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Liang Chen,1 Xiu-Di Han,2 Yan-Li Li,3 Chun-Xiao Zhang,4 Xi-Qian Xing5 1Department of Infectious Diseases, Beijing Jishuitan Hospital, 4th Medical College of Peking University, Beijing, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, Qingdao City, Shandong Province, People’s Republic of China; 3Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Beijing Huimin Hospital, Beijing, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, The 2nd People’s Hospital of Yunnan Province, Kunming City, Yunnan Province, People’s Republic of ChinaCorrespondence: Liang Chen Tel +8613810438037Email chenliang1995@sina.comPurpose: Respiratory viruses are important etiologies of community-acquired pneumonia (CAP). However, the impact of different RVs on the outcomes of CAP is not well elucidated. This study aims to compare the clinical features and severity of influenza (Flu-p) and non-influenza respiratory viruses-related pneumonia (NIRVs-p) onset in the community among immunocompetent adults.Methods: The data of the patients hospitalized with laboratory-confirmed RVs-p were retrospectively reviewed from five teaching hospitals in China from January 2013 to May 2019. Univariate and multivariate logistic regressions were performed to compare the clinical characteristics and outcomes between Flu-p and NIRVs-p.Results: A total of 1079 patients with Flu-p and 341 patients with NIRVs-p were included in this study. A multivariate logistic regression model revealed chronic pulmonary disease [odd ratio (OR) 0.341, 95% confidence interval (CI) 0.225– 0.515, p < 0.001], solid malignant tumor (OR 0.330, 95% CI 0.163– 0.668, p = 0.002), myalgia (OR 1.697, 95% CI 1.236– 2.330, p < 0.001), lymphocytes < 0.8× 109/L (OR 10.811, 95% CI 6.949– 16.818, p < 0.001) and blood albumin < 35 g/L (OR 0.327, 95% CI 0.242– 0.442, p < 0.001) were predictors for Flu-p. After adjusting for confounders, the multivariate logistic regression analysis confirmed that influenza B-related pneumonia (FluB-p) (OR 0.419, 95% CI 0.272– 0.646, p < 0.001) and NIRVs-p (OR 0.260, 95% CI 0.158– 0.467, p < 0.001) were associated with a decreased risk of 30-day mortality compared with the influenza A-related pneumonia (FluA-p).Conclusion: Our results showed that patients with FluA-p experience a more severe disease than those with FluB-p and NIRVs-p. Some clinical features are helpful to distinguish between NIRVs-p and Flu-p.Keywords: influenza, respiratory virus, pneumonia, clinical characteristics, severity

Xiang-Dong Han,1 Zhi-Wei Zhou,2–4 Wei Yang,1 Hang-Cheng Ye,1 Ying-Zi Xu,1 Yun-Feng Huang,1 Tong Zhang,1 Shu-Feng Zhou2 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3Guizhou Provincial Key Laboratory for Regenerative Medicine, 4Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guizhou Medical University, Guiyang, People’s Republic of China Abstract: Ischemic heart disease (IHD) is the leading cause of death worldwide and remains a major life-threatening factor in humans. Apoptosis has been implicated in the pathogenesis of IHD. The Chinese herbal formula Huo Luo Xiao Ling Dan (HLXLD), one of the commonly used Chinese herbal formulas, consists of Salviae miltiorrhizae, Angelica sinensis, Gummi olibanum, and Commiphora myrrha, with a wide spectrum of pharmacological activity. However, the mechanism of action and molecular targets of HLXLD in the treatment of IHD are unclear. This study aimed to computationally predict the molecular interactions between the major active components of HLXLD and key regulators of apoptosis and then examine the effect of HLXLD on coronary artery ligation-induced acute myocardial ischemia in rats. The molecular interactions between the major active components of HLXLD, including ferulic acid, ligustilide, succinic acid, vanillic acid, tanshinone IIA, tanshinone IIB, danshensu, salvianolic acid A, salvianolic acid C, protocatechuic aldehyde, and β-boswellic acid and human protein molecules including B cell lymphoma-extra large (Bcl-xl), B cell lymphoma 2 antagonist/killer 1 (Bak1), B cell lymphoma 2 (Bcl-2), procaspase 3, and caspase 9 with regard to hydrogen bond formation, charge interaction, and π-π stacking using Discovery Studio® program 3.1. The 12 HLXLD components were predicted by ADMET (absorption, distribution, metabolism, excretion and toxicity) Predictor to have favorable pharmacokinetic and low hepatotoxicity profiles. The acute myocardial ischemia was established by surgical ligation of the left anterior descending coronary artery. The rats were divided into a sham operative group, a model group, a positive control group treated with 0.2 mg/kg isosorbide mononitrate, and groups treated with 2.7, 5.4, or 10.8 g/kg HLXLD. The results showed that administration of HLXLD increased mean arterial pressure, left ventricular systolic pressure, heart rate, and maximal rate of rise/descent of left ventricular pressure levels. Administration of HLXLD significantly ameliorated coronary artery ligation-induced tissue damage in the left ventricle, with restored arrangement of myocardial fibers and recovered myoplasm in rats. Furthermore, HLXLD markedly increased the expression level of Bcl-2 but decreased the level of cleaved caspase 3. Taken together, administration of HLXLD attenuated acute myocardial ischemia-induced damage in cardiomyocytes and inhibited apoptotic death of cardiomyocytes, thereby exerting a cardioprotective effect in rats with IHD. These findings suggest that HLXLD may represent a promising herbal formula for the treatment of cardiovascular disease by counteracting apoptotic cell death via multiple active compounds. More studies are warranted to fully elucidate the mechanisms of action, identify the therapeutic targets, and validate the efficacy and safety of HLXLD in the treatment of IHD. Keywords: Huo Luo Xiao Ling Dan, myocardial ischemia, coronary artery ligation, hemodynamics, apoptosis, molecular docking

Background: Food addiction and an impulsive personality can increase overeating, which can lead to weight gain. The amygdala and nucleus accumbens (NAcc) are critical for regulating obesogenic behaviour. However, whether the amygdala or the NAcc acts as the neural basis for the regulation of food addiction, impulsive personality, and body weight remains unclear., Methods: We examined the differences in the volume of the amygdala and NAcc, especially the lateralization index (LI), between 33 obese participants and 39 age- and sex-matched healthy controls. The associations of the LI of each brain region with clinical variables and body mass index (BMI) were identified using network analysis. Finally, we explored the relationships among the LIs of brain regions, impulsive personality, food addiction, and BMI through a multiple chain mediation model., Results: We observed a significant decrease in the LI of the amygdala in the obese group compared with the healthy group (F = 20.276, p < 0.001), which indicates that the right amygdala was larger than the left amygdala in the obese group. Network analysis revealed that the LI of the amygdala was very closely associated with nonplanning impulsivity, food addiction and BMI. The results of the mediation analysis indicated that increased nonplanning impulsiveness could lead to weight gain through increased food addiction (β = 0.069, SE = 0.043, 95% CI [0.014, 0.184]). Moreover, in this symptom chain, the LI of the amygdala can mediate the relationship between food addiction and BMI (β = 0.018, SE = 0.014, 95% CI [0.002, 0.061])., Conclusion: Our observations indicate a substantial reduction in the LI of the amygdala among individuals with obesity, suggesting a structural predisposition. The findings reveal a potential neural mechanism that can help explain the interplay between impulsivity, food addiction, and obesity.

