Search

Gui-yun Jiang,1 Qun Li,2 Yun-xiang Lv2,3 1Department of Clinical Laboratory, The Second People’s Hospital of Bengbu, Bengbu, Anhui 233000, People’s Republic of China; 2Department of Respiratory Medicine, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233000, People’s Republic of China; 3Department of Pulmonary Medical, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, People’s Republic of China Background: Plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are elevated in subjects with COPD, and high plasma NT-proBNP levels are correlated with a poor prognosis. Thus, it is crucial to decrease the plasma NT-proBNP levels at the early stage of disease. We aimed to assess the effects of short-term treatment of irbesartan and hydrochlorothiazide on plasma NT-proBNP levels and health-related quality of life (HRQOL) in subjects with acute exacerbations of COPD (AECOPD). Subjects and methods: Eighty subjects with AECOPD and high plasma NT-proBNP levels, without any clinical evidence of cor pulmonale, were enrolled. The subjects were randomly allocated into two groups of 40 subjects. In addition to standard treatment for AECOPD, the subjects in group I were treated with irbesartan alone, and those in group II were treated with irbesartan and hydrochlorothiazide for a week. Forty subjects with stable COPD were enrolled as a control group. Plasma NT-proBNP concentrations were measured on admission and on the first, fourth, and seventh days. The subjects’ health-related quality of life was evaluated applying the 36-item short-form questionnaire on the first day before treatment and on the seventh day after treatment. Results: Treatment of irbesartan and hydrochlorothiazide significantly decreased plasma NT-proBNP levels in subjects with AECOPD, and this reduction was more significant in group II than that in group I. There were no significant differences in 36-item short-form domain scores between subjects with stable COPD and those with AECOPD who were treated with irbesartan and hydrochlorothiazide. Conclusion: Treatment of irbesartan and hydrochlorothiazide rapidly decreased plasma NT-proBNP levels in subjects with AECOPD, and the treatment did not impair their physical status. Keywords: COPD, health-related quality of life, hydrochlorothiazide, irbesartan, NT-proBNP

Objective: To assess whether these characteristics of less misclassification and greater area under receiver operator characteristic (ROC) curve of the new injury severity score (NISS) are better than the injury severity score (ISS) as applying it to our multiple trauma patients registered into the emergency intensive care unit (EICU).Methods: This was a retrospective review of registry data from 2 286 multiple trauma patients consecutively registered into the EICU from January 1,1997 to December 31, 2006 in the Second Affiliated Hospital, Medical School of Zhejiang University in China. Comparisons between ISS and NISS were made using misclassification rates, ROC curve analysis, and the H-L statistics by univariate and multivariate logistic progression model.Results: Among the 2 286 patients, 176 (7.7%) were excluded because of deaths on arrival or patients less than 16 years of age. The study population therefore comprised 2 110 patients. Mean EICU length of stay (LOS) was 7.8 days ?2.4 days. Compared with the blunt injury group, the penetrating injury group had a higher percentage of male, lower mean EICU LOS and age. The most frequently injured body regions were extremities and head/neck, followed by thorax, face and abdomen in the blunt injury group; whereas, thorax and abdomen were more frequently seen in the penetrating injury group. The minimum misclassification rate for NISS was slightly less than ISS in all groups (4.01% versus 4.49%). However, NISS had more tendency to misclassify in the penetrating injury group. This, we noted, was attributed mainly to a higher false-positive rate (21.04% versus 15.55% for ISS, t equal to 3.310, P less than 0.001), resulting in an overall misclassification rate of 23.57% for NISS versus 18.79% for ISS (t equal to 3.290, P less than 0.001). In the whole sample, NISS presented equivalent discrimination (area under ROC curve: NISS equal to 0.938 versus ISS equal to 0.943). The H-L statistics showed poorer calibration (48.64 versus 32.11, t equal to 3.305, P less than 0.001) in the penetrating injury group.Conclusions: NISS should not replace ISS because they share similar accuracy and calibration in predicting multiple blunt trauma patients. NISS may be more sensitive but less specific than ISS in predicting mortality in certain penetrating injury patients. [ABSTRACT FROM AUTHOR]

