techniques into clinical practice., Key Points: Liver-specific MRI is a fast-growing field, with many technological and protocol advancements. Gadoxetic acid-enhanced MRI demonstrates value for detecting and characterizing focal liver lesions. Gadoxetic acid-enhanced MRI shows promise in regional functional assessment and patient monitoring. Further developments are needed to translate cutting-edge techniques into clinical practice.

We report data from the final analysis of the Chinese subset of the GIDEON (the Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) study, which evaluated the safety and efficacy of sorafenib in Child-Pugh A, B and C patients with unresectable hepatocellular carcinoma (uHCC) in real-life clinical practice. Patient demographics, disease characteristics and treatment history were recorded at enrollment; dose, adverse events (AEs) and efficacy were recorded at follow-up. Of the 338 evaluable patients, 98.5% started on 800 mg/day sorafenib, regardless of their Child-Pugh status. The median treatment duration (21.1 vs. 18.8 weeks) and median overall survival (322 vs 240 days) were longer in patients with Child-Pugh A compared with the Child-Pugh B, progression-free survival were 183 vs. 208 days, respectively). AEs (all grades) were comparable in the Child-Pugh B vs A group (56.3% vs. 50.4%, respectively), moreover, the Child-Pugh B group also had comparable rates of drug-related AEs (35.4% vs. 27.2%, respectively) and serious AEs (25.0% vs. 23.0%, respectively) compared with the Child-Pugh A group. The overall dosing strategy was consistent in Chinese patients across Child-Pugh subgroups. Tolerability and safety data suggest that Child-Pugh B patients might be safely treated with sorafenib. The findings from our study showed that safety profile of sorafenib in terms of rate and type of AEs is similar to the global international GIDEON study as well as other pivotal studies.