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Yang Tai,1,* Lin-Hao Zhang,1,* Jin-Hang Gao,1,2 Chong Zhao,2 Huan Tong,1 Cheng Ye,1 Zhi-Yin Huang,1 Rui Liu,2 Cheng-Wei Tang1,21Laboratory of Gastroenterology & Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, People’s Republic of China; 2Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, People’s Republic of China *These authors contributed equally to this workPurpose: Biomarkers are lacking in hepatocellular carcinoma (HCC). Cyclooxygenase-2 (COX-2) and its metabolites play crucial roles in the process of inflammation-tumor transformation. This study was aimed to detect COX-2 expression in HCC tissues and evaluate the effects of a COX-2 inhibitor, celecoxib, on biological behaviors of HCC cell lines in vitro.Methods: COX-2 expression was detected by immunohistochemistry on a human HCC tissue microarray. The correlations of COX-2 expression with tumor clinicopathological variables and overall survival were analyzed. The proliferation, apoptosis, cell cycle distribution, invasion capacity, and related signaling molecules of HCC cells after incubated with COX-2 inhibitor celecoxib were evaluated in vitro.Results: Expression levels of COX-2 in HCC tissues were significantly higher than those in paracancerous tissues. The TNM stage III-IV, tumor size >5 cm, lymphovascular invasion and distant metastasis was higher in high COX-2 expression group compared with that in low COX-2 expression group. Patients with low COX-2 expression achieved better 5-year overall survival than those with high COX-2 expression. Treatment with celecoxib was sufficient to inhibit cell proliferation, promote apoptosis, and induce G0/G1 cell cycle arrest in HCC cells with concentration- and time-dependent manners. Celecoxib up-regulated E-cadherin protein through inhibiting COX-2-prostaglandin E2 (PGE2)-PGE2 receptor 2 (EP2)-p-Akt/p-ERK signaling pathway to suppress HCC cells migration and invasion.Conclusion: High COX-2 expression was associated with advanced TNM stage, larger tumor size, increased lymphovascular invasion and short survival. Targeting inhibition of COX-2 by celecoxib exhibited anti-tumor activities by suppressing proliferation, promoting apoptosis, and inhibiting the aggressive properties of HCC cells.Keywords: cyclooxygenase-2, hepatocellular carcinoma, celecoxib, survival

Tai Y, Zhang LH, Gao JH, et al. Cancer Manag Res. 2019;11:2831–2848. The authors have advised due to an error that occurred inadvertently at the time of figure assembly, Figure 7A on page 2842 is incorrect. The correct Figure 7 is shown in Download Article. Figure 7 Celecoxib up-regulated E-cadherin via inhibition of COX-2–PGE2–EP2–p-Akt/p-ERK in Bel7402 cells. Compared with DMSO-treated and empty plasmid-transfected Bel7402 cells, overexpression of COX-2 by using COX-2 ORF plasmid induced reduction of E-cadherin expression and increase of p-Akt and p-ERK expression determined by IF (A) and Western blot (D). Compared with DMSO-treated cells, the expression of E-cadherin quantified by IF (B and C) and Western blot (E and F) was upregulated by EP2 inhibitor AH6809, Akt inhibitor MK2206, and ERK inhibitor AZD6244, but down-regulated by PGE2, which could be reversed by AH6809. Meanwhile, the expression of p-Akt and p-ERK was significantly suppressed by treatment with celecoxib and AH6809 but was enhanced by treatment with PGE2, which could be inhibited by AH6809 (E). Scale bar =50 μm for IF. The authors apologize for these errors and advise they do not affect the interpretation of data or the conclusion of the study. Read the original article

Jianbin Shen,1,* Xiagang Luo,2,* Xiao Zhou,3 Chengwu Tang,1 Huanyu Ju,2 Yongqiang Xu,1 Lianjin Qin1 1Department of General Surgery, First People’s Hospital Affiliated to Huzhou Normal College, Huzhou, Zhejiang, 2Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 3Department of Orthopedics, People’s Hospital of Zhangqiu, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Objective: The aim of this study was to investigate the effect of Xiaozhi decoction (XZD) on posthemorrhoidectomy pain and analgesic medication consumption.Methods: From May 2013 to March 2015, 315 patients who underwent open hemorrhoidectomy in our hospital were enrolled in this study, of whom, 160 patients were randomly assigned to accept sitz bath with warm water after hemorrhoidectomy (control group) and 155 patients were randomly assigned to accept sitz bath with XZD (XZD group) after hemorrhoidectomy. Postoperative pain at 12 hours after surgery and on postoperative days (PODs) 1, 2, 7, 14 and 28 was evaluated by Visual Analog Scale (VAS). Pain on defecation on PODs 1, 2, 7, 14 and 28 was also recorded using the VAS. The consumption of analgesics was also analyzed.Results: No significant difference was found in baseline characteristics between the two groups. Postoperative pain score of the XZD group was significantly lower on POD 2 (6.04±1.11 vs 6.33±1.14, P=0.0229), POD 7 (3.35±0.75 vs 4.22±0.87, P=0.0000) and POD 14 (2.87±0.64 vs 3.64±0.77, P=0.0000) than that of the control group. Similarly, patients in the XZD group experienced significantly less pain on defecation on POD 2 (5.02±1.34 vs 5.43±1.56, P=0.0130), POD 7 (3.08±1.17 vs 3.52±1.29, P=0.0017) and POD 14 (2.31±0.85 vs 2.68±0.99, P=0.0004). Patients in the XZD group consumed significantly less analgesic medication on POD 2 (P=0.0136), POD 7 (P=0.0074) and POD 14 (P=0.0046) than the control group. Conclusion: XZD could effectively relieve postoperative pain and reduce analgesic medication consumption after hemorrhoidectomy. Keywords: hemorrhoids, hemorrhoidectomy, traditional Chinese medicine, posthemorrhoidectomy pain

Cheng Wu Tang,1 Ming Zhu,2 Wen Ming Feng,1 Ying Bao,1 Yin Yuan Zheng3 1Department of General Surgery, 2Department of Nephrology, 3Department of Radiology, First People’s Hospital Affiliated to Huzhou University Medical College, Huzhou, People’s Republic of China Objective: This study aimed to investigate the efficacy of Jianpi Ligan decoction (JLD) as an adjuvant therapy for patients with unresectable hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE).Methods: From March 2007 to March 2013, 103 patients with unresectable HCC who underwent TACE in our center were included in this retrospective study. Among the 103 patients, 53 patients accepted JLD along with TACE (JLD group) and 50 patients accepted TACE alone (control group). Indices including complication, toxicity, treatment success rate, and long-term survival were obtained for analysis and comparison.Results: There was no significant difference in patient characteristics between the two groups. No procedure-related deaths or encephalopathy occurred. Fewer patients from the JLD group experienced constipation (7/53 vs 15/50, P=0.0377), abdominal bloating (5/53 vs 12/50, P=0.0466), and lack of appetite (35/53 vs 42/50, P=0.0360). The JLD group had lesser and lighter hepatic toxicity (P=0.0265) and gastrointestinal toxicity (P=0.0445) such as nausea and vomiting. The JLD group had a significantly higher treatment success rate than the control group (51/53 vs 40/50, P=0.0103). Three-year overall survival probability was significantly higher in the JLD group than in the control group (37.74% vs 26.00%; hazard ratio [HR] 0.6171; 95% confidence interval [CI], 0.3832–0.9938; P=0.0365 by log-rank test). No significant difference was found in 3-year overall survival probability (39.22% vs 32.50%; HR, 0.7449; 95% CI, 0.4398–1.2614; P=0.2491 by log-rank test) or 3-year intrahepatic recurrence-free survival probability in patients who achieved treatment success (37.25% vs 30.00%; HR, 0.7280; 95% CI, 0.4332–1.2233; P=0.2087 by log-rank test) between the two groups.Conclusion: Application of JLD was effective for reduction of side effects and improvement of long-term survival for patients with unresectable HCC treated by TACE. Keywords: hepatocellular carcinoma, transarterial chemoembolization, traditional Chinese medicine, overall survival