Background: General anesthesia is commonly used in the surgical management of gastrointestinal tumors; however, it can lead to emergence agitation (EA). EA is a common complication associated with general anesthesia, often characterized by behaviors, such as crying, struggling, and involuntary limb movements in patients. If treatment is delayed, there is a risk of incision cracking and bleeding, which can significantly affect surgical outcomes. Therefore, having a proper understanding of the factors influencing the occurrence of EA and implementing early preventive measures may reduce the incidence of agitation during the recovery phase from general anesthesia, which is beneficial for improving patient prognosis., Aim: To analyze influencing factors and develop a risk prediction model for EA occurrence following general anesthesia for primary liver cancer., Methods: Retrospective analysis of clinical data from 200 patients who underwent hepatoma resection under general anesthesia at Wenzhou Central Hospital (January 2020 to December 2023) was conducted. Post-surgery, the Richmond Agitation-Sedation Scale was used to evaluate EA presence, noting EA incidence after general anesthesia. Patients were categorized by EA presence postoperatively, and the influencing factors were analyzed using logistic regression. A nomogram-based risk prediction model was constructed and evaluated for differentiation and fit using receiver operating characteristics and calibration curves., Results: EA occurred in 51 (25.5%) patients. Multivariate analysis identified advanced age, American Society of Anesthesiologists (ASA) grade III, indwelling catheter use, and postoperative pain as risk factors for EA ( P < 0.05). Conversely, postoperative analgesia was a protective factor against EA ( P < 0.05). The area under the curve of the nomogram was 0.972 [95% confidence interval (CI): 0.947-0.997] for the training set and 0.979 (95%CI: 0.951-1.000) for the test set. Hosmer-Lemeshow test showed a good fit ( χ 2 = 5.483, P = 0.705), and calibration curves showed agreement between predicted and actual EA incidence., Conclusion: Age, ASA grade, catheter use, postoperative pain, and analgesia significantly influence EA occurrence. A nomogram constructed using these factors demonstrates strong predictive accuracy., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: Melanoma, with its high degree of malignancy, stands as one of the most dangerous skin cancers and remains the primary cause of death from skin cancer. With studies demonstrating the potential of traditional Chinese medicine to intervene and treat melanoma, we turned our attention to celastrol. Celastrol is a triterpene compound extracted from the traditional Chinese medicine derived from Tripterygium wilfordii. Previous studies have shown that celastrol exerts inhibitory effects on various malignant tumors, including melanoma. Hence, our goal was to clarify the impact of celastrol on cell viability, apoptosis, and cell cycle progression by elucidating its effects on the PI3K/AKT/mTOR pathway., Methods: CCK-8 and wound healing assays were used to determine the effect of celastrol on the viability and migration of B16-F10 cells. Changes in cell apoptosis, cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential were detected by flow cytometry. PI3K/AKT/mTOR pathway proteins and HIF-α mRNA expression in B16-F10 cells were detected by western blotting and qPCR. Moreover, the addition of a PI3K activator demonstrated that celastrol could inhibit the function of B16-F10 cells via the PI3K/AKT/mTOR pathway., Results: Celastrol inhibited the viability and migration of B16-F10 cells. Through the inhibition of the PI3K/AKT/mTOR pathway down-regulates the expression of HIF-α mRNA, thereby causing an increase of ROS in cells and a decrease in the mitochondrial membrane potential to promote cell apoptosis and cell cycle arrest. The inhibitory effect of celastrol on B16-F10 cells was further demonstrated by co-culturing with a PI3K activator., Conclusion: Celastrol inhibits the function of B16-F10 cells by inhibiting the PI3K/AKT/mTOR cellular pathway and regulating the expression of downstream HIF-α mRNA., (© 2024. The Author(s).)

Drinking water treatment sludge (DWTS) is a by-product of water treatment, and it is difficult to recycle to high value and poses potential environmental risks. Recycling DWTS into cement-based materials is an effective measure to achieve its high-volume utilization and reduce its environmental load. DWTS is rich in silica-alumina phases and has potential pozzolanic activity after drying, grinding and calcination, giving it similar properties to traditional supplementary cementitious materials. Adjusting the sludge production process and coagulant type will change its physical and chemical properties. Adding a small amount of DWTS can generate additional hydration products and refine the pore structure of the cement sample, thus improving the mechanical properties and durability of the sample. However, adding high-volume DWTS to concrete causes microstructural deterioration, but it is feasible to use high-volume DWTS to produce artificial aggregates, lightweight concrete, and sintered bricks. Meanwhile, calcined DWTS has similar compositions to clay, which makes it a potential raw material for cement clinker production. Cement-based materials can effectively solidify heavy metal ions in DWTS, and alkali-activated binders, magnesium-based cement, and carbon curing technology can further reduce the risk of heavy metal leaching. This review provides support for the high-value utilization of DWTS in cement-based materials and the reduction of its potential environmental risks., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Ventricular arrhythmias (VAs) mainly occur in the early post-myocardial infarction (MI) period. However, studies examining the association between total myocardial ischemia time interval and the risk of new-onset VAs during a long-term follow-up are scarce., Methods: This study (symptom-to-balloon time and VE ntricular a R rh Y thmias in patients with STEMI , VERY-STEMI study) was a multicenter, observational cohort and real-world study, which included patients with ST-segment elevation MI (STEMI) undergoing percutaneous coronary intervention (PCI). The primary endpoint was cumulative new-onset VAs during follow-up. The secondary endpoints were the major adverse cardiovascular events (MACE) and changes in left ventricular ejection fraction (ΔLVEF, %)., Results: A total of 517 patients with STEMI were included and 236 primary endpoint events occurred. After multivariable adjustments, compared to patients with S2BT of 24 h-7d, those with S2BT ≤ 24 h and S2BT > 7d had a lower risk of primary endpoint. RCS showed an inverted U-shaped relationship between S2BT and the primary endpoint, with an S2BT of 68.4 h at the inflection point. Patients with S2BT ≤ 24 h were associated with a lower risk of MACE and a 4.44 increase in LVEF, while there was no significant difference in MACE and LVEF change between the S2BT > 7d group and S2BT of 24 h-7d group., Conclusions: S2BT of 24 h-7d in STEMI patients was associated with a higher risk of VAs during follow-up. There was an inverted U-shaped relationship between S2BT and VAs, with the highest risk at an S2BT of 68.4 h., Competing Interests: 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., (© 2024 The Authors.)

The world's population is ageing at a rate unprecedented in human history. As the number of older people increases, so does the prevalence of lung disease in the elderly, making it essential to understand the pathophysiology of elderly patients with lung disease. Age-related changes in immune system function and lung parenchyma occur throughout a person's life. Immunosenescence refers to the tendency for innate and adaptive immunity to decline in the elderly. As we age, changes in the innate and adaptive immune systems can lead to dysregulation and reduced immune function. A low-level chronic inflammatory state is known as inflamm-aging and is driven by immunosenescence. This review discusses the role of immunosenescence and inflamm-aging in pulmonary diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and lung infections. Understanding the different manifestations of lung diseases between the elderly and the young, finding new therapeutic sites, or improving clinical outcomes in hospitalized patients will provide clinicians with new ideas.

Background: Hepatocellular carcinoma (HCC) remains a leading life-threatening health challenge worldwide, with pressing needs for novel therapeutic strategies. Sphingosine kinase 1 (SphK1), a well-established pro-cancer enzyme, is aberrantly overexpressed in a multitude of malignancies, including HCC. Our previous research has shown that genetic ablation of Sphk1 mitigates HCC progression in mice. Therefore, the development of PF-543, a highly selective SphK1 inhibitor, opens a new avenue for HCC treatment. However, the anti-cancer efficacy of PF-543 has not yet been investigated in primary cancer models in vivo, thereby limiting its further translation., Methods: Building upon the identification of the active form of SphK1 as a viable therapeutic target in human HCC specimens, we assessed the capacity of PF-543 in suppressing tumor progression using a diethylnitrosamine-induced mouse model of primary HCC. We further delineated its underlying mechanisms in both HCC and endothelial cells. Key findings were validated in Sphk1 knockout mice and lentiviral-mediated SphK1 knockdown cells., Results: SphK1 activity was found to be elevated in human HCC tissues. Administration of PF-543 effectively abrogated hepatic SphK1 activity and significantly suppressed HCC progression in diethylnitrosamine-treated mice. The primary mechanism of action was through the inhibition of tumor neovascularization, as PF-543 disrupted endothelial cell angiogenesis even in a pro-angiogenic milieu. Mechanistically, PF-543 induced proteasomal degradation of the critical glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, thus restricting the energy supply essential for tumor angiogenesis. These effects of PF-543 could be reversed upon S1P supplementation in an S1P receptor-dependent manner., Conclusions: This study provides the first in vivo evidence supporting the potential of PF-543 as an effective anti-HCC agent. It also uncovers previously undescribed links between the pro-cancer, pro-angiogenic and pro-glycolytic roles of the SphK1/S1P/S1P receptor axis. Importantly, unlike conventional anti-HCC drugs that target individual pro-angiogenic drivers, PF-543 impairs the PFKFB3-dictated glycolytic energy engine that fuels tumor angiogenesis, representing a novel and potentially safer therapeutic strategy for HCC., (© 2024. The Author(s).)

Background: Waist circumference can be used as an anthropometric measure to assess central obesity and is easier and more convenient than the waist-to-hip ratio in identifying the risk of obesity and medical problems. Most studies showing an association between obesity and infertility in women have used BMI to measure obesity. Our goal was to examine any potential association between waist circumference and infertility., Methods: This cross-sectional study, which formed part of the National Health and Nutrition Examination Survey (NHANES), comprised women ages 18 to 45 between 2017 and 2020. Participants without waist circumference data or information on infertility were removed from the study. The independent relationship between waist circumference and infertility was investigated using weighted binary logistic regression and subgroup analysis., Results: We investigated 1509 participants and discovered that the prevalence of infertility rose as the WC trisection rose. (tertile 1, 7.55%; tertile 2, 10.56%; tertile 3, 15.28%; trend < 0.001). Multivariate logistic regression showed that after total adjustment, higher WC levels were associated with an increased likelihood of infertility in women (OR1.02; 95% CI 1.01-1.03), and There was a 2% rise in the incidence of infertility for every unit (cm) increased WC. Subgroup analysis and interaction tests showed no significant dependence of the effects of marital status, diabetes, hypertension, and high cholesterol on the association between WC and infertility ( p for all interaction tests > 0.05). The inflection point of the positive non-linear relationship between WC and infertility was 116.6 cm., Conclusion: Excessive waist circumference assessment may increase the probability of infertility, and more attention should be paid to the management of waist circumference should be given more attention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yin, Zhou, Lu, Chen, Liu, Lu, Han and Wu.)