Chronic total occlusions (CTO) of the coronary arteries are common among patients presenting to the cardiac catheterization laboratory, and data suggests a worse overall prognosis in patients with CTOs. Percutaneous coronary intervention (PCI) of CTOs has been shown to improve anginal symptoms in observational studies and in a limited number of randomized trials. However, CTO PCI has not been shown to lead to a reduction in other important end points such as myocardial infarction or death. Furthermore, despite recent advances in the field, CTO PCI still carries higher risks and a lower likelihood of success compared with non-CTO PCI. Thus, determining which patients may be appropriate for CTO PCI is challenging and must involve a comprehensive risk-benefit analysis and discussion with the patient. Therefore, we review the currently available data regarding CTO PCI, including the clinical outcomes, the role of preprocedural ischemia testing, and various procedural success and risk stratification scores. Finally, we present our approach to the patient referred for CTO PCI., Competing Interests: Declaration of competing interest Dr. Yeh reports a relation with Abbott Vascular Inc., Medtronic, and Boston Scientific Corporation that includes consulting or advisory and funding grants. Dr. Yeh reports a relation with Fastwave, CathWorks, Elixir Medical Corporation, and Shockwave Medical Inc. that includes consulting or advisory. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Regulation of the redox system by branched-chain amino acid transferase 1 (BCAT1) is of great significance in the occurrence and development of diseases, but the relationship between BCAT1 and subarachnoid hemorrhage (SAH) is still unknown. Ferroptosis, featured by iron-dependent lipid peroxidation accompanied by the depletion of glutathione peroxidase 4 (GPX4), has been implicated in the pathological process of early brain injury after subarachnoid hemorrhage. This study established SAH model by endovascular perforation and adding oxyhemoglobin (Hb) to HT22 cells and delved into the mechanism of BCAT1 in SAH-induced ferroptotic neuronal cell death. It was found that SAH-induced neuronal ferroptosis could be inhibited by BCAT1 overexpression (OE) in rats and HT22 cells, and BCAT1 OE alleviated neurological deficits and cognitive dysfunction in rats after SAH. In addition, the effect of BCAT1 could be reversed by the Ly294002, a specific inhibitor of the PI3K pathway. In summary, our present study indicated that BCAT1 OE alleviated early brain injury EBI after SAH by inhibiting neuron ferroptosis via activation of PI3K/AKT/mTOR pathway and the elevation of GPX4. These results suggested that BCAT1 was a promising therapeutic target for subarachnoid hemorrhage., Competing Interests: Declaration of competing interest All of the contributing authors declared no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Biofilms are widely used and play important roles in biological processes. Low temperature of wastewater inhibits the development of biofilms derived from wastewater activated sludge. However, the specific mechanism of temperature on biofilm development is still unclear. This study explored the mechanism of temperature on biofilm development and found a feasible method to enhance biofilm development at low temperature. The amount of biofilm development decreased by approximately 66 % and 55 % at 4 °C and 15 °C, respectively, as compared to 28 °C. The cyclic dimeric guanosine monophosphate (c-di-GMP) concentration also decreased at low temperature and was positively correlated with extracellular polymeric substance (EPS) content, formation, and adhesion strength. Microbial community results showed that low temperature inhibited the normal survival of most microorganisms, but promoted the growth of some psychrophile bacteria like Sporosarcina, Caldilineaceae, Gemmataceae, Anaerolineaceae and Acidobacteriota. Further analysis of functional genes demonstrated that the abundance of functional genes related to the synthesis of c-di-GMP (K18968, K18967 and K13590) decreased at low temperature. Subsequently, the addition of exogenous spermidine increased the level of intracellular c-di-GMP and alleviated the inhibition effect of low temperature on biofilm development. Therefore, the possible mechanism of low temperature on biofilm development could be the inhibition of the microorganism activity and reduction of the communication level between cells, which is the closely related to the EPS content, formation, and adhesion strength. The enhancement of c-di-GMP level through the exogenous addition of spermidine provides an alternative strategy to enhance biofilm development at low temperatures. The results of this study enhance the understanding of the influence of temperature on biofilm development and provide possible strategies for enhancing biofilm development at low temperatures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Stochastic and deterministic processes are the major themes governing microbial community assembly; however, their roles in bioreactors are poorly understood. Herein, the mechanisms underlying microbial assembly and the effect of rare taxa were studied in biofilters. Phylogenetic tree analysis revealed differences in microbial communities at various stages. Null model analysis showed that stochastic processes shaped the community assembly, and deterministic processes emerged only in the inoculated activated sludge after domestication. This finding indicates the dominant role of stochastic factors (biofilm formation, accumulation, and aging). The Sloan neutral model corroborated the advantages of stochastic processes and mainly attributed these advantages to rare taxa. Cooccurrence networks revealed the importance of rare taxa, which accounted for more than 85% of the keystones. Overall, these results provide good foundations for understanding community assembly, especially the role of rare taxa, and offer theoretical support for future community design and reactor regulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Recent advances in heart failure (HF) care have sought to shift management from inpatient to outpatient and observation settings. We evaluated the association among HF treatment in the (1) inpatient; (2) observation; (3) emergency department (ED); and (4) outpatient settings with 30-day mortality, hospitalizations and cost., Methods: Using 100% Medicare inpatient, outpatient and Part B files from 2011-2018, 1,534,708 unique patient encounters in which intravenous (IV) diuretics were received for a primary diagnosis of HF were identified. Encounters were sorted into mutually exclusive settings: (1) inpatient; (2) observation; (3) ED; or (4) outpatient IV diuretic clinic. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 30-day hospitalization and total 30-day costs. Multivariable logistic and linear regression were used to examine the association between treatment location and the primary and secondary outcomes., Results: Patients treated in observation and outpatient settings had lower 30-day mortality rates (observation OR 0.67, 95% CI 0.66-0.69; P < 0.001; outpatient OR 0.53, 95% CI 0.51-0.55; P < 0.001) compared to those treated in inpatient settings. Observation and outpatient treatment were also associated with decreased 30-day total cost compared to inpatient treatment. Observation relative cost -$5528.77, 95% CI -$5613.63 to -$5443.92; outpatient relative cost -$7005.95; 95% CI -$7103.94 to -$6907.96). Patients treated in the emergency department and discharged had increased mortality rates (OR 1.15, 95% CI 1.13-1.17; P < 0.001) and increased rates of hospitalization (OR 1.72, 95% CI 1.70-1.73; P < 0.001) compared to patients treated as inpatients., Conclusions: Medicare beneficiaries who received IV diuresis for acute HF in the outpatient and observation settings had lower mortality rates and decreased costs of care compared to patients treated as inpatients. Outpatient and observation management of acute decompensated HF, when available, is a safe and cost-effective strategy in certain populations of patients with HF., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A Gram-stain-negative, non-spore-forming, flagellated, motile, aerobic, rod-shaped bacteria strain, designated YY2X T , was isolated from chromium-contaminated soil. Phylogenetic analysis based on 16S rRNA gene, recA gene, and whole genome indicated that the strain represented a new member of the genus Ochrobactrum, family Brucellaceae, class Alphaproteobacteria. The phylogenetic trees based on 16 s rRNA gene, revealed that Falsochrobactrum ovis DSM26720 T (96.7%), Ochrobactrum gallinifaecis DSM15295 T (96.2%), and Pseudochrobactrum asaccharolyticum DSM25619 T (96.2%) are the most closely related phylogenetic neighbors of strain YY2X T . The draft genome of YY2X T was approximately 4,650,646 bp in size with a G + C content of 53.0 mol%. Average nucleotide identity and digital DNA-DNA hybridization values among strain YY2X T and the selected Brucellaceae species were 71.4-83.1% and 13.5-42.7%, which are below the recommended cut-off values for species delineation. Growth of strain YY2X T occurred within pH 5-10 (optimum, pH 7-8), 4 ℃-42 °C (optimum, 30 °C), and NaCl concentrations of 0.0-6.0% (optimum, 1.0%). Major quinone system was ubiquinone 10, the major fatty acids were C 16:0 , C 18:1 ω7c, and C 16:1 ω7c and the major polyamines were spermidine and putrescine. Major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, and four undefined lipids. On the basis of the phenotypic, genotypic and chemotaxonomic traits, strain YY2X T was considered to represent a novel species of the genus Ochrobactrum, for which the name Ochrobactrum chromiisoli sp. nov. is proposed. The type strain is YY2X T (= CCTCC AB 2023035 T  = JCM 36000 T )., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Bacterial communication interruption based on quorum quenching (QQ) has been proven its potential in biofilm formation inhibition and biofouling control. However, it would be more satisfying if QQ could be combined with the efficient degradation of contaminants in environmental engineering. In this study, we engineered a biofilm of Pseudomonas putida through introducing a QQ synthetic gene, which achieved both biofilm formation inhibition and efficient degradation of benzene series in wastewater. The aiiO gene introduced into the P. putida by heat shock method was highly expressed to produce QQ enzyme to degrade AHL-based signal molecules. The addition of this engineered P. putida reduced the AHLs concentration, quorum sensing gene expression, and connections of the microbial community network in activated sludge and therefore inhibited the biofilm formation. Meanwhile, the sodium benzoate degradation assay indicated an enhanced benzene series removal ability of the engineering bacteria on activated sludge. Besides, we also demonstrated a controllable environmental risk of this engineered bacteria through monitoring its abundance and horizontal gene transfer test. Overall, the results of this study suggest an alternative strategy to solve multiple environmental problems through genetic engineering means and provide support for the application of engineered bacteria in environmental biotechnology., 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 Ltd. All rights reserved.)

Ferroptosis is a novel form of cell death that plays a critical role in the pathological and physiological processes of early brain injury following subarachnoid hemorrhage. Melatonin, as the most potent endogenous antioxidant, has shown strong protective effects against pathological changes following subarachnoid hemorrhage, but its impact on ferroptosis induced by subarachnoid hemorrhage remains unexplored. In our study, we established a subarachnoid hemorrhage model in male SD rats. We found that subarachnoid hemorrhage induced changes in ferroptosis-related indicators such as lipid peroxidation and iron metabolism, while intraperitoneal injection of melatonin (40 mg/kg) effectively ameliorated these changes to a certain degree. Moreover, in a subset of rats with subarachnoid hemorrhage who received pre-treatment via intravenous injection of the melatonin receptor antagonist Luzindole (1 mg/kg) and 4P-PDOT (1 mg/kg), we found that the protective effect of melatonin against subarachnoid hemorrhage includes inhibition of lipid peroxidation and reduction of iron accumulation depended on melatonin receptor 1B (MT2). Furthermore, our study demonstrated that melatonin inhibited neuronal ferroptosis by activating the NRF2 signaling pathway, as evidenced by in vivo inhibition of NRF2. In summary, melatonin acts through MT2 and activates NRF2 and downstream genes such as HO-1/NQO1 to inhibit ferroptosis in subarachnoid hemorrhage-induced neuronal injury, thereby improving neurological function in rats. These results suggest that melatonin is a promising therapeutic target for subarachnoid hemorrhage., Competing Interests: Declaration of competing interest All of the contributing authors declared no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The existence of quorum sensing (QS) and quorum quenching (QQ) plays important roles in biofilm formation. However, direct detection of QS ability is difficult due to the low concentrations of signal molecules inside the biofilm. Therefore, QQ activity is typically used to indicate the attribution of QS/QQ to the biofilm. Nevertheless, current detection methods of QQ activity based on biosensors present undesirable operability and accuracy. In this study, the 96-well plate assay based on a specific biosensor, Agrobacterium tumefaciens A136, and a colorimetric substance, X-gal was established. The reliable fitting results were obtained by standardizing the composition of the A136 X-gal assay solution and optimizing the operating conditions. This method improved the accuracy of QQ activity detection and reduced time and cost consumption. Finally, the 96-well plate assay was successfully applied to detect the QQ activities of biofilm samples and explore possible environmental influencing factors. In general, this study provided a new strategy for understanding the QQ effect in biofilm systems., 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 Ltd. All rights reserved.)