This study aimed to investigate the feasibility of using an immortal keratinocyte cell line, HaCaT cells, to effectively deliver epidermal growth factor (EGF) in a skin substitute to treat burn wounds. The skin equivalent was constructed with human EGF (hEGF) gene modified HaCaT cells obtained through stable gene transfection; these were applied to full thickness burn wounds in a rat model. The results showed that the hEGF gene modified HaCaT cells produced more than 390ng/l of bioactive hEGF in the culture supernatant. K19 and integrin-[beta]1 as keratinocyte differentiation markers were elevated in the hEGF gene modified HaCaT cells which were shown to be non-tumorigenic. The skin equivalent constructed with hEGF gene modified HaCaT cells demonstrated improved epidermal morphogenesis with a thick and compact epidermis. Wound healing was accelerated noticeably when applied with this skin substitute seeded with hEGF gene modified HaCaT cells in vivo. The results suggest that HaCaT cells modified with hEGF gene might be promising seed cells for construction of genetically modified skin substitute which can effectively secrete hEGF to accelerate wound repair and regeneration. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social defects often accompanied with emotional comorbidities. Aberrations in synaptic function and plasticity are the core feature in the pathophysiology of ASD. Targeting soluble epoxide hydrolase (sEH) has been found to exert protection in a wide-range of pathological conditions. However, the regulation of sEH deficiency on the synaptic deficits of ASD and the underlying mechanisms remain unclear. The valproate (VPA)-treated ASD animal model with genetic sEH knockout was applied in the present study. The results showed that the sEH expression was significantly increased in the prefrontal cortex of VPA-treated animals. Although no effect was found on tail malformation and body weight loss, genetic sEH deletion alleviated social deficits, and fear learning and memory extinction in the VPA-treated mice. After a series of electrophysiological assessments, we found that the beneficial effects of sEH deletion focused on the long-term synaptic plasticity, rather than presynaptic efficiency, in the VPA-treated mice. Furthermore, we observed that the dysregulated AMPK-mTOR pathway was restored under genetic sEH deletion in VPA-treated mice. Taken together, these findings uncovered an important role of sEH deficiency in the synaptic dysfunctions of ASD mediated by AMPK-mTOR pathway, providing a novel therapeutic target for ASD., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: NK cells play a vital role in tumor immune resistance. Various factors affect NK cell activity. While NK cell dysfunction has been observed in numerous malignancies, the underlying mechanisms in gastric cancer remain unclear., Method: Flow cytometry was used to identify the phenotypic distribution and expression of activated receptors on NK cells. ELISA was used to determine the expression of cytokines. We examined the expression of NK cell-related genes and explored their association with survival and prognosis. Additionally, we conducted PCR detection of miR-552-5p expression levels in plasma exosomes of patients and investigated its correlation with phenotypic distribution and activated receptors. We used flow cytometry and ELISA to verify the role of miR-552-5p in NK cell dysfunction. Furthermore, we investigated the potential role of PD-1/PD-L1 in regulating NK cell dysfunction in patients' cells., Results: We observed a significant decrease in the percentage of NKG2D and NKp30 and IFN-γ and TNF-α in patients than in healthy volunteers. Patients with low levels of CD56, CD16, NKG2D, and NKP46 exhibited poorer survival prognoses. Moreover, increased expression levels of plasma exosomal miR-552-5p in patients were negatively associated with NK cell phenotypic distribution and activated receptor expression. MiR-552-5p downregulated the secretion of perforin, granzyme, and IFN-γ as well as the expression of NKp30, NKp46, and NKG2D. Additionally, it suppressed the cytotoxicity of NK cells. The inhibitory effect of miR-552-5p, on NK cell function was reversed when anti-PD-L1 antibodies were used., Conclusion: Exosomal miR-552-5p targets the PD-1/PD-L1 axis, leading to impaired NK cell function., (© 2024. The Author(s).)

Extended exposure to seawater results in the erosion of the structural high-strength steels utilized in marine equipment, primarily due to the infiltration of hydrogen. Consequently, this erosion leads to a decrease in the mechanical properties of the material. In this investigation, the mechanical responses of Q690 structural high-strength steel specimens were investigated by considering various hydrogen charging parameters, such as the current density, charging duration, and solution concentration values. The findings highlighted the significant impacts of electrochemical hydrogen charging parameters on the mechanical behaviors of Q690 steel samples. Specifically, a linear relationship was observed between the mechanical properties and the hydrogen charging current densities, while the associations with the charging duration and solution concentration were nonlinear. Additionally, the fracture morphology under various hydrogen charging parameters was analyzed and discussed. The results demonstrate that the mechanical properties of the material degrade with increasing hydrogen charging parameters, with tensile strength and yield stress decreasing by approximately 2-4%, and elongation after fracture reducing by about 20%. The findings also reveal that macroscopic fractures exhibit significant necking in uncharged conditions. As hydrogen charging parameters increase, macroscopic necking gradually diminishes, the number of microscopic dimples decreases, and the material ultimately transitions to a fully brittle fracture.

Objectives: Patients with cirrhosis are more susceptible to coronavirus disease 2019 (COVID-19) due to immune dysfunction. In this retrospective study we aimed to investigate whether suppression of mild systemic inflammation with selective cyclooxygenase-2 inhibitor (COX-2-I) during chronic care of cirrhotic patients would reduce the occurrence of acute decompensated events and improve patient prognosis of COVID-19., Methods: Medical records of cirrhotic patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were sequentially reviewed. The patients were divided into the COX-2-I and control groups depending on whether they took oral selective COX-2-I for over 3 months or not. The primary outcomes included the occurrence of severe/critical COVID-19, acute decompensated events, and acute-on-chronic liver failure (ACLF)., Results: After propensity score matching analysis, there were 314 cases in the control group and 118 cases in the COX-2-I group. Compared with the control group, the risk of severe/critical COVID-19 in the COX-2-I group was significantly decreased by 83.1% (p = 0.004). Acute decompensated events and ACLF occurred in 23 (7.32%) and nine (2.87%) cases in the control group, but none in the COX-2-I group (p = 0.003 and 0.122). The rate of hospitalization in the COX-2-I group was significantly lower than that of the control group (3.39% vs 13.06%, p = 0.003). No patient in the COX-2-I group required intensive care unit admission., Conclusions: Long-term intermittent oral administration of selective COX-2-I in cirrhotic patients significantly reduces the occurrence of severe/critical COVID-19, acute decompensated events, and ACLF. It may also be used for systemic inflammation caused by other pathogens., (© 2024 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.)