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P >0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

Background: Combinatorial immunotherapy strategies for enhancing the responsiveness of immune system have shown great promise for cancer therapy. Engineered nanoformulation incorporated toll-like receptor (TLR) 9 agonist CpG ODN has shown more positive results in suppressing tumor growth and can significantly enhance other immunotherapy activity with combinatorial effects due to the innate and adaptive immunostimulatory effects of CpG., Results: In the present work, protamine sulfate (PS) and carboxymethyl β-glucan (CMG) were used as nanomaterials to form nanoparticles through a self-assembly approach for CpG ODN encapsulation to generate CpG ODN-loaded nano-adjuvant (CNPs), which was subsequently mixed with the mixture of mouse melanoma-derived antigens of tumor cell lysates (TCL) and neoantigens to develop vaccine for anti-tumor immunotherapy. The obtained results showed that CNPs was able to effectively deliver CpG ODN into murine bone marrow-derived dendritic cells (DC) in vitro, and remarkably stimulate the maturation of DC cells with proinflammatory cytokine secretion. In addition, in vivo analysis showed that CNPs enhanced anti-tumor activity of PD1 antibody and CNPs-adjuvanted vaccine based on the mixture antigens of melanoma TCL and melanoma-specific neoantigen could not only induce anti-melanoma cellular immune responses, but also elicit melanoma specific humoral immune responses, which significantly inhibited xenograft tumor growth. Furthermore, CD16 CAR-T cells were generated by expressing CD16-CAR in CD3 + CD8 + murine T cells., Conclusion: Our results eventually showed that anti-melanoma antibodies induced by CNPs-adjuvanted TCL vaccines were able to collaborate with CD16-CAR-T cells to generate an enhanced targeted anti-tumor effects through ADCC (antibody dependent cell cytotoxicity) approach. CD16 CAR-T cells has thus a great potential to be an universal promising strategy targeting on solid tumor synergistic immunotherapy via co-operation with TCL-based vaccine., (© 2023. The Author(s).)

Background: Left ventricular thrombus is a rare condition, for which appropriate treatments are not extensively studied. Although it can be treated by thrombectomy, such surgery can be difficult and risky, and not every patient can tolerate the surgery., Case Summary: We report a case of a middle-aged man receiving veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for acute myocardial infarction who developed left ventricular thrombus despite systemic anticoagulation. After systemic thrombolysis with urokinase, the left ventricular thrombus disappeared, ECMO was successfully withdrawn 9 days later, and the patient recovered and was discharged from hospital., Conclusion: Systemic thrombolysis is a treatment option for left ventricular thrombus in addition to anticoagulation and thrombectomy., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

For eutrophic water bodies, potassium permanganate is an effective pre-oxidant to remove algae and its residue in water treatment sludge. Recycling water treatment sludge in concrete is an environmentally friendly and high-value utilization measure. However, little research has been done on the effect of manganese-rich drinking water sludge ash (DWSA) on concrete. The effect of water-binder ratio (w/b) on strength, shrinkage and microstructural characteristics of concrete containing DWSA was investigated, and the structural behavior was explained from a nanoscale perspective. The results show that recycling 10 % DWSA in concrete improved the strength and shrinkage resistance of the samples. Reducing the w/b effectively increased the strength of DWSA-modified concrete and reduced the shrinkage deformation. The paste with high w/b had higher contents of non-evaporated water and calcium hydroxide, as well as higher reaction degree of DWSA. Nanoscale characterization shows that reducing the w/b reduced the volume fraction of pore and unhydrated phases in the matrix and increased the proportion of high-density C-S-H. Meanwhile, reducing the w/b also reduced the interfacial transition zone width of DWSA-modified concrete. Recycling DWSA in concrete effectively reduced the total carbon footprint and cost of the mixture. The combined application of reducing the w/b and incorporating DWSA effectively improved the economic and environmental benefits of concrete material. For the concrete modified with 10 % DWSA (w/b = 0.3), its cost and carbon emissions are reduced by 14 %-21 % and 19 %-25 % compared with the reference sample, respectively. Overall, this study reveals the action mechanism of DWSA in cement system at different w/b from nanoscale perspective, and gives a new insight on determining the optimal w/b in full-scale application of DWSA concrete., 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 © 2023 Elsevier B.V. All rights reserved.)

Cue-induced food cravings are strong desires directed toward specific foods, usually ones with high caloric content, and can lead to overeating. However, although food cravings vary according to individual preferences for specific high-calorie food subtypes, a structured library of food craving-inducing pictures including multiple categories of high-calorie foods does not yet exist. Here, we developed and validated a picture library of Chinese foods (PLCF) consisting of five subtypes of high-calorie foods (i.e., sweets, starches, salty foods, fatty foods, and sugary drinks) to allow for more nuanced future investigations in food craving research, particularly in Chinese cultural contexts. We collected 100 food images representing these five subtypes, with four food items per subtype depicted in five high-resolution photographs each. We recruited 241 individuals with overweight or obesity to rate the food pictures based on craving, familiarity, valence, and arousal dimensions. Of these participants, 213 reported the severity of problematic eating behaviors as a clinical characteristic. Under the condition of mixing multiple subtypes of high-calorie foods, we did not observe significant differences in craving ratings for high- and low-calorie food images ( p tukey > 0.05). Then, we compared each subtype of high-calorie food images to low-calorie ones, and found craving ratings were greater for the images of salty foods and sugary drinks ( ps < 0.05). Furthermore, we conducted a subgroup analysis of individuals according to whether they did or did not meet the criteria for food addiction (FA) and found that greater cravings induced by the images of high-calorie food subtypes (i.e., salty foods and sugary drinks) only appeared in the subgroup that met the FA criteria. The results show that the PLCF is practical for investigating food cravings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cai, Zhang, Zheng, Xu, Liu, Ban, Di, Yuan and Han.)

Objectives: Excessive accumulation of adipose tissue may accelerate brain aging, but the underlying mechanisms are poorly understood. Several adiposity indices were proposed to assess obesity, while their linkage with brain health in older adults remained unclear. Here we aimed to examine the associations of adiposity indices with global and regional cerebral blood flow (CBF) in older adults, while considering insulin resistance., Design: This was a cross-sectional population-based study that included older adults derived from the baseline participants in the ongoing Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-China) study., Setting and Participants: The study included 103 Chinese rural-dwelling older adults (age≥60 years; 69.9% women) who underwent brain magnetic resonance imaging scans., Methods: We estimated eight adiposity indices based on anthropometric measures. We automatically quantified global and regional CBF using the arterial spin labeling scans. Insulin resistance was assessed using the triglyceride-glucose index and then dichotomized into high and low levels according to the median. Data were analyzed using general linear model and voxel-wise analysis., Results: Of the eight examined adiposity indices, only higher waist-to-height ratio (WHtR) and body roundness index (BRI) were associated with reduced global CBF (multivariable-adjusted β-coefficients and 95%CI: -1.76; -3.25, -0.27 and -1.77; -3.25, -0.30, respectively) and hypoperfusion in bilateral middle temporal gyri, angular gyri and superior temporal gyri, left middle cingulum and precuneus (P<0.05). There were statistical interactions of WHtR and BRI with levels of insulin resistance on CBF, such that the significant associations of higher WHtR and BRI with lower global and regional CBF existed only in people with high insulin resistance (P<0.05)., Conclusion: Higher WHtR and BRI are associated with cerebral hypoperfusion in older adults, especially in people with high insulin resistance. This may highlight the pathological role of visceral fat in vascular brain aging., Competing Interests: All authors declare no conflicts of interest.

Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer, the third leading cause of cancer-associated death worldwide. With the increasing prevalence of metabolic conditions, non-alcoholic fatty liver disease (NAFLD) is emerging as the fastest-growing HCC risk factor, and it imposes an additional layer of difficulty in HCC management. Dysregulated hepatic lipids are generally believed to constitute a deleterious environment cultivating the development of NAFLD-associated HCC. However, exactly which lipids or lipid regulators drive this process remains elusive. We report herein that sphingosine kinase 2 (SphK2), a key sphingolipid metabolic enzyme, plays a critical role in NAFLD-associated HCC. Ablation of Sphk2 suppressed HCC development in NAFLD livers via inhibition of hepatocyte proliferation both in vivo and in vitro. Mechanistically, SphK2 deficiency led to downregulation of ceramide transfer protein (CERT) that, in turn, decreased the ratio of pro-cancer sphingomyelin (SM) to anti-cancer ceramide. Overexpression of CERT restored hepatocyte proliferation, colony growth and cell cycle progression. In conclusion, the current study demonstrates that SphK2 is an essential lipid regulator in NAFLD-associated HCC, providing experimental evidence to support clinical trials of SphK2 inhibitors as systemic therapies against HCC., (© 2022. The Author(s).)