Background: The goal of the Affordable Care Act was to improve health outcomes through expanding insurance, including through Medicaid expansion. We systematically reviewed the available literature on the association of Affordable Care Act Medicaid expansion with cardiac outcomes., Methods: Consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we performed systematic searches in PubMed, the Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature using the keywords such as Medicaid expansion and cardiac, cardiovascular, or heart to identify titles published from 1/2014 to 7/2022 that evaluated the association between Medicaid expansion and cardiac outcomes., Results: A total of 30 studies met inclusion and exclusion criteria. Of these, 14 studies (47%) used a difference-in-difference study design and 10 (33%) used a multiple time series design. The median number of postexpansion years evaluated was 2 (range, 0.5-6) and the median number of expansion states included was 23 (range, 1-33). Commonly assessed outcomes included insurance coverage of and utilization of cardiac treatments (25.0%), morbidity/mortality (19.6%), disparities in care (14.3%), and preventive care (41.1%). Medicaid expansion was generally associated with increased insurance coverage, reduction in overall cardiac morbidity/mortality outside of acute care settings, and some increase in screening for and treatment of cardiac comorbidities., Conclusions: Current literature demonstrates that Medicaid expansion was generally associated with increased insurance coverage of cardiac treatments, improvement in cardiac outcomes outside of acute care settings, and some improvements in cardiac-focused prevention and screening. Conclusions are limited because quasi-experimental comparisons of expansion and nonexpansion states cannot account for unmeasured state-level confounders., Competing Interests: Disclosures None.

Biofilters inoculated with activated sludge are widely used for odor control in WWTP. In this process, biofilm community evolution plays an important role in the function of reactor and is closely related to reactor performance. However, the trade-offs in biofilm community and bioreactor function during the operation are still unclear. Herein, an artificially constructed biofilter for odorous gas treatment was operated for 105 days to study the trade-offs in the biofilm community and function. Biofilm colonization was found to drive community evolution during the start-up phase (phase 1, days 0-25). Although the removal efficiency of the biofilter was unsatisfactory at this phase, the microbial genera related to quorum sensing and extracellular polymeric substance secretion led to the rapid accumulation of the biofilm (2.3 kg biomass/m 3 filter bed /day). During the stable operation phase (phase 2, days 26-80), genera related to target-pollutant degradation showed increases in relative abundance, which accompanied a high removal efficiency and a stable accumulation of biofilm (1.1 kg biomass/m 3 filter bed/day). At the clogging phase (phase 3, days 81-105), a sharp decline in the biofilm accumulation rate (0.5 kg biomass/m 3 filter bed /day) and fluctuating removal efficiency were observed. The quorum quenching-related genera and quenching genes of signal molecules increased, and competition for resources among species drove the evolution of the community in this phase. The results of this study highlight the trade-offs in biofilm community and functions during the operation of bioreactors, which could help improve bioreactor performance from a biofilm community perspective., 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 Ltd. All rights reserved.)

Objectives: Knowledge regarding thymic EBV-related poorly differentiated nonkeratinizing squamous cell carcinoma (PDNKSCC), also known as lymphoepithelial carcinoma (LEC), is extremely limited due to its rarity., Materials and Methods: This multi-institutional study enrolled 85 patients with thymic PDNKSCC. DNA in situ hybridization was performed to evaluate the EBV status of all 85 cases. Immunohistochemistry and next generation sequencing were performed to compare the differences in the clinicopathological and molecular features between EBV-related and EBV-unrelated PDNKSCC. Tumor-infiltrating lymphocytes (TILs) were also analyzed by these methods., Results: The 85 cases were classified into 27 EBV-related PDNKSCCs (31.8 %) and 58 EBV-unrelated PDNKSCCs (68.2 %) according to the EBV status, and 35 Lymphoepithelioma pattern (LP) (41.2 %) and 50 desmoplastic pattern (DP) (58.8 %) according to the histological characteristics. Compared to the EBV-unrelated PDNKSCC, EBV-related PDNKSCC showed a younger patient predominance and more commonly displayed a LP subtype. Additionally, LP-type cases were divided into two groups: Group 1 (EBV-related, 20/85) and Group 2 (EBV-unrelated, 15/85); the DP-type cases were divided into Group 3 (EBV-unrelated, 43/85) and Group 4 (EBV-related, 7/85). The four Groups showed a significant association with patients' OS and PFS. EBV-related PDNKSCC had significantly higher PD-L1 + tumor cells (TCs) and PD-L1 + and CD8 + immune cells (ICs) than EBV-unrelated PDNKSCC. The tumor microenvironment immune type (TMIT) I (PDL1-Tumor+/CD8-High) was more common in EBV-related PDNKSCC, especially in Group 1(LP and EBV related) with more than 90 % cases belonged to TMIT I. Molecular analysis demonstrated that EBV-related PDNKSCC had a significantly higher tumour mutational burden and frequency of somatic mutations than EBV-unrelated cases., Conclusions: EBV-related PDNKSCC, especially the Group 1, could be a candidate for immunotherapy and EBV positivity may provide an indication for the selection of targeted therapy due to their high tumour mutational burden., 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. Published by Elsevier B.V.)

Molecularly imprinted polymers (MIPs) were combined with surface-enhanced Raman scattering (SERS) and AgNPs were prepared by in situ reduction within the MIP for selective and sensitive detection of sulfamethazine (SMZ). The MIP@AgNPs composites were characterized in detail by several analytical techniques, showing the generation of polymers and the formation of AgNPs hot spots. The specific affinity and rapid adsorption equilibrium rates of MIP@AgNPs composites were verified by static and kinetic adsorption studies. The MIP@AgNPs with high selectivity and excellent sensitivity were used as SERS substrates to detect SMZ. A good linear correlation (R 2  = 0.996) in rang of 10 -10 -10 -6  mol L -1 was observed between the Raman signal (1596 cm -1 ) and the concentration of SMZ. The limit of detection (LOD) was as low as 8.10 × 10 -11  mol L -1 with relative standard deviations (RSD) of 6.32%. The good stability and reproducibility are also fully reflected in the SERS detection based on MIP@AgNPs. The method was successfully applied to the analysis of lake water samples, with recoveries in the range 85.1% to 102.5%. In summary, SERS detection based on MIP@AgNPs can be developed for a wider and broader range of practical applications. Schematic illustration of MIP@AgNPs sensor for the SERS detection of sulfamethazine., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The association of mitral regurgitation (MR) severity and mortality in heart failure with preserved ejection fraction (HFpEF) is uncertain. We sought to evaluate the relation between MR severity on transthoracic echocardiography (TTE) and subsequent all-cause mortality in Medicare beneficiaries with HFpEF. We linked 57,608 patients referred for TTE at Beth Israel Deaconess Medical Center to Medicare inpatient claims from 2003 to 2017. In those with a history of HF and a physician-reported left ventricular ejection fraction ≥50%, we evaluated the relation of MR severity and time to the primary end point of all-cause mortality using Kaplan-Meier methods. A total of 7,778 individuals (14.5%) met inclusion criteria (mean age 75.5 years ± 11.9, 55.9% female). Over a median follow-up of 8.1 years, 2,016 (25.9%) died at a median (interquartile range) of 1.7 (0.3 to 4.1) years. At 1 year, 15.8% with 3 to 4+ MR had died versus 10.5% with 0 to 2+ MR (hazard ratio 1.54, 95% confidence interval 1.22 to 1.95, p <0.001). After multivariable adjustment, 3 to 4+ MR continued to be associated with increased all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.14 to 1.94, p = 0.004) except in the subset with atrial fibrillation (interaction p = 0.03) or recent (<3 months) HF hospitalization (p = 0.54). In conclusion, in this large, single-institution retrospective study of Medicare beneficiaries with HFpEF who underwent TTE, moderate-to-severe and severe MR were significantly associated with an increased risk of all-cause mortality after multivariable adjustment, except in those with atrial fibrillation or recent HF. Prospective studies are needed to assess the role of MR reduction in mitigating this risk., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Controlling excess biomass accumulation and clogging is important for maintaining the performance of gas biofilters and reducing energy consumption. Interruption of bacterial communication (quorum quenching) can modulate gene expression and alter biofilm properties. However, whether the problem of excess biomass accumulation in gas biofilters can be addressed by interrupting bacterial communication remains unknown., Results: In this study, parallel laboratory-scale gas biofilters were operated with Rhodococcus sp. BH4 (QQBF) and without Rhodococcus sp. BH4 (BF) to explore the effects of quorum quenching (QQ) bacteria on biomass accumulation and clogging. QQBF showed lower biomass accumulation (109 kg/m 3 ) and superior operational stability (85-96%) than BF (170 kg/m 3 ; 63-92%) at the end of the operation. Compared to BF, the QQBF biofilm had lower adhesion strength and decreased extracellular polymeric substance production, leading to easier detachment of biomass from filler surface into the leachate. Meanwhile, the relative abundance of quorum sensing (QS)-related species was found to decrease from 67 (BF) to 56% (QQBF). The QS function genes were also found a lower relative abundance in QQBF, compared with BF. Moreover, although both biofilters presented aromatic compounds removal performance, the keystone species in QQBF played an important role in maintaining biofilm stability, while the keystone species in BF exhibited great potential for biofilm formation. Finally, the possible influencing mechanism of Rhodococcus sp. BH4 on biofilm adhesion was demonstrated. Overall, the results of this study achieved excess biomass control while maintaining stable biofiltration performance (without interrupting operation) and greatly promoted the use of QQ technology in bioreactors. Video Abstract., (© 2022. The Author(s).)