Antibody drugs are becoming increasingly popular in disease diagnosis, targeted therapy, and immunoprevention owing to their characteristics of high targeting ability, strong specificity, low toxicity, and mild side effects. The demand for antibody drugs is steadily increasing, and their production scale is expanding. Upstream cell culture technology has been greatly improved by the high-capacity production of monoclonal antibodies. However, the downstream purification of antibodies presents a bottleneck in the production process. Moreover, the purification cost of antibodies is extremely high, accounting for approximately 50%-80% of the total cost of antibody production. Chromatographic technology, given its selectivity and high separation efficiency, is the main method for antibody purification. This process usually involves three stages: antibody capture, intermediate purification, and polishing. Different chromatographic techniques, such as affinity chromatography, ion-exchange chromatography, hydrophobic interaction chromatography, mixed-mode chromatography, and temperature-responsive chromatography, are used in each stage. Affinity chromatography, mainly protein A affinity chromatography, is applied for the selective capture and purification of antibodies from raw biofluids or harvested cell culture supernatants. Other chromatographic techniques, such as ion-exchange chromatography, hydrophobic interaction chromatography, and mixed-mode chromatography, are used for intermediate purification and antibody polishing. Affinity biomimetic chromatography and hydrophobic charge-induction chromatography can produce antibodies with purities comparable with those obtained through protein A chromatography, by employing artificial chemical/short peptide ligands with good selectivity, high stability, and low cost. Temperature-responsive chromatography is a promising technique for the separation and purification of antibodies. In this technique, antibody capture and elution is controlled by simply adjusting the column temperature, which greatly eliminates the risk of antibody aggregation and inactivation under acidic elution conditions. The combination of different chromatographic methods to improve separation selectivity and achieve effective elution under mild conditions is another useful strategy to enhance the yield and quality of antibodies. This review provides an overview of recent advances in the field of antibody purification using chromatography and discusses future developments in this technology.

Background: Hyperglycemia affects the outcomes of endovascular therapy (EVT) for acute ischemic stroke (AIS). This study compares the predictive ability of diabetes status and glucose measures on EVT outcomes using nationwide registry data., Methods: The study included 1,097 AIS patients who underwent EVT from the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke. The variables analyzed included diabetes status, admission glucose, glycated hemoglobin (HbA1c), admission glucose-to-HbA1c ratio (GAR), and outcomes such as 90-day poor functional outcome (modified Rankin Scale score ≥ 2) and symptomatic intracranial hemorrhage (SICH). Multivariable analyses investigated the independent effects of diabetes status and glucose measures on outcomes. A receiver operating characteristic (ROC) analysis was performed to compare their predictive abilities., Results: The multivariable analysis showed that individuals with known diabetes had a higher likelihood of poor functional outcomes (odds ratios [ORs] 2.10 to 2.58) and SICH (ORs 3.28 to 4.30) compared to those without diabetes. Higher quartiles of admission glucose and GAR were associated with poor functional outcomes and SICH. Higher quartiles of HbA1c were significantly associated with poor functional outcomes. However, patients in the second HbA1c quartile (5.6-5.8%) showed a non-significant tendency toward good functional outcomes compared to those in the lowest quartile (<5.6%). The ROC analysis indicated that diabetes status and admission glucose had higher predictive abilities for poor functional outcomes, while admission glucose and GAR were better predictors for SICH., Conclusion: In AIS patients undergoing EVT, diabetes status, admission glucose, and GAR were associated with 90-day poor functional outcomes and SICH. Admission glucose was likely the most suitable glucose measure for predicting outcomes after EVT., 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 author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hsieh, Hsieh, Yang, Sung, Hsieh, Lee, Lin, Chen, Lin, Sung, Tang, Chu, Tsai, Chou, Lin, Wei, Chen, Yan, Chen, Hsiao, Chan, Huang, Liu, Tang, Lee, Lien, Chiou, Lee and Jeng.)

Background: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase)., Methods: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis., Results: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata., Conclusions: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy., Competing Interests: Disclosures None.

Background: /Objectives: Persistent organ failure (OF) in severe acute pancreatitis (SAP) is caused by activation of cytokine cascades, resulting in inflammatory injury. Anti-inflammation may be helpful in OF remission in early SAP. To assess the efficacy of anti-inflammatory regimens for OF prevention and remission in patients with predicted SAP and display clinical doctors' acceptance of these strategies, we conducted this retrospective study in the real world., Methods: Clinical data of patients with predicted SAP from 2010 to 2017 were retrospectively reviewed. Cases were divided into conventional support (C), C+ somatostatin/octreotide (C + S/O), and C + S/O + Cyclooxygenase-2-inhibitors (C + S/O + COX-2-I). The occurrence of SAP, OF, changes of proportion for three strategies, length of hospital stay, meperidine injection, and cytokine levels were compared. The constituent ratios of the three schemes over eight years were evaluated., Results: A total of 580 cases (C = 124, C + S/O = 290, C + S/O + COX-2-I = 166) were included. The occurrences of SAP in the C + S/O (28.3 %) and C + S/O + COX-2-I (18.1 %) groups were significantly lower than that in C group (60.5 %, P < 0.001), mainly by reducing persistent respiratory failure (P < 0.001) and renal failure (P = 0.002). C + S/O and C + S/O + COX-2-I regimens significantly decreased new onset OF and enhanced OF amelioration within 48 h when compared with C treatment (P < 0.001) in patients with OF score <2 and ≥ 2 on admission, respectively. C + S/O and C + S/O + COX-2-I as compared with C group significantly decrease OF occurrences in a multivariate logistic regression analysis (P < 0.05)., Conclusions: Somatostatin or its analogs and cyclooxygenase-2 inhibitors are promising for OF prevention and remission in patients with predicted SAP. The acceptance of combined strategies in the real world has increased, and the occurrence of SAP has decreased annually., Competing Interests: Declaration of competing interest All authors have no conflicts of interests relevant to this article to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Motor recovery is still limited for people with stroke especially those with greater functional impairments. In order to improve outcome, we need to understand more about the mechanisms underpinning recovery. Task-unbiased, blood flow-independent post-stroke neural activity can be acquired from resting brain electrophysiological recordings and offers substantial promise to investigate physiological mechanisms, but behaviourally relevant features of resting-state sensorimotor network dynamics have not yet been identified. Thirty-seven people with subcortical ischaemic stroke and unilateral hand paresis of any degree were longitudinally evaluated at 3 weeks (early subacute) and 12 weeks (late subacute) after stroke. Resting-state magnetoencephalography and clinical scores of motor function were recorded and compared with matched controls. Magnetoencephalography data were decomposed using a data-driven hidden Markov model into 10 time-varying resting-state networks. People with stroke showed statistically significantly improved Action Research Arm Test and Fugl-Meyer upper extremity scores between 3 weeks and 12 weeks after stroke (both P < 0.001). Hidden Markov model analysis revealed a primarily alpha-band ipsilesional resting-state sensorimotor network which had a significantly increased life-time (the average time elapsed between entering and exiting the network) and fractional occupancy (the occupied percentage among all networks) at 3 weeks after stroke when compared with controls. The life-time of the ipsilesional resting-state sensorimotor network positively correlated with concurrent motor scores in people with stroke who had not fully recovered. Specifically, this relationship was observed only in ipsilesional rather in contralesional sensorimotor network, default mode network or visual network. The ipsilesional sensorimotor network metrics were not significantly different from controls at 12 weeks after stroke. The increased recruitment of alpha-band ipsilesional resting-state sensorimotor network at subacute stroke served as functionally correlated biomarkers exclusively in people with stroke with not fully recovered hand paresis, plausibly reflecting functional motor recovery processes., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Concrete cracks and local damage can affect the bond performance between concrete and steel bars, thereby reducing the durability of reinforced concrete structures. Compared with general concrete crack repair methods, biomineralization repair not only has effective bonding capabilities but is also particularly environmentally friendly. Therefore, this study aimed to apply biomineralization technology to repair damaged fiber-reinforced lightweight aggregate concrete (LWAC). Two groups of LWAC specimens were prepared. The experimental group used lightweight aggregates (LWAs) containing bacterial spores and nutrient sources, while the control group used LWAs without bacterial spores and nutrient sources. These specimens were first subjected to compression tests and pull-out tests, respectively, and thus were damaged. After the damaged specimen healed itself in different ways for 28 days, secondary compression and pull-out tests were conducted. The self-healing method of the control group involved placing the specimens in an incubator. The experimental group was divided into experimental group I and experimental group II according to the self-healing method. The self-healing method of experimental group I was the same as that of the control group. The self-healing method of experimental group II involved soaking the specimen in a mixed solution of urea and calcium acetate for two days, and then taking it out and placing it in an incubator for two days, with a cycle of four days. The test results show that in terms of the relative bond strength ratio, the experimental group II increased by 17.9% compared with the control group. Moreover, the precipitate formed at the cracks in the sample was confirmed to be calcium carbonate with the EDS and XRD analysis results, which improved the compressive strength and bond strength after self-healing. This indicates that the biomineralization self-healing method used in experimental group II is more effective.