The present study revealed that palmitic acid (PA) treatment induced epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, which are involved in the progression of proliferative vitreoretinopathy (PVR). ARPE-19 cells were treated with PA followed by miRNA screening and EMT marker detection using qRT-PCR. Then, miR-124 mimic or inhibitor was transfected into ARPE-19 cells to explore the role of miR-124 on the EMT of ARPE-19 cells using transwell assay. The underlying mechanism of miRNA were predicted by bioinformatics method and confirmed by luciferase activity reporter assay. Furthermore, gain-of-function strategy was also used to explore the role of LIN7C in the EMT of ARPE-19 cells. The expression of miRNA or mRNA expression was determined by qRT-PCR and the protein expression was determined using western blot assay. The result presented that PA reduced the expression of E-cadherin/ZO-1 whilst increasing the expression of fibronectin/α-SMA. In addition, PA treatment enhanced the expression of microRNA (miR)-124 in ARPE-19 cells. Overexpression of miR-124 enhanced PA-induced upregulation of E-cadherin and ZO-1 expression and downregulation of fibronectin and α-SMA. Moreover, miR-124 mimic also enhanced the migration of ARPE-19 cells induced by PA treatment. Inversely, miR-124 inhibitor presented opposite effect on PA-induced EMT and cell migration in ARPE-19 cells. Luciferase activity reporter assay confirmed that Lin-7 homolog C (LIN7C) was a direct target of miR-124 in ARPE-19 cells. Overexpression of LIN7C was found to suppress the migration ability and expression of fibronectin and α-SMA, while increasing expression of E-cadherin and ZO-1; miR-124 mimic abrogated the inhibitive effect of LIN7C on the EMT of ARPE-19 cells and PA further enhanced this abolishment. Collectively, these findings suggest that miR-124/LIN7C can modulate EMT and cell migration in RPE cells, which may have therapeutic implications in the management of PVR diseases., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Han et al.)

Coronavirus disease (COVID-19) and tuberculosis (TB) are two respiratory infectious diseases with a high incidence of transmission, mainly via respiratory droplets and both can weaken the immune system and lower the number of CD4 + T cells in patients. COVID-19 can occur before, at the same time or after the diagnosis of TB. Patients with pulmonary TB are more likely to have co-infection when they have a history of epidemiological exposure to COVID-19. At present, many cases of nosocomial infection of COVID-19 caused by ineffective prevention and control measures in tuberculosis hospitals have been reported successively at domestic and overseas. Therefore, it is urgent to strengthen the prevention and control of nosocomial infections in tuberculosis hospitals. The superposition of the two diseases can lead to a worsening prognosis, aggravating the patient's condition and making treatment more difficult. In addition, in the context of the new coronavirus epidemic, early recognition of co-infection with new coronavirus should be made when TB patients in chest hospitals present with symptoms such as aggregated fever or progressive disease. At the same time, we should focus on identifying the clinical and imaging manifestations of TB and COVID-19 co-infection. At present, research on COVID-19 complicated with pulmonary TB is scarce, and there are disputes on many aspects. As a country with a high prevalence of tuberculosis, it is of great practical significance to identify the clinical characteristics, outcomes, and treatment of the two infectious diseases in China.

Impulsiveness is a stable personal characteristic that contributes to obesity and may interact with it. Specifically, obesity is caused by unrestrained impulse eating that is not consciously controlled and leads to a hormonal imbalance that also can impair impulse control. However, the mechanism of this relationship is unclear. In our study, 35 obese individuals (body mass index, BMI > 28) were recruited and matched with 31 healthy controls (BMI < 24) in age and education level. All the participants underwent a resting-state fMRI and completed the Barratt Impulsiveness Scale-11. The results showed that patients with obesity had a significantly lower fractional amplitude of low-frequency fluctuations (fALFF) in the bilateral dorsolateral prefrontal cortex (dlPFC) and higher fALFF in the left fusiform cortex. In addition, non-planning impulsiveness was positively correlated with BMI. Importantly, we found that the right dlPFC completely mediated the relationship between non-planning impulsiveness and BMI. Our findings suggest that impulsivity is statistically more likely to precede obesity than to precede impulsivity and contributes to obesity by downregulating spontaneous activity in the dlPFC. This suggests that the dlPFC, which is associated with executive control, may be able a potential target for treating obesity., Competing Interests: QL was employed in Siemens Healthcare Ltd. The remaining 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 Han, Zhang, Xu, Liu, Cai, Liu, Li, Zheng, Xu and Yuan.)

We report here that polysubstituted cyclopent-2-enols can be constructed by the one-pot reaction of doubly activated cyclopropanes and α-EWG substituted acetonitriles under mild basic conditions via a domino-ring-opening-cyclization/deacylation/oxidation sequence. Moreover, the synthetic applications of these cyclopent-2-enols have been demonstrated in the late-stage derivatization into functionalized cyclopentapyrimidin-4-ones and 2-hydroxy cyclopentanones with good yields.

Introduction: Sepsis is a primary cause of death in critically ill patients and is characterized by multiple organ dysfunction, including sepsis-induced acute kidney injury (AKI), which contributes to high mortality in sepsis. However, its pathophysiological mechanisms remain unclear. The kidney has one of the richest and most diversified endothelial cell populations in the body. This study was designed to investigate the effects of endothelial dysfunction in sepsis-induced AKI and explore possible intervention measures to offer new insight into the pathogenesis and treatment of sepsis-induced AKI., Methods: The circulating levels of endothelial adhesion molecules were detected in patients with sepsis and healthy controls to observe the role of endothelial damage in sepsis and sepsis-induced AKI. A murine sepsis model induced by cecal ligation and perforation was pretreated with a phosphoinositide 3-kinase gamma (PI3Kγ) inhibitor (CZC24832), and survival, kidney damage, and renal endothelial injury were assessed by pathological examination, immunohistochemistry, quantitative polymerase chain reaction, and Western blotting. Lipopolysaccharides and CZC24832 were administered to human umbilical vein endothelial cells in vitro, and endothelial cell function and the expression of adhesion molecules were evaluated., Results: Endothelial damage was more serious in sepsis-induced AKI than that in non-AKI, and the inhibition of PI3Kγ alleviates renal endothelial injury in a murine sepsis model, protecting endothelial cell function and repairing endothelial cell injury through the Akt signaling pathway., Conclusions: In this study, endothelial cell dysfunction plays an important role in sepsis-induced AKI, and the inhibition of PI3Kγ alleviates endothelial cell injury in sepsis-induced AKI through the PI3Kγ/Akt pathway, providing novel targets for treating sepsis and related kidney injury., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Periodontitis is an inflammatory disease resulting from subgingival microorganisms. Human periodontal ligament stem cells (hPDLSCs) can be applied in periodontal tissue regeneration. This study investigated the effect of hPDLSC-derived extracellular vesicles (EVs) on periodontitis. hPDLSC-derived EVs were isolated and identified. The murine model of periodontitis was established by ligation, and the cell model of periodontitis was established by treatment of macrophages with lipopolysaccharide (LPS). The effects of EVs on macrophage pyroptosis and periodontal inflammatory injury were measured by the means of HE staining, detection of LDH content, CCK-8 assay, Calcein-AM/PI staining, ELISA, Western blot, as well as measurement of caspase-1, SOD, and MDA. miR-590-3p expression was detected using RT-qPCR. miR-590-3p expression was then intervened to validate the effect of miR-590-3p on macrophage pyroptosis. The binding relationship between miR-590-3p and TLR4 was verified using dual-luciferase assay. Functional rescue experiment was performed to validate the role of TLR4 in macrophage pyroptosis. The results showed that inflammatory levels and macrophage pyroptosis were enhanced in the in vivo and in vitro models of periodontitis, evidenced by the increased NLRP3, GSDMD-N, caspase-1, IL-1β, IL-18, TNF-α, and MDA and decreased IL-10 and SOD. EVs alleviated periodontal inflammatory injury and macrophage pyroptosis. Physiologically, EVs carried miR-590-3p into macrophages to upregulate miR-590-3p expression and thereby suppress TLR4 transcription. miR-590-3p silencing or TLR4 overexpression reduced the inhibitory effect of EVs on macrophage pyroptosis. Collectively, EVs carried miR-590-3p into macrophages to subsequently inhibit TLR4 transcription, thereby reducing macrophage pyroptosis and alleviating periodontal inflammatory injury., (© 2021 S. Karger AG, Basel.)