Saliva contains similar molecular components to serum. Analysis of saliva can provide important diagnostic information about the body. Here we report an artificial intelligence (AI) aided home-based method that can let pregnant women perform daily monitoring on their pregnant status and accurate prediction on their delivery date by the pattern analysis of their salivary crystals. The method was developed based on the information obtained from our investigation on the saliva samples of 170 pregnant women about the correlation of the salivary crystal pattern with pregnant age and fetal status. It demonstrated that the patterns of salivary crystallization could act as indicators of the pregnant age, fetal state, and some medical conditions of pregnant women. On this basis, with the aid of AI recognition and analysis of the fractal dimension and some characteristic crystals in the salivary crystallization, we performed estimation on the delivery date in both quantitative and qualitative manners. The accuracy of the prediction on 15 pregnant women was satisfactory: 100% delivering in the predicted week, 93.3% within the estimated three days, and 86.7% on the day as the prediction. We also developed a simple smartphone-based AI-aided salivary crystal imaging and analysis device as an auxiliary means to let pregnant women monitor their fetal status daily at home and predict their delivery date with adequate accuracy.

PTEN is known as a tumor suppressor and plays essential roles in brain development. Here, we report that PTEN in primary sensory neurons is involved in processing itch and thermal information in adult mice. Deletion of PTEN in the dorsal root ganglia (DRG) is achieved in adult Drg11-Cre ER : PTEN flox/flox (PTEN CKO) mice with oral administration of tamoxifen, and CKO mice develop pathological itch and elevated itch responses on exposure to various pruritogens. PTEN deletion leads to ectopic expression of TRPV1 and MrgprA3 in IB4 + non-peptidergic DRG neurons, and the TRPV1 is responsive to capsaicin. Importantly, the elevated itch responses are no longer present in Drg11-Cre ER : PTEN flox/flox : TRPV1 flox/flox (PTEN: TRPV1 dCKO) mice. In addition, thermal stimulation is enhanced in PTEN CKO mice but blunted in dCKO mice. PTEN-involved regulation of itch-related gene expression in DRG neurons provides insights for understanding molecular mechanism of itch and thermal sensation at the spinal level., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

BACKGROUND Venous thrombosis (VTE) is a common adverse event among inpatients, which can cause pulmonary embolism, and greatly increases mortality. The effects of rivaroxaban in patients undergoing brain glioma surgery have still not been explored. This single-center study of 94 patients undergoing surgery for cerebral glioma aimed to compare postoperative thromboprophylaxis with and without rivaroxaban. MATERIAL AND METHODS We designed a randomized, controlled, double-blind study to evaluate the effect of rivaroxaban on 94 patients undergoing brain glioma surgery. These patients were divided into a rivaroxaban group (administered at 10 mg per day from admission to discharge) and a placebo group. The primary study endpoint was incidence of VTE at discharge. The secondary endpoints included safety outcomes of major bleeding, allergy, or VTE-related death. RESULTS A total of 94 patients were enrolled in the study: 47 in the rivaroxaban group and 47 in the placebo group. Baseline characteristics of participants were well-matched in both groups. A significant reduction was found in the incidence of VTE in the rivaroxaban treatment group versus the placebo group (1/47 vs 10/47 patients, P=0.008). The rate of major bleeding events was quite low in both group (1/47 vs 1/47 patients). One patient in the placebo group died due to a pulmonary embolism and intractable concomitant underlying diseases. CONCLUSIONS Our results indicate that treatment with rivaroxaban is a safe and effective thromboprophylaxis treatment in patients undergoing surgery for malignant cerebral glioma.

Background: The gene mutation of isocitrate dehydrogenase-1 (IDH1) is commonly found in LGG and some GBM patients and usually carries tumor protein 53 (TP53) mutations. However, the underlying mechanisms on both mutations of glioma patients in IDH1 and TP53 are still unclear. Aim: To find the potential target markers in GBM and LGG patients with IDH1 and TP53 mutation. Method: A total of 1122 glioma patients from The Cancer Genome Atlas were enrolled and divided as wild-type (without IDH1 and TP53 mutations) or both mutant (both IDH1 and TP53 mutations). The data of clinicopathological characteristics, mRNA, mutations, and copy number alteration were analyzed. Results: IDH1 and TP53 mutations, not gene expression, affect the survival probability of GBM and LGG patients, which might be related to neuron function, immune function, tumor invasion, and metastasis. The effects of the selected gene (EMILIN3, SAA1, VSTM2A, HAMP, IFT80, and CHIC2) on glioma patients could be regulated by IDH1 and TP53 mutations and had a higher survival possibility in these patients. Conclusions: The selected genes in GBM and LGG patients with IDH1 and TP53 mutations could be a potential prognosis marker in the future.

Neuroinflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Genistein is an estrogen-like phytoestrogen that can exert biological effects via the crosstalk of estrogen receptor and insulin-like growth factor 1 receptor (IGF-1R). The present study aimed to evaluate the involvement of G protein-coupled estrogen receptor (GPER) and IGF-1R in the anti-inflammatory effects of genistein against lipopolysaccharide (LPS)-induced nigrostriatal injury in ovariectomized rats. Our results showed that genistein treatment could ameliorate the apomorphine-induced rotational behavior in LPS-induced inflammatory PD rat model. Genistein attenuated LPS-induced decrease of the contents of dopamine (DA) and its metabolites in striatum as well as the loss of tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantia nigra (SN) of the lesioned side, which could be blocked by GPER antagonist G15 or IGF-1R antagonist JB1. Meanwhile, G15 or JB1 could attenuate the anti-inflammatory effects of genistein in LPS-induced microglial activation and production of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, genistein could inhibit the LPS-induced phosphorylation of p38, JNK, ERK and IκB in the lesioned side of SN and these effects could also be blocked by G15 or JB1. Taken together, our data provide the first evidence that genistein can inhibit the increase of microglia and protect dopaminergic neurons at least in part via GPER and IGF-1R signaling pathways in ovariectomized PD rat model., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Rationale: Thymic adenocarcinoma is an extremely rare thymic carcinoma. The exact genetic alteration associated with thymic adenocarcinoma is unclear. Here, we report a case of thymic adenocarcinoma accompanied by type A thymoma and pulmonary minimally invasive adenocarcinoma (MIA)., Patient Concerns: A 53-year-old woman presented with multiple nodules in the mediastinum and lung. Thoracic computed tomography revealed nodules in the anterior superior mediastinum and anterior mediastinum near the right pericardium and ground-glass opacity (GGO) in the right superior lobe of the lung., Diagnosis: The tumor in the anterior superior mediastinum was diagnosed as primary thymic papillary adenocarcinoma. The tumor in the anterior mediastinum near the right pericardium was diagnosed as type A thymoma. The GGO of the right superior lobe of the lung was diagnosed as a MIA., Intervention: The patient underwent thoracoscopic mediastinal tumor resection and partial lobectomy in our hospital., Outcomes: The postoperative course was uneventful. The patient is alive and free of the disease for 22 months after diagnosis., Lessons: Thyroid transcription factor 1 (TTF-1) was positive in this case of thymic adenocarcinoma, which indicated that a thymic adenocarcinoma with TTF-1-positive may not necessarily be a metastasis of lung or thyroid adenocarcinoma. The positive staining of CD5 and CD117 can help us to confirm the thymic origin. Molecular genetic analysis indicated that these tumors harbored different mutations. The thymic adenocarcinoma and type A thymoma both had the mutation of KMT2A, but the mutation sites were different. KMT2A mutation may be a common genetic change in thymic tumorigenesis. The genetic alterations disclosed in this study will help expand the understanding of thymic tumors., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The aim of this study was to observe the liver function recovery of COVID-19 patients after discharge. Patients and Methods: A total of 253 discharged COVID-19 patients in Shenzhen city, China were selected. The clinical characteristics of these patients were assessed. A 2-month follow-up and laboratory hematology test were performed to examine the status of patients' liver function. Results: Patients combined with liver diseases, especially fatty liver, are more likely to progress to severe condition ( P< 0.05). Patients in severe condition and those with liver diseases have higher rates of liver injuries during hospitalization, characterized by a significant increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P< 0.01). The ALT, AST/ALT, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), and A/G levels showed significant differences in comparison with the control group ( P< 0.05, and P< 0.001); and the outlier ratio of A/G, ALT, GGT and ALP of patients remained abnormal higher within 14 days after discharge ( P< 0.001). Liver injuries of COVID-19 patients may be related to the epidemiological characteristics, clinical indexes, basic diseases, symptoms, drug treatment during hospitalization and the complications. Indicators of liver function were correlated with cardiac function, renal function, thyroid function, lipid metabolism, glucose metabolism, immune index, leukocyte, erythrocyte, hemoglobin and platelet related indexes. The outlier ratio of TP, ALB and GLB remained extremely low throughout the follow-up period; the outlier ratio of ALT, AST and GGT decreased below 10% from a high level at 40 days after discharged. However, the outlier ratio of A/G, AST/ALT and ALP remained high during the follow-up period. Conclusions : Abnormal liver function might indicate worse recovery of COVID-19 patients. Changes in liver function should be emphasized during long-term follow-up of COVID-19 patients after hospital discharge; the necessity of employing appropriate interventions for liver function repair should be emphasized., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To observe the effect of round magnetic needle tapping along meridians on the back plus acupuncture at "Qi Shen Zhen"（including Shenting ［GV24］, Benshen ［GB13］, Sishenchong ［EX-HN1］）, and Baihui （GV20）, Shenmen （HT7） on gastrointestinal function, daily living activities and anxiety status in post-stroke anxiety disorder (PSAD) patients., Methods: Fifty-seven PSAD patients were randomly divided into acupuncture group (28 cases) and medication group (29 cases). On the basis of routine treatment and physical therapy, patients of the acupuncture group were treated by applying round magnetic needle to mildly tapping the second line→the first line of the Bladder Meridian→Jiaji acupoints→Governor Meridian on the back from outside to the inside in sequence for 20 min, followed by needling GV24, GV20, GB13, EX-HN1 and HT7, respectively, with the needles retained for 30 min after one minute's twisting. The treatment was conducted once daily, 5 times a week, for 6 weeks. Patients of the medication group were asked to take Escitalopram Oxalate tablets (5-20 mg/d) for 6 weeks. The Hamilton Anxiety Rating Scale (HAMA) was used to assess the patient's severity of anxiety, cognition, somatic sensation, symptoms of cardiovascular, respiratory, gastrointestinal, urogenital, automatic and muscular systems, the Barthel Index (BI) used to evaluated the activities of daily living (ADL), and the gastrointestinal function （Spleen-stomach Symptom Score ［SSS］） assessed according to the "Standards for Diagnosis and Curative Effect Evaluation of Syndromes of Traditional Chinese Medicine". The adverse reactions were observed at the end of treatment., Results: After the treatment, the HAMA scores at the 2nd, 4th and 6th week and the SSS scores at the 4th and 6th week were significantly decreased ( P <0.05), and the BI scores at the 2nd， 4th and 6th week were considerably increased in both acupuncture and medication groups compared with their own pre-treatment ( P <0.05). The HAMA score at the 2nd week, and the SSS scores at the 2nd, 4th and 6th week were obviously lower( P <0.05), and the BI score at the 6th week was notably higher in the acupuncture group than in the medication group ( P <0.05). No significant diffe-rence was found between the two groups in the therapeutic effect of anxiety state ( P >0.05). The acupuncture group had fewer adverse reactions than the medication group ( P <0.05)., Conclusion: The round magnetic needle tapping plus "Qi Shen Zhen" needling has a significant therapeutic effect in improving PSAD patients' anxiety state, being similar to Escitalopram Oxalate tablets in reducing anxiety state and being superior to Escitalopram in improving gastrointestinal function and daily living activities.

Objective: To evaluate the clinical efficacy of oblique lateral interbody fusion combined posterior percutaneous pedicle screw fixation in the treatment of single segment lumbar tuberculosis., Methods: Patients who underwent surgical treatment for single segment lumbar tuberculosis from 2015 to 2018 in our department were retrospectively included in this study. The included patients were divided into two groups, namely oblique lateral interbody fusion combined percutaneous pedicle screw fixation (OLIF) group and traditional posterior transforaminal or transpedicular approach debridement and pedicle screws fixation (PTA) group, according to the surgical methods. Outcomes including operative time, operative blood loss, hospital stay, visual analogue scale (VAS) score, Oswestry disability index (ODI), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), Cobb angle correction and loss, bone fusion time, ASIA grade and complications were all recorded and compared., Results: A total of 60 patients were included in this study, involving 23 patients in the OLIF group and 37 patients in the PTA group. The OLIF group had less operative time, blood loss and shorter hospital stay compared with the PTA group (P < 0.05). Both the two groups achieved significant improvements in ESR, CRP and ASIA grade at the last follow-up (P < 0.05), but no significant differences were found between them (P>0.05). There were no significant differences in Cobb angle correction and loss between the two groups (P > 0.05), but the bone graft fusion time of the OLIF group was significantly shorter than the PTA group (P < 0.05). The two groups achieved similar improvement in VAS score and ODI at 12 months postoperative and the last follow-up, however, OLIF group had a lower VAS score and ODI at 1 month, 3 months and 6 months postoperative (P < 0.05). No significant difference was found in complications between the two groups (P > 0.05) and all patients were cured after active treatment., Conclusions: Both OLIF and PTA can achieve satisfactory clinical efficacy in the surgical treatment of single segment lumbar TB, but OLIF has the advantages of less surgical trauma, faster postoperative recovery and shorter bone fusion time., (Copyright © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to explore the dynamic changes in characteristic serum metabolic markers and pathways during early sepsis in rats. By using cecal ligation and puncture (CLP), we made rat models of sepsis, which were randomly divided into 5 groups with 10 rats in each group: group A, group B, group C, group D, and group E. We collected 2 mL of arterial blood at 0, 6, 12, 24, and 48 hours from rats in group A-E respectively and isolated serum via centrifugation. Next, adopting metabolomics analysis methods, we screened for metabolites from the animal serum with statistically and biologically significant abundance changes, and used the KEGG database to analyze the respective metabolic pathways. In all, our findings reveal that D-glucosamine 6-phosphate, D-glucosamine phosphate, α-D-glucosamine 1-phosphate, D-glucosamine 1-phosphate, and 5-hydroxy isocyanate decline continuously from 12 hours, while L-phenylalanine, (S) -α-amino-β-phenylpropionic acid, 5-methoxy indole acetic acid salt, 5-methoxy indole acetic acid, goose deoxyglycolic acid salt, goose deoxyglycolic acid, and Chen's deoxygenated sugar alcohol started to decrease from 6 hours. Additionally, 3.2,3-Bis-O-(geranyl geranyl)-sn-glycerol- 1-phosphoric acid-L-serine levels rose continuously from 12 hours. We found 13 differentially regulated ions, primarily ones involved in pathways responsible for the metabolism of sugar, amino acids, and lipids, which are related to the disorder of energy metabolism. Our findings mark serum-derived D-glucosamine and its phosphorous derivatives as characteristic metabolic markers of sepsis in rats., (Copyright 2020 Biolife Sas. www.biolifesas.org.)