Background: The incidence of stroke in young patients (20-50 years old) has increased in recent decades. Unlike the use of good functional outcomes to evaluate prognosis, excellent functional outcomes are a better indicator of return to work among younger patients. The rate of return to work increases with time after stroke. This study investigated the short term (3 months) and long term (1 year) predictors of excellent functional outcomes in young patients after endovascular thrombectomy (EVT)., Methods: We included young patients who underwent EVT for acute ischemic stroke (AIS) due to large vessel occlusion within 6 hours after stroke onset between 2015 and 2021. Patients with intracerebral hemorrhage on pretreatment CT were excluded. The associations between clinical, imaging, and procedure variables, and excellent functional outcomes were analyzed using univariate and multivariable logistic regression analyses. An excellent functional outcome was defined as a modified Rankin Scale score of ≤1., Results: Of the 361 patients with AIS eligible for EVT, 55 young patients (aged 24-50 years) were included. Of these, 36.4% and 41.8% achieved excellent functional outcomes at 3 and 12 months, respectively. Multivariate analysis revealed that smoking was the independent negative predictor of both 3 month (adjusted OR (aOR) 0.232, 95% CI 0.058 to 0.928; p=0.039) and 12 month (aOR 0.180, 95% CI 0.044 to 0.741; p=0.018) excellent functional outcomes., Conclusions: Current or former smoking habit was an independent negative predictor of both short term and long term excellent functional outcomes in young adults with AIS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The pathological form of synaptic plasticity, ischemic long-term potentiation (iLTP), induced by oxygen and glucose deprivation (OGD), is implicated in the acute phase of stroke with the potentiation of N-methyl-D-aspartate receptor (NMDAR). While there has been widespread attention on the excitatory system, a recent study reported that γ-aminobutyric acid (GABA)ergic system is also involved in iLTP. Valproic acid (VPA), a histone deacetylase inhibitor, protects against ischemic damage. However, whether VPA regulates early phase plasticity in ischemic stroke remains unknown. The present study aims to investigate the potential role and mechanism of VPA in ischemic stroke., Methods: A brief exposure of OGD on the hippocampal slices and the induction of photothrombotic ischemia (PTI) were used as ex vivo and in vivo models of ischemic stroke, respectively., Results: Using extracellular recordings, iLTP was induced in the hippocampal Schaffer collateral pathway following OGD exposure. VPA treatment abolished hippocampal iLTP via GABA A receptor enhancement and extracellular signal-regulated kinase (ERK) phosphorylation. Administration of VPA reduced brain infarct volume and motor dysfunction in mice with PTI. Moreover, VPA protected against ischemic injury by upregulating the GABAergic system and ERK phosphorylation, as well as by reducing of matrix metalloproteinase in a PTI-induced ischemic stroke model., Conclusions: Together, this study revealed the protection of VPA in ex vivo OGD-induced pathological form of neuroplasticity and in vivo PTI-induced brain damage and motor dysfunction through rescuing GABAergic deficiency and the pathological hallmarks of ischemia., (© 2023. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

This case study aimed to compare the differences in the durability and prestress loss between normal-weight-concrete (NC) and lightweight-aggregate-concrete (LWC) prestressed box girders, which were constructed at the same time in the same area, so as to verify the superiority of using synthetic lightweight aggregate (LWA) made from reservoir sediments in prestressed bridges. For the NCs and LWCs used in the prestressed box girders, the basic mechanical properties (compressive strength, flexural strength, splitting tensile strength, and elastic modulus) were tested, as well as the durability properties (chloride ion penetration resistance and rapid chloride permeability). Then, through the prestress-monitoring system, the prestress losses of the two groups of prestressed box girders were tracked. The results of the durability test confirmed that LWC can inhibit the penetration of air, water, and chloride ions by strengthening the interfacial transition zone between the aggregate and the cement paste, thereby improving its durability. Moreover, the magnetic-flux prestress loss of the NC prestressed box girder reached 8.1%. In contrast, the magnetic-flux prestress losses on both sides of the LWC prestressed box girder were 4.6% and 4.9%, respectively. This verified that, under the same environmental conditions, the use of LWC produced less of a prestress loss than the use of NC.