Objective: To study the clinical efficacy and complications of Endobutton titanium plate and clavicle hook plate in the treatment of acromioclavicular dislocation., Methods: Total 48 patients with Rockwood Ⅲ to Ⅴ acromioclavicular joint dislocation from March 2015 to May 2019 were retrospectively divided into two groups according to different surgical methods. Among the patients, 23 patients were treated with Endobutton loop titanium plate fixation (observation group), including 15 males and 8 females, ranging in age from 23 to 59 years old, with an average of(36.2±8.1) years old;Rockwood type Ⅲ in 6 cases, type Ⅳ in 11 cases and type Ⅴ in 6 cases. Twenty-five patients were treated with clavicular hook plate(control group), including 17 males and 8 females, ranging in age from 22 to 54 years old, with an average of (34.7±6.4) years old; Rockwood type Ⅲ in 6 cases, type Ⅳ in 14 cases and type Ⅴ in 5 cases. The operation time, intraoperative bleeding, hospitalization time, visual analogue scale (VAS) of pain, Constant-Murley score of shoulder function and postoperative complications were compared between the two groups., Results: All the patients were followed up, and the duration ranged from 24 to 51 months, with a mean of (30.5±6.5) months. The amountof bleeding and hospitalization time in the observation group were (71.9±4.0) ml and(8.2±1.6) d respectively;and those in the control group were (97.6±13.4) ml and (12.8±1.2) d respectively. There was significant difference between the two groups ( P <0.05). There was no significant difference in operation time between the two groups( P >0.05). The VAS scores of the observation group immediately after operation and 12 months after operation were 4.00±0.39 and 1.58±0.13 respectively, which were statistically significant compared with 7.32±0.43 and 3.09±0.23 in the control group ( P <0.05). The Constant-Murley scores of shoulder function in the observation group were 59.65±0.15 and 85.97 ±0.73 immediately and 12 months after operation, which were significantly different from those in the control group 52.77±0.19 and 55.78±0.19( P <0.05). In the observation group, there were 1 case of shoulder pain and 1 case of ectopic ossification; in the control group, there were 1 case of internal fixation failure, 3 cases of acromion impact, 3 cases of shoulder pain and 3 cases of ectopic ossification. There was significant difference between the two groups ( P <0.05)., Conclusion: Compared with clavicular hook plate internal fixation in the treatment of acromioclavicular joint dislocation, Endobutton loop titanium plate internal fixation technology has the advantages of less surgical bleeding, shorter hospitalization time, less postoperative pain, good recovery of shoulder joint function and less complications.

Objective: To discuss the diagnostic value of calcitonin(CT), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), pro-gastrin releasing peptide (Pro-GRP) and chromogranin A (CgA) in the identification of medullary thyroid carcinoma (MTC). Methods: The CT levels in 105 cases of MTC, 50 cases of papillary thyroid carcinoma, 10 cases of thyroid follicular carcinoma, 5 cases of undifferentiated thyroid carcinoma, 50 cases of benign thyroid diseases, 30 cases of non-thyroid malignant tumors and 50 cases of healthy controls were measured from February 2017 to August 2019 at the Department of Clinical Laboratory, Cancer Hospital affliated to Fudan University. Additionally, 79 cases of MTC, 30 cases of non-MTC thyroid malignant tumors and 30 healthy controls were selected for the measurement of CEA, NSE, Pro-GRP and CgA levels. The receiver operating curve was utilized to clarify the area under the curve (AUC), sensitivity, and specificity of each indicator to distinguish between different groups. Results: The medians of CT concentrations in the group of MTC patients was 607.2 (152.5,2 777.5)pg/ml, which was statistically significantly higher than that of the subjects in the group of papillary thyroid carcinoma 1.48 (0.5,2.91)pg/ml, follicular thyroid carcinoma 1.90 (0.82,2.99)pg/ml, undifferentiated thyroid carcinoma 0.50 (0.50,4.93)pg/ml, benign thyroid disease 1.30 (0.50,2.79)pg/ml, non-thyroid malignancies 1.36 (0.50,2.89)pg/ml and healthy controls 2.05 (0.89,3.18)pg/ml. The sensitivity, specificity and AUC of CT to distinguish MTC vs. non-MTC patients was 96.2%, 99.3% and 0.99, respectively. The maximum diameter (>1 cm, P =0.001, OR =15.74) and number (>1, P =0.04, OR =3.4) of nodules were two independent risk factors for elevated CT. CEA (AUC=0.94), NSE (AUC=0.65), Pro-GRP (AUC=0.94) and CgA (AUC=0.83) could all distinguish MTC vs. non-MTC thyroid malignancies. The AUC, sensitivity and specificity by combining CT, CEA, NSE, Pro-GRP and CgA to differentiate MTC vs. non-MTC thyroid malignancies was 1, 100% and 100%, respectively. Conclusions: CT, CEA, NSE, Pro-GRP and CgA may be helpful for the auxiliary diagnosis of MTC. The combination of these indicators in the diagnosis of MTC has high sensitivity and specificity.

K. galanga is an aromatic medicinal herb. It is locally to India and distributed in China, Myanmar, Indonesia, Malaysia, and Thailand. K. galanga is a Traditional Chinese Herb Medicine (TCHM), which has been applied to treat cold, dry cough, toothaches, rheumatism, hypertension and so on. In addition, it has been used widely as spices since its highly aromas. The aim of this review is to compile and update the current progresses of ethnomedicinal uses, phytochemistry, pharmacology and toxicology of K. galanga . All the data on K. galanga were based on different classical literary works, multiple electronic databases including SciFinder, Web of Science, PubMed, etc. The results showed that ninety-seven compounds have been identified from rhizome of K. galanga , including terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids and esters. Modern pharmacology studies revealed that extracts or secondary metabolites of the herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, and anti-angiogenesis effects, which were closely related to its abundant ethnomedicinal uses. In conclusion, although previous research works have provided various information of K. galanga , more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb., 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 © 2021 Wang, Zhao, Xu, Han, Wu, Xu, Yang, Göransson and Liu.)

Background: Pseudomyxoma peritonei (PMP) is a rare mucinous neoplasm with a relatively low incidence of 1 to 2 per million individuals. It is typically characterized by a type of gelatinous ascites named "jelly belly". Most cases of PMP occur in association with ruptured primary mucinous tumors of the appendix (90%). Periodically, PMP can originate from mucinous carcinomas at other sites, including the colorectum, gallbladder, and pancreas. However, unusual origin can occur, as noted in this case report., Case Summary: A 52-year-old woman had an unusual derivation of PMP from intestinal duplication. The patient complained of abdominal distension and increasing abdominal girth. Abdominal contrast-enhanced computed tomography showed a mass in the greater omentum located on the left side of the abdomen, likely to be a cystic mass of peritoneal origin. A PMP diagnosis was presumed based on the specific signs of the mass with flocculent and stripe-like echoes in ultrasound images. Ultrasound-guided percutaneous aspiration suggested a high likelihood of PMP. Once the PMP diagnosis was recognized, identification of the origin of the primary tumor was indicated. Thus, an exploratory laparoscopy was performed. In the absence of a primary tumor of appendix origin, the diagnosis of a low-grade mucinous neoplasm of intestinal duplication origin was finally confirmed by histopathology., Conclusion: PMP is secondary to mucinous carcinomas of the appendix mostly. This case resulted from an unusual derivation from intestinal duplication., Competing Interests: Conflict-of-interest statement: All authors report no conflicts of interest related to this manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Smoking and Candida albicans (C. albicans) infection are risk factors for many oral diseases. Several studies have reported a close relationship between smoking and the occurrence of C. albicans infection. However, the exact underlying mechanism of this relationship remains unclear. We established a rat infection model and a C. albicans-Leuk1 epithelial cell co-culture model with and without smoke exposure to investigate the mechanism by which smoking contributes to C. albicans infection. Oral mucosa samples from healthy individuals and patients with oral leucoplakia were also analysed according to their smoking status. Our results indicated that smoking induced oxidative stress and redox dysfunction in the oral mucosa. Smoking-induced Nrf2 negatively regulated the NLRP3 inflammasome, impaired the oral mucosal defence response and increased the oral mucosa susceptibility to C. albicans. The results suggest that the Nrf2 pathway could be involved in the pathogenesis of oral diseases by mediating an antioxidative response to cigarette smoke exposure and suppressing host immunity against C. albicans., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Purpose: To investigate the correlation of clinicopathologic factors and immunophenotypic features with betel nut chewing in oral squamous cell carcinoma(OSCC)., Methods: The data of 88 patients with OSCC were collected. According to the habit of betel nut chewing, the clinicopathologic factors and immunohistochemical parameters were analyzed. The relationship between clinicopathologic factors of OSCC and betel nut chewing was analyzed with univariate analysis and multivariate analysis using SPSS 17.0 software package., Results: 46.6% of patients had the habit of betel nut chewing and 67.0% of patients had tongue cancer and buccal cancer. The pathological stages were mainly T2 (40.9%). From univariate analysis of the results, differentiation degree, ki-67, p53 was significantly correlated with the habit of betel nut chewing(P<0.05); while gender, age, location, pathological T stage and cervical lymph node metastasis were not significantly correlated with habit of betel nut chewing (P>0.05). From multivariate analysis of the results, location and differentiation degree were significantly correlated with the habit of betel nut chewing (P<0.05)., Conclusions: ki-67 and p53 protein are lowly expressed in OSCC patients with the habit of betel nut chewing, suggesting that clinicopathologic factors such as the proliferation activity, malignancy, differentiation and prognosis of tumor are much better. Differentiation degree are relatively good in OSCC patients with the habit of betel nut chewing. Cheek and tongue are the most common site of OSCC.