The aim of the present study was to explore the antitumor effects of sinoporphyrin sodium (DVDMS)‑mediated photodynamic therapy (PDT) and sonodynamic therapy (SDT) in glioma, and to reveal the underlying mechanisms. The uptake of DVDMS by U‑118 MG cells was detected by flow cytometry (FCM). A 630‑nm semiconductor laser and 1‑MHz ultrasound were used to perform PDT and SDT, respectively. Cell proliferation and apoptosis were evaluated using the Cell Counting Kit‑8 assay, FCM and Hoechst 33258 staining, respectively. Western blot analysis was used to detect protein expression and phosphorylation levels. BALB/c nude mice were used to establish a xenograft model of U‑118 MG cells. DVDMS was injected intravenously and PDT and SDT were performed 24 h later. An in vivo imaging system was used to evaluate the fluorescence of DVDMS, to measure tumor sizes, and to evaluate the therapeutic effects. The uptake of DVDMS by U‑118 MG cells was optimal after 4 h. PDT and SDT following DVDMS injection significantly inhibited the proliferation and increased apoptosis of glioma cells in vitro (P<0.05, P<0.01) respectively. In vivo, the fluorescence intensity of DVDMS was lower in the PDT and SDT groups compared with the DVDMS group, while tumor cell proliferation and weight were lower in the PDT and SDT groups than in the control group (P<0.05, P<0.01). However, there was no significant difference when laser, ultrasound or DVDMS were applied individually, compared with the control group. Hematoxylin and eosin staining suggested that both PDT and SDT induced significant apoptosis and vascular obstruction in cancer tissues. DVDMS‑mediated PDT and SDT inhibited the expression levels of proliferating cell nuclear antigen (PCNA) and Bcl‑xL, increased cleaved ‑caspase 3 levels, and decreased the protein phosphorylation of the PI3K/AKT/mTOR signaling pathway. Changes in the expression of PCNA, and Bcl‑xL and in the levels of cleaved‑caspase 3 were partly reversed by N‑acetyl‑L‑cysteine, a reactive oxygen species (ROS) scavenger. Similar results were obtained with FCM. DVDMS‑mediated PDT and SDT inhibited glioma cell proliferation and induced cell apoptosis in vitro and in vivo, potentially by increasing the generation of ROS and affecting protein expression and phosphorylation levels.

Rationale: Thymic carcinoma with adenoid cystic carcinoma-like features is a special subtype of thymic adenocarcinoma, and the occurrence of this condition is extremely rare. Herein, we report a case of primary thymic carcinoma with adenoid cystic carcinoma-like features in a young man., Patient Concerns: A 38-year-old man had an incidental finding of space-occupying lesion in the anterior mediastinum during a routine health examination. The patient complained of occasional mild chest tightness during hot weather but had no obvious cough, sputum, chest pain, or fever. Contrast-enhanced computed tomography scan of the chest revealed a space-occupying lesion in the anterior mediastinum, which is likely benign., Diagnosis: The lesion was diagnosed as a primary thymic carcinoma with adenoid cystic carcinoma-like features., Intervention: The patient underwent thoracoscopic resection of left anterior mediastinal mass and enlarged resection of thymectomy and mediastinal fat in our hospital., Outcomes: The postoperative course was uneventful., Lessons: The tissue characteristic of this tumor was extremely similar to that of adenoid cystic carcinoma. A precise pathological examination is extremely important to prevent misdiagnoses of the lesion as adenoid cystic carcinoma or other thymic tumors. Immunohistochemical staining is extremely useful for the pathological and differential diagnoses of this tumor.

Importance: The US Centers for Medicare & Medicaid Services have implemented national value-based programs that incentivize hospitals to deliver better cardiovascular care. However, it is unclear how hospitals recognized for high-quality cardiovascular care by American Heart Association (AHA) and American College of Cardiology (ACC) national quality improvement initiatives (termed award hospitals) have performed under value-based programs., Objective: To determine if hospitals that received awards for high-quality cardiovascular care from the AHA/ACC were less likely to be penalized under the Hospital Readmissions Reduction Program (HRRP) and the Hospital Value-Based Purchasing Program (VBP) compared with other hospitals., Design, Setting, and Participants: This national cross-sectional study included data from short-term acute care hospitals in the United States that were participating in the HRRP or VBP in fiscal year 2018., Exposures: Recognition awards for high-quality care from the AHA's Get With The Guidelines-Heart Failure and ACC's Chest Pain-MI (myocardial infarction) Registry national quality improvement initiatives., Main Outcomes and Measures: Proportion of hospitals that received a financial penalty or financial reward under the HRRP or VBP, median payment adjustments, and hospital-level 30-day mortality rates., Results: This study included 3175 hospitals participating in the HRRP and 2781 hospitals participating in the VBP in fiscal year 2018. Under the HRRP, a higher proportion of award hospitals received financial penalties compared with other hospitals (419 [85.5%] vs 2112 [78.7%]; P < .001), although payment reductions were similar (median, 0.39% [interquartile range (IQR), 0.08%-0.84%] vs 0.33% [IQR, 0.03%-0.89%]; P = .17). Under the VBP, a higher proportion of award hospitals received penalties compared with other hospitals (250 [51.7%] vs 950 [41.4%]; P < .001), and fewer award hospitals received financial rewards (234 [48.4%] vs 1347 [58.6%]; P < .001). Median payment reductions were higher for award hospitals than other hospitals (0.01% [IQR, 0.00%-0.38%] vs 0.0% [IQR, 0.00%-0.28%]; P < .001), and median payment increases were lower (0.0% [IQR, 0.00%-0.34%] vs 0.13% [IQR, 0.00%-0.60%]; P < .001). Thirty-day mortality at award hospitals was similar (acute myocardial infarction, 13.2% vs 13.2%; P = .76) or slightly lower (heart failure, 11.3% vs 11.7%; P = .001) compared with other hospitals., Conclusions and Relevance: Hospitals that received awards for high-quality cardiovascular care from the AHA/ACC were more likely to be penalized and less likely to be financially rewarded by federal value-based programs. These findings highlight the potential need to standardize measurement of cardiovascular care quality.

Extensive phytochemical investigation from the roots of Aconitum kirinense Nakai led to the identification of fifteen new compounds, including four ranaconitine type C 18 -diterpenoid alkaloids (kirisines A-D, 1-4), one lappaconitine type C 18 -diterpenoid alkaloid (kirisine E, 5), seven denudatine type C 20 -diterpenoid alkaloids (kirisines F-L, 6-12), and three napelline type C 20 -diterpenoid alkaloids (kirisines M-O, 13-15), together with 25 known ones. Their structures were elucidated by extensive spectroscopic analyses. Among them, compounds 1 and 2 are rare diterpenoid alkaloid with 9,14-methylenedioxy group, and the latter also has a rare chloro-substituent. The diterpenoid alkaloids isolated were C 18 , C 19 and C 20 -category, which might provide further clues for understanding the chemotaxonomic significance of this plant. The isolated compounds were tested for neuroprotective activity and acetylcholinesterase inhibitory activity. Compounds 7, 18, 30 and 40 which exhibited moderate activity at 80 μM against acetylcholinesterase., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Glioma, especially glioblastoma, is pathologically characterized by high aggressiveness, which largely contributed to the ineffectiveness of current therapies. It has been recently reported that intrinsic PD-L1 can regulate tumor malignancy, whereas underlying mechanisms remain mostly unclear. Here, we report a novel mechanism by which PD-L1 promotes glioma cell infiltration. In orthotopic glioma models, PD-L1 expression was up-regulated predominantly in glioma cells in the infiltrating front. For PD-L1-overexpressed glioma cells, PI3K/Akt and actin regulations were among the top six most altered signaling pathways as detected by RNA-sequencing. PD-L1 significantly activated Akt/F-actin signaling while suppressed autophagic signaling upon cell starvation. Mechanistically, PD-L1 preferentially bound to Akt among various PI3K/Akt signaling proteins. Serial truncation identified the interaction between the 128-237aa fragment of PD-L1 and the 112-480aa fragment of Akt, which facilitates the membrane translocation/activation of Akt, and was unaffected by Perifosin (specific p-Akt inhibitor targeting Akt PH-domain). Taken together, our data indicate that in glioma cells, PD-L1 is induced to prevent autophagic cytoskeleton collapse via Akt binding/activation, facilitating glioma cell invasion upon starvation stress., (Copyright © 2019 Chen, Xu, Liu, Li, Li, Li, Jiang, Hu, Liu, Pan, Qiu and Chen.)