Background: Chronic pancreatitis (CP) is a fibroinflammatory syndrome leading to reduced quality of life and shortened life expectancy. Population-based estimates of the incidence, prevalence, and comorbidities of CP in China are scarce., Aim: To characterize the incidence, prevalence, and comorbidities of CP in Sichuan Province, China, with population-based data., Methods: Data on CP from 2015 to 2021 were obtained from the Health Information Center of Sichuan Province. During the study period, a total of 38090 individuals were diagnosed with CP in Sichuan Province. The yearly incidence rate and point prevalence rate (December 31, 2021) of CP were calculated. The prevalence of comorbid conditions in CP patients was estimated. The annual number of CP-related hospitalizations, hospital length of stay, and hospitalization costs for CP were evaluated. Yearly incidence rates were standardized for age by the direct method using the permanent population of Sichuan Province in the 2020 census as the standard population. An analysis of variance test for the linearity of scaled variables and the Cochran-Armitage trend test for categorical data were performed to investigate the yearly trends, and a two-sided test with P < 0.05 was considered statistically significant., Results: The 38090 CP patients comprised 23280 males and 14810 females. The mean age of patients at CP diagnosis was 57.83 years, with male patients (55.87 years) being younger than female patients (60.11 years) ( P < 0.001). The mean incidence rate of CP during the study period was 6.81 per 100000 person-years, and the incidence of CP increased each year, from 4.03 per 100000 person-years in 2015 to 8.27 per 100000 person-years in 2021 ( P < 0.001). The point prevalence rate of CP in 2021 was 45.52 per 100000 individuals for the total population, with rates of 55.04 per 100000 individuals for men and 35.78 per 100000 individuals for women ( P < 0.001). Individuals aged 65 years or older had the highest prevalence of CP (113.38 per 100000 individuals) ( P < 0.001). Diabetes (26.32%) was the most common comorbidity in CP patients. The number of CP-related hospitalizations increased from 3739 in 2015 to 11009 in 2021. The total costs for CP-related hospitalizations for CP patients over the study period were 667.96 million yuan, with an average of 17538 yuan per patient., Conclusion: The yearly incidence of CP is increasing, and the overall CP hospitalization cost has increased by 1.4 times during the last 7 years, indicating that CP remains a heavy health burden., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke, especially in Asian populations, which has a high risk of recurrent stroke and cardiovascular comorbidities. The present guidelines aim to provide updated evidence-based recommendations for diagnosis and management of patients with ICAD. Taiwan Stroke Society guideline consensus group developed recommendations for management of patients with ICAD via consensus meetings based on updated evidences. Each proposed class of recommendation and level of evidence was approved by all members of the group. The guidelines cover six topics, including (1) epidemiology and diagnostic evaluation of ICAD, (2) nonpharmacological management of ICAD, (3) medical therapy for symptomatic ICAD, (4) endovascular thrombectomy and rescue therapy for acute ischemic stroke with underlying ICAD, (5) endovascular interventional therapy for postacute symptomatic intracranial arterial stenosis, and (6) surgical treatment of chronic symptomatic intracranial arterial stenosis. Intensive medical treatment including antiplatelet therapy, risk factor control, and life style modification are essential for patients with ICAD., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Background: Given the escalating epidemic of obesity and diabetes coupled with redefined diagnostic criteria, it is critical to identify the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD). We sought to determine the prevalence and mortality outcomes of MAFLD subtypes based on diagnostic criteria in the USA over the past three decades., Methods: Eleven cycles of the National Health and Nutrition Examination Surveys (NHANES; 1988-1994 and 1999-2020) were used, and 72,224 participants were included. MAFLD was defined according to the 2020 International Expert Consensus. Based on diagnostic criteria and risk factors, MAFLD was categorized into seven subtypes: type 1 (obesity subtype), 2 (metabolic unhealthy subtype), 3 (diabetes subtype), 4 (metabolic unhealthy non-diabetes subtype), 5 (obesity and diabetes subtype), 6 (metabolic unhealthy non-obesity subtype), and 7 (mixed subtype)., Results: Over the study period, the estimated prevalence of MAFLD increased significantly from 22% in 1988-1994 to 36% in 2017-2020. The prevalence of Type 4 was the highest, followed by that of Type 7, whereas other types were low and almost unchanged over time. Individuals with MAFLD had 19% and 38% increased mortality risks from all causes and cardiovascular disease, respectively. Among them, the metabolically unhealthy participants with normal weight demonstrated a 116% higher risk for all-cause mortality [hazard ratio (HR): 2.16, 95% CI: 1.52-3.08] and a 222% higher risk for cardiovascular mortality (HR: 3.22, 95% CI: 1.72-6.04). Interestingly, stratification and interaction analyses demonstrated a significant impact of metabolic parameters on the relationship between MAFLD and all-cause mortality., Conclusions: In conclusion, our study identified an increase in MAFLD prevalence and a significant association between metabolic derangements in MAFLD and all-cause or cardiovascular mortality., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest or financial ties to disclose., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Bihemispheric transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) can simultaneously modulate bilateral corticospinal excitability and interhemispheric interaction. However, how tDCS affects subacute stroke recovery remains unclear. We investigated the effects of bihemispheric tDCS on motor recovery in subacute stroke patients., Methods: We enrolled subacute inpatients who had first-ever ischemic stroke at subcortical regions and moderate-to-severe baseline Fugl-Meyer Assessment of Upper Extremity (FMA-UE) score 2-56. Participants between 14 and 28 days after stroke were double-blind, randomly assigned (1:1) to receive real (n = 13) or sham (n = 14) bihemispheric tDCS (with ipsilesional M1 anode and contralesional M1 cathode, 20 min, 2 mA) during task practice twice daily for 20 sessions in two weeks. Residual integrity of the ipsilesional corticospinal tract was stratified between groups. The primary efficacy outcome was the change in FMA-UE score from baseline (responder as an increase ≥ 10). The secondary measures included changes in the Action Research Arm Test (ARAT), FMA-Lower Extremity (FMA-LE) and explorative resting-state MRI functional connectivity (FC) of target regions after intervention and three months post-stroke., Results: Twenty-seven participants completed the study without significant adverse effects. Nineteen patients (70%) had no recordable baseline motor-evoked potentials (MEP-negative) from the paretic forearm. Compared with the sham group, the real tDCS group showed enhanced improvement of FMA-UE after intervention (p < 0.01, effect size η 2  = 0.211; responder rate: 77% vs. 36%, p = 0.031), which sustained three months post-stroke (p < 0.01), but not ARAT. Interestingly, in the MEP-negative subgroup analysis, the FMA-UE improvement remained but delayed. Additionally, the FMA-LE improvement after real tDCS was not significantly greater until three months post-stroke (p < 0.01). We found that the individual FMA-UE improvements after real tDCS were associated with bilateral intrahemispheric, rather than interhemispheric, FC strengths in the targeted cortices, while the improvements after sham tDCS were associated with predominantly ipsilesional FC changes after adjustment for age and sex (p < 0.01)., Conclusions: Bihemispheric tDCS during task-oriented training may facilitate motor recovery in subacute stroke patients, even with compromised corticospinal tract integrity. Further studies are warranted for tDCS efficacy and network-specific neuromodulation., Trial Registration: This study is registered with ClinicalTrials.gov: (ID: NCT02731508)., (© 2023. The Author(s).)

Significant lifetime enhancement, up to an eight-fold increase in T 90 , has been demonstrated in blue organic light-emitting diode (OLED) devices through the deuteration of host and hole transport materials. We observed a progressive increase in T 90 using a series of anthracene-based hydrocarbon hosts with incremental deuteration in the emitting layer. In addition, we realized further lifetime improvement using a deuterated hole-transport layer along with the deuterated emitting layer. To elucidate the deuteration effects, we utilized laser desorption/ionization-time-of-flight (LDI-TOF) mass spectrometry for in situ UV irradiation to induce photodegradation and immediate chemical analysis of the resultant photodegradation species. Adducts between the host and moieties from transport materials were identified in UV-degraded films comprising a mixture of host and transport materials, indicating that similar species could be produced in OLED devices using these materials. Deuteration, in effect, mediated the formation of these adduct species, presumably electroluminescence quenchers, and thus improved the device lifetime. An approximate agreement was obtained between the kinetic isotope effect of the photodegradation reactions and the enhancement in device lifetime with deuteration.

Objectives: Elderly acute ischemic stroke (AIS) patients (≥80 years) would have dismal clinical outcomes even after successful endovascular revascularization for large vessel occlusion (LVO) in the anterior circulation. We aimed to identify predictors of 30-day mortality after endovascular thrombectomy (EVT) in the elderly., Materials and Methods: We included older patients who underwent EVT for AIS due to LVO within 6 h after stroke onset in the anterior circulation between 2017 and 2019. Patients due to posterior circulation stroke, with intracerebral hemorrhage (ICH) or pre-stroke modified Rankin Scale (mRS) score of 4 and 5 were excluded. The primary outcome was mortality within 30 days of EVT. The association between clinical, imaging, procedural, follow-up imaging and mortality were analyzed. Successful reperfusion was defined as modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b or 3. Possible predictors of 30-day mortality were assessed by univariate and multivariable logistic regression., Results: Total 238 AIS patients eligible for EVT were identified with 58 patients aged 80 years or more. 48 patients met inclusion criteria. Median age was 86 years (age range, 82-102 years). Successful reperfusion was achieved in 38 (79.2%) patients. The 30-day and 90-day mortality rate were 25% and 33.3%, respectively. The independent predictors of 30-day mortality were collateral scores <3 on mCTA (adjusted OR, 16.571; 95% CI, 1.041-263.868; p  = 0.047) and number of passes (adjusted OR, 2.475; 95% CI, 1.047-5.847; p  = 0.039)., Conclusions: Lower collateral scores on mCTA and higher number of passes in thrombectomy were independently predictive of 30-day mortality in the elderly.

Portal hypertension, as a common and complex hepatic vascular disease, is a key pathophysiological link in many events of acute cirrhosis decompensation and the progression of multiple organ failure. The most effective measure to reduce portal hypertension is a transjugular intrahepatic portosystemic shunt (TIPS). Maintaining liver function, reducing complications, and improving patients' quality of life and survival time are positively impacted by early TIPS insertion. Patients with cirrhosis have a risk of portal vein thrombosis (PVT) that is 1 000 times higher than that of the normal population. Hepatic sinusoidal obstruction syndrome has a severe clinical course and a high mortality risk. The primary treatment approaches for PVT and HSOS are anticoagulation and TIPS. The innovative magnetic anastomosis vascular technique significantly shortens the anhepatic time and restores normal liver function in patients following liver transplantation.

Oxidative steam reforming of ethanol (OSRE) to produce hydrogen has been investigated over a series of supported PtRu catalysts, with different supports. Bimetallic PtRu-based catalysts were prepared by the impregnation method using H 2 PtCl 6 and RuCl 3 as precursors. Six supports (reducible oxides of ZrO 2 , CeO 2 , and Co 3 O 4 , and irreducible oxides of ZnO, Al 2 O 3 , and NiO) were chosen to fabricate bimetallic catalysts. The catalytic performance of the OSRE reaction in the series of PtRu-based samples was evaluated using a fixed-bed flow reactor under atmospheric pressure. In front reaction, the catalyst was pre-activated by reduction under 200°C for 3 h. The gas hourly space velocity was adjusted at 66,000 h -1 , and the optimal molar ratios of the H 2 O/EtOH and O 2 /EtOH feeds were 4.9 and 0.44, respectively. The results indicated that the PtRu supported on the ZrO 2 and CeO 2 exhibited superior catalytic performance in the OSRE reaction under a low temperature (a T R of approximately 320°C) for producing the main products of H 2 and CO 2 with lower CO and CH 4 by-products. Also, it was quite stable during a long time evaluation; the maximum Y H2 maintained at 4.5-4.2, and the CO distribution approached 3.3-3.5 mol% around 84 h test at 340°C over the PtRu/ZrO 2 catalyst., 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 Tang, Liu, Yu and Wang.)

Taiwan has used technology in reservoir sediments and industrial waste to produce high-performance lightweight aggregate (LWA). LWA can be used to manufacture lightweight aggregate concrete (LWAC) with structural strength ratings. At present, Taiwan's offshore wind turbines are gradually developing and are moving from coastal areas to deep-sea areas. With this in mind, this study aimed to investigate the feasibility of applying LWAC with synthetic LWA from reservoir sediments to floating offshore wind turbine foundations. LWAC and normal-weight concretes (NWC) of different strengths were prepared, and their fresh, hardened, and durability properties were tested. In addition, reinforced concrete and steel sheets were immersed in a tank of high salinity seawater to examine their resistance to seawater-accelerated corrosion. The test results showed that the total passing charge of the two groups of concrete within six hours was less than 1000 coulombs. Both groups of concrete were classified as having "Very Low" chloride permeability. The average corrosion potential of most reinforced concrete specimens was found to be greater than -200 mV, which means that the corrosion probability of the steel bars was less than 10%. Furthermore, the use of coatings for seawater corrosion protection on steel sheets was not found to be as effective as reinforced concrete. This shows that the use of LWAC with synthetic LWA from reservoir sediments for the floating foundations of offshore wind turbines is feasible and has design flexibility.

In the field of civil engineering, concrete self-healing technology plays an important role. Concrete self-healing should be able to effectively heal cracks, not only improving the internal structure, but also improving the mechanical properties and durability of the concrete structure. The biomineralization-repair method is characterized by its potential for long-lasting, rapid, and active crack repair potential. Biomineralization repair has an effective bond ability, is compatible with concrete components, and is also environmentally friendly. This study used biomineralization to explore the self-healing of fiber-reinforced lightweight concrete after its exposure to high temperatures. Concrete specimens of a control group (using lightweight aggregate without bacterial spores and a nutrient source) and an experimental group (using lightweight aggregate containing bacterial spores and a nutrient source) were prepared. The repair effect of the microbial self-healing concrete after the exposure to high temperature was observed by a crack-width gauge, field-emission scanning electron microscopy (FESEM), energy-dispersive spectroscopy (EDS), and X-ray diffraction (XRD). According to the EDS and XRD analyses, the precipitate formed at the crack was calcium carbonate. After 28 days of self-healing, the water absorption rate of the experimental group was lower than that of the control group. This is because the specimens of the penetration test were taken from the middle of the concrete cylinder after high temperature, and their bacterial survival rate was higher, which made the mineralization more significant. However, the mechanical test results of the control and experimental groups after the self-healing in the water were not substantially different, which indicated that the bacterial mineralization in the experimental group was slow in the absence of an adequate source of nutrients.

Objectives: Metastasis is the principal cause of breast cancer mortality. Vaccines targeting breast cancer antigens have yet to demonstrate clinical efficacy, and there remains an unmet need for safe and effective treatment to reduce the risk of metastasis, particularly for people with triple-negative breast cancer (TNBC). Certain glycolipids can act as vaccine adjuvants by specifically stimulating natural killer T (NKT) cells to provide a universal form of T-cell help., Methods: We designed and made a series of conjugate vaccines comprising a prodrug of the NKT cell-activating glycolipid α-galactosylceramide covalently linked to tumor-expressed peptides, and assessed these using E0771- and 4T1-based breast cancer models in vivo . We employed peptides from the model antigen ovalbumin and from clinically relevant breast cancer antigens HER2 and NY-ESO-1., Results: Glycolipid-peptide conjugate vaccines that activate NKT cells led to antigen-presenting cell activation, induced inflammatory cytokines, and, compared with peptide alone or admixed peptide and α-galactosylceramide, specifically enhanced CD8 + T-cell responses against tumor-associated peptides. Primary tumor growth was delayed by vaccination in all tumor models. Using 4T1-based cell lines expressing HER2 or NY-ESO-1, a single administration of the relevant conjugate vaccine prevented tumor colonisation of the lung following intravenous inoculation of tumor cells or spontaneous metastasis from breast, respectively., Conclusion: Glycolipid-peptide conjugate vaccines that activate NKT cells prevent lung metastasis in breast cancer models and warrant investigation as adjuvant therapies for high-risk breast cancer., Competing Interests: IH and GP are inventors on patents licensed to or owned by biotech start‐up Avalia Immunotherapies Limited., (© 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Full-spectrum flow cytometry is now routinely used in many laboratories internationally, and the demand for this technology is rapidly increasing. With capacity to use larger and more complex staining panels, standardized protocols are required for optimal panel design and analysis. Importantly, for ex vivo analysis, tissue preparation methods also need to be optimized to ensure samples are truly representative of tissues in situ. This is particularly relevant given the recent interest in adaptive immune cells that form residency in specific organs. Here we provide optimized protocols for tissue processing and phenotyping of memory T cells and natural killer T (NKT) cell subsets from liver, lung, spleen, and lymph node using full-spectrum flow cytometry. We provide a 21-color antibody panel for identification of different memory subsets, including tissue-resident memory T (T RM ) cells, which are increasingly regarded as important effectors in adaptive immunity. We show that processing procedures can affect outcomes, with liver T RM cells particularly sensitive to heat, such that accurate evaluation requires fast processing at defined temperatures. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Processing mouse liver for flow cytometric analysis of memory T and NKT cell subsets Basic Protocol 2: Processing mouse spleen for flow cytometric analysis of memory T and NKT cell subsets Basic Protocol 3: Processing mouse lungs for flow cytometric analysis of memory T and NKT cell subsets Basic Protocol 4: Processing mouse lymph nodes for flow cytometric analysis of memory T and NKT cell subsets Basic Protocol 5: Staining and flow cytometric analysis of samples for memory T and NKT cell subsets Support Protocol: Obtaining cell counts from flow cytometry data., (© 2022 Wiley Periodicals LLC.)

Background: Endotoxemia is related to worse clinical outcomes in acute liver failure (ALF), but its management remains unsatisfactory. In this study, we aimed to assess whether the application of bone marrow mesenchymal stem cells (BMSCs) could eliminate endotoxemia and protect rats against ALF induced by thioacetamide (TAA)., Methods: BMSCs were isolated from rats and identified by the specific morphology, differentiation potential, and surface markers. The optimal dose of TAA for this study was explored and TAA-induced ALF rats were randomized to three groups: the normal control group (Saline), ALF group (TAA + Saline), and BMSCs-treated group (TAA + BMSCs). The intestinal migration and differentiation of BMSCs was tracked in vivo, and intestinal permeability, endotoxin and inflammatory cytokines, histology, and mortality were analyzed. Moreover, we added the inhibitor of the PI3K/AKT/mTOR signaling pathway into the co-culture system of BMSCs with enterocytes and then performed CK and Villin expression experiments to assess the role of PI3K/AKT/mTOR signal pathway in the intestinal differentiation of BMSCs., Results: BMSCs migrated to the intestinal injury sites and differentiated into enterocytes, intestinal permeability was decreased compared with the ALF group. The higher expression of endotoxin and inflammatory cytokines were reversed after BMSCs transplantation in rats with ALF. Mortality and intestinal lesion were significantly decreased. Blocking the PI3K/AKT/mTOR signal pathway inhibited BMSCs' intestinal differentiation in vitro., Conclusion: BMSCs can eliminate endotoxemia and reduce mortality in rats with ALF, and the PI3K/AKT/mTOR signal pathway is involved in intestinal differentiation. BMSCs transplantation could be a potential candidate for the treatment of endotoxemia in ALF., (© 2022. The Author(s).)

The aim of this study was to investigate the development of a process for manufacturing lightweight aggregates (LWAs) by incorporating sludge from wastewater treatment plants in industrial parks with reservoir sediments. The research was divided into two stages: laboratory-scale firing and large-scale firing. In the laboratory-scale stage, a high-temperature furnace was used for trial firing. In the large-scale stage, a commercial rotary kiln was used for trial firing for mass production. The test results showed that the water absorption, dry loose bulk density, and crushing strength of the sintered LWAs were 14.2-26.9%, 634-753 kg/m 3 , and 1.29-2.90 MPa, respectively. Moreover, the water absorption of the sintered LWAs increased as the percentage of added sludge increased. In addition, the dry loose bulk density of the sintered LWAs gradually decreased as the percentage of added sludge increased. Moreover, the results of the heavy metal toxicity characteristic leaching procedure (TCLP) dissolution test for the LWAs produced by blending 30-50% sludge were all lower than the standard value required by the Taiwan Environmental Protection Agency for general industrial waste. The strength grade of the sintered LWAs was 20 MPa. From this point of view, the sintered LWAs that were studied under the test conditions could be used as aggregates for lightweight concrete and would allow it to have a reasonable strength of greater than 20 MPa.

Objective: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden., Methods: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements., Results: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases., Conclusion: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the efficacy and safety of additional S-1 chemotherapy to S-1 plus oxaliplatin (SOX) regimen chemotherapy for Stage III gastric carcinoma (GC) after radical resection., Patients and Methods: A total of 161 patients who were pathologically diagnosed as Stage III GC after D2 gastrectomy and received SOX regimen adjuvant chemotherapy between January 2012 and April 2016 were included in this retrospective study. SOX regimen postoperative chemotherapy was composed of Oxaliplatin and S-1, administrated every 3 weeks for 8 scheduled courses. After SOX chemotherapy, 76 patients preferred additional chemotherapy with S-1 (the ACT group), while additional S-1 chemotherapy was not given to the other 85 patients (control group). The ACT with S-1 was administrated every 3 weeks for 8 scheduled courses. Treatment was terminated in case of life-threatening adverse events or tumor progression, or patients' demand for termination. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed., Results: ACT group obtained markedly improved 3-year PFS [ p  = 0.04; hazard ratio (HR) for disease progression, 0.58; 95% confidence interval (CI), 0.34-0.98] and OS than the control group ( p  = 0.0469; HR for death, 0.56; 95% CI, 0.32-0.99). No chemotherapy-related mortality occurred. Patients of the ACT group suffered more common and severer hand-foot syndrome (HFS) ( p  = 0.02)., Conclusions: Additional S-1 chemotherapy may be helpful for improving the disease progression and survival for patients with Stage III GC after radical resection with an acceptable safety profile.

The increase of harmful carbon monoxide (CO) caused by incomplete combustion can affect human health even lead to suffocation. Therefore reducing the CO discharged by vehicles or factories is urgent to improve the air quality. The spinel cobalt (II, III) oxide (Co₃O₄) is an active catalyst for CO abatement. In this study, we tried to fabricate dispersing Co₃O₄ via the dispersion-precipitation method with acetic acid, formic acid, and oxalic acid as the chelating dispersants. Then, the asprepared samples were calcined at 300 ºC for 4 h to obtain active catalysts, and assigned as Co(A), Co(F) and Co(O) respectively, the amount of the dispersants used are labeled as I (0.12 mole), II (0.03 mole) and III (0.01 mole). For comparison, another CoAP sample was prepared via alkaliinduced precipitation and calcined at 300 ºC. All samples were characterized by X-ray diffraction (XRD), temperature-programmed reduction (TPR), scanning electron microscope (SEM), and nitrogen adsorption/desorption system, and the catalytic activity focused on the CO oxidation. The influence of chelating dispersant on the performance of abatement of CO was pursued in this study. Apparently, the results showed that the chelating dispersant can influence the catalytic activity of CO abatement. An optimized ratio of dispersant can improve the performance, while excess dispersant lessens the surface area and catalytic performance. The series of Co(O) samples can easily donate the active oxygen since the labile Co-O bonding and indicated the preferential performance than both Co(A) and Co(F) samples. The nanorod Co(O)-II showed preferential for CO oxidation, T 50 and T 90 approached 96 and 127 ºC, respectively. Also, the favorable durability of Co(O)-II sample maintains 95% conversion still for 50 h at 130 ºC and does not emerge deactivation.

Background: Young stroke incidence has increased worldwide with lifestyle changes. Etiology and risk factors for both ischemic and hemorrhagic stroke in young Asians remain underexplored., Methods: We retrospectively reviewed consecutive acute stroke patients aged 16-45 years admitted to the Taipei Veterans General Hospital between 2009 and 2019 to analyze etiologic subtypes, risk factors, and serial modified Rankin Scale scores for 1 year and compare the age groups of 16-30 and 31-45 years., Results: Among 670 young Taiwanese patients (mean age at onset 37.5 ± 7.0 years; male 65.1%), there were 366 nontraumatic spontaneous hemorrhagic stroke (including 259 intracerebral hemorrhage [ICH] and 107 subarachnoid hemorrhage, SAH), 292 ischemic stroke and 12 cerebral venous thromboses. Notably, ICH was more prevalent in patients aged 16-30 than in those aged 31-45 (54.8% vs 36.8%). Specifically, structural vasculopathy (e.g., arteriovenous malformation, cavernoma) was the most common etiologic subtype in patients aged 16-30 (p < 0.001), whereas hypertensive ICH was the most common subtype in patients aged 31-45 (p < 0.001). On the other hand, the top ischemic subtype for both age groups was other determined diseases (e.g., arterial dissection, autoimmune diseases, moyamoya disease, etc.) rather than large artery atherosclerosis. Hyperlipidemia, diabetes, and cigarette smoking were more common risk factors for infarction than ICH. Familial stroke patients whose first- or second-degree relatives had a stroke by age 80 (n = 104, 15.5%) had more infarctions than those without a familial stroke history. In multivariate analyses, initial stroke severity, and infarction type were important predictors of favorable outcomes after 3 months. At the 1-year follow-up, patients with ICH and SAH had worse functional outcomes and survival rates than those with infarction., Conclusion: An aggressive approach to elucidate the etiology of stroke is indicated because structural vasculopathy-induced ICH and other determined infarction are distinctively prevalent in young adults, particularly those aged 16-30., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Due to the dense structure of ultra-high-performance concrete (UHPC), it is prone to explosive spalling at high temperatures. In this paper, flexural testing of UHPC and high-strength concrete (HSC) beams was carried out at room temperature and after being subjected to different levels of thermal exposure (300-500 °C). The cross-section of the beam specimen was 150 (width) × 200 (depth) mm, and its length was 1500 mm. The flexural and shear design of the beam specimens were carried out in accordance with the ACI 318M-14 code. All of the beams were singly reinforced with two #4 rebars (minimum reinforcement ratio) as a longitudinal tensile reinforcement at the bottom of the specimen and at an effective depth of 165 mm. The flexural load was applied using the three-point load method. The results show that, at room temperature and after being subjected to different thermal exposures, compared with the HSC specimens, the stiffness of the UHPC specimens in the post-cracking stage was relatively larger and the deflection under a given load was smaller. Moreover, whether at room temperature or after exposure to different thermal exposures, the ductility of the UHPC specimens was better than that of the HSC specimens.

Mood dysregulation refers to the inability of a person to control their negative emotions, and it is linked to various stressful experiences. Dysregulated neural synaptic plasticity and actin-filament dynamics are important regulators of stress response in animal models. However, until now, there is no evidence to differential the mechanisms of synaptic plasticity and actin-filament dynamics in stress susceptibility and stress-resistant. Here we found that depression-like behaviour was observed in the susceptible group following chronic social defeat stress (CSDS) exposure, but not in stress-resistant mice. High-frequency stimulation-induced long-term potentiation (LTP) was impaired in the CSDS-induced depression-susceptible group. Further, the levels of pro-brain derived neurotrophic factor (BDNF), mature BDNF, PSD-95, phosphorylated CaMKII, and phosphorylated Cofilin, an actin-filament dynamics regulator, were reduced in CSDS-induced depression-susceptible mice unlike in stress-resistant mice. These results demonstrate that synaptic plasticity-related molecules, such as BDNF and phosphorylated Cofilin, are important for maintaining synaptic functions and structure in mice that experience more stress., 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 © 2021 Elsevier Inc. All rights reserved.)

Primary biliary cholangitis (PBC) is a common autoimmune liver disease manifested by the infiltration of CD4 + T cells, and the subsequent targeted injury of biliary epithelial cells (BECs). As important components of CD4 subsets, the Treg/Th17 axis maintains an immunological balance between self-tolerance and inflammation in the liver microenvironment. However, the role and regulatory mechanism of the Treg/Th17 axis in PBC remain unclear. In this study, we examined the Treg/Th17 axis in PBC patients and found that the Treg/Th17 axis was imbalanced in PBC at both the transcriptional and cellular levels, with Treg being a weak candidate, which correlates with the PBC progression. This imbalanced Treg/Th17 axis was likely to be affected by the FoxP3 hypermethylation, which was related to the increase of DNA methyltransferase. Furthermore, the effect of 5-Aza-2-deoxycytidine (DAC)-mediated FoxP3 demethylation on PBC mice was investigated. We verified that DAC significantly suppressed the FoxP3 methylation and rebuilt the Treg/Th17 balance, resulting in the alleviation of liver lesions and inflammation. Taken together, our data indicate that DAC plays a positive role in alleviating the progression of PBC through the inhibition of DNA methylation of FoxP3 to rebuild the balanced Treg/Th17 axis. DAC could be considered as a potential candidate for the development of new anti-inflammation strategies in the treatment of PBC., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Gastrointestinal involvement in Behçet's disease (GIBD) and Crohn's disease (CD) are inflammatory diseases sharing a considerable number of similarities. However, different from CD, the operative and postoperative management of GIBD remains largely empirical because of the lack of comprehensive treatment guidelines., Aim: To compare surgical patients with GIBD and those with CD in a medical center and identify notable clinical features and effective postoperative treatment for surgical patients with GIBD., Methods: We searched patients diagnosed with CD and GIBD who underwent operations for gastrointestinal complications from 2009 to 2015 at West China Hospital of Sichuan University. A total of 10 surgical patients with GIBD and 106 surgical patients with CD were recruited. Information including demographic data, medication, and operative and postoperative parameters were collected and analyzed. As the incidence of surgical GIBD is low, their detailed medical records were reviewed and compared to previous studies. Moreover, the prognoses of CD and GIBD were evaluated respectively between groups treated with biological and non-biological agents., Results: Indication for first surgery was often acute intestinal perforation for GIBD patients (7/10 vs 0/106, P < 0.001), whereas intestinal fistulae (0/10 vs 44/106, P = 0.013) and ileus (0/10 vs 40/106, P = 0.015) were the indications for surgical CD patients. Approximately 40% of patients with GIBD and 23.6% of patients with CD developed postoperative complications, 50% of patients with GIBD and 38.7% of patients with CD had recurrence postoperatively, and 40% (4/10) of patients with GIBD and 26.4% (28/106) of patients with CD underwent reoperations. The average period of postoperative recurrence was 7.87 mo in patients with Behçet's disease (BD) and 10.43 mo in patients with CD, whereas the mean duration from first surgery to reoperation was 5.75 mo in BD patients and 18.04 mo in CD patients. Surgical patients with GIBD more often used corticosteroids (6/10 vs 7/106, P < 0.001) and thalidomide (7/10 vs 9/106, P < 0.001) postoperatively, whereas surgical patients with CD often used infliximab (27/106), azathioprine, or 6-mercaptopurine (74/106) for maintenance therapy., Conclusion: Patients suffering GIBD require surgery mostly under emergency situations, which may be more susceptible to recurrence and reoperation and need more aggressive postoperative treatment than patients with CD., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Rich information is provided by 360-degree videos. However, non-uniform geometric deformation caused by sphere-to-plane projection significantly decreases tracking accuracy of existing trackers, and the huge amount of data makes it difficult to achieve real-time tracking. Thus, this paper proposes a Siamese networks-based people tracker using template update for 360-degree equi-angular cubemap (EAC) format videos. Face stitching overcomes the problem of content discontinuity of the EAC format and avoids raising new geometric deformation in stitched images. Fully convolutional Siamese networks enable tracking at high speed. Mostly important, to be robust against combination of non-uniform geometric deformation of the EAC format and partial occlusions caused by zero padding in stitched images, this paper proposes a novel Bayes classifier-based timing detector of template update by referring to the linear discriminant feature and statistics of a score map generated by Siamese networks. Experimental results show that the proposed scheme significantly improves tracking accuracy of the fully convolutional Siamese networks SiamFC on the EAC format with operation beyond the frame acquisition rate. Moreover, the proposed score map-based timing detector of template update outperforms state-of-the-art score map-based timing detectors.

This paper aims to study the uniaxial bond stress-slip characteristics of reinforcing bars embedded in concrete with different strengths. Tests were conducted on tension-pull specimens that had a cross-sectional dimension with a reinforcing bar embedded in the center section. The experimental variable was the concrete compressive strength (20, 40, and 60 MPa). The test results show that in the specimen subjected to any fixed load, the maximum value of the concrete strain occurred around the central position, and its value increased as the compressive strength of the concrete increased. Depending on the embedded position of the steel bars, the bond stress-slip relationship was also different. In addition, the analytical results indicate that the proposed bond stress-slip constitutive relationship is very accurate in describing the true bond stress-slip relationship.