Thirty mice were used to establish a sepsis model with cecal ligation and puncture. 15 mg/kg methylene blue or isotonic saline were injected intraperitoneally to observe liver tissue pathological changes. Changes in macrophage frequency and expressional condition of M1 and M2-type hepatic inflammatory factors were detected. After LPS stimulation, the expression level of macrophage inflammatory factor were detected. The results showed that the pathological liver injury was significantly reduced in the MB mice group ( P < 0.05), and the frequency of liver macrophage was not statistically significantly different ( P > 0.05). MB elevation had promoted the expression of M2-type hepatic inflammatory factor ( P < 0.05) and macrophage inflammatory factor ( P < 0.05). MB can play a role in preventing septic liver injury by inducing macrophages polarization to M2-type.

We report here that a series of bridged O,O-ketal fused spiro piperidone-cyclopropane derivatives 3 can be constructed with excellent yields and good diastereoselectivity by the one-pot reaction of 1-acylcyclopropanecarboxamides 1 with electron-deficient alkene 2a (EWG = CHO) via the domino process involving [4 + 2] annulation/intermolecular electrophilic addition/intramolecular cyclization. Furthermore, reactions of 1 with 2b/2c (EWG = CN, COOMe), leading to spiro piperidone-cyclopropane derivatives 4 or 5 by base catalyst selection, were also presented.

The screening of marker compound is of great significance to the quality control of traditional Chinese medicine (TCM). One approach which combines fingerprint and biological evaluation has developed rapidly. Multi-wavelength fusion fingerprints and antioxidant activity screening are integrated in this study to evaluate the quality of NAODESHENG. Characteristic multiwavelength fusion fingerprints of 14 batches of samples were generated at five different wavelengths and evaluated by quantitative fingerprinting with ultra-performance liquid chromatography (UPLC). In the quantitative fingerprinting method, 21 components in NAODESHENG were qualitatively and quantitatively analyzed by external standard method. The antioxidant activities of these 21 components was determined by pre-column antioxidant activity test. Multivariate statistical methods such as hierarchical clustering analysis and principal component analysis(PCA) was used to reduce the dimensions and variables from a large number of original data to screening marker compound with bioactivity. Based on the above results, it is suggested that 3'-Methoxy Puerarin and 11 other components should be used as the quality marker of NAODESHENG. This study demonstrates the feasibility of multi-wavelength fusion fingerprinting combined with antioxidant activity analysis, which associates quality control with bioactivity, providing a reliable and efficient method for quantitative assessment of TCM quality consistency., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Liver failure has high mortality and poor prognosis, and establishing new reliable markers for predicting its prognosis is necessary. Mucosal-associated invariant T (MAIT) cells are a novel population of innate-like lymphocytes involved in inflammatory liver disease, and their potential role in liver failure remains unclear., Aim: To investigate alteration of circulating MAIT cells and assess its prognostic value in patients with hepatitis B virus (HBV)-related liver failure., Methods: We recruited 55 patients with HBV-related liver failure, 48 patients with chronic hepatitis B and 40 healthy controls (HCs) from Nantong Third People's Hospital Affiliated to Nantong University. Peripheral blood mononuclear cells were isolated, and the percentage and number of circulating MAIT cells were detected by flow cytometry. Plasma levels of interleukin (IL)-7, IL-12p70, IL-18 and interferon-α were measured by Luminex assay., Results: Circulating MAIT cells were significantly decreased in HBV-related liver failure patients (percentage: 2.00 ± 1.22 vs 5.19 ± 1.27%, P < 0.0001; number: 5.47 ± 4.93 vs 84.43 ± 19.59, P < 0.0001) compared with HCs. More importantly, there was a significant reduction of MAIT cells in patients with middle/late-stage compared with early-stage liver failure. Circulating MAIT cells partially recovered after disease improvement, both in percentage (4.01 ± 1.21 vs 2.04 ± 0.95%, P < 0.0001) and in cell count (17.24 ± 8.56 vs 7.41 ± 4.99, P < 0.0001). The proportion (2.29 ± 1.01 vs 1.58 ± 1.38%, P < 0.05) and number (7.30 ± 5.70 vs 2.94 ± 1.47, P < 0.001) of circulating MAIT cells were significantly higher in the survival group than in the dead/liver transplantation group, and the Kaplan-Meier curve showed that lower expression of circulating MAIT cells (both percentage and cell count) predicted poor overall survival ( P < 0.01). Also, the levels of IL-12 (20.26 ± 5.42 pg/mL vs 17.76 ± 2.79 pg/mL, P = 0.01) and IL-18 (1470.05 ± 1525.38 pg/mL vs 362.99 ± 109.64 pg/mL, P < 0.0001) were dramatically increased in HBV-related liver failure patients compared with HCs., Conclusion: Circulating MAIT cells may play an important role in the process of HBV-related liver failure and can be an important prognostic marker., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ethnopharmacological Relevance: Tripterygium wilfordii Hook F. (TwHF), a traditional Chinese herb medicine, has been widely used for clinical treatment of various rheumatic immune diseases. Tripterygium glycosides (TG) extracted from TwHF has been verified to process multiple bioactivities, including immunosuppressive, anti-inflammatory and anti-cancer effects. However, the clinical application of TG is limited due to its severe toxicity and narrow therapeutic window. For the clinical safety of TG usage, attenuation of toxicity is the key issue to be solved., Purpose: Tripterygium glycoside fraction n2 (TG-n2) is a detoxified mixture obtained from TG using a new preparation method. In our previous study, we have demonstrated that TG-n2 has a lower toxicity than TG. The aim of the present study was to screen the renal protective effect of TG-n2 in nephrotic syndrome (NS) induced by adriamycin (ADR) in rats and its effect on apoptosis, as well as the effective difference between TG-n2 and TG., Materials and Methods: The ADR-induced NS rat model was established. Rats were intravenously injected with ADR (6 mg/kg), then treated with either TG-n2 (10 mg/kg/day) or TG (10 mg/kg/day) by oral gavage for 4 weeks. Clinical indexes in each group were determined. HE staining and electron microscopic analysis were used to evaluate renal histopathological damage. Caspase-3 activity reagent and TUNEL staining were used to estimate renal apoptosis. Protein levels of caspase-3, caspase-9, caspase-8, caspase-12, Bax, Bcl-2, p53, TNF-R1, FLIP and podocin were measured by Western Blot., Results: TG-n2 and TG intervention ameliorated renal function as assessed by the levels of 24-h proteinuria, Cr, BUN, TC, TG, ALB and LDL-c. TG-n2 and TG alleviated the decrease of podocin protein expression and morphological injury of podocyte as screened by Western Blot and electron microscopic analysis. Besides, renal tubular injury was reduced as inspected by light microscopic analysis. TG-n2 and TG could significantly inhibit the apoptosis and activity of caspase-3 in kidney tissues as examined by fluorescence microscopic analysis and reagent. After intervention of TG-n2 and TG, protein levels of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax, p53 and TNF-R1 in renal issues were significantly decreased compared with ADR group. In contrast, protein level of Bcl-2 was elevated remarkedly., Conclusions: Our data suggested that attenuated TG-n2 may have a similar protective effect with TG in ADR-induced NS in rats by inhibiting activation of apoptosis., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In previous report, polyvinyl alcohol/liquefied ball-milled chitin (PVA/LBMC) blend films with good antibacterial activity were successfully prepared. To further develop a biodegradable food packaging material, various amounts of nano-silica were introduced in situ by the hydrolysis of Na 2 SiO 3 to give a series of silica-reinforced PVA/LBMC blend films. Their structure, morphology, mechanical and thermal properties, food preservation and degradation behavior in soil were comprehensively characterized. The results showed that when the content of Na 2 SiO 3 was 0.2 wt %, the blend film 4PVA-LBMC-0.2Si displayed the optimized performance. Its tensile strength, and the maximum weight loss rate temperature reached 51 MPa and 307 ℃, respectively, which were significantly improved than those of silica-free film. The preservation tests of cherries showed its good fresh keeping performance. Although the degradation rate of silica-reinforced blend films in the soil was slightly decreased, it remained at a good level of 43 % after 30 days of burial., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Inconsistencies exist regarding the severity of illness caused by different influenza strains. The aim of this study was to compare the clinical outcomes of hospitalized adults and adolescents with influenza-related pneumonia (Flu-p) from type A and type B strains in China., Methods: We retrospectively reviewed data from Flu-p patients in five hospitals in China from January 2013 to May 2019. Multivariate logistic and Cox regression models were used to assess the effects of influenza virus subtypes on clinical outcomes, and to explore the risk factors of 30-day mortality for Flu-p patients., Results: In total, 963 laboratory-confirmed influenza A-related pneumonia (FluA-p) and 386 influenza B-related pneumonia (FluB-p) patients were included. Upon adjustment for confounders, multivariate logistic regression models showed that FluA-p was associated with an increased risk of invasive ventilation (adjusted odds ratio [aOR]: 3.824, 95% confidence interval [CI]: 2.279-6.414; P <  0.001), admittance to intensive care unit (aOR: 1.630, 95% CI: 1.074-2.473, P = 0.022) and 30-day mortality (aOR: 2.427, 95% CI: 1.568-3.756, P <  0.001) compared to FluB-p. Multivariate Cox regression models confirmed that influenza A virus infection (hazard ratio: 2.637, 95% CI: 1.134-6.131, P = 0.024) was an independent predictor for 30-day mortality in Flu-p patients., Conclusions: The severity of illness and clinical outcomes of FluA-p patients are more severe than FluB-p. This highlights the importance of identifying the virus strain during the management of severe influenza.

Objective: To explore the incidence, risk factors of cardiovascular events (CVE) and their impact on 30-day mortality in patients hospitalized with community-acquired pneumonia (CAP). Methods: This is a multicenter, retrospective study. Patients hospitalized with CAP from 5 teaching hospitals in Beijing, Shandong and Yunnan provinces during 1 January 2013 to 31 December 2015 were included and clinical data were retrieved from the Hospital Information System (HIS), and patients were divided into CVE group and non-CVE group. Age, sex, comorbidities, pneumonia severity index(PSI)/CURB-65 score, routine blood test, biochemical examinations, radiological findings on admission and mortality on 30-day after admission were analyzed. The primary endpoint was acute CVE during hospitalization, the secondary endpoint was 30-day death after admission. Multivariate Cox regression analysis was used to explore the risk factors for CVE. Kaplan-Meier survival curve was used to compare the difference on 30-day mortality between CVE patients and non-CVE patients by Log-rank test. Multivariate Cox regression model was used to assess the impact of CVE on the 30-day mortality among CAP patients after adjustment with age, sex, comorbidities, PSI/CURB-65 score. Results: A total of 3 561 CAP patients were included into the final analysis, including 210 (5.9%) patients in CVE group and 3 351 (94.1%) patients in non-CVE group. Compared with patients in non-CVE group, patients in CVE group were older ( P< 0.001), prevalence of hypertension, coronary heart disease, chronic heart failure, cerebrovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, aspiration risk and bedrid were significantly higher (all P< 0.001); prevalence of CURB-65 score 3-5 and PSI risk class Ⅳ/Ⅴ were also significantly higher (both P< 0.001). The proportion of axillary temperature<36 ℃, respiratory rate≥30 beats/minutes, confusion, leukocytes>10×10(9)/L, hemoglobin < 100 g/L, platelets>300×10(9)/L, albumin < 35 g/L, blood urea nitrogen > 7 mmol/L, fasting blood glucose>11 mmol/L, serum C-reaction protein > 100 mg/L, serum procalcitonin≥2 μg/L, arterial pH<7.35, arterial PO(2)/FiO(2)≤300 mmHg (1 mmHg=0.133 kPa), and multilobar infiltrates and pleural effusion on chest X-ray or CT scan were significantly higher in CVE group than in non-CVE group(all P< 0.05); the 30-day mortality was significantly higher in CVE group than in non-CVE group( P< 0.001). The incidence of CVE was significantly higher in patients with cardiovascular and cerebrovascular disease(CVD) than in patients without CVD (13.9%(150/1 079) vs. 2.4%(60/2 482), χ(2)=178.737, P< 0.001). Meanwhile, the incidence of CVE increased with PSI in patients with Ⅰ/Ⅱ, Ⅲ and Ⅳ/Ⅴ class, respectively(χ(2)=228.350, P< 0.001); and CURB-65 score 0-1, 2 and 3-5, respectively (χ(2)=387.154, P< 0.001). Cox regression analysis revealed that age ( HR =1.05, 95 %CI 1.02-1.09, P= 0.002), coronary heart disease ( HR =1.88, 95 %CI 1.01-3.51, P= 0.048), chronic heart failure ( HR =4.25, 95 %CI 1.89-9.52, P< 0.001), PSI risk class ( HR =1.66, 95 %CI 1.50-2.62, P= 0.029) and serum procalcitonin≥ 2 μg/L ( HR =3.72, 95 %CI 1.60-8.66, P= 0.002) were independent risk factors for CVE in CAP patients. Kaplan-Meier curve showed that the survival probability of patients with CVE was significantly lower than patients without CVE ( P< 0.001). After adjustment for age, sex, comorbidities and PSI/CURB-65 score, Cox regression model showed that CVE was associated with increased 30-day mortality in CAP patients ( HR =6.05, 95 %CI 3.11-11.76, P< 0.001). Conclusions: Although the incidence of CVE is not high in Chinese patients hospitalized with CAP, CVE is common in patients with severe pneumonia and in patients with CVD. Age, cardiovascular disease, PSI risk class and serum procalcitonin are the risk factors for CVE in this patient cohort. CVE is related to increased 30-day mortality in CAP patients.

Background: There are few comparative studies of the clinical outcomes after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). The aim of the study was to compare diabetes- and metabolic disorder-related outcomes following RYGB and SG, based on data for matched participants., Methods: This was a retrospective matched study using data from 2011-2018. Patients with type-2 diabetes undergoing RYGB (n=35) were matched with up to 2 RYGB participants (n=56) regarding age, sex, body mass index, hemoglobin A1c level, medication use, diabetes duration, and blood pressure., Results: All surgeries were performed laparoscopically without complications or malnutrition during 24 months of follow-up. Both surgical procedures achieved excellent diabetes remission and weight loss. RYGB was associated with a significantly higher diabetes medication discontinuation rate 24 months postoperatively (RYGB: 87.5% vs. SG: 68.6%; P<0.05), better reduction in serum cholesterol and low-density lipoprotein-c levels, as well as better diabetes control compared with SG. The incidence of microvascular and macrovascular complications showed no significant difference between two groups., Conclusions: In this matched retrospective study, although RYGB and SG were both excellent surgeries for treating obesity in patients with type-2 diabetes, RYGB was associated with better results compared with SG regarding dyslipidemia remission and metabolic disorder-related medication reduction., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Objective: To summarize the clinical and genetic characteristics of children with mitochondrial epilepsy. Methods: Clinical data of 62 children who were clinically and genetically diagnosed with mitochondrial epilepsy by the Department of Neurology, Beijing Children's Hospital from October 2011 to December 2018 were analyzed retrospectively, and the control of epilepsy was followed up. T test or χ(2) test were used to analyze the related factors affecting the prognosis of epilepsy between the effective group and the ineffective group. Results: Of the 62 patients, 33 were male and 29 were female. The age of onset was 3.38 (0-12.00) years; for the type of seizures, 68% (42/62) of the patients had focal seizures, generalized or secondary generalized tonic-clonic seizures were seen in 32% (20/62), myoclonic seizures in 23% (14/62), spastic seizures in 7 cases, tonic seizures in 4 cases, absence seizure, atonic seizure and clonic seizure in 1 case each; 16 cases (26%) had status epilepticus, of whom 6 cases had epilepsia partialis continua; 52% (32/62) had 2 or more types of seizures. The clinical phenotypes were mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) in 29 cases, Leigh syndrome (LS) in 11 cases, combined oxidative phosphorylation deficiency in 6 cases, myoclonus epilepsy with ragged-red fibers in 5 cases, Alpers syndrome in 4 cases, pontocerebellar hypoplasia type 6 and mitochondrial DNA depletion syndrome 9 in 2 cases each, mitochondrial complex Ⅰ deficiency nuclear type 20, progressive cavitating leukoencephalopathy, and biotinidase deficiency in 1 case each. Of the 62 cases, 40 cases (65%) had mitochondrial DNA (mtDNA) variations, of which 26 cases had m.3243A>G variants, 6 cases had m.8344A>G variants, and 3 cases had m.8993T>G/C variants, m.3271T>C, m.3481G>A, m.3946G>A, m.13094T>C, m.14487T>C variant was in 1 case each; nuclear DNA (nDNA) variations were identified in 22 cases (35%), of which 7 cases carrying variations in mitochondrial ammonia acyl tRNA synthetase coding gene, mutations in POLG and the gene encoding complex Ⅰ were in 4 cases each, variations in SUCLG1 and SDHA genes were in 2 cases each, and variations in PDHA1, BTD and TRIT1 genes were in 1 case each. Forty-three patients were followed up, and the follow-up time was 20 (3-84) months. According to the follow-up results, the anti-epilepsy treatment was effective in 19 cases (44%) and ineffective in other 24 cases (56%). The onset age of the effective group was 3.42 (0-11.50) years and that of the ineffective group was 0.92 (0-9.50) years. The onset duration of the effective group was 0 (0-7.00) years and that of the ineffective group was 0 (0-4.83) years. There was no significant difference between the effective group and the ineffective group ( t= 1.662, 0.860; P= 0.104, 0.395). In the effective group and the ineffective group, 12 cases and 9 cases used less than 2 kinds of antiepileptic drugs, 7 cases and 15 cases used more than or equal to 2 kinds of antiepileptic drugs, 13 and 15 cases had first epilepsy, 6 and 9 cases had non-first epilepsy, 14 and 11 cases had mtDNA variation, 5 and 13 cases had nDNA variation, respectively. There was no significant difference between the two groups (χ(2)=2.794, 0.164, 3.380; P= 0.095, 0.686, 0.066). Conclusions: The types of seizures with mitochondrial epilepsy in children varied, with focal motor seizures being the most common, followed by generalized or secondary generalized tonic-clonic seizures. Most children have more than two types of seizures. MELAS is the most common clinical phenotype, followed by LS; mtDNA variation is the dominant gene variation, of which m.3243A>G variation is the most common hotspot variation, followed by gene variation encoding mitochondrial aminoacyl tRNA synthase.

Triptolide(T9) is a predominant bioactive component extracted from Chinese herb Tripterygium wilfordii Hook F. (TwHF), and has multiple pharmacological activities, such as immunosuppressive and anti-inflammatory activities, et al. However, severe adverse effects and toxicity, particularly nephrotoxicity, limit its clinical application. It has been demonstrated that the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway could alleviate T9-induced nephrocyte damage. The aim of this study was to investigate the potential protective role of triptriolide (T11) against T9-induced nephrocyte apoptosis in vitro and in vivo. Renal injury models were established in human kidney 2 (HK2) cells and BALB/c mice using T9, and the protective effects of T11 were probed in vitro and in vivo, respectively. T9 induced nephrocyte damage in HK2 cells and BALB/c mice by induction of reactive oxygen species (ROS), lactate dehydrogenase (LDH), malondialdehyde (MDA) and glutathione (GSH) and reduction of superoxide dismutase (SOD), which resulted in the apoptosis of nephrocyte and injury of renal function. While, pretreatment of T11 effectively reversed these changes, resulting in the obvious decrease of oxidative stress and renal function parameters, ameliorated nephrocyte apoptosis, improved cell morphology, and higher increase of Nrf2, NAD(P)H: quinine oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) protein levels in vitro and in vivo. Altogether, T11 protected against T9-induced nephrocyte apoptosis possibly via suppressing oxidative stress., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To explore the feasibility of using da Vinci Surgical System to perform supraomohyoid neck dissection (SOND) to avoid visible scar and reduce trauma. Methods: Between September 2017 and December 2018, twenty patients (two females and 18 males, mean age, 54.8 years) with oral cancer treated in the Department of Stomatology, Hainan Hospital of General Hospital of Chinese PLA were enrolled in this study. Eight patients were assigned into robotic surgery group, and received robot-assisted SOND with retroauricular hairline incision. After the da Vinci Surgical System robotic platform was positioned, the neck dissection was performed in level Ⅱb, Ⅱa, Ⅲ, Ⅰb and Ⅰa orderly from the near region to far region. The other 12 patients were assigned into traditional surgery group, and received SOND with a traditional incision. The operation time, bleeding and amount of lymph node dissected were compared between two groups. Results: All the 8 cases of robot-assisted SOND were completed smoothly. Operation time [(4.5±1.0) h] was significantly longer in robotic surgery group than that [(2.5±1.0) h] in traditional surgery group ( P< 0.05). The amount of bleeding in robotic surgery group [30.0 (27.5) ml] was significantly lower than that in traditional surgery group [(100.0 (87.5) ml, P <0.05]. There's no difference in the number of lymph nodes dissected between robotic surgery group (23.6±5.2) and traditional surgery group (22.8±6.0)( P> 0.05). No postoperative hemorrhage, symptoms of nerve injury, flap necrosis and secondary healing were observed in robotic surgery group. Conclusions: SOND through retroauricular hairline incision is feasible with the assistance of da Vinci Surgical System. The main advantage of this method is superior esthetic effects due to a hidden incision with minimal bleeding. There was no obvious differences in the amount of lymph nodes dissected and postoperative complications between two methods. However, robotic surgery costs a significantly longer operation time than traditional neck dissection.

InP-InAs-InP multi-shell nanowires (NWs) were grown in the wurtzite (WZ) or zincblende (ZB) crystal phase and their photoluminescence (PL) properties were investigated at low temperature (≈6 K) for different measurement geometries. PL emissions from the NWs were carefully studied in a wide energy range from 0.7 to 1.6 eV. The different features observed in the PL spectra for increasing energies are attributed to four distinct emitting domains of these nano-heterostructures: the InAs island (axially grown), the thin InAs capping shell (radially grown), the crystal-phase quantum disks arising from the coexistence of InP ZB and WZ segments in the same NW, and the InP portions of the NW. These results provide a useful frame for the rational implementation of InP-InAs-InP multi-shell NWs containing various quantum confined domains as polychromatic optically active components in nanodevices for quantum information and communication technologies.

Background: The Tripterygium glycosides (TG) is the main active extractive of Tripterygium wilfordii Hook F and is widely used in clinical practice to treat inflammatory diseases (including inflammatory bowel disease). However, due to its severe toxicity, TG is restricted to the treatment of many diseases. Therefore, it is necessary to study a new method to obtain the attenuated and synergistic extracts from TG., Purpose: Tripterygium glycosides-n2 (TG-n2) was obtained from TG by a new preparation method. In this study, we aimed to investigate the difference in the chemical compositions between TG and TG-n2, further explored its toxicity and therapeutic effects on DSS-induced colitis in mice., Methods: The major chemical compositions of TG and TG-n2 were analyzed by ultra-performance liquid chromatography (UPLC). Subsequently, acute toxicity test was applied to evaluate the toxicity difference between TG and TG-n2. Dextran sulfate sodium (DSS)-induced acute colitis model was used to explore the therapeutic effect of TG and TG-n2 and their potential mechanisms of action., Results: We found that the chemical compositions of TG-n2 is different from TG. The main difference is the ratio of triptriolide (T11) / triptolide (T9). Acute toxicity test proved that TG-n2 was less toxic than TG. Base on this, further studies showed that TG-n2 has a similar therapeutic effect as compared to TG on attenuating the symptoms of colitis, such as diarrhea, bloody stools, body weight loss, colonic atrophy, histopathological changes, inhibiting cytokines secretion and reducing absolute lymph number. In addition, TG and TG-n2 can increase the apoptosis of T lymphocyte in vivo. Further investigated showed that TG and TG-n2 could increase the expressions of Bax and p62 on CD3-positive T cells., Conclusion: This study showed that oral administration of TG-n2 is safer than TG. Moreover, the attenuated TG-n2 has the similar therapeutic effect on treating experimental colitis in mice when compared to TG. Its mechanism may be related to activating the expression of Bax in T cells and inducing T cells autophagy to regulate the survival of T lymphocytes in colitis mice, thus reducing inflammation in colon., (Copyright © 2019. Published by Elsevier GmbH.)

Background/objectives: Drug reaction with eosinophilia and systemic symptoms (DRESS) is rare but potentially fatal in children. Fever and rash, which are salient features of DRESS, may mimic other commonly encountered pediatric conditions. We profiled the DRESS cases in a tertiary children's hospital in Singapore., Methods: The medical records of all pediatric DRESS patients diagnosed from 2006 to 2016. Data on epidemiology, inciting drugs, clinical, pathologic manifestations, and treatment were assessed., Results: Ten patients aged 4-16 years old were diagnosed with DRESS within the 10-year period. Drugs implicated were antibiotics, such as trimethoprim-sulfamethoxazole, and anticonvulsants, such as carbamazepine, phenobarbitone, and levetiracetam. All patients had fever and pruritic exanthems. Desquamation, purpura, and oral mucositis were also observed. Lymphadenopathy, hepatomegaly, and facial edema occurred frequently. There was liver involvement in all cases, but none progressed to liver failure. Seven patients had eosinophilia, and nine had atypical lymphocytosis. Other laboratory abnormalities included low hemoglobin, thrombocytosis, and prolonged coagulation times. All patients received systemic corticosteroids of varying durations and dosages. Systemic steroids were weaned after 19 days to 4 months. Disease resolution, with liver enzyme levels returning to normal, occurred within 28-90 days. One patient developed TSH-receptor-antibody-positive hyperthyroidism 6 months after the onset of DRESS, while another patient developed chronic urticaria 4 months after resolution of DRESS., Conclusion: Early recognition of DRESS is important to ensure that the inciting drug is discontinued, and supportive treatment started expediently. Liver involvement was very common but responded well to systemic steroids., (© 2019 Wiley Periodicals, Inc.)