MXenes have attracted great attention for their potential applications in electrochemical and electronic devices due to their excellent characteristics. Traditional sound sources based on the thermoacoustic effect demonstrated that a conductor needs to have an extremely low heat capacity and high thermal conductivity. Hence, a thin MXene film with a low heat capacity per unit area (HCPUA) and special layered structure is emerging as a promising candidate to build loudspeakers. However, the use of MXenes in a sound source device has not been explored. Herein, we have successfully prepared sound source devices on an anodic aluminum oxide (AAO) and a flexible polyimide (PI) substrates by using the prepared Ti 3 C 2 MXene nanoflakes. Due to the larger interlayer distance of MXene, the MXene-based sound source device has a higher sound pressure level (SPL) than that of graphene of the same thickness. High-quality Ti 3 C 2 MXene nanoflakes were fabricated by selectively etching the Ti 3 AlC 2 powder. The as-fabricated MXene sound source device on an AAO substrate exhibits a higher SPL of 68.2 dB ( f = 15 kHz) and has a very stable sound spectrum output with frequency varying from 100 Hz to 20 kHz. A theoretical model has been built to explain the mechanism of the sound source device on an AAO substrate, matching well with the experimental results. Furthermore, the MXene sound source device based on a flexible PI substrate has been attached to the arms, back of the hand, and fingers, indicating an excellent acoustic wearability. Then, the MXene film is packaged successfully into a commercial earphone case and shows an excellent performance at high frequencies, which is very suitable for human audio equipment.

With the rapid development of liver surgery,minimally invasive techniques have been widely used in liver surgery. Many challenging liver can be performed laparoscopically to decrease the surgical trauma. At the same time,the efficiency and accuracy of liver surgeries have been highly improved by the advanced assisted technology of liver surgery. The purpose of this article is to summarize the current situation of liver surgery as well as the future of liver surgery.

Objective: To analyse the immunogenicity of a fusion protein containing cell epitopes of Mycobacterium tuberculosis genes Rv 2660 c , Rv 2460 c , Rv 3875 and Rv 3804, and to evaluate the feasibility of using it as a novel target antigen for developing multi-stage TB vaccines., Methods: Cell epitopes of Rv 2660 c , Rv 2460 c , Rv 3875 and Rv 3804 c were fused in series to form a new antigen gene (named msv ). Then msv was cloned into the prokaryotic expression vector pEASY -Blunt E1. The fusion protein msv was expressed by pEASY -Blunt E1 under the induction of isopropyl-β-d-thiogalactoside (IPTG). Purified the protein by affinity chromatography and identified the protein by SDS-PAGE and Western blot. To evaluate the immunogenicity of the protein, the mice were immunized with the purified fusion protein, and the titer of the antibody in mice serum was evaluated by ELISA. Besides, splenocytes of immunized mice were separated and splenocytes proliferation was determined under the stimulation of the protein., Results: The prokaryotic expression plasmid carrying msv gene was constructed successfully and msv protein could be expressed by the plasmid under the induction of IPTG. SDS-PAGE and Western blot results confirmed that a purified protein (relative molecular mass was 41.3×10 3 ) was obtained. ELISA result indicated that the titer of the antibody in msv immunized mice serum was about 1:81 920.The spleen lymphocyte proliferation assay showed that after immunization with msv protein, significant proliferation of antigen-sensitized lymphocytes was observed., Conclusions: The fusion protein msv was successfully expressed and purified, which can induce humoral and cellular immunity in mice. It may be used as an antigen component for the development of TB vaccine in the future., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

The prevalence of overweight-obesity has increased sharply among undergraduates worldwide. In 2016, approximately 52% of adults were overweight-obese. This cross-sectional study aimed to investigate the prevalence of overweight-obesity and explore in depth the connection between eating habits and overweight-obesity among Chinese undergraduates.The study population included 536 undergraduates recruited in Shijiazhuang, China, in 2017. They were administered questionnaires for assessing demographic and daily lifestyle characteristics, including sex, region, eating speed, number of meals per day, and sweetmeat habit. Anthropometric status was assessed by calculating the body mass index (BMI). The determinants of overweight-obesity were investigated by the Pearson χ test, Spearman rho test, multivariable linear regression, univariate/multivariate logistic regression, and receiver operating characteristic curve analysis.The prevalence of undergraduate overweight-obesity was 13.6%. Sex [male vs female, odds ratio (OR): 1.903; 95% confidence interval (95% CI): 1.147-3.156], region (urban vs rural, OR: 1.953; 95% CI: 1.178-3.240), number of meals per day (3 vs 2, OR: 0.290; 95% CI: 0.137-0.612), and sweetmeat habit (every day vs never, OR: 4.167; 95% CI: 1.090-15.933) were significantly associated with overweight-obesity. Eating very fast was positively associated with overweight-obesity and showed the highest OR (vs very slow/slow, OR: 5.486; 95% CI: 1.622-18.553). However, the results of multivariate logistic regression analysis indicated that only higher eating speed is a significant independent risk factor for overweight/obesity (OR: 17.392; 95% CI, 1.614-187.363; P = .019).Scoremeng = 1.402 × scoresex + 1.269 × scoreregion + 19.004 × scoreeatin speed + 2.546 × scorenumber of meals per day + 1.626 × scoresweetmeat habit and BMI = 0.253 × Scoremeng + 18.592. These 2 formulas can help estimate the weight status of undergraduates and predict whether they will be overweight or obese.

Background: Central nervous system (CNS) metastases represent a significant source of morbidity and mortality for patients with ALK tyrosine kinase gene (ALK)-positive NSCLC. Alectinib has demonstrated robust CNS activity in both crizotinib-naive and crizotinib-resistant settings. However, the CNS efficacy of alectinib has not been established in patients with untreated symptomatic, large CNS metastases., Methods: In this retrospective study, patients were eligible if they had advanced ALK-positive NSCLC with large (defined as ≥1 cm) or symptomatic CNS metastases and received alectinib. Medical records and radiographic imaging were reviewed to determine treatment outcomes. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1., Results: Of the 19 patients, 15 (79%) had measurable CNS disease at baseline and were evaluable for response. The CNS objective response rate in these patients was 73.3% (95% confidence interval [CI]: 44.9%-92.2%), the CNS disease control rate was 100.0% (95% CI: 78.2%-100.0%), and the median CNS duration of response was 19.3 months (95% CI: 14.3 months-not evaluable). In 18 evaluable patients with measurable and/or nonmeasurable baseline CNS disease, the CNS objective response rate was 72.2% (95% CI: 46.5%-90.3%), the CNS disease control rate was 100.0% (95% CI: 81.5%-100.0%), and the median CNS duration of response was 17.1 months (95% CI: 14.3 months-not evaluable). All eight patients with symptoms attributable to CNS metastases had clinical improvement upon starting alectinib therapy. Six patients (32%) eventually required salvage brain radiotherapy., Conclusions: Alectinib demonstrated meaningful CNS efficacy in patients with ALK-positive NSCLC with untreated symptomatic or large brain metastases., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Following publication of the original article.

Objective: To analyze the clinicopathological characteristics and prognosis of diffuse midline glioma (DMG) with H3K27M mutation. Methods: Thirty cases of DMG were collected in Guangdong Sanjiu Brain Hospital from October 2016 to May 2018. The patients' clinicopathological data including age, tumor site and histological grade, treatment and follow-up data were collected and analyzed. Results: There were 21 males and 9 females, with a mean age of 26 years (range 5-53 years). Fourteen tumors were located in thalamus, 12 in brainstem (one involved both thalamus and brainstem), and one each in hypothalamus, fourth ventricle, and sellar region, respectively. Two cases presented as diffuse intracranial lesions. Three cases (10.0%) were of WHO grade Ⅰ, 10 cases (33.3%) were grade Ⅱ, eight cases (26.7%) were grade Ⅲ, and nine cases (30.0%) were grade Ⅳ.All patients with gradeⅠ tumors were older than 20 years. Histologically, all were pilocytic astrocytoma-like. Immunohistochemical staining demonstrated that all tumors were IDH1 negative. Twenty-eight tumors showed diffuse expression of H3K27M, and two showed focal expression. Twenty-one tumors(100.0%, 21/21) showed absent expression of H3K27me3. Sixteen tumors (57.1%, 16/28) showed strongly positive expression of p53, and ATRX was negative in eight tumors (38.1%, 8/21). The Ki-67 proliferation index ranged from 5% to 40%. Eight cases (including two cases of H3K27M expression of individual cells) showed K27M mutation in H3F3A gene. Intracranial and spinal cord dissemination occurred in six cases (20.0%, 6/30). Median progression-free survival (PFS) was 9.5 months and median overall survival (OS) was 34 months. Mean PFS was 11.2 months and mean OS was 24.3 months. Compared with adults (>20 years old), children/adolescents (no more than 20 years old) had significantly shorter median OS (8 months vs. 34 months, P= 0.013). There was no significant difference in PFS and OS between DMGs located in the brain stem/thalamus and other sites within midline ( P> 0.05). There was no significant difference in PFS and OS between WHO grade ⅠDMGs and WHO grade Ⅱ-Ⅳ DMGs ( P> 0.05). Conclusions: DMGs occur more commonly in children and adolescents with male predominance. DMGs present with WHO Ⅰ-Ⅳ tumors morphologically, and pilocytic astrocytoma-like lesions with WHO Ⅰ are more common in adults. Expression of H3K27M but not H3K27me3 is helpful for diagnosis of DMG. The prognosis of children/adolescents is significantly worse than that of adults, whereas histological grade and tumor location do not affect prognosis.

Objective: To evaluate clinical efficaly of intractable lateral epicondylitis by extracurricular arthroscopic operation based on pressure point., Methods: From October 2015 to September 2017, 19 patients with intractable lateral epicondylitis were treated with extraarticylar arthroscopic operation based in pressure point. Among patients, including 7 males and 12 females, aged from 33 to 62 years old with an average of(43.16±8.12) years old, The courses of conservative treatment ranged from 7 to 41 months, with an average of(15.47±7.08) months. Postoperative complications were observed, VAS score and Mayo score before and after operation at 3 months were observed and compared., Results: All patients were followed up from 6 to 26 months, with an average (17.16±5.25) months. No infection, skin necrosis and nerve injury occurred. No group weakness occurred within six months after operation. VAS score decreased from 4.42±1.17 before operation to 0.53±0.61 after operation at 3 months. Mago was improved from 62.63±7.88 before operation to 93.42±5.28 after operation at 3 months. According to Mayo score, 17 cases got excellent results, and 2 cases were good., Conclusions: Intractable lateral epicondylitis by arthroscopic extracurricular operation based on pressure point, which deal with main extracurricular root cause, could anatomical level is understand easily, field of vision is good and diseased tissue is cleaned up thoroughly, and has obvious curative effect., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Aims: Postmenopausal osteoporosis is a bone metabolism disease that is caused by an imbalance between bone-resorbing osteoclast and bone-forming osteoblast actions. Herein, we describe the role of troxerutin (TRX), a trihydroxyethylated derivative of rutin, in ovariectomy (OVX)-induced osteoporosis and its effects on the regulation of osteoclasts and osteoblasts., Main Methods: In vivo, OVX female mice were intraperitoneally injected with either saline, 50 mg/kg TRX, or 150 mg/kg TRX for 6 weeks and then sacrificed for micro-computed tomography analyses, histological analyses, and biomechanical testing. In vitro, RAW264.7 cell-derived osteoclasts and MC3T3-E1 cell-derived osteoblasts were treated with different concentrations of TRX to examine the effect of TRX on osteoclastogenesis and bone resorption, as well as on osteogenesis and mineralization., Key Findings: In this study, we demonstrated that TRX prevented cortical and trabecular bone loss in ovariectomized mice by reducing osteoclastogenesis and promoting osteogenesis in vivo. In vitro, TRX inhibited the formation and activity of RAW264.7-derived osteoclasts and the expression of nuclear factor of activated T-cells 1 and cathepsin K. Meanwhile, TRX improved the osteogenesis and mineralization of MC3T3-E1 by enhancing the expression of Runt-related transcription factor 2, Osterix, and collagen type 1 alpha 1., Significance: Our data demonstrated that TRX could prevent OVX-induced osteoporosis and be used in a novel treatment for postmenopausal osteoporosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Several studies have been performed to investigate the association between SMAD3 gene polymorphism and osteoarthritis (OA), but the results were inconclusive. This study aims to determine whether SMAD3 polymorphism is associated with risk of OA., Method: A comprehensive literature search in PubMed, Embase, and ISI Web of Science for relevant studies was performed. After extracting data from eligible studies, we chose the fixed or random effect model according to the heterogeneity test. Estimation of publication bias and sensitivity analysis were conducted to confirm the stability of this meta-analysis., Results: In total, 10 studies from 6 articles with 5093 OA patients and 5699 controls were enrolled in this meta-analysis. The combined results revealed significant association between SMAD3 rs12901499 polymorphism and the risk of OA (allele model: OR 1.21, 95% CI 1.07-1.38). Subgroup analysis revealed that G allele increased the risk of OA in Caucasians, but not in Asians (allele model: Caucasians: OR 1.31, 95% CI 1.18-1.44; Asians: OR 1.24, 95% CI 0.95-1.61). And the pooled results revealed significant association between SMAD3 rs12901499 polymorphism and both knee and hip OA (knee OA: OR 1.18, 95% CI 1.04-1.34; hip OA: OR 1.31, 95% CI 1.18-1.44)., Conclusion: The current meta-analysis revealed that the G variant of SMAD3 rs12901499 polymorphism increased the risk of OA in Caucasians. Further well-designed studies with larger sample size in different ethnic populations are required to confirm these results.

The odd-skipped related 1 (OSR1) gene encodes a zinc-finger transcription factor. The expression and significance of OSR1 in human tumors remains unclear. We found that OSR1 was downregulated in lung cancers, and its expression was correlated with poor differentiation. Overexpression of OSR1 by OSR1 gene transfection into H1299 cells (H1299-OSR1) inhibited the proliferation and invasion of lung cancer cells. Knockdown of OSR1 with small interfering (si)RNA against OSR1 in A549 cells (A549-siOSR1) enhanced the proliferation and invasion of lung cancer cells. Western blot analysis showed that the expression level of GSK3β increased, while that of p-GSK3β, nuclear β-catenin, cyclin D1, c-Myc and matrix metallopeptidase 7 significantly decreased in the H1299-OSR1 cells, and this pattern was reversed in the A549-siOSR1 cells compared to that in the control cells. Furthermore, upregulation of sex-determining region Y-box 9 (SOX9) by SOX9 gene transfection increased the expression of β-catenin, which was inhibited by OSR1. The mRNA and protein expression levels of SOX9 and β-catenin were reduced in H1299-OSR1 cells and increased in A549-siOSR1 cells. In conclusion, the expression of OSR1 was more reduced in lung cancer tissues than in normal lung tissues, and was correlated with poor differentiation. OSR1 downregulated the activity of the Wnt signaling pathway by suppressing the expression of SOX9 and β-catenin., